[Pathogenicity factors of bacteria with glycosylating activity].

PubMed

Tartakovskaia, D I; Araslanova, V A; Belyĭ, Iu F

2011-01-01

A and B toxins of Clostridium difficile, a-toxin of C. novyi, lehal toxin of C. sordellii, and TpeL toxin of C. perfringens belong to the group of the so-called large Clostridium toxins. These toxins modify low-molecular weight guanosine triphosphate-binding proteins of the Rho/Ras family by their glycosylation that results in inactivation of major signal pathways in eukaryotic cells. Lgt glycosyltransferases, a new group of pathogenicity factors also capable of inactivating eukaryotic substrates via glycosylation, have recently been identified in Legionella. They are transported into cytoplasm of eukaryotic target cells by type 4 secretory system of Legionella. After translocation, the enzyme inhibits protein synthesis by attaching glucose residue to Ser53 of 1A elongation factor. The available data suggest an important role of bacterial glycosylating factors in the action of pathogens causing infectious diseases.

Campylobacter ureolyticus

PubMed Central

O'Donovan, Dylan; Corcoran, Gerard D; Lucey, Brigid; Sleator, Roy D

2014-01-01

Herein, we provide a brief overview of the emerging bacterial pathogen Campylobacter ureolyticus. We describe the identification of the pathogen by molecular as opposed to classical culture based diagnostics and discuss candidate reservoirs of infection. We also review the available genomic data, outlining some of the major virulence factors, and discuss how these mechanisms likely contribute to pathogenesis of the organism. PMID:24717836

Transcriptome analyses suggest a disturbance of iron homeostasis in soybean leaves during white mould disease establishment

USDA-ARS?s Scientific Manuscript database

Sclerotinia sclerotiorum is a serious pathogen of numerous crops around the world. The major virulence factor of this pathogen is oxalic acid (OA). Mutants that cannot produce OA do not cause disease, and plants that express enzymes that degrade OA, such as oxalate oxidase (OxO) are very resistant t...

Evolution of Compatibility Range in the Rice-Magnaporthe oryzae System: An Uneven Distribution of R Genes Between Rice Subspecies.

PubMed

Gallet, Romain; Fontaine, Colin; Bonnot, François; Milazzo, Joëlle; Tertois, Christophe; Adreit, Henri; Ravigné, Virginie; Fournier, Elisabeth; Tharreau, Didier

2016-04-01

Efficient strategies for limiting the impact of pathogens on crops require a good understanding of the factors underlying the evolution of compatibility range for the pathogens and host plants, i.e., the set of host genotypes that a particular pathogen genotype can infect and the set of pathogen genotypes that can infect a particular host genotype. Until now, little is known about the evolutionary and ecological factors driving compatibility ranges in systems implicating crop plants. We studied the evolution of host and pathogen compatibility ranges for rice blast disease, which is caused by the ascomycete Magnaporthe oryzae. We challenged 61 rice varieties from three rice subspecies with 31 strains of M. oryzae collected worldwide from all major known genetic groups. We determined the compatibility range of each plant variety and pathogen genotype and the severity of each plant-pathogen interaction. Compatibility ranges differed between rice subspecies, with the most resistant subspecies selecting for pathogens with broader compatibility ranges and the least resistant subspecies selecting for pathogens with narrower compatibility ranges. These results are consistent with a nested distribution of R genes between rice subspecies.

Invited review: Mastitis in dairy heifers: nature of the disease, potential impact, prevention, and control.

PubMed

De Vliegher, S; Fox, L K; Piepers, S; McDougall, S; Barkema, H W

2012-03-01

Heifer mastitis is a disease that potentially threatens production and udder health in the first and subsequent lactations. In general, coagulase-negative staphylococci (CNS) are the predominant cause of intramammary infection and subclinical mastitis in heifers around parturition, whereas Staphylococcus aureus and environmental pathogens cause a minority of the cases. Clinical heifer mastitis is typically caused by the major pathogens. The variation in proportions of causative pathogens between studies, herds, and countries is considerable. The magnitude of the effect of heifer mastitis on an individual animal is influenced by the form of mastitis (clinical versus subclinical), the virulence of the causative pathogen(s) (major versus minor pathogens), the time of onset of infection relative to calving, cure or persistence of the infection when milk production has started, and the host's immunity. Intramammary infection in early lactation caused by CNS does not generally have a negative effect on subsequent productivity. At the herd level, the impact will depend on the prevalence and incidence of the disease, the nature of the problem (clinical, subclinical, nonfunctional quarters), the causative pathogens involved (major versus minor pathogens), the ability of the animals to cope with the disease, and the response of the dairy manager to control the disease through management changes. Specific recommendations to prevent and control mastitis in late gestation in periparturient heifers are not part of the current National Mastitis Council mastitis and prevention program. Control and prevention is currently based on avoidance of inter-sucking among young stock, fly control, optimal nutrition, and implementation of hygiene control and comfort measures, especially around calving. More risk factors for subclinical and clinical heifer mastitis have been identified (e.g., season, location of herd, stage of pregnancy) although they do not lend themselves to the development of specific intervention strategies designed to prevent the disease. Pathogen-specific risk factors and associated control measures need to be identified due to the pathogen-related variation in epidemiology and effect on future performance. Prepartum intramammary treatment with antibiotics has been proposed as a simple and effective way of controlling heifer mastitis but positive long-lasting effects on somatic cell count and milk yield do not always occur, ruling out universal recommendation of this practice. Moreover, use of antibiotics in this manner is off-label and results in an increased risk of antibiotic residues in milk. Prepartum treatment can be implemented only as a short-term measure to assist in the control of a significant heifer mastitis problem under supervision of the herd veterinarian. When CNS are the major cause of intramammary infection in heifers, productivity is not affected, making prepartum treatment redundant and even unwanted. In conclusion, heifer mastitis can affect the profitability of dairy farming because of a potential long-term negative effect on udder health and milk production and an associated culling risk, specifically when major pathogens are involved. Prevention and control is not easy but is possible through changes in young stock and heifer management. However, the pathogenesis and epidemiology of the disease remain largely unknown and more pathogen-specific risk factors should be identified to optimize current prevention programs. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Pathogen bacteria adhesion to skin mucus of fishes.

PubMed

Benhamed, Said; Guardiola, Francisco A; Mars, Mohammed; Esteban, María Ángeles

2014-06-25

Fish are always in intimate contact with their environment; therefore they are permanently exposed to very vary external hazards (e.g. aerobic and anaerobic bacteria, viruses, parasites, pollutants). To fight off pathogenic microorganisms, the epidermis and its secretion, the mucus acts as a barrier between the fish and the environment. Fish are surrounded by a continuous layer of mucus which is the first physical, chemical and biological barrier from infection and the first site of interaction between fish's skin cells and pathogens. The mucus composition is very complex and includes numerous antibacterial factors secreted by fish's skin cells, such as immunoglobulins, agglutinins, lectins, lysins and lysozymes. These factors have a very important role to discriminate between pathogenic and commensal microorganisms and to protect fish from invading pathogens. Furthermore, the skin mucus represents an important portal of entry of pathogens since it induces the development of biofilms, and represents a favorable microenvironment for bacteria, the main disease agents for fish. The purpose of this review is to summarize the current knowledge of the interaction between bacteria and fish skin mucus, the adhesion mechanisms of pathogens and the major factors influencing pathogen adhesion to mucus. The better knowledge of the interaction between fish and their environment could inspire other new perspectives to study as well as to exploit the mucus properties for different purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war?

PubMed

Yang, Da-Rong; Zhu, Hai-Zhen

2015-04-07

Hepatitis C virus (HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon (IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes (ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection.

Microbiology and risk factors associated with war-related wound infections in the Middle East.

PubMed

Sahli, Z T; Bizri, A R; Abu-Sittah, G S

2016-10-01

The Middle East region is plagued with repeated armed conflicts that affect both civilians and soldiers. Injuries sustained during war are common and frequently associated with multiple life-threatening complications. Wound infections are major consequences of these war injuries. The microbiology of war-related wound infections is variable with predominance of Gram-negative bacteria in later stages. The emergence of antimicrobial resistance among isolates affecting war-related wound injuries is a serious problem with major regional and global implications. Factors responsible for the increase in multidrug-resistant pathogens include timing and type of surgical management, wide use of antimicrobial drugs, and the presence of metallic or organic fragments in the wound. Nosocomial transmission is the most important factor in the spread of multidrug-resistant pathogens. Wound management of war-related injuries merits a multidisciplinary approach. This review aims to describe the microbiology of war-related wound infections and factors affecting their incidence from conflict areas in Iraq, Syria, Israel, and Lebanon.

Mobile DNA in the pathogenic Neisseria

PubMed Central

Obergfell, Kyle P.; Seifert, H. Steven

2015-01-01

The genus Neisseria contains two pathogenic species of notable public health concern: Neisseria gonorrhoeae and Neisseria meningitidis. These pathogens display a notable ability to undergo frequent programmed recombination events. The recombination mediated pathways of transformation and pilin antigenic variation in the Neisseria are well studied systems that are critical for pathogenesis. Here we will detail the conserved and unique aspects of transformation and antigenic variation in the Neisseria. Transformation will be followed from initial DNA binding through recombination into the genome with consideration to the factors necessary at each step. Additional focus is paid to the unique type IV secretion system that mediates donation of transforming DNA in the pathogenic Neisseria. The pilin antigenic variation system uses programed recombinations to alter a major surface determinant which allows immune avoidance and promotes infection. We discuss the trans- and cis- acting factors which facilitate pilin antigenic variation and present the current understanding of the mechanisms involved in the process. PMID:25866700

Preoperative biliary colonization/infection caused by multidrug-resistant (MDR) pathogens in patients undergoing major hepatectomy with extrahepatic bile duct resection.

PubMed

Sugawara, Gen; Yokoyama, Yukihiro; Ebata, Tomoki; Igami, Tsuyoshi; Yamaguchi, Junpei; Mizuno, Takashi; Yagi, Tetsuya; Nagino, Masato

2018-05-01

The aim of this study was to review the surgical outcomes of patients who underwent major hepatectomy with extrahepatic bile duct resection after preoperative biliary drainage with a particular focus on the impact of preoperative biliary colonization/infection caused by multidrug-resistant pathogens. Medical records of patients who underwent hepatobiliary resection after preoperative external biliary drainage between 2001 and 2015 were reviewed retrospectively. Prophylactic antibiotics were selected according to the results of drug susceptibility tests of surveillance bile cultures. In total, 565 patients underwent surgical resection. Based on the results of bile cultures, the patients were classified into three groups: group A, patients with negative bile cultures (n = 113); group B, patients with positive bile cultures without multidrug-resistant pathogen growth (n = 416); and group C, patients with multidrug-resistant pathogen-positive bile culture (n = 36). The incidence of organ/space surgical site infection, bacteremia, median duration of postoperative hospital stay, and the mortality rate did not differ among the three groups. The incidence of incisional surgical site infection and infectious complications caused by multidrug-resistant pathogens was significantly higher in group C than in groups A and B. Fifty-two patients had postoperative infectious complications caused by multidrug-resistant pathogens. Multivariate analysis identified preoperative multidrug-resistant pathogen-positive bile culture as a significant independent risk factor for postoperative infectious complications caused by multidrug-resistant pathogens (P< .001). Major hepatectomy with extrahepatic bile duct resection after biliary drainage can be performed with acceptable rates of morbidity and mortality using appropriate antibiotic prophylaxis, even in patients with biliary colonization/infection caused by multidrug-resistant pathogens. Copyright © 2018 Elsevier Inc. All rights reserved.

Lethal factor is not required for Bacillus anthracis virulence in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Blachinsky, Eran; Kobiler, David

2011-11-01

The major virulence factor of Bacillus anthracis is the tripartite anthrax toxin, comprising the protective antigen (PA), lethal factor (LF) and edema factor (EF). The LF of B. anthracis is a metalloprotease that has been shown to play an important role in pathogenicity. Deletion of this gene (lef) in the Sterne strain was reported to dramatically reduce the pathogenicity of this strain in mice, and was reported to be as dramatic as the deletion of PA. We evaluated the effect on pathogenicity of the lef deletion in the fully virulent Vollum strain in guinea pigs and NZW rabbits by either subcutaneous injection or intranasal instillation. In guinea pigs, no major differences between the mutant strain and the wild type could be detected in the LD(50) or mean time to death values. On the other hand, the lef deletion caused death of 50-70% of all rabbits infected with the mutant spores at doses equivalent or higher than the wild type LD(50). The surviving rabbits, which were infected with spore doses higher than the wild type LD(50), developed a protective immune response that conferred resistance to challenge with the wild type strain. These findings may indicate that the mutant lacking the LF is capable of host colonization which causes death in 50-70% of the animals and a protective immune response in the others. These results indicate that unlike the data obtained in mice, the LF mutation does not abolish B. anthracis pathogenicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Complement factor H in host defense and immune evasion.

PubMed

Parente, Raffaella; Clark, Simon J; Inforzato, Antonio; Day, Anthony J

2017-05-01

Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

Demonstrating effective RNAi product line to control honeybee colony collapse factors

USDA-ARS?s Scientific Manuscript database

The Colony Collapse Disorder (CCD) phenomenon affecting honey bees is still not fully understood, but there is a strong consensus that some specific pathogens and pests are major contributing factors to colony losses. Viruses, microsporidia, and the Varroa mite are considered the top three contribut...

Vimentin, a Novel NF-κB Regulator, Is Required for Meningitic Escherichia coli K1-Induced Pathogen Invasion and PMN Transmigration across the Blood-Brain Barrier.

PubMed

Huang, Sheng-He; Chi, Feng; Peng, Liang; Bo, Tao; Zhang, Bao; Liu, Li-Qun; Wu, Xuedong; Mor-Vaknin, Nirit; Markovitz, David M; Cao, Hong; Zhou, Yan-Hong

NF-κB activation, pathogen invasion, polymorphonuclear leukocytes (PMN) transmigration (PMNT) across the blood-brain barrier (BBB) are the pathogenic triad hallmark features of bacterial meningitis, but the mechanisms underlying these events remain largely unknown. Vimentin, which is a novel NF-κB regulator, is the primary receptor for the major Escherichia coli K1 virulence factor IbeA that contributes to the pathogenesis of neonatal bacterial sepsis and meningitis (NSM). We have previously shown that IbeA-induced NF-κB signaling through its primary receptor vimentin as well as its co-receptor PTB-associated splicing factor (PSF) is required for pathogen penetration and leukocyte transmigration across the BBB. This is the first in vivo study to demonstrate how vimentin and related factors contributed to the pathogenic triad of bacterial meningitis. The role of vimentin in IbeA+ E. coli K1-induced NF-κB activation, pathogen invasion, leukocyte transmigration across the BBB has now been demonstrated by using vimentin knockout (KO) mice. In the in vivo studies presented here, IbeA-induced NF-κB activation, E. coli K1 invasion and polymorphonuclear neutrophil (PMN) transmigration across the BBB were significantly reduced in Vim-/- mice. Decreased neuronal injury in the hippocampal dentate gyrus was observed in Vim-/- mice with meningitis. The major inflammatory regulator α7 nAChR and several signaling molecules contributing to NF-κB activation (p65 and p-CamKII) were significantly reduced in the brain tissues of the Vim-/- mice with E. coli meningitis. Furthermore, Vim KO resulted in significant reduction in neuronal injury and in α7 nAChR-mediated calcium signaling. Vimentin, a novel NF-κB regulator, plays a detrimental role in the host defense against meningitic infection by modulating the NF-κB signaling pathway to increase pathogen invasion, PMN recruitment, BBB permeability and neuronal inflammation. Our findings provide the first evidence for Vim-dependent mechanisms underlying the pathogenic triad of bacterial meningitis.

Vimentin, a Novel NF-κB Regulator, Is Required for Meningitic Escherichia coli K1-Induced Pathogen Invasion and PMN Transmigration across the Blood-Brain Barrier

PubMed Central

Zhang, Bao; Liu, Li-Qun; Wu, Xuedong; Mor-Vaknin, Nirit; Markovitz, David M.; Cao, Hong; Zhou, Yan-Hong

2016-01-01

Background NF-κB activation, pathogen invasion, polymorphonuclear leukocytes (PMN) transmigration (PMNT) across the blood-brain barrier (BBB) are the pathogenic triad hallmark features of bacterial meningitis, but the mechanisms underlying these events remain largely unknown. Vimentin, which is a novel NF-κB regulator, is the primary receptor for the major Escherichia coli K1 virulence factor IbeA that contributes to the pathogenesis of neonatal bacterial sepsis and meningitis (NSM). We have previously shown that IbeA-induced NF-κB signaling through its primary receptor vimentin as well as its co-receptor PTB-associated splicing factor (PSF) is required for pathogen penetration and leukocyte transmigration across the BBB. This is the first in vivo study to demonstrate how vimentin and related factors contributed to the pathogenic triad of bacterial meningitis. Methodology/Principal Findings The role of vimentin in IbeA+ E. coli K1-induced NF-κB activation, pathogen invasion, leukocyte transmigration across the BBB has now been demonstrated by using vimentin knockout (KO) mice. In the in vivo studies presented here, IbeA-induced NF-κB activation, E. coli K1 invasion and polymorphonuclear neutrophil (PMN) transmigration across the BBB were significantly reduced in Vim-/- mice. Decreased neuronal injury in the hippocampal dentate gyrus was observed in Vim-/- mice with meningitis. The major inflammatory regulator α7 nAChR and several signaling molecules contributing to NF-κB activation (p65 and p-CamKII) were significantly reduced in the brain tissues of the Vim-/- mice with E. coli meningitis. Furthermore, Vim KO resulted in significant reduction in neuronal injury and in α7 nAChR-mediated calcium signaling. Conclusion/Significance Vimentin, a novel NF-κB regulator, plays a detrimental role in the host defense against meningitic infection by modulating the NF-κB signaling pathway to increase pathogen invasion, PMN recruitment, BBB permeability and neuronal inflammation. Our findings provide the first evidence for Vim-dependent mechanisms underlying the pathogenic triad of bacterial meningitis. PMID:27657497

Emerging bacterial pathogens: the past and beyond.

PubMed

Vouga, M; Greub, G

2016-01-01

Since the 1950s, medical communities have been facing with emerging and reemerging infectious diseases, and emerging pathogens are now considered to be a major microbiologic public health threat. In this review, we focus on bacterial emerging diseases and explore factors involved in their emergence as well as future challenges. We identified 26 major emerging and reemerging infectious diseases of bacterial origin; most of them originated either from an animal and are considered to be zoonoses or from water sources. Major contributing factors in the emergence of these bacterial infections are: (1) development of new diagnostic tools, such as improvements in culture methods, development of molecular techniques and implementation of mass spectrometry in microbiology; (2) increase in human exposure to bacterial pathogens as a result of sociodemographic and environmental changes; and (3) emergence of more virulent bacterial strains and opportunistic infections, especially affecting immunocompromised populations. A precise definition of their implications in human disease is challenging and requires the comprehensive integration of microbiological, clinical and epidemiologic aspects as well as the use of experimental models. It is now urgent to allocate financial resources to gather international data to provide a better understanding of the clinical relevance of these waterborne and zoonotic emerging diseases. Copyright © 2015. Published by Elsevier Ltd.

Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen.

PubMed

Awad, Milena M; Johanesen, Priscilla A; Carter, Glen P; Rose, Edward; Lyras, Dena

2014-01-01

The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward determining the virulence factors and pathogenesis mechanisms used by this organism to cause disease. C. difficile is an opportunist pathogen that employs many factors to infect and damage the host, often with devastating consequences. This review will focus on the role of the 2 major virulence factors, toxin A (TcdA) and toxin B (TcdB), as well as the role of other putative virulence factors, such as binary toxin, in C. difficile-mediated infection. Consideration is given to the importance of spores in both the initiation of disease and disease recurrence and also to the role that surface proteins play in host interactions.

Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen

PubMed Central

Awad, Milena M; Johanesen, Priscilla A; Carter, Glen P; Rose, Edward; Lyras, Dena

2014-01-01

The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward determining the virulence factors and pathogenesis mechanisms used by this organism to cause disease. C. difficile is an opportunist pathogen that employs many factors to infect and damage the host, often with devastating consequences. This review will focus on the role of the 2 major virulence factors, toxin A (TcdA) and toxin B (TcdB), as well as the role of other putative virulence factors, such as binary toxin, in C. difficile-mediated infection. Consideration is given to the importance of spores in both the initiation of disease and disease recurrence and also to the role that surface proteins play in host interactions. PMID:25483328

The Major Histocompatibility Complex in Bovines: A Review

PubMed Central

Behl, Jyotsna Dhingra; Verma, N. K.; Tyagi, Neha; Mishra, Priyanka; Behl, Rahul; Joshi, B. K.

2012-01-01

Productivity in dairy cattle and buffaloes depends on the genetic factors governing the production of milk and milk constituents as well as genetic factors controlling disease resistance or susceptibility. The immune system is the adaptive defense system that has evolved in vertebrates to protect them from invading pathogens and also carcinomas. It is remarkable in the sense that it is able to generate an enormous variety of cells and biomolecules which interact with each other in numerous ways to form a complex network that helps to recognize, counteract, and eliminate the apparently limitless number of foreign invading pathogens/molecules. The major histocompatibility complex which is found to occur in all mammalian species plays a central role in the development of the immune system. It is an important candidate gene involved in susceptibility/resistance to various diseases. It is associated with intercellular recognition and with self/nonself discrimination. It plays major role in determining whether transplanted tissue will be accepted as self or rejected as foreign. PMID:23738132

Cryptic chytridiomycosis linked to climate and genetic variation in amphibian populations of the southeastern United States

PubMed Central

Hoffman, Eric A.; Tye, Matthew R.; Hether, Tyler D.; Savage, Anna E.

2017-01-01

North American amphibians have recently been impacted by two major emerging pathogens, the fungus Batrachochytrium dendrobatidis (Bd) and iridoviruses in the genus Ranavirus (Rv). Environmental factors and host genetics may play important roles in disease dynamics, but few studies incorporate both of these components into their analyses. Here, we investigated the role of environmental and genetic factors in driving Bd and Rv infection prevalence and severity in a biodiversity hot spot, the southeastern United States. We used quantitative PCR to characterize Bd and Rv dynamics in natural populations of three amphibian species: Notophthalmus perstriatus, Hyla squirella and Pseudacris ornata. We combined pathogen data, genetic diversity metrics generated from neutral markers, and environmental variables into general linear models to evaluate how these factors impact infectious disease dynamics. Occurrence, prevalence and intensity of Bd and Rv varied across species and populations, but only one species, Pseudacris ornata, harbored high Bd intensities in the majority of sampled populations. Genetic diversity and climate variables both predicted Bd prevalence, whereas climatic variables alone predicted infection intensity. We conclude that Bd is more abundant in the southeastern United States than previously thought and that genetic and environmental factors are both important for predicting amphibian pathogen dynamics. Incorporating both genetic and environmental information into conservation plans for amphibians is necessary for the development of more effective management strategies to mitigate the impact of emerging infectious diseases. PMID:28448517

The Composition and Spatial Patterns of Bacterial Virulence Factors and Antibiotic Resistance Genes in 19 Wastewater Treatment Plants

PubMed Central

Zhang, Bing; Xia, Yu; Wen, Xianghua; Wang, Xiaohui; Yang, Yunfeng; Zhou, Jizhong; Zhang, Yu

2016-01-01

Bacterial pathogenicity and antibiotic resistance are of concern for environmental safety and public health. Accumulating evidence suggests that wastewater treatment plants (WWTPs) are as an important sink and source of pathogens and antibiotic resistance genes (ARGs). Virulence genes (encoding virulence factors) are good indicators for bacterial pathogenic potentials. To achieve a comprehensive understanding of bacterial pathogenic potentials and antibiotic resistance in WWTPs, bacterial virulence genes and ARGs in 19 WWTPs covering a majority of latitudinal zones of China were surveyed by using GeoChip 4.2. A total of 1610 genes covering 13 virulence factors and 1903 genes belonging to 11 ARG families were detected respectively. The bacterial virulence genes exhibited significant spatial distribution patterns of a latitudinal biodiversity gradient and a distance-decay relationship across China. Moreover, virulence genes tended to coexist with ARGs as shown by their strongly positive associations. In addition, key environmental factors shaping the overall virulence gene structure were identified. This study profiles the occurrence, composition and distribution of virulence genes and ARGs in current WWTPs in China, and uncovers spatial patterns and important environmental variables shaping their structure, which may provide the basis for further studies of bacterial virulence factors and antibiotic resistance in WWTPs. PMID:27907117

A bacterial siren song: intimate interactions between neutrophils and pathogenic Neisseria

PubMed Central

Criss, Alison K.; Seifert, H. Steven

2012-01-01

Preface Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that are exquisitely adapted for growth at human mucosal surfaces and for efficient transmission between hosts. One factor that is essential to neisserial pathogenesis is the interaction between the bacteria and neutrophils, which are recruited in high numbers during infection. Although this vigorous host response could simply reflect effective immune recognition of the bacteria, there is mounting evidence that in fact these obligate human pathogens manipulate the innate immune response to promote infectious processes. This Review summarizes the mechanisms used by pathogenic neisseriae to resist and modulate the antimicrobial activities of neutrophils. It also details some of the major outstanding questions about the Neisseria–neutrophil relationship and proposes potential benefits of this relationship for the pathogen. PMID:22290508

Comparative Phenotypic Analysis of the Major Fungal Pathogens Candida parapsilosis and Candida albicans

PubMed Central

Holland, Linda M.; Schröder, Markus S.; Turner, Siobhán A.; Taff, Heather; Andes, David; Grózer, Zsuzsanna; Gácser, Attila; Ames, Lauren; Haynes, Ken; Higgins, Desmond G.; Butler, Geraldine

2014-01-01

Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CTG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of C. parapsilosis strains carrying double allele deletions of 100 transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in >40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance, and of CAP1 in the oxidative stress response. Others are unique to one species. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis but not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified seven transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1 and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. Two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic, and that Cph2 and Bcr1 are major biofilm regulators in C. parapsilosis. PMID:25233198

Multiple activities of the plant pathogen type III effector proteins WtsE and AvrE require WxxxE motifs.

PubMed

Ham, Jong Hyun; Majerczak, Doris R; Nomura, Kinya; Mecey, Christy; Uribe, Francisco; He, Sheng-Yang; Mackey, David; Coplin, David L

2009-06-01

The broadly conserved AvrE-family of type III effectors from gram-negative plant-pathogenic bacteria includes important virulence factors, yet little is known about the mechanisms by which these effectors function inside plant cells to promote disease. We have identified two conserved motifs in AvrE-family effectors: a WxxxE motif and a putative C-terminal endoplasmic reticulum membrane retention/retrieval signal (ERMRS). The WxxxE and ERMRS motifs are both required for the virulence activities of WtsE and AvrE, which are major virulence factors of the corn pathogen Pantoea stewartii subsp. stewartii and the tomato or Arabidopsis pathogen Pseudomonas syringae pv. tomato, respectively. The WxxxE and the predicted ERMRS motifs are also required for other biological activities of WtsE, including elicitation of the hypersensitive response in nonhost plants and suppression of defense responses in Arabidopsis. A family of type III effectors from mammalian bacterial pathogens requires WxxxE and subcellular targeting motifs for virulence functions that involve their ability to mimic activated G-proteins. The conservation of related motifs and their necessity for the function of type III effectors from plant pathogens indicates that disturbing host pathways by mimicking activated host G-proteins may be a virulence mechanism employed by plant pathogens as well.

Unprecedented Abundance of Protein Tyrosine Phosphorylation Modulates Shigella flexneri Virulence.

PubMed

Standish, Alistair James; Teh, Min Yan; Tran, Elizabeth Ngoc Hoa; Doyle, Matthew Thomas; Baker, Paul J; Morona, Renato

2016-10-09

Evidence is accumulating that protein tyrosine phosphorylation plays a crucial role in the ability of important human bacterial pathogens to cause disease. While most works have concentrated on its role in the regulation of a major bacterial virulence factor, the polysaccharide capsule, recent studies have suggested a much broader role for this post-translational modification. This prompted us to investigate protein tyrosine phosphorylation in the human pathogen Shigella flexneri. We first completed a tyrosine phosphoproteome, identifying 905 unique tyrosine phosphorylation sites on at least 573 proteins (approximately 15% of all proteins). This is the most tyrosine-phosphorylated sites and proteins in a single bacterium identified to date, substantially more than the level seen in eukaryotic cells. Most had not previously been identified and included proteins encoded by the virulence plasmid, which is essential for S. flexneri to invade cells and cause disease. In order to investigate the function of these phosphorylation sites in important virulence factors, phosphomimetic and ablative mutations were constructed in the type 3 secretion system ATPase Spa47 and the master virulence regulator VirB. This revealed that tyrosine residues phosphorylated in our study are critical for Spa47 and VirB activity, and tyrosine phosphorylation likely regulates their functional activity and subsequently the virulence of this major human pathogen. This study suggests that tyrosine phosphorylation plays a critical role in regulating a wide variety of virulence factors in the human pathogen S. flexneri and serves as a base for future studies defining its complete role. Copyright © 2016 Elsevier Ltd. All rights reserved.

Study on Interactions between the Major Apple Valsa Canker Pathogen Valsa mali and Its Biocontrol Agent Saccharothrix yanglingensis Hhs.015 Using RT-qPCR

PubMed Central

Fan, Dongying; Li, Yanfang; Zhao, Lingyun; Li, Zhengpeng; Huang, Lili; Yan, Xia

2016-01-01

The mechanism of biocontrol agent Saccharothrix yanglingensis Hhs.015 action against Valsa mali, a major apple Valsa canker pathogen, was examined using a novel, sensitive (minimum detection limit 100 pg/μL) and reliably RT-qPCR technique. Prior to lesion formation, total concentration of V. mali in the bark showed a significant decrease (p<0.05) after 24 h of Hhs.015 treatment. This was more pronounced at 48 and 96 h post treatment. After lesion formation, levels of V. mali remained constant at the boundary between infected and uninfected bark tissues, although the relative expansion rate of the lesion was significantly reduced (p<0.05). Gene expression levels of endo-polygalacturonase, a marker for fungal pathogenicity, were sharply reduced while host induced resistance callose synthase levels increased significantly (p<0.05) at the boundary bark at 9 d after Hhs.015 treatment. The results showed that biocontrol agent Hhs.015 prevented infection of V. mali by inhibiting pathogen growth, down-regulating pathogenicity factor expression and inducing a high level of host resistance. PMID:27611855

The Staphylococcus aureus RNome and Its Commitment to Virulence

PubMed Central

Felden, Brice; Vandenesch, François; Bouloc, Philippe; Romby, Pascale

2011-01-01

Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of bacteria to use RNAs to rapidly modify gene expression, including virulence factors in response to stress or environmental changes, and to survive in a host is an evolving concept. Here, we focus on the recently inventoried S. aureus regulatory RNAs, with emphasis on those with identified functions, two of which are directly involved in pathogenicity. PMID:21423670

Microbiological Food Safety for Vulnerable People

PubMed Central

Lund, Barbara M.

2015-01-01

Foodborne pathogens are more likely to cause infection and to result in serious consequences in vulnerable people than in healthy adults. People with some increase in susceptibility may form nearly 20% of the population in the UK and the USA. Conditions leading to increased susceptibility are listed. The main factors leading to foodborne disease caused by major pathogens are outlined and examples are given of outbreaks resulting from these factors. Measures to prevent foodborne disease include procedures based on Hazard Analysis Critical Control Point principles and prerequisite programmes and, especially for vulnerable people, the use of lower-risk foods in place of higher-risk products. PMID:26308030

Functional Metagenomics of Spacecraft Assembly Cleanrooms: Presence of Virulence Factors Associated with Human Pathogens

PubMed Central

Bashir, Mina; Ahmed, Mahjabeen; Weinmaier, Thomas; Ciobanu, Doina; Ivanova, Natalia; Pieber, Thomas R.; Vaishampayan, Parag A.

2016-01-01

Strict planetary protection practices are implemented during spacecraft assembly to prevent inadvertent transfer of earth microorganisms to other planetary bodies. Therefore, spacecraft are assembled in cleanrooms, which undergo strict cleaning and decontamination procedures to reduce total microbial bioburden. We wanted to evaluate if these practices selectively favor survival and growth of hardy microorganisms, such as pathogens. Three geographically distinct cleanrooms were sampled during the assembly of three NASA spacecraft: The Lockheed Martin Aeronautics' Multiple Testing Facility during DAWN, the Kennedy Space Center's Payload Hazardous Servicing Facility (KSC-PHSF) during Phoenix, and the Jet Propulsion Laboratory's Spacecraft Assembly Facility during Mars Science Laboratory. Sample sets were collected from the KSC-PHSF cleanroom at three time points: before arrival of the Phoenix spacecraft, during the assembly and testing of the Phoenix spacecraft, and after removal of the spacecraft from the KSC-PHSF facility. All samples were subjected to metagenomic shotgun sequencing on an Illumina HiSeq 2500 platform. Strict decontamination procedures had a greater impact on microbial communities than sampling location Samples collected during spacecraft assembly were dominated by Acinetobacter spp. We found pathogens and potential virulence factors, which determine pathogenicity in all the samples tested during this study. Though the relative abundance of pathogens was lowest during the Phoenix assembly, potential virulence factors were higher during assembly compared to before and after assembly, indicating a survival advantage. Decreased phylogenetic and pathogenic diversity indicates that decontamination and preventative measures were effective against the majority of microorganisms and well implemented, however, pathogen abundance still increased over time. Four potential pathogens, Acinetobacter baumannii, Acinetobacter lwoffii, Escherichia coli and Legionella pneumophila, and their corresponding virulence factors were present in all cleanroom samples. This is the first functional metagenomics study describing presence of pathogens and their corresponding virulence factors in cleanroom environments. The results of this study should be considered for microbial monitoring of enclosed environments such as schools, homes, hospitals and more isolated habitation such the International Space Station and future manned missions to Mars. PMID:27667984

[Preoperatiove Airway Bacterial Colonization: the Missing Link between Non-small Cell Lung Cancer Following Lobectomy and Postoperative Pneumonia?

PubMed

Gao, Ke; Lai, Yutian; Huang, Jian; Wang, Yifan; Wang, Xiaowei; Che, Guowei

2017-04-20

Surgical procedure is the main method of treating lung cancer. Meanwhile, postoperative pneumonia (POP) is the major cause of perioperative mortality in lung cancer surgery. The preoperative pathogenic airway bacterial colonization is an independent risk factor causing postoperative pulmonary complications (PPC). This cross-sectional study aimed to explore the relationship between preoperative pathogenic airway bacterial colonization and POP in lung cancer and to identify the high-risk factors of preoperative pathogenic airway bacterial colonization. A total of 125 patients with non-small cell lung cancer (NSCLC) underwent thoracic surgery in six hospitals of Chengdu between May 2015 and January 2016. Preoperative pathogenic airway bacterial colonization was detected in all patients via fiber bronchoscopy. Patients' PPC, high-risk factors, clinical characteristics, and the serum surfactant protein D (SP-D) level were also analyzed. The incidence of preoperative pathogenic airway bacterial colonization among NSCLC patients was 15.2% (19/125). Up to 22 strains were identified in the colonization positive group, with Gram-negative bacteria being dominant (86.36%, 19/22). High-risk factors of pathogenic airway bacterial colonization were age (≥75 yr) and smoking index (≥400 cigarettes/year). PPC incidence was significantly higher in the colonization-positive group (42.11%, 8/19) than that in the colonization-negative group (16.04%, 17/106)(P=0.021). POP incidence was significantly higher in the colonization-positive group (26.32%, 5/19) than that in the colonization-negative group (6.60%, 7/106)(P=0.019). The serum SP-D level of patients in the colonization-positive group was remarkably higher than that in the colonization-negative group [(31.25±6.09) vs (28.17±5.23)](P=0.023). The incidence of preoperative pathogenic airway bacterial colonization among NSCLC patients with POP was 41.67% (5/12). This value was 3.4 times higher than that among the patients without POP (OR=3.363, 95%CI: 1.467-7.711). An intimate correlation was observed between POP and pathogenic airway bacterial colonization in lung cancer. The high-risk factors of pathogenic airway bacterial colonization were age and smoking index.

Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases.

PubMed

Massberg, Steffen; Grahl, Lenka; von Bruehl, Marie-Luise; Manukyan, Davit; Pfeiler, Susanne; Goosmann, Christian; Brinkmann, Volker; Lorenz, Michael; Bidzhekov, Kiril; Khandagale, Avinash B; Konrad, Ildiko; Kennerknecht, Elisabeth; Reges, Katja; Holdenrieder, Stefan; Braun, Siegmund; Reinhardt, Christoph; Spannagl, Michael; Preissner, Klaus T; Engelmann, Bernd

2010-08-01

Blood neutrophils provide the first line of defense against pathogens but have also been implicated in thrombotic processes. This dual function of neutrophils could reflect an evolutionarily conserved association between blood coagulation and antimicrobial defense, although the molecular determinants and in vivo significance of this association remain unclear. Here we show that major microbicidal effectors of neutrophils, the serine proteases neutrophil elastase and cathepsin G, together with externalized nucleosomes, promote coagulation and intravascular thrombus growth in vivo. The serine proteases and extracellular nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a process involving local proteolysis of the coagulation suppressor tissue factor pathway inhibitor. During systemic infection, activation of coagulation fosters compartmentalization of bacteria in liver microvessels and reduces bacterial invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived serine proteases and nucleosomes can contribute to large-vessel thrombosis, the main trigger of myocardial infarction and stroke. The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense.

Burkholderia cenocepacia K56-2 trimeric autotransporter adhesin BcaA binds TNFR1 and contributes to induce airway inflammation.

PubMed

Mil-Homens, Dalila; Pinto, Sandra N; Matos, Rute G; Arraiano, Cecília; Fialho, Arsenio M

2017-04-01

Chronic lung disease caused by persistent bacterial infections is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). CF pathogens acquire antibiotic resistance, overcome host defenses, and impose uncontrolled inflammation that ultimately may cause permanent damage of lungs' airways. Among the multiple CF-associated pathogens, Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria have become prominent contributors of disease progression. Here, we demonstrate that BcaA, a trimeric autotransporter adhesin (TAA) from the epidemic strain B. cenocepacia K56-2, is a tumor necrosis factor receptor 1-interacting protein able to regulate components of the tumor necrosis factor signaling pathway and ultimately leading to a significant production of the proinflammatory cytokine IL-8. Notably, this study is the first to demonstrate that a protein belonging to the TAA family is involved in the induction of the inflammatory response during B. cenocepacia infections, contributing to the success of the pathogen. Moreover, our results reinforce the relevance of the TAA BcaA as a multifunctional protein with a major role in B. cenocepacia virulence. © 2016 John Wiley & Sons Ltd.

Delineation of the function of a major gamma delta T cell subset during infection.

PubMed

Andrew, Elizabeth M; Newton, Darren J; Dalton, Jane E; Egan, Charlotte E; Goodwin, Stewart J; Tramonti, Daniela; Scott, Philip; Carding, Simon R

2005-08-01

Gammadelta T cells play important but poorly defined roles in pathogen-induced immune responses and in preventing chronic inflammation and pathology. A major obstacle to defining their function is establishing the degree of functional redundancy and heterogeneity among gammadelta T cells. Using mice deficient in Vgamma1+ T cells which are a major component of the gammadelta T cell response to microbial infection, a specific immunoregulatory role for Vgamma1+ T cells in macrophage and gammadelta T cell homeostasis during infection has been established. By contrast, Vgamma1+ T cells play no significant role in pathogen containment or eradication and cannot protect mice from immune-mediated pathology. Pathogen-elicited Vgamma1+ T cells also display different functional characteristics at different stages of the host response to infection that involves unique and different populations of Vgamma1+ T cells. These findings, therefore, identify distinct and nonoverlapping roles for gammadelta T cell subsets in infection and establish the complexity and adaptability of a single population of gammadelta T cells in the host response to infection that is not predetermined, but is, instead, shaped by environmental factors.

Phosphorylation of a WRKY transcription factor by two pathogen-responsive MAPKs drives phytoalexin biosynthesis in Arabidopsis.

PubMed

Mao, Guohong; Meng, Xiangzong; Liu, Yidong; Zheng, Zuyu; Chen, Zhixiang; Zhang, Shuqun

2011-04-01

Plant sensing of invading pathogens triggers massive metabolic reprogramming, including the induction of secondary antimicrobial compounds known as phytoalexins. We recently reported that MPK3 and MPK6, two pathogen-responsive mitogen-activated protein kinases, play essential roles in the induction of camalexin, the major phytoalexin in Arabidopsis thaliana. In search of the transcription factors downstream of MPK3/MPK6, we found that WRKY33 is required for MPK3/MPK6-induced camalexin biosynthesis. In wrky33 mutants, both gain-of-function MPK3/MPK6- and pathogen-induced camalexin production are compromised, which is associated with the loss of camalexin biosynthetic gene activation. WRKY33 is a pathogen-inducible transcription factor, whose expression is regulated by the MPK3/MPK6 cascade. Chromatin immunoprecipitation assays reveal that WRKY33 binds to its own promoter in vivo, suggesting a potential positive feedback regulatory loop. Furthermore, WRKY33 is a substrate of MPK3/MPK6. Mutation of MPK3/MPK6 phosphorylation sites in WRKY33 compromises its ability to complement the camalexin induction in the wrky33 mutant. Using a phospho-protein mobility shift assay, we demonstrate that WRKY33 is phosphorylated by MPK3/MPK6 in vivo in response to Botrytis cinerea infection. Based on these data, we conclude that WRKY33 functions downstream of MPK3/MPK6 in reprogramming the expression of camalexin biosynthetic genes, which drives the metabolic flow to camalexin production in Arabidopsis challenged by pathogens.

Thrombospondin-1 protects against pathogen-induced lung injury by limiting extracellular matrix proteolysis

PubMed Central

Qu, Yanyan; Olonisakin, Tolani; Bain, William; Zupetic, Jill; Brown, Rebecca; Hulver, Mei; Xiong, Zeyu; Shanks, Robert M.Q.; Bomberger, Jennifer M.; Cooper, Vaughn S.; Zegans, Michael E.; Han, Jongyoon; Pilewski, Joseph; Ray, Anuradha; Ray, Prabir; Lee, Janet S.

2018-01-01

Acute lung injury is characterized by excessive extracellular matrix proteolysis and neutrophilic inflammation. A major risk factor for lung injury is bacterial pneumonia. However, host factors that protect against pathogen-induced and host-sustained proteolytic injury following infection are poorly understood. Pseudomonas aeruginosa (PA) is a major cause of nosocomial pneumonia and secretes proteases to amplify tissue injury. We show that thrombospondin-1 (TSP-1), a matricellular glycoprotein released during inflammation, dose-dependently inhibits PA metalloendoprotease LasB, a virulence factor. TSP-1–deficient (Thbs1–/–) mice show reduced survival, impaired host defense, and increased lung permeability with exaggerated neutrophil activation following acute intrapulmonary PA infection. Administration of TSP-1 from platelets corrects the impaired host defense and aberrant injury in Thbs1–/– mice. Although TSP-1 is cleaved into 2 fragments by PA, TSP-1 substantially inhibits Pseudomonas elastolytic activity. Administration of LasB inhibitor, genetic disabling of the PA type II secretion system, or functional deletion of LasB improves host defense and neutrophilic inflammation in mice. Moreover, TSP-1 provides an additional line of defense by directly subduing host-derived proteolysis, with dose-dependent inhibition of neutrophil elastase from airway neutrophils of mechanically ventilated critically ill patients. Thus, a host matricellular protein provides dual levels of protection against pathogen-initiated and host-sustained proteolytic injury following microbial trigger. PMID:29415890

Sexually Transmitted Diseases and Infertility

PubMed Central

TSEVAT, Danielle G.; WIESENFELD, Harold C.; Parks, Caitlin; PEIPERT, Jeffrey F.

2016-01-01

Female infertility, including tubal factor infertility, is a major public health concern worldwide. Most cases of tubal factor infertility are attributable to untreated sexually transmitted diseases that ascend along the reproductive tract and are capable of causing tubal inflammation, damage, and scarring. Evidence has consistently demonstrated the effects of Chlamydia trachomatis and Neisseria gonorrhoeae as pathogenic bacteria involved in reproductive tract morbidities including tubal factor infertility and pelvic inflammatory disease. There is limited evidence in the medical literature that other sexually transmitted organisms, including Mycoplasma genitalium, Trichomonas vaginalis, and other microorganisms within the vaginal microbiome may be important factors involved in the pathology of infertility. Further investigation into the vaginal microbiome and other potential pathogens is necessary in order to identify preventable causes of tubal factor infertility. Improved clinical screening and prevention of ascending infection may provide a solution to the persistent burden of infertility. PMID:28007229

Pathogen evolution across the agro-ecological interface: implications for disease management.

PubMed

Burdon, Jeremy J; Thrall, Peter H

2008-02-01

Infectious disease is a major causal factor in the demography of human, plant and animal populations. While it is generally accepted in medical, veterinary and agricultural contexts that variation in host resistance and pathogen virulence and aggressiveness is of central importance to understanding patterns of infection, there has been remarkably little effort to directly investigate causal links between population genetic structure and disease dynamics, and even less work on factors influencing host-pathogen coevolution. The lack of empirical evidence is particularly surprising, given the potential for such variation to not only affect disease dynamics and prevalence, but also when or where new diseases or pathotypes emerge. Increasingly, this lack of knowledge has led to calls for an integrated approach to disease management, incorporating both ecological and evolutionary processes. Here, we argue that plant pathogens occurring in agro-ecosystems represent one clear example where the application of evolutionary principles to disease management would be of great benefit, as well as providing model systems for advancing our ability to generalize about the long-term coevolutionary dynamics of host-pathogen systems. We suggest that this is particularly the case given that agro-ecological host-pathogen interactions represent a diversity of situations ranging from those that only involve agricultural crops through to those that also include weedy crop relatives or even unrelated native plant communities. We begin by examining some of the criteria that are important in determining involvement in agricultural pathogen evolution by noncrop plants. Throughout we use empirical examples to illustrate the fact that different processes may dominate in different systems, and suggest that consideration of life history and spatial structure are central to understanding dynamics and direction of the interaction. We then discuss the implications that such interactions have for disease management in agro-ecosystems and how we can influence those outcomes. Finally, we identify several major gaps where future research could increase our ability to utilize evolutionary principles in managing disease in agro-ecosystems.

Coiled Coil Rich Proteins (Ccrp) Influence Molecular Pathogenicity of Helicobacter pylori

PubMed Central

Schätzle, Sarah; Specht, Mara; Waidner, Barbara

2015-01-01

Pathogenicity of the human pathogen Helicobacter pylori relies on its capacity to adapt to a hostile environment and to escape the host response. Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its contribution to virulence. In this study we have explored the influence of coiled coil rich proteins (Ccrp) cytoskeletal elements on pathogenicity factors of H. pylori. Deletion of any of the ccrp resulted in a strongly decreased activity of the main pathogenicity factor urease. We further investigated their role using in vitro co-culture experiments with the human gastric adenocarcinoma cell line AGS modeling H. pylori - host cell interactions. Intriguingly, host cell showed only a weak “scattering/hummingbird” phenotype, in which host cells are transformed from a uniform polygonal shape into a severely elongated state characterized by the formation of needle-like projections, after co-incubation with any ccrp deletion mutant. Furthermore, co-incubation with the ccrp59 mutant resulted in reduced type IV secretion system associated activities, e.g. IL-8 production and CagA translocation/phosphorylation. Thus, in addition to their role in maintaining the helical cell shape of H. pylori Ccrp proteins influence many cellular processes and are thereby crucial for the virulence of this human pathogen. PMID:25822999

A pivotal role for the Streptococcus iniae extracellular polysaccharide in triggering proinflammatory cytokines transcription and inducing death in rainbow trout.

PubMed

Eyngor, Marina; Lublin, Avishay; Shapira, Roni; Hurvitz, Avshalom; Zlotkin, Amir; Tekoah, Yoram; Eldar, Avi

2010-04-01

Streptococcus iniae is a major pathogen of fish, causing considerable economic losses in Israel, the United States and the Far East. Containment of mortalities through vaccination was recently compromised due to the emergence of novel vaccine-escape strains that are distinguished from previous strains by their ability to produce large amounts of extracellular polysaccharide (EPS) that is released to the medium. In vitro and in vivo data now indicate that the EPS is a major virulence factor, capable of triggering the proinflammatory cytokine machinery and inducing mortality of fish. Streptococcus iniae EPS might therefore be considered to be responsible for sepsis and death just as lipopolysaccharide is for Gram-negative pathogens.

Novel Insights into Cell Entry of Emerging Human Pathogenic Arenaviruses.

PubMed

Fedeli, Chiara; Moreno, Héctor; Kunz, Stefan

2018-06-22

Viral hemorrhagic fevers caused by emerging RNA viruses of the Arenavirus family are among the most devastating human diseases. Climate change, global trade, and increasing urbanization promote the emergence and re-emergence of these human pathogenic viruses. Emerging pathogenic arenaviruses are of zoonotic origin and reservoir-to-human transmission is crucial for spillover into human populations. Host cell attachment and entry are the first and most fundamental steps of every virus infection and represent major barriers for zoonotic transmission. During host cell invasion, viruses critically depend on cellular factors, including receptors, co-receptors, and regulatory proteins of endocytosis. An in-depth understanding of the complex interaction of a virus with cellular factors implicated in host cell entry is therefore crucial to predict the risk of zoonotic transmission, define the tissue tropism, and assess disease potential. Over the past years, investigation of the molecular and cellular mechanisms underlying host cell invasion of human pathogenic arenaviruses uncovered remarkable viral strategies and provided novel insights into viral adaptation and virus-host co-evolution that will be covered in the present review. Copyright © 2018. Published by Elsevier Ltd.

Using participatory epidemiology to assess factors contributing to common enteric pathogens in Ontario: results from a workshop held at the Ontario Veterinary College, University of Guelph, Ontario

PubMed Central

2014-01-01

Background Common enteric pathogens that cause gastrointestinal illness are transmitted to humans through food, water or direct contact. This poses a significant concern to public health as enteric pathogens can cause disease in a large number of people, and cost a substantial amount to treat and prevent. In order to gain a better understanding of the occurrence of enteric disease in Ontario, this study explored public health professionals’ perceptions of major contributing factors for common enteric pathogens. Methods A case study was conducted as part of a two week training workshop in Participatory Epidemiology held at the Ontario Veterinary College, University of Guelph, in May 2013. Eight semi-structured interviews and four focus groups were conducted with representatives from the Public Health Agency of Canada, the University of Guelph, and three health regions in Southern Ontario. Written notes and pictures captured the qualitative information provided. Results were then analyzed using the mixed methods techniques of triangulation, convergence, and paradox. Results A total of fifty factors that contribute to enteric disease were identified across all interviews and focus groups. These contributing factors were grouped into key themes (travel, food handling, industry (farm-to-fork), water, geography, demographics, and behaviours) and were categorized as either a risk factor or susceptibility factor. Informants emphasized the complex relationships between the identified factors, and highlighted why these complexities make it difficult to determine where and how a person most likely acquired an enteric pathogen. Workshop participants observed differences in the type and quality of information collected during interviews and focus groups; we hypothesize that this may be attributed to the dynamics between group members (i.e. focus group discussions) as opposed to one-on-one interviews. Conclusions The information gathered will serve as a starting point to further explore contributing factors for common enteric pathogens. The identified complexities would be best explored by conducting additional surveillance, as well as interviews and focus groups with a more diverse group of stakeholders. This type of qualitative study can enhance knowledge of enteric pathogen surveillance and contribute to the development of resources and initiatives to holistically address the occurrence of gastrointestinal illness. PMID:24767430

Intestinal parasitic infections: Current prevalence and risk factors among schoolchildren in capital area of the Republic of Marshall Islands.

PubMed

Liao, Chien-Wei; Chuang, Ting-Wu; Huang, Ying-Chieh; Chou, Chia-Mei; Chiang, Chia-Lien; Lee, Fei-Peng; Hsu, Yun-Ting; Lin, Jia-Wei; Briand, Kennar; Tu, Chia-Ying; Fan, Chia-Kwung

2017-12-01

Intestinal parasitic infections (IPIs) among schoolchildren in Republic of Marshall Islands (RMI) largely remains unknown, thus investigation on IPIs status to establish the baseline data is urgently needed. This cross-sectional study intended to investigate the current IPIs status and associated risk factors among schoolchildren at capital of RMI. Single stool sample from 400 schoolchildren (207 boys and 193 girls) aged 9.73±2.50 yrs old was examined by employing merthiolate-iodine-formaldehyde concentration method. Demographic characteristics, uncomfortable symptoms and risk factors were obtained by questionnaires investigation. The overall prevalence of IPIs in schoolchildren was 22.8% (91/400), of them 24.2% harbored at least 2 different parasites. Notably, the majority was infected by waterborne protozoan parasites (82.4%, 75/91). Nine different intestinal parasites have been identified, of which six were pathogenic including Hook worm, Trichuris trichiura, Enterobius vermicularis, Entamoeba histolytica/dispar, Giardia intestinalis and Blastocystis hominis. Schoolchildren who ever complained dizziness or headache showed a significant higher prevalence of pathogenic IPIs than those who did not (p<0.05). Schoolchildren who lived in urban area than rural area had higher chance to acquire pathogenic IPIs (p=0.03). However, none of risk factors were identified to be associated with pathogenic IPIs. Copyright © 2017 Elsevier B.V. All rights reserved.

A systematic review exploring the relationship between infection and sudden unexpected death between 2000 and 2016: A forensic perspective.

PubMed

Kruger, Mia M; Martin, Lorna J; Maistry, Sairita; Heathfield, Laura J

2018-05-21

Death due to infectious diseases is a major health concern worldwide. This is of particular concern in developing countries where poor-socio economic status and a lack of healthcare resources contribute to the high burden of disease. In some cases death due to infection can be acute and aggressive, and death may occur without a diagnosis whilst the person is still alive. These deaths may ultimately lead to a medico-legal autopsy being performed. There are various mechanisms by which sudden death due to infection may occur. In addition, there are many risk factors associated with sudden death due to infection, which differ between infants and older individuals. However, it is unclear which pathogens and risk factors are most frequently associated with sudden death due to infection. Therefore a systematic review of articles and case reports published between 1 January 2000 and 30 June 2016 was undertaken in order to (1) explore the relationship between pathogens and their causative role and (2) identify the relationship between predisposing and/or risk factors associated with sudden death due to infection. Major databases were searched and after critical appraisal 143 articles were identified. It was found that respiratory infections and deaths involving bacterial pathogens were most commonly associated with these deaths. In addition the most common risk factors in infants were exposure to tobacco smoke and co-sleeping. In adults the most common risk factors were co-morbid conditions and illnesses. This information aids in a better understanding of these deaths and highlights the need for more research in this field, particularly in developing countries. Copyright © 2018 Elsevier B.V. All rights reserved.

How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer.

PubMed

Dhar, Poshmaal; Ng, Garrett Z; Sutton, Philip

2016-09-01

The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain completely asymptomatic, despite the presence of pathogenic bacteria that drive a chronic gastritis that lasts many decades. This indicates the presence of highly effective regulatory processes in the host that, in most cases, keeps a check on inflammation and protect against disease. In this minireview we discuss such known host factors and how they prevent the development of H. pylori-associated pathologies. Copyright © 2016 the American Physiological Society.

Properties of hemagglutination by Prevotella melaninogenica.

PubMed

Haraldsson, Gunnsteinn; Meurman, Jukka H; Könönen, Eija; Holbrook, W Peter

2005-10-01

Although Prevotella melaninogenica belongs to the commensal oral microbiota, some strains possess putative virulence factors. For example, we have previously described fimbriated, hemagglutinating strains of P. melaninogenica, isolated from patients with periodontal disease. The aim of this investigation was to compare some chemical and physical properties of hemagglutination (HA) of P. melaninogenica with those of other pigmented gram-negative anaerobes. HA of 13 P. melaninogenica strains proved to be considerably weaker than that of the major periodontal pathogen, Porphyromonas gingivalis. Vigorous shaking reduced HA of shaken cells but the shaken supernatant had the same hemagglutinating activity as non-shaken cells. The hemagglutinating agent on P. melaninogenica seemed to be a protein, which can be separated from the cell and binds to lactose-, galactose-, and raffinose-containing carbohydrates on the erythrocytes. Adherence to epithelial cells did not differ significantly between the hemagglutinating and non-hemagglutinating strains of P. melaninogenica. Although P. melaninogenica is able to agglutinate erythrocytes, this potential virulence factor is of a considerably lower magnitude than that of major periodontal pathogens.

Virulence determinants of the human pathogenic fungus Aspergillus fumigatus protect against soil amoeba predation.

PubMed

Hillmann, Falk; Novohradská, Silvia; Mattern, Derek J; Forberger, Tilmann; Heinekamp, Thorsten; Westermann, Martin; Winckler, Thomas; Brakhage, Axel A

2015-08-01

Filamentous fungi represent classical examples for environmentally acquired human pathogens whose major virulence mechanisms are likely to have emerged long before the appearance of innate immune systems. In natural habitats, amoeba predation could impose a major selection pressure towards the acquisition of virulence attributes. To test this hypothesis, we exploited the amoeba Dictyostelium discoideum to study its interaction with Aspergillus fumigatus, two abundant soil inhabitants for which we found co-occurrence in various sites. Fungal conidia were efficiently taken up by D. discoideum, but ingestion was higher when conidia were devoid of the green fungal spore pigment dihydroxynaphtalene melanin, in line with earlier results obtained for immune cells. Conidia were able to survive phagocytic processing, and intracellular germination was initiated only after several hours of co-incubation which eventually led to a lethal disruption of the host cell. Besides phagocytic interactions, both amoeba and fungus secreted cross inhibitory factors which suppressed fungal growth or induced amoeba aggregation with subsequent cell lysis, respectively. On the fungal side, we identified gliotoxin as the major fungal factor killing Dictyostelium, supporting the idea that major virulence attributes, such as escape from phagocytosis and the secretion of mycotoxins are beneficial to escape from environmental predators. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Disarming Fungal Pathogens: Bacillus safensis Inhibits Virulence Factor Production and Biofilm Formation by Cryptococcus neoformans and Candida albicans

PubMed Central

2017-01-01

ABSTRACT Bacteria interact with each other in nature and often compete for limited nutrient and space resources. However, it is largely unknown whether and how bacteria also interact with human fungal pathogens naturally found in the environment. Here, we identified a soil bacterium, Bacillus safensis, which potently blocked several key Cryptococcus neoformans virulence factors, including formation of the antioxidant pigment melanin and production of the antiphagocytic polysaccharide capsule. The bacterium also inhibited de novo cryptococcal biofilm formation but had only modest inhibitory effects on already formed biofilms or planktonic cell growth. The inhibition of fungal melanization was dependent on direct cell contact and live bacteria. B. safensis also had anti-virulence factor activity against another major human-associated fungal pathogen, Candida albicans. Specifically, dual-species interaction studies revealed that the bacterium strongly inhibited C. albicans filamentation and biofilm formation. In particular, B. safensis physically attached to and degraded candidal filaments. Through genetic and phenotypic analyses, we demonstrated that bacterial chitinase activity against fungal cell wall chitin is a factor contributing to the antipathogen effect of B. safensis. PMID:28974618

Using genomics for surveillance of veterinary infectious agents.

PubMed

Mathijs, E; Vandenbussche, F; Van Borm, S

2016-04-01

Factors such as globalisation, climate change and agricultural intensification can increase the risk of microbial emergence. As a result, there is a growing need for flexible laboratory-based surveillance tools to rapidly identify, characterise and monitor global (re-)emerging diseases. Although many tools are available, novel sequencing technologies have launched a new era in pathogen surveillance. Here, the authors review the potential applications of high-throughput genomic technologies for the surveillance of veterinary pathogens. They focus on the two types of surveillance that will benefit most from these new tools: hazard-specific surveillance (pathogen identification and typing) and early-warning surveillance (pathogen discovery). The paper reviews how the resulting sequencing data can be used to improve diagnosis and concludes by highlighting the major challenges that hinder the routine use of this technology in the veterinary field.

The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae.

PubMed

Gross, Roy; Guzman, Carlos A; Sebaihia, Mohammed; dos Santos, Vítor A P Martins; Pieper, Dietmar H; Koebnik, Ralf; Lechner, Melanie; Bartels, Daniela; Buhrmester, Jens; Choudhuri, Jomuna V; Ebensen, Thomas; Gaigalat, Lars; Herrmann, Stefanie; Khachane, Amit N; Larisch, Christof; Link, Stefanie; Linke, Burkhard; Meyer, Folker; Mormann, Sascha; Nakunst, Diana; Rückert, Christian; Schneiker-Bekel, Susanne; Schulze, Kai; Vorhölter, Frank-Jörg; Yevsa, Tetyana; Engle, Jacquelyn T; Goldman, William E; Pühler, Alfred; Göbel, Ulf B; Goesmann, Alexander; Blöcker, Helmut; Kaiser, Olaf; Martinez-Arias, Rosa

2008-09-30

Bordetella petrii is the only environmental species hitherto found among the otherwise host-restricted and pathogenic members of the genus Bordetella. Phylogenetically, it connects the pathogenic Bordetellae and environmental bacteria of the genera Achromobacter and Alcaligenes, which are opportunistic pathogens. B. petrii strains have been isolated from very different environmental niches, including river sediment, polluted soil, marine sponges and a grass root. Recently, clinical isolates associated with bone degenerative disease or cystic fibrosis have also been described. In this manuscript we present the results of the analysis of the completely annotated genome sequence of the B. petrii strain DSMZ12804. B. petrii has a mosaic genome of 5,287,950 bp harboring numerous mobile genetic elements, including seven large genomic islands. Four of them are highly related to the clc element of Pseudomonas knackmussii B13, which encodes genes involved in the degradation of aromatics. Though being an environmental isolate, the sequenced B. petrii strain also encodes proteins related to virulence factors of the pathogenic Bordetellae, including the filamentous hemagglutinin, which is a major colonization factor of B. pertussis, and the master virulence regulator BvgAS. However, it lacks all known toxins of the pathogenic Bordetellae. The genomic analysis suggests that B. petrii represents an evolutionary link between free-living environmental bacteria and the host-restricted obligate pathogenic Bordetellae. Its remarkable metabolic versatility may enable B. petrii to thrive in very different ecological niches.

The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae

PubMed Central

Gross, Roy; Guzman, Carlos A; Sebaihia, Mohammed; Martins dos Santos, Vítor AP; Pieper, Dietmar H; Koebnik, Ralf; Lechner, Melanie; Bartels, Daniela; Buhrmester, Jens; Choudhuri, Jomuna V; Ebensen, Thomas; Gaigalat, Lars; Herrmann, Stefanie; Khachane, Amit N; Larisch, Christof; Link, Stefanie; Linke, Burkhard; Meyer, Folker; Mormann, Sascha; Nakunst, Diana; Rückert, Christian; Schneiker-Bekel, Susanne; Schulze, Kai; Vorhölter, Frank-Jörg; Yevsa, Tetyana; Engle, Jacquelyn T; Goldman, William E; Pühler, Alfred; Göbel, Ulf B; Goesmann, Alexander; Blöcker, Helmut; Kaiser, Olaf; Martinez-Arias, Rosa

2008-01-01

Background Bordetella petrii is the only environmental species hitherto found among the otherwise host-restricted and pathogenic members of the genus Bordetella. Phylogenetically, it connects the pathogenic Bordetellae and environmental bacteria of the genera Achromobacter and Alcaligenes, which are opportunistic pathogens. B. petrii strains have been isolated from very different environmental niches, including river sediment, polluted soil, marine sponges and a grass root. Recently, clinical isolates associated with bone degenerative disease or cystic fibrosis have also been described. Results In this manuscript we present the results of the analysis of the completely annotated genome sequence of the B. petrii strain DSMZ12804. B. petrii has a mosaic genome of 5,287,950 bp harboring numerous mobile genetic elements, including seven large genomic islands. Four of them are highly related to the clc element of Pseudomonas knackmussii B13, which encodes genes involved in the degradation of aromatics. Though being an environmental isolate, the sequenced B. petrii strain also encodes proteins related to virulence factors of the pathogenic Bordetellae, including the filamentous hemagglutinin, which is a major colonization factor of B. pertussis, and the master virulence regulator BvgAS. However, it lacks all known toxins of the pathogenic Bordetellae. Conclusion The genomic analysis suggests that B. petrii represents an evolutionary link between free-living environmental bacteria and the host-restricted obligate pathogenic Bordetellae. Its remarkable metabolic versatility may enable B. petrii to thrive in very different ecological niches. PMID:18826580

Meta-analysis to estimate the load of Leptospira excreted in urine: beyond rats as important sources of transmission in low-income rural communities.

PubMed

Barragan, Veronica; Nieto, Nathan; Keim, Paul; Pearson, Talima

2017-01-28

Leptospirosis is a major zoonotic disease with widespread distribution and a large impact on human health. Carrier animals excrete pathogenic Leptospira primarily in their urine. Infection occurs when the pathogen enters a host through mucosa or small skin abrasions. Humans and other animals are exposed to the pathogen by direct contact with urine, contaminated soil or water. While many factors influence environmental cycling and the transmission of Leptospira to humans, the load of pathogenic Leptospira in the environment is likely to play a major role. Peridomestic rats are often implicated as a potential source of human disease; however exposure to other animals is a risk factor as well. The aim of this report is to highlight the importance of various carrier animals in terms of the quantity of Leptospira shed into the environment. For this, we performed a systematic literature review and a meta-analysis of the amount of pathogen that various animal species shed in their urine. The quantity of pathogen has been reported for cows, deer, dogs, humans, mice, and rats, in a total of 14 research articles. We estimated the average Leptospira per unit volume shed by each animal species, and the daily environmental contribution by considering the total volume of urine excreted by each carrier animal. Rats excrete the highest quantity of Leptospira per millilitre of urine (median = 5.7 × 10 6  cells), but large mammals excrete much more urine and thus shed significantly more Leptospira per day (5.1 × 10 8 to 1.3 × 10 9  cells). Here we illustrate how, in a low-income rural Ecuadorian community, host population demographics, and prevalence of Leptospira infection can be integrated with estimates of shed Leptospira to suggest that peridomestic cattle may be more important than rats in environmental cycling and ultimately, transmission to humans.

Dengue virus life cycle: viral and host factors modulating infectivity.

PubMed

Rodenhuis-Zybert, Izabela A; Wilschut, Jan; Smit, Jolanda M

2010-08-01

Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited dengue fever, an increasing number of patients present more severe manifestations, such as dengue hemorrhagic fever and dengue shock syndrome. In this review we will give an overview of the infectious life cycle of DENV and will discuss the viral and host factors that are important in controlling DENV infection.

Waterborne Pathogens: Detection Methods and Challenges

PubMed Central

Ramírez-Castillo, Flor Yazmín; Loera-Muro, Abraham; Jacques, Mario; Garneau, Philippe; Avelar-González, Francisco Javier; Harel, Josée; Guerrero-Barrera, Alma Lilián

2015-01-01

Waterborne pathogens and related diseases are a major public health concern worldwide, not only by the morbidity and mortality that they cause, but by the high cost that represents their prevention and treatment. These diseases are directly related to environmental deterioration and pollution. Despite the continued efforts to maintain water safety, waterborne outbreaks are still reported globally. Proper assessment of pathogens on water and water quality monitoring are key factors for decision-making regarding water distribution systems’ infrastructure, the choice of best water treatment and prevention waterborne outbreaks. Powerful, sensitive and reproducible diagnostic tools are developed to monitor pathogen contamination in water and be able to detect not only cultivable pathogens but also to detect the occurrence of viable but non-culturable microorganisms as well as the presence of pathogens on biofilms. Quantitative microbial risk assessment (QMRA) is a helpful tool to evaluate the scenarios for pathogen contamination that involve surveillance, detection methods, analysis and decision-making. This review aims to present a research outlook on waterborne outbreaks that have occurred in recent years. This review also focuses in the main molecular techniques for detection of waterborne pathogens and the use of QMRA approach to protect public health. PMID:26011827

Micrococcus species-related peritonitis in patients receiving peritoneal dialysis.

PubMed

Kao, Chih-Chin; Chiang, Chih-Kang; Huang, Jenq-Wen

2014-01-01

Peritonitis is a major complication of peritoneal dialysis (PD) and remains the most common cause of PD failure. Micrococci are catalase-positive, coagulase-negative, and gram-positive cocci that are spherical, often found in tetrad, and belong to the family Micrococcaceae. Micrococcus species are commonly found in the environment, and it is now recognized that Micrococcus species can be opportunistic pathogens in immunocompromised patients. The only consistent predisposing factor for Micrococcus infection is an immunocompromised state. We report three cases of Micrococcus PD peritonitis. Improper practice of PD may have been the causative factor. Although Micrococcus species are low-virulence pathogens, infection could result in refractory peritonitis and subsequent PD failure. Intraperitoneal administration of vancomycin for at least 2 weeks is recommended for Micrococcus peritonitis.

Genome-wide pleiotropy and shared biological pathways for resistance to bovine pathogens

PubMed Central

Zeng, Y.; Yin, T.; Brügemann, K.

2018-01-01

Host genetic architecture is a major factor in resistance to pathogens and parasites. The collection and analysis of sufficient data on both disease resistance and host genetics has, however, been a major obstacle to dissection the genetics of resistance to single or multiple pathogens. A severe challenge in the estimation of heritabilities and genetic correlations from pedigree-based studies has been the confounding effects of the common environment shared among relatives which are difficult to model in pedigree analyses, especially for health traits with low incidence rates. To circumvent this problem we used genome-wide single-nucleotide polymorphism data and implemented the Genomic-Restricted Maximum Likelihood (G-REML) method to estimate the heritabilities and genetic correlations for resistance to 23 different infectious pathogens in calves and cows in populations undergoing natural pathogen challenge. Furthermore, we conducted gene-based analysis and generalized gene-set analysis to understand the biological background of resistance to infectious diseases. The results showed relatively higher heritabilities of resistance in calves than in cows and significant pleiotropy (both positive and negative) among some calf and cow resistance traits. We also found significant pleiotropy between resistance and performance in both calves and cows. Finally, we confirmed the role of the B-lymphocyte pathway as one of the most important biological pathways associated with resistance to all pathogens. These results both illustrate the potential power of these approaches to illuminate the genetics of pathogen resistance in cattle and provide foundational information for future genomic selection aimed at improving the overall production fitness of cattle. PMID:29608619

Distribution of triclosan-resistant genes in major pathogenic microorganisms revealed by metagenome and genome-wide analysis

PubMed Central

Khan, Raees; Roy, Nazish; Choi, Kihyuck

2018-01-01

The substantial use of triclosan (TCS) has been aimed to kill pathogenic bacteria, but TCS resistance seems to be prevalent in microbial species and limited knowledge exists about TCS resistance determinants in a majority of pathogenic bacteria. We aimed to evaluate the distribution of TCS resistance determinants in major pathogenic bacteria (N = 231) and to assess the enrichment of potentially pathogenic genera in TCS contaminated environments. A TCS-resistant gene (TRG) database was constructed and experimentally validated to predict TCS resistance in major pathogenic bacteria. Genome-wide in silico analysis was performed to define the distribution of TCS-resistant determinants in major pathogens. Microbiome analysis of TCS contaminated soil samples was also performed to investigate the abundance of TCS-resistant pathogens. We experimentally confirmed that TCS resistance could be accurately predicted using genome-wide in silico analysis against TRG database. Predicted TCS resistant phenotypes were observed in all of the tested bacterial strains (N = 17), and heterologous expression of selected TCS resistant genes from those strains conferred expected levels of TCS resistance in an alternative host Escherichia coli. Moreover, genome-wide analysis revealed that potential TCS resistance determinants were abundant among the majority of human-associated pathogens (79%) and soil-borne plant pathogenic bacteria (98%). These included a variety of enoyl-acyl carrier protein reductase (ENRs) homologues, AcrB efflux pumps, and ENR substitutions. FabI ENR, which is the only known effective target for TCS, was either co-localized with other TCS resistance determinants or had TCS resistance-associated substitutions. Furthermore, microbiome analysis revealed that pathogenic genera with intrinsic TCS-resistant determinants exist in TCS contaminated environments. We conclude that TCS may not be as effective against the majority of bacterial pathogens as previously presumed. Further, the excessive use of this biocide in natural environments may selectively enrich for not only TCS-resistant bacterial pathogens, but possibly for additional resistance to multiple antibiotics. PMID:29420585

PathogenFinder--distinguishing friend from foe using bacterial whole genome sequence data.

PubMed

Cosentino, Salvatore; Voldby Larsen, Mette; Møller Aarestrup, Frank; Lund, Ole

2013-01-01

Although the majority of bacteria are harmless or even beneficial to their host, others are highly virulent and can cause serious diseases, and even death. Due to the constantly decreasing cost of high-throughput sequencing there are now many completely sequenced genomes available from both human pathogenic and innocuous strains. The data can be used to identify gene families that correlate with pathogenicity and to develop tools to predict the pathogenicity of newly sequenced strains, investigations that previously were mainly done by means of more expensive and time consuming experimental approaches. We describe PathogenFinder (http://cge.cbs.dtu.dk/services/PathogenFinder/), a web-server for the prediction of bacterial pathogenicity by analysing the input proteome, genome, or raw reads provided by the user. The method relies on groups of proteins, created without regard to their annotated function or known involvement in pathogenicity. The method has been built to work with all taxonomic groups of bacteria and using the entire training-set, achieved an accuracy of 88.6% on an independent test-set, by correctly classifying 398 out of 449 completely sequenced bacteria. The approach here proposed is not biased on sets of genes known to be associated with pathogenicity, thus the approach could aid the discovery of novel pathogenicity factors. Furthermore the pathogenicity prediction web-server could be used to isolate the potential pathogenic features of both known and unknown strains.

Trans-cinnamaldehyde, carvacrol, and eugenol reduce Campylobacter jejuni colonization factors and expression of virulence genes in vitro

USDA-ARS?s Scientific Manuscript database

Campylobacter jejuni is a major foodborne pathogen that causes severe gastroenteritis in humans characterized by fever, diarrhea and abdominal cramps. In the human gut, Campylobacter adheres and invades the intestinal epithelium followed by cytolethal distending toxin mediated cell death, and enteri...

Compartmentalized gene regulatory network of the pathogenic fungus Fusarium graminearum

USDA-ARS?s Scientific Manuscript database

Head blight caused by Fusarium graminearum (Fg) is a major limiting factor of wheat production with both yield loss and mycotoxin contamination. Here we report a model for global Fg gene regulatory networks (GRNs) inferred from a large collection of transcriptomic data using a machine-learning appro...

An emerging mycoplasma associated with trichomoniasis, vaginal infection and disease.

PubMed

Fettweis, Jennifer M; Serrano, Myrna G; Huang, Bernice; Brooks, J Paul; Glascock, Abigail L; Sheth, Nihar U; Strauss, Jerome F; Jefferson, Kimberly K; Buck, Gregory A

2014-01-01

Humans are colonized by thousands of bacterial species, but it is difficult to assess the metabolic and pathogenic potential of the majority of these because they have yet to be cultured. Here, we characterize an uncultivated vaginal mycoplasma tightly associated with trichomoniasis that was previously known by its 16S rRNA sequence as "Mnola." In this study, the mycoplasma was found almost exclusively in women infected with the sexually transmitted pathogen Trichomonas vaginalis, but rarely observed in women with no diagnosed disease. The genomes of four strains of this species were reconstructed using metagenome sequencing and assembly of DNA from four discrete mid-vaginal samples, one of which was obtained from a pregnant woman with trichomoniasis who delivered prematurely. These bacteria harbor several putative virulence factors and display unique metabolic strategies. Genes encoding proteins with high similarity to potential virulence factors include two collagenases, a hemolysin, an O-sialoglycoprotein endopeptidase and a feoB-type ferrous iron transport system. We propose the name "Candidatus Mycoplasma girerdii" for this potential new pathogen.

Gene flow in environmental Legionella pneumophila leads to genetic and pathogenic heterogeneity within a Legionnaires' disease outbreak.

PubMed

McAdam, Paul R; Vander Broek, Charles W; Lindsay, Diane S J; Ward, Melissa J; Hanson, Mary F; Gillies, Michael; Watson, Mick; Stevens, Joanne M; Edwards, Giles F; Fitzgerald, J Ross

2014-01-01

Legionnaires' disease is a severe form of pneumonia caused by the environmental bacterium Legionella pneumophila. Outbreaks commonly affect people with known risk factors, but the genetic and pathogenic complexity of L. pneumophila within an outbreak is not well understood. Here, we investigate the etiology of the major Legionnaires' disease outbreak that occurred in Edinburgh, UK, in 2012, by examining the evolutionary history, genome content, and virulence of L. pneumophila clinical isolates. Our high resolution genomic approach reveals that the outbreak was caused by multiple genetic subtypes of L. pneumophila, the majority of which had diversified from a single progenitor through mutation, recombination, and horizontal gene transfer within an environmental reservoir prior to release. In addition, we discover that some patients were infected with multiple L. pneumophila subtypes, a finding which can affect the certainty of source attribution. Importantly, variation in the complement of type IV secretion systems encoded by different genetic subtypes correlates with virulence in a Galleria mellonella model of infection, revealing variation in pathogenic potential among the outbreak source population of L. pneumophila. Taken together, our study indicates previously cryptic levels of pathogen heterogeneity within a Legionnaires' disease outbreak, a discovery that impacts on source attribution for future outbreak investigations. Furthermore, our data suggest that in addition to host immune status, pathogen diversity may be an important influence on the clinical outcome of individual outbreak infections.

Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano

PubMed Central

Banskar, Sunil; Bhute, Shrikant S.; Suryavanshi, Mangesh V.; Punekar, Sachin; Shouche, Yogesh S.

2016-01-01

Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals. PMID:27845426

Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano.

PubMed

Banskar, Sunil; Bhute, Shrikant S; Suryavanshi, Mangesh V; Punekar, Sachin; Shouche, Yogesh S

2016-11-15

Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.

Bacteriology of peritonsillar abscess: the changing trend and predisposing factors.

PubMed

Tsai, Yi-Wen; Liu, Yu-Hsi; Su, Hsing-Hao

2017-07-17

Peritonsillar abscess is the most common deep neck infection. The infectious microorganism may be different according to clinical factors. To identify the major causative pathogen of peritonsillar abscess and investigate the relationship between the causative pathogen, host clinical factors, and hospitalization duration. This retrospective study included 415 hospitalized patients diagnosed with peritonsillar abscess who were admitted to a tertiary medical center from June 1990 to June 2013. We collected data by chart review and analyzed variables such as demographic characteristics, underlying systemic disease, smoking, alcoholism, betel nut chewing, bacteriology, and hospitalization duration. A total of 168 patients had positive results for pathogen isolation. Streptococcus viridans (28.57%) and Klebsiella pneumoniae (23.21%) were the most common microorganisms identified through pus culturing. The isolation rate of anaerobes increased to 49.35% in the recent 6 years (p=0.048). Common anaerobes were Prevotella and Fusobacterium spp. The identification of K. pneumoniae increased among elderly patients (age>65 years) with an odds ratio (OR) of 2.76 (p=0.03), and decreased in the hot season (mean temperature>26°C) (OR=0.49, p=0.04). No specific microorganism was associated with prolonged hospital stay. The most common pathogen identified through pus culturing was S. viridans, followed by K. pneumoniae. The identification of anaerobes was shown to increase in recent years. The antibiotics initially selected should be effective against both aerobes and anaerobes. Bacterial identification may be associated with host clinical factors and environmental factors. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus.

PubMed

Shelburne, Samuel A; Keith, David; Horstmann, Nicola; Sumby, Paul; Davenport, Michael T; Graviss, Edward A; Brennan, Richard G; Musser, James M

2008-02-05

Although central to pathogenesis, the molecular mechanisms used by microbes to regulate virulence factor production in specific environments during host-pathogen interaction are poorly defined. Several recent ex vivo and in vivo studies have found that the level of group A Streptococcus (GAS) virulence factor gene transcripts is temporally related to altered expression of genes encoding carbohydrate utilization proteins. These findings stimulated us to analyze the role in pathogenesis of catabolite control protein A (CcpA), a GAS ortholog of a key global regulator of carbohydrate metabolism in Bacillus subtilis. Inasmuch as the genomewide effects of CcpA in a human pathogen are unknown, we analyzed the transcriptome of a DeltaccpA isogenic mutant strain grown in nutrient-rich medium. CcpA influences the transcript levels of many carbohydrate utilization genes and several well characterized GAS virulence factors, including the potent cytolysin streptolysin S. Compared with the wild-type parental strain, the DeltaccpA isogenic mutant strain was significantly less virulent in a mouse model of invasive infection. Moreover, the isogenic mutant strain was significantly impaired in ability to colonize the mouse oropharynx. When grown in human saliva, a nutrient-limited environment, CcpA influenced production of several key virulence factors not influenced during growth in nutrient-rich medium. Purified recombinant CcpA bound to the promoter region of the gene encoding streptolysin S. Our discovery that GAS virulence and complex carbohydrate utilization are directly linked through CcpA provides enhanced understanding of a mechanism used by a Gram-positive pathogen to modulate virulence factor production in specific environments.

Major Histocompatibility Complex, demographic, and environmental predictors of antibody presence in a free-ranging mammal.

PubMed

Ruiz-López, María José; Monello, Ryan J; Schuttler, Stephanie G; Lance, Stacey L; Gompper, Matthew E; Eggert, Lori S

2014-12-01

Major Histocompatibility Complex (MHC) variability plays a key role in pathogen resistance, but its relative importance compared to environmental and demographic factors that also influence resistance is unknown. We analyzed the MHC II DRB exon 2 for 165 raccoons (Procyon lotor) in Missouri (USA). For each animal we also determined the presence of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to two highly virulent pathogens, canine distemper virus (CDV) and parvovirus. We investigated the role of MHC polymorphism and other demographic and environmental factors previously associated with predicting seroconversion. In addition, using an experimental approach, we studied the relative importance of resource availability and contact rates. We found important associations between IgG antibody presence and several MHC alleles and supertypes but not between IgM antibody presence and MHC. No effect of individual MHC diversity was found. For CDV, supertype S8, one allele within S8 (Prlo-DRB(∗)222), and a second allele (Prlo-DRB(∗)204) were positively associated with being IgG+, while supertype S4 and one allele within the supertype (Prlo-DRB(∗)210) were negatively associated with being IgG+. Age, year, and increased food availability were also positively associated with being IgG+, but allele Prlo-DRB(∗)222 was a stronger predictor. For parvovirus, only one MHC allele was negatively associated with being IgG+ and age and site were stronger predictors of seroconversion. Our results show that negative-frequency dependent selection is likely acting on the raccoon MHC and that while the role of MHC in relation to other factors depends on the pathogen of interest, it may be one of the most important factors predicting successful immune response. Copyright © 2014 Elsevier B.V. All rights reserved.

Insights into Vibrio cholerae Intestinal Colonization from Monitoring Fluorescently Labeled Bacteria

PubMed Central

Millet, Yves A.; Alvarez, David; Ringgaard, Simon; von Andrian, Ulrich H.; Davis, Brigid M.; Waldor, Matthew K.

2014-01-01

Vibrio cholerae, the agent of cholera, is a motile non-invasive pathogen that colonizes the small intestine (SI). Most of our knowledge of the processes required for V. cholerae intestinal colonization is derived from enumeration of wt and mutant V. cholerae recovered from orogastrically infected infant mice. There is limited knowledge of the distribution of V. cholerae within the SI, particularly its localization along the villous axis, or of the bacterial and host factors that account for this distribution. Here, using confocal and intravital two-photon microscopy to monitor the localization of fluorescently tagged V. cholerae strains, we uncovered unexpected and previously unrecognized features of V. cholerae intestinal colonization. Direct visualization of the pathogen within the intestine revealed that the majority of V. cholerae microcolonies attached to the intestinal epithelium arise from single cells, and that there are notable regiospecific aspects to V. cholerae localization and factors required for colonization. In the proximal SI, V. cholerae reside exclusively within the developing intestinal crypts, but they are not restricted to the crypts in the more distal SI. Unexpectedly, V. cholerae motility proved to be a regiospecific colonization factor that is critical for colonization of the proximal, but not the distal, SI. Furthermore, neither motility nor chemotaxis were required for proper V. cholerae distribution along the villous axis or in crypts, suggesting that yet undefined processes enable the pathogen to find its niches outside the intestinal lumen. Finally, our observations suggest that host mucins are a key factor limiting V. cholerae intestinal colonization, particularly in the proximal SI where there appears to be a more abundant mucus layer. Collectively, our findings demonstrate the potent capacity of direct pathogen visualization during infection to deepen our understanding of host pathogen interactions. PMID:25275396

CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens.

PubMed

Qiu, Tianyi; Yang, Yiyan; Qiu, Jingxuan; Huang, Yang; Xu, Tianlei; Xiao, Han; Wu, Dingfeng; Zhang, Qingchen; Zhou, Chen; Zhang, Xiaoyan; Tang, Kailin; Xu, Jianqing; Cao, Zhiwei

2018-05-02

Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major

PubMed Central

Ricci-Azevedo, Rafael; Oliveira, Aline Ferreira; Conrado, Marina C. A. V.; Carvalho, Fernanda Caroline; Roque-Barreira, Maria Cristina

2016-01-01

ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) release; otherwise, transforming growth factor-beta (TGF-β) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an appropriate molecular template for the construction of an efficient anti-infective agent. PMID:27058234

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major.

PubMed

Ricci-Azevedo, Rafael; Oliveira, Aline Ferreira; Conrado, Marina C A V; Carvalho, Fernanda Caroline; Roque-Barreira, Maria Cristina

2016-04-01

ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) release; otherwise, transforming growth factor-beta (TGF-β) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an appropriate molecular template for the construction of an efficient anti-infective agent.

Well-known surface and extracellular antigens of pathogenic microorganisms among the immunodominant proteins of the infectious microalgae Prototheca zopfii

PubMed Central

Irrgang, Alexandra; Murugaiyan, Jayaseelan; Weise, Christoph; Azab, Walid; Roesler, Uwe

2015-01-01

Microalgae of the genus Prototheca (P.) are associated with rare but severe infections (protothecosis) and represent a potential zoonotic risk. Genotype (GT) 2 of P. zopfii has been established as pathogenic agent for humans, dogs, and cattle, whereas GT1 is considered to be non-pathogenic. Since pathogenesis is poorly understood, the aim of this study was to determine immunogenic proteins and potential virulence factors of P. zopfii GT2. Therefore, 2D western blot analyses with sera and isolates of two dogs naturally infected with P. zopfii GT2 have been performed. Cross-reactivity was determined by including the type strains of P. zopfii GT2, P. zopfii GT1, and P. blaschkeae, a close relative of P. zopfii, which is known to cause subclinical forms of bovine mastitis. The sera showed a high strain-, genotype-, and species-cross-reactivity. A total of 198 immunogenic proteins have been analyzed via MALDI—TOF MS. The majority of the 86 identified proteins are intracellularly located (e.g., malate dehydrogenase, oxidoreductase, 3-dehydroquinate synthase) but some antigens and potential virulence factors, known from other pathogens, have been found (e.g., phosphomannomutase, triosephosphate isomerase). One genotype-specific antigen could be identified as heat shock protein 70 (Hsp70), a well-known antigen of eukaryotic pathogens with immunological importance when located extracellularly. Both sera were reactive to glyceraldehyde-3-phosphate-dehydrogenase of all investigated strains. This house-keeping enzyme is found to be located on the surface of several pathogens as virulence factor. Flow-cytometric analysis revealed its presence on the surface of P. blaschkeae. PMID:26484314

Use of Antibiotics and Antimicrobial Resistance in Veterinary Medicine as Exemplified by the Swine Pathogen Streptococcus suis.

PubMed

Seitz, Maren; Valentin-Weigand, Peter; Willenborg, Jörg

2016-01-01

Use of antimicrobial agents in veterinary medicine is essential to control infectious diseases, thereby keeping animals healthy and animal products safe for the consumer. On the other hand, development and spread of antimicrobial resistance is of major concern for public health. Streptococcus (S.) suis reflects a typical bacterial pathogen in modern swine production due to its facultative pathogenic nature and wide spread in the pig population. Thus, in the present review we focus on certain current aspects and problems related to antimicrobial use and resistance in S. suis as a paradigm for a bacterial pathogen affecting swine husbandry worldwide. The review includes (i) general aspects of antimicrobial use and resistance in veterinary medicine with emphasis on swine, (ii) genetic resistance mechanisms of S. suis known to contribute to bacterial survival under antibiotic selection pressure, and (iii) possible other factors which may contribute to problems in antimicrobial therapy of S. suis infections, such as bacterial persister cell formation, biofilm production, and co-infections. The latter shows that we hardly understand the complexity of factors affecting the success of antimicrobial treatment of (porcine) infectious diseases and underlines the need for further research in this field.

Receiver-operating characteristic curves for somatic cell scores and California mastitis test in Valle del Belice dairy sheep.

PubMed

Riggio, Valentina; Pesce, Lorenzo L; Morreale, Salvatore; Portolano, Baldassare

2013-06-01

Using receiver-operating characteristic (ROC) curve methodology this study was designed to assess the diagnostic effectiveness of somatic cell count (SCC) and the California mastitis test (CMT) in Valle del Belice sheep, and to propose and evaluate threshold values for those tests that would optimally discriminate between healthy and infected udders. Milk samples (n=1357) were collected from 684 sheep in four flocks. The prevalence of infection, as determined by positive bacterial culture was 0.36, 87.7% of which were minor and 12.3% major pathogens. Of the culture negative samples, 83.7% had an SCC<500,000/mL and 97.4% had <1,000,000cells/mL. When the associations between SC score (SCS) and whole sample status (culture negative vs. infected), minor pathogen status (culture negative vs. infected with minor pathogens), major pathogen status (culture negative vs. infected with major pathogens), and CMT results were evaluated, the estimated area under the ROC curve was greater for glands infected with major compared to minor pathogens (0.88 vs. 0.73), whereas the area under the curve considering all pathogens was similar to the one for minor pathogens (0.75). The estimated optimal thresholds were 3.00 (CMT), 2.81 (SCS for the whole sample), 2.81 (SCS for minor pathogens), and 3.33 (SCS for major pathogens). These correctly classified, respectively, 69.0%, 73.5%, 72.6% and 91.0% of infected udders in the samples. The CMT appeared only to discriminate udders infected with major pathogens. In this population, SCS appeared to be the best indirect test of the bacteriological status of the udder. Copyright © 2012 Elsevier Ltd. All rights reserved.

Disease ecology and the global emergence of zoonotic pathogens.

PubMed

Wilcox, Bruce A; Gubler, Duane J

2005-09-01

The incidence and frequency of epidemic transmission of zoonotic diseases, both known and newly recognized, has increased dramatically in the past 30 years. It is thought that this dramatic disease emergence is primarily the result of the social, demographic, and environmental transformation that has occurred globally since World War II. However, the causal linkages have not been elucidated. Investigating emerging zoonotic pathogens as an ecological phenomenon can provide significant insights as to why some of these pathogens have jumped species and caused major epidemics in humans. A review of concepts and theory from biological ecology and of causal factors in disease emergence previously described suggests a general model of global zoonotic disease emergence. The model links demographic and societal factors to land use and land cover change whose associated ecological factors help explain disease emergence. The scale and magnitude of these changes are more significant than those associated with climate change, the effects of which are largely not yet understood. Unfortunately, the complex character and non-linear behavior of the human-natural systems in which host-pathogen systems are embedded makes specific incidences of disease emergence or epidemics inherently difficult to predict. Employing a complex systems analytical approach, however, may show how a few key ecological variables and system properties, including the adaptive capacity of institutions, explains the emergence of infectious diseases and how an integrated, multi-level approach to zoonotic disease control can reduce risk.

Management of children with prolonged diarrhea

PubMed Central

Giannattasio, Antonietta; Guarino, Alfredo; Lo Vecchio, Andrea

2016-01-01

Prolonged diarrhea is usually defined as acute-onset diarrhea lasting 7 days or more, but less than 14 days. Its trend has been declining in recent years because of improvement in the management of acute diarrhea, which represents the ideal strategy to prevent prolonged diarrhea. The pathogenesis of prolonged diarrhea is multifactorial and essentially based on persistent mucosal damage due to specific infections or sequential infections with different pathogens, host-related factors including micronutrient and/or vitamin deficiency, undernutrition and immunodeficiency, high mucosal permeability due to previous infectious processes and nutrient deficiency with consequential malabsorption, and microbiota disruption. Infections seem to play a major role in causing prolonged diarrhea in both developing and developed areas. However, single etiologic pathogens have not been identified, and the pattern of agents varies according to settings, host risk factors, and previous use of antibiotics and other drugs. The management of prolonged diarrhea is complex. Because of the wide etiologic spectrum, diagnostic algorithms should take into consideration the age of the patient, clinical and epidemiological factors, and the nutritional status and should always include a search for enteric pathogens. Often, expensive laboratory evaluations are of little benefit in guiding therapy, and an empirical approach may be effective in the majority of cases. The presence or absence of weight loss is crucial for driving the initial management of prolonged diarrhea. If there is no weight loss, generally there is no need for further evaluation. If weight loss is present, empiric anti-infectious therapy or elimination diet may be considered once specific etiologies have been excluded. PMID:26962439

Management of children with prolonged diarrhea.

PubMed

Giannattasio, Antonietta; Guarino, Alfredo; Lo Vecchio, Andrea

2016-01-01

Prolonged diarrhea is usually defined as acute-onset diarrhea lasting 7 days or more, but less than 14 days. Its trend has been declining in recent years because of improvement in the management of acute diarrhea, which represents the ideal strategy to prevent prolonged diarrhea. The pathogenesis of prolonged diarrhea is multifactorial and essentially based on persistent mucosal damage due to specific infections or sequential infections with different pathogens, host-related factors including micronutrient and/or vitamin deficiency, undernutrition and immunodeficiency, high mucosal permeability due to previous infectious processes and nutrient deficiency with consequential malabsorption, and microbiota disruption. Infections seem to play a major role in causing prolonged diarrhea in both developing and developed areas. However, single etiologic pathogens have not been identified, and the pattern of agents varies according to settings, host risk factors, and previous use of antibiotics and other drugs. The management of prolonged diarrhea is complex. Because of the wide etiologic spectrum, diagnostic algorithms should take into consideration the age of the patient, clinical and epidemiological factors, and the nutritional status and should always include a search for enteric pathogens. Often, expensive laboratory evaluations are of little benefit in guiding therapy, and an empirical approach may be effective in the majority of cases. The presence or absence of weight loss is crucial for driving the initial management of prolonged diarrhea. If there is no weight loss, generally there is no need for further evaluation. If weight loss is present, empiric anti-infectious therapy or elimination diet may be considered once specific etiologies have been excluded.

Roles of thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) in Vibrio parahaemolyticus

PubMed Central

Raghunath, Pendru

2015-01-01

Vibrio parahaemolyticus is the leading cause of seafood borne bacterial gastroenteritis in the world, often associated with the consumption of raw or undercooked seafood. However, not all strains of V. parahaemolyticus are pathogenic. The thermostable direct hemolysin (TDH) or TDH-related hemolysin (TRH) encoded by tdh and trh genes, respectively, are considered major virulence factors in V. parahaemolyticus. However, about 10% of clinical strains do not contain tdh and/or trh. Environmental isolates of V. parahaemolyticus lacking tdh and/or trh are also highly cytotoxic to human gastrointestinal cells. Even in the absence of these hemolysins, V. parahaemolyticus remains pathogenic indicating other virulence factors exist. This mini review aims at discussing the possible roles of tdh and trh genes in clinical and environmental isolates of V. parahaemolyticus. PMID:25657643

Roles of thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) in Vibrio parahaemolyticus.

PubMed

Raghunath, Pendru

2014-01-01

Vibrio parahaemolyticus is the leading cause of seafood borne bacterial gastroenteritis in the world, often associated with the consumption of raw or undercooked seafood. However, not all strains of V. parahaemolyticus are pathogenic. The thermostable direct hemolysin (TDH) or TDH-related hemolysin (TRH) encoded by tdh and trh genes, respectively, are considered major virulence factors in V. parahaemolyticus. However, about 10% of clinical strains do not contain tdh and/or trh. Environmental isolates of V. parahaemolyticus lacking tdh and/or trh are also highly cytotoxic to human gastrointestinal cells. Even in the absence of these hemolysins, V. parahaemolyticus remains pathogenic indicating other virulence factors exist. This mini review aims at discussing the possible roles of tdh and trh genes in clinical and environmental isolates of V. parahaemolyticus.

Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma.

PubMed

Deml, Brett; Reis, Linda M; Lemyre, Emmanuelle; Clark, Robin D; Kariminejad, Ariana; Semina, Elena V

2016-04-01

Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing. Analysis of 83 known A/M factors identified pathogenic/likely pathogenic variants in PAX6, OTX2 and NDP in three patients. A novel heterozygous likely pathogenic variant in PAX6, c.767T>C, p.(Val256Ala), was identified in two brothers with bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea and congenital glaucoma; the unaffected mother appears to be a mosaic carrier. While A/M has been reported as a rare feature, this is the first report of congenital primary aphakia in association with PAX6 and the identified allele represents the first variant in the PAX6 homeodomain to be associated with A/M. A novel pathogenic variant in OTX2, c.651delC, p.(Thr218Hisfs*76), in a patient with syndromic bilateral anophthalmia and a hemizygous pathogenic variant in NDP, c.293 C>T, p.(Pro98Leu), in two brothers with isolated bilateral microphthalmia and sclerocornea were also identified. Pathogenic/likely pathogenic variants were not discovered in the 25 remaining A/M cases. This study underscores the utility of whole-exome sequencing for identification of causative mutations in highly variable ocular phenotypes as well as the extreme genetic heterogeneity of A/M conditions.

Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma

PubMed Central

Deml, Brett; Reis, Linda M; Lemyre, Emmanuelle; Clark, Robin D; Kariminejad, Ariana; Semina, Elena V

2016-01-01

Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing. Analysis of 83 known A/M factors identified pathogenic/likely pathogenic variants in PAX6, OTX2 and NDP in three patients. A novel heterozygous likely pathogenic variant in PAX6, c.767T>C, p.(Val256Ala), was identified in two brothers with bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea and congenital glaucoma; the unaffected mother appears to be a mosaic carrier. While A/M has been reported as a rare feature, this is the first report of congenital primary aphakia in association with PAX6 and the identified allele represents the first variant in the PAX6 homeodomain to be associated with A/M. A novel pathogenic variant in OTX2, c.651delC, p.(Thr218Hisfs*76), in a patient with syndromic bilateral anophthalmia and a hemizygous pathogenic variant in NDP, c.293 C>T, p.(Pro98Leu), in two brothers with isolated bilateral microphthalmia and sclerocornea were also identified. Pathogenic/likely pathogenic variants were not discovered in the 25 remaining A/M cases. This study underscores the utility of whole-exome sequencing for identification of causative mutations in highly variable ocular phenotypes as well as the extreme genetic heterogeneity of A/M conditions. PMID:26130484

Modeling Surface Cross-contamination of Salmonella spp. on Ready-to-Eat Meat via Slicing Operation

USDA-ARS?s Scientific Manuscript database

Food pathogen cross-contamination occurring at home, retail food service or production site is one of the major factors causing foodborne illness. Studies on Salmonella Typhimurium surface transfer on ready-to-eat (RTE) deli meat and the slicer used for slicing RTE products are needed to ensure RTE...

Ghrelin receptor null mice have reduced visceral fat and improved insulin sensitivity during aging

USDA-ARS?s Scientific Manuscript database

Aging is associated with a higher incidence of Type 2 diabetes; one in five Americans over age 65 has diabetes. Loss of lean mass and accumulation of fat, particularly visceral fat, during aging result in increased insulin resistance. Insulin resistance is a major pathogenic factor for Type 2 diabet...

Horizontal transmission of Salmonella Enteritidis in experimentally infected laying hens housed in conventional or enriched cages

USDA-ARS?s Scientific Manuscript database

The majority of human illnesses caused by Salmonella Enteritidis are attributed to contaminated eggs, and the prevalence of this pathogen in commercial laying flocks has been identified as a leading epidemiologic risk factor. Flock housing and management systems can affect opportunities for the intr...

[Climate change - a pioneer for the expansion of canine vector-borne diseases?].

PubMed

Krämer, F; Mencke, N

2011-01-01

Vector-transmitted diseases are one of the major contributors to the global burden of disease in humans and animals. Climate change is consistently held responsible for the spread of parasitic acarid and insect vectors such as ticks, fleas, sand flies and mosquitoes, and their transmitted pathogens (in the case of the dog the so-called canine vector-borne diseases [CVBD]). Currently, there is only insufficient data available to prove whether climate change is a major driving force for vector and disease expansion, but the evidence is growing. Other reasons, such as ecological, demographic and socio-economic factors, e.g. pet travel into and pet import from endemic areas, also play a role in this development. Apart from all the controversial discussion of the factors leading to vector and disease expansion, preventative measures should include dog owners' education as they are responsible for individual parasite protection as well as for the minimisation of adverse risk behaviour, e.g. regarding pet travel. Broad-spectrum vector control should be practised by using parasiticides that repel and kill blood feeders in order to minimize the risk of CVBD-pathogen transmission.

Inhibition of proinflammatory activities of major periodontal pathogens by aqueous extracts from elder flower (Sambucus nigra).

PubMed

Harokopakis, Evlambia; Albzreh, Mohamad H; Haase, Elaine M; Scannapieco, Frank A; Hajishengallis, George

2006-02-01

Prolonged induction of excessive levels of inflammatory mediators contributes to the pathogenesis of chronic disease states, such as periodontitis. It is thus important to develop safe and effective anti-inflammatory strategies for therapeutic reasons. In this study, we determined the ability of aqueous extracts from elder flower (Sambucus nigra) to inhibit the proinflammatory activity of major virulence factors from the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. Monocytes/macrophages or neutrophils were incubated with whole cells of P. gingivalis, A. actinomycetemcomitans, or purified components thereof (lipopolysaccharide and fimbriae) in the absence or presence of elder flower extract and were assayed for cytokine production, integrin activation, or induction of the oxidative burst. The elder flower extract was found to potently inhibit all proinflammatory activities tested. Investigation of the underlying mechanisms revealed that the anti-inflammatory extract inhibited activation of the nuclear transcription factor kappaB and of phosphatidylinositol 3-kinase. The elder flower extract displays useful anti-inflammatory properties that could be exploited therapeutically for the control of inflammation in human periodontitis.

A single regulatory gene is sufficient to alter Vibrio aestuarianus pathogenicity in oysters.

PubMed

Goudenège, David; Travers, Marie Agnès; Lemire, Astrid; Petton, Bruno; Haffner, Philippe; Labreuche, Yannick; Tourbiez, Delphine; Mangenot, Sophie; Calteau, Alexandra; Mazel, Didier; Nicolas, Jean Louis; Jacq, Annick; Le roux, Frédérique

2015-11-01

Oyster diseases caused by pathogenic vibrios pose a major challenge to the sustainability of oyster farming. In France, since 2012 a disease affecting specifically adult oysters has been associated with the presence of Vibrio aestuarianus. Here, by combining genome comparison, phylogenetic analyses and high-throughput infections of strains isolated before or during the recent outbreaks, we show that virulent strains cluster into two V. aestuarianus lineages independently of the sampling dates. The bacterial lethal dose was not different between strains isolated before or after 2012. Hence, the emergence of a new highly virulent clonal strain is unlikely. Each lineage comprises nearly identical strains, the majority of them being virulent, suggesting that within these phylogenetically coherent virulent lineages a few strains have lost their pathogenicity. Comparative genomics allowed the identification of a single frameshift in a non-virulent strain. This mutation affects the varS gene that codes for a signal transduction histidine-protein kinase. Genetic analyses confirmed that varS is necessary for infection of oysters and for a secreted metalloprotease expression. For the first time in a Vibrio species, we show here that VarS is a key factor of pathogenicity. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells.

PubMed

Yang, Chih-Wei; Wu, Mai-Szu; Pan, Ming-Jeng; Hsieh, Wang-Ju; Vandewalle, Alain; Huang, Chiu-Ching

2002-08-01

Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein-1 (MCP-1), RANTES, nitrite, and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 microg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-alpha mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor-kappaB (NF-kappaB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.

Basic leucine zipper domain transcription factors: the vanguards in plant immunity.

PubMed

Noman, Ali; Liu, Zhiqin; Aqeel, Muhammad; Zainab, Madiha; Khan, Muhammad Ifnan; Hussain, Ansar; Ashraf, Muhammad Furqan; Li, Xia; Weng, Yahong; He, Shuilin

2017-12-01

Regulation of spatio-temporal expression patterns of stress tolerance associated plant genes is an essential component of the stress responses. Eukaryotes assign a large amount of their genome to transcription with multiple transcription factors (TFs). Often, these transcription factors fit into outsized gene groups which, in several cases, exclusively belong to plants. Basic leucine zipper domain (bZIP) transcription factors regulate vital processes in plants and animals. In plants, bZIPs are implicated in numerous fundamental processes like seed development, energy balance, and responses to abiotic or biotic stresses. Systematic analysis of the information obtained over the last two decades disclosed a constitutive role of bZIPs against biotic stress. bZIP TFs are vital players in plant innate immunity due to their ability to regulate genes associated with PAMP-triggered immunity, effector-triggered immunity, and hormonal signaling networks. Expression analysis of studied bZIP genes suggests that exploration and functional characterization of novel bZIP TFs in planta is helpful in improving crop resistance against pathogens and environmental stresses. Our review focuses on major advancements in bZIP TFs and plant responses against different pathogens. The integration of genomics information with the functional studies provides new insights into the regulation of plant defense mechanisms and engineering crops with improved resistance to invading pathogens. Conclusively, succinct functions of bZIPs as positive or negative regulator mediate resistance to the plant pathogens and lay a foundation for understanding associated genes and TFs regulating different pathways. Moreover, bZIP TFs may offer a comprehensive transgenic gizmo for engineering disease resistance in plant breeding programs.

Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD).

PubMed

Lattante, Serena; Ciura, Sorana; Rouleau, Guy A; Kabashi, Edor

2015-05-01

Several genetic causes have been recently described for neurological diseases, increasing our knowledge of the common pathological mechanisms involved in these disorders. Mutation analysis has shown common causative factors for two major neurodegenerative disorders, ALS and FTD. Shared pathological and genetic markers as well as common neurological signs between these diseases have given rise to the notion of an ALS/FTD spectrum. This overlap among genetic factors causing ALS/FTD and the coincidence of mutated alleles (including causative, risk and modifier variants) have given rise to the notion of an oligogenic model of disease. In this review we summarize major advances in the elucidation of novel genetic factors in these diseases which have led to a better understanding of the common pathogenic factors leading to neurodegeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distribution and risk factors for spread of amphibian chytrid fungus Batrachochytrium dendrobatidis in the Tasmanian Wilderness World Heritage Area, Australia.

PubMed

Pauza, Matthew D; Driessen, Michael M; Skerratt, Lee F

2010-11-01

Chytridiomycosis is an emerging infectious disease caused by the pathogen Batrachochytrium dendrobatidis (Bd) and is the cause of the decline and extinction of amphibian species throughout the world. We surveyed the distribution of Bd within and around the Tasmanian Wilderness World Heritage Area (TWWHA), a 1.38 million ha area of significant fauna conservation value, which provides the majority of habitat for Tasmania's 3 endemic frog species (Litoria burrowsae, Bryobatrachus nimbus and Crinia tasmaniensis). Bd was detected at only 1 (3%) of the 33 sites surveyed within the TWWHA and at 15 (52%) of the 29 sites surveyed surrounding the TWWHA. The relatively low incidence of the disease within the TWWHA suggests that the majority of the TWWHA is currently free of the pathogen despite the fact that the region provides what appears to be optimal conditions for the persistence of Bd. For all survey sites within and around the TWWHA, the presence of Bd was strongly associated with the presence of gravel roads, forest and < 1000 m altitude--factors that in this study were associated with human-disturbed landscapes around the TWWHA. Conversely, the presence of walking tracks was strongly associated with the absence of Bd, suggesting an association of absence with relatively remote locations. The wide distribution of Bd in areas of Tasmania with high levels of human disturbance and its very limited occurrence in remote wilderness areas suggests that anthropogenic activities may facilitate the dissemination of the pathogen on a landscape scale in Tasmania. Because the majority of the TWWHA is not readily accessible and appears to be largely free of Bd, and because Tasmanian frogs reproduce in ponds rather than streams, it may be feasible to control the spread of the disease in the TWWHA.

Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease.

PubMed

Kagawa, T F; Cooney, J C; Baker, H M; McSweeney, S; Liu, M; Gubba, S; Musser, J M; Baker, E N

2000-02-29

Pathogenic bacteria secrete protein toxins that weaken or disable their host, and thereby act as virulence factors. We have determined the crystal structure of streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is a major virulence factor of the human pathogen Streptococcus pyogenes and participates in invasive disease episodes, including necrotizing fasciitis. The structure, determined for the 40-kDa precursor form of SpeB at 1.6-A resolution, reveals that the protein is a distant homologue of the papain superfamily that includes the mammalian cathepsins B, K, L, and S. Despite negligible sequence identity, the protease portion has the canonical papain fold, albeit with major loop insertions and deletions. The catalytic site differs from most other cysteine proteases in that it lacks the Asn residue of the Cys-His-Asn triad. The prosegment has a unique fold and inactivation mechanism that involves displacement of the catalytically essential His residue by a loop inserted into the active site. The structure also reveals the surface location of an integrin-binding Arg-Gly-Asp (RGD) motif that is a feature unique to SpeB among cysteine proteases and is linked to the pathogenesis of the most invasive strains of S. pyogenes.

Antagonistic Microbial Interactions: Contributions and Potential Applications for Controlling Pathogens in the Aquatic Systems

PubMed Central

Feichtmayer, Judith; Deng, Li; Griebler, Christian

2017-01-01

Despite the active and intense treatment of wastewater, pathogenic microorganisms and viruses are frequently introduced into the aquatic environment. For most human pathogens, however, this is a rather hostile place, where starvation, continuous inactivation, and decay generally occur, rather than successful reproduction. Nevertheless, a great diversity of the pathogenic microorganisms can be detected, in particular, in the surface waters receiving wastewater. Pathogen survival depends majorly on abiotic factors such as irradiation, changes in water ionic strength, temperature, and redox state. In addition, inactivation is enhanced by the biotic interactions in the environment. Although knowledge of the antagonistic biotic interactions has been available since a long time, certain underlying processes and mechanisms still remain unclear. Others are well-appreciated and increasingly are applied to the present research. Our review compiles and discusses the presently known biotic interactions between autochthonous microbes and pathogens introduced into the aquatic environment, including protozoan grazing, virus-induced bacterial cell lysis, antimicrobial substances, and predatory bacteria. An overview is provided on the present knowledge, as well as on the obvious research gaps. Individual processes that appear promising for future applications in the aquatic environment are presented and discussed. PMID:29184541

Legionella phospholipases implicated in virulence.

PubMed

Kuhle, Katja; Flieger, Antje

2013-01-01

Phospholipases are diverse enzymes produced in eukaryotic hosts and their bacterial pathogens. Several pathogen phospholipases have been identified as major virulence factors acting mainly in two different modes: on the one hand, they have the capability to destroy host membranes and on the other hand they are able to manipulate host signaling pathways. Reaction products of bacterial phospholipases may act as secondary messengers within the host and therefore influence inflammatory cascades and cellular processes, such as proliferation, migration, cytoskeletal changes as well as membrane traffic. The lung pathogen and intracellularly replicating bacterium Legionella pneumophila expresses a variety of phospholipases potentially involved in disease-promoting processes. So far, genes encoding 15 phospholipases A, three phospholipases C, and one phospholipase D have been identified. These cell-associated or secreted phospholipases may contribute to intracellular establishment, to egress of the pathogen from the host cell, and to the observed lung pathology. Due to the importance of phospholipase activities for host cell processes, it is conceivable that the pathogen enzymes may mimic or substitute host cell phospholipases to drive processes for the pathogen's benefit. The following chapter summarizes the current knowledge on the L. pneumophila phospholipases, especially their substrate specificity, localization, mode of secretion, and impact on host cells.

New monoclonal antibodies against a novel subtype of Shiga toxin 1 produced by Enterobacter cloacae and their use in analysis of human serum

USDA-ARS?s Scientific Manuscript database

Shiga toxin (Stx) is a major virulence factor for several bacterial pathogens that cause potentially fatal illness, including Escherichia coli and Shigella spp. The continual emergence of new subtypes of Stxs presents challenges in clinical diagnosis of infections caused by Shiga toxin-producing org...

An Emerging Mycoplasma Associated with Trichomoniasis, Vaginal Infection and Disease

PubMed Central

Fettweis, Jennifer M.; Serrano, Myrna G.; Huang, Bernice; Brooks, J. Paul; Glascock, Abigail L.; Sheth, Nihar U.; Strauss, Jerome F.; Jefferson, Kimberly K.; Buck, Gregory A.

2014-01-01

Humans are colonized by thousands of bacterial species, but it is difficult to assess the metabolic and pathogenic potential of the majority of these because they have yet to be cultured. Here, we characterize an uncultivated vaginal mycoplasma tightly associated with trichomoniasis that was previously known by its 16S rRNA sequence as “Mnola.” In this study, the mycoplasma was found almost exclusively in women infected with the sexually transmitted pathogen Trichomonas vaginalis, but rarely observed in women with no diagnosed disease. The genomes of four strains of this species were reconstructed using metagenome sequencing and assembly of DNA from four discrete mid-vaginal samples, one of which was obtained from a pregnant woman with trichomoniasis who delivered prematurely. These bacteria harbor several putative virulence factors and display unique metabolic strategies. Genes encoding proteins with high similarity to potential virulence factors include two collagenases, a hemolysin, an O-sialoglycoprotein endopeptidase and a feoB-type ferrous iron transport system. We propose the name “Candidatus Mycoplasma girerdii” for this potential new pathogen. PMID:25337710

Phages and the Evolution of Bacterial Pathogens: from Genomic Rearrangements to Lysogenic Conversion

PubMed Central

Brüssow, Harald; Canchaya, Carlos; Hardt, Wolf-Dietrich

2004-01-01

Comparative genomics demonstrated that the chromosomes from bacteria and their viruses (bacteriophages) are coevolving. This process is most evident for bacterial pathogens where the majority contain prophages or phage remnants integrated into the bacterial DNA. Many prophages from bacterial pathogens encode virulence factors. Two situations can be distinguished: Vibrio cholerae, Shiga toxin-producing Escherichia coli, Corynebacterium diphtheriae, and Clostridium botulinum depend on a specific prophage-encoded toxin for causing a specific disease, whereas Staphylococcus aureus, Streptococcus pyogenes, and Salmonella enterica serovar Typhimurium harbor a multitude of prophages and each phage-encoded virulence or fitness factor makes an incremental contribution to the fitness of the lysogen. These prophages behave like “swarms” of related prophages. Prophage diversification seems to be fueled by the frequent transfer of phage material by recombination with superinfecting phages, resident prophages, or occasional acquisition of other mobile DNA elements or bacterial chromosomal genes. Prophages also contribute to the diversification of the bacterial genome architecture. In many cases, they actually represent a large fraction of the strain-specific DNA sequences. In addition, they can serve as anchoring points for genome inversions. The current review presents the available genomics and biological data on prophages from bacterial pathogens in an evolutionary framework. PMID:15353570

Epigenetic Regulation of the Nitrosative Stress Response and Intracellular Macrophage Survival by Extraintestinal Pathogenic Escherichia coli

PubMed Central

Bateman, Stacey L.; Seed, Patrick C.

2013-01-01

Summary Extraintestinal pathogenic Escherichia coli (ExPEC) reside in the enteric tract as a commensal reservoir, but can transition to a pathogenic state by invading normally sterile niches, establishing infection, and disseminating to invasive sites like the bloodstream. Macrophages are required for ExPEC dissemination, suggesting the pathogen has developed mechanisms to persist within professional phagocytes. Here, we report that FimX, an ExPEC-associated DNA invertase that regulates the major virulence factor type 1 pili (T1P), is also an epigenetic regulator of a LuxR-like response regulator HyxR. FimX regulated hyxR expression through bidirectional phase inversion of its promoter region at sites different from the type 1 pili promoter and independent of integration host factor IHF. In vitro, transition from high to low HyxR expression produced enhanced tolerance of reactive nitrogen intermediates (RNI), primarily through de-repression of hmpA, encoding a nitric oxide detoxifying flavohemoglobin. However, in the macrophage, HyxR produced large effects on intracellular survival in the presence and absence of RNI and independent of Hmp. Collectively, we have shown that the ability of ExPEC to survive in macrophages is contingent upon the proper transition from high to low HyxR expression through epigenetic regulatory control by FimX. PMID:22221182

UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies

PubMed Central

Terlizzi, Maria E.; Gribaudo, Giorgio; Maffei, Massimo E.

2017-01-01

Urinary tract infections (UTIs) are one of the most common pathological conditions in both community and hospital settings. It has been estimated that about 150 million people worldwide develop UTI each year, with high social costs in terms of hospitalizations and medical expenses. Among the common uropathogens associated to UTIs development, UroPathogenic Escherichia coli (UPEC) is the primary cause. UPEC strains possess a plethora of both structural (as fimbriae, pili, curli, flagella) and secreted (toxins, iron-acquisition systems) virulence factors that contribute to their capacity to cause disease, although the ability to adhere to host epithelial cells in the urinary tract represents the most important determinant of pathogenicity. On the opposite side, the bladder epithelium shows a multifaceted array of host defenses including the urine flow and the secretion of antimicrobial substances, which represent useful tools to counteract bacterial infections. The fascinating and intricate dynamics between these players determine a complex interaction system that needs to be revealed. This review will focus on the most relevant components of UPEC arsenal of pathogenicity together with the major host responses to infection, the current approved treatment and the emergence of resistant UPEC strains, the vaccine strategies, the natural antimicrobial compounds along with innovative anti-adhesive and prophylactic approaches to prevent UTIs. PMID:28861072

Plant pathogen nanodiagnostic techniques: forthcoming changes?

PubMed Central

Khiyami, Mohammad A.; Almoammar, Hassan; Awad, Yasser M.; Alghuthaymi, Mousa A.; Abd-Elsalam, Kamel A.

2014-01-01

Plant diseases are among the major factors limiting crop productivity. A first step towards managing a plant disease under greenhouse and field conditions is to correctly identify the pathogen. Current technologies, such as quantitative polymerase chain reaction (Q-PCR), require a relatively large amount of target tissue and rely on multiple assays to accurately identify distinct plant pathogens. The common disadvantage of the traditional diagnostic methods is that they are time consuming and lack high sensitivity. Consequently, developing low-cost methods to improve the accuracy and rapidity of plant pathogens diagnosis is needed. Nanotechnology, nano particles and quantum dots (QDs) have emerged as essential tools for fast detection of a particular biological marker with extreme accuracy. Biosensor, QDs, nanostructured platforms, nanoimaging and nanopore DNA sequencing tools have the potential to raise sensitivity, specificity and speed of the pathogen detection, facilitate high-throughput analysis, and to be used for high-quality monitoring and crop protection. Furthermore, nanodiagnostic kit equipment can easily and quickly detect potential serious plant pathogens, allowing experts to help farmers in the prevention of epidemic diseases. The current review deals with the application of nanotechnology for quicker, more cost-effective and precise diagnostic procedures of plant diseases. Such an accurate technology may help to design a proper integrated disease management system which may modify crop environments to adversely affect crop pathogens. PMID:26740775

Horizontal Acquisition and Transcriptional Integration of Novel Genes in Mosquito-Associated Spiroplasma.

PubMed

Lo, Wen-Sui; Kuo, Chih-Horng

2017-12-01

Genetic differentiation among symbiotic bacteria is important in shaping biodiversity. The genus Spiroplasma contains species occupying diverse niches and is a model system for symbiont evolution. Previous studies have established that two mosquito-associated species have diverged extensively in their carbohydrate metabolism genes despite having a close phylogenetic relationship. Notably, although the commensal Spiroplasma diminutum lacks identifiable pathogenicity factors, the pathogenic Spiroplasma taiwanense was found to have acquired a virulence factor glpO and its associated genes through horizontal transfer. However, it is unclear if these acquired genes have been integrated into the regulatory network. In this study, we inferred the gene content evolution in these bacteria, as well as examined their transcriptomes in response to glucose availability. The results indicated that both species have many more gene acquisitions from the Mycoides-Entomoplasmataceae clade, which contains several important pathogens of ruminants, than previously thought. Moreover, several acquired genes have higher expression levels than the vertically inherited homologs, indicating possible functional replacement. Finally, the virulence factor and its functionally linked genes in S. taiwanense were up-regulated in response to glucose starvation, suggesting that these acquired genes are under expression regulation and the pathogenicity may be a stress response. In summary, although differential gene losses are a major process for symbiont divergence, gene gains are critical in counteracting genome degradation and driving diversification among facultative symbionts. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Tissue adaptation: Implications for gut immunity and tolerance

PubMed Central

2017-01-01

Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function. PMID:28432200

Apnea in Children Hospitalized With Bronchiolitis

PubMed Central

Mansbach, Jonathan M.; Stevenson, Michelle; Macias, Charles G.; Fisher, Erin Stucky; Barcega, Besh; Sullivan, Ashley F.; Espinola, Janice A.; Piedra, Pedro A.; Camargo, Carlos A.

2013-01-01

OBJECTIVE: To identify risk factors for inpatient apnea among children hospitalized with bronchiolitis. METHODS: We enrolled 2207 children, aged <2 years, hospitalized with bronchiolitis at 16 sites during the winters of 2007 to 2010. Nasopharyngeal aspirates (NPAs) were obtained on all subjects, and real-time polymerase chain reaction was used to test NPA samples for 16 viruses. Inpatient apnea was ascertained by daily chart review, with outcome data in 2156 children (98%). Age was corrected for birth <37 weeks. Multivariable logistic regression was performed to identify independent risk factors for inpatient apnea. RESULTS: Inpatient apnea was identified in 108 children (5%, 95% confidence interval [CI] 4%–6%). Statistically significant, independent predictors of inpatient apnea included: corrected ages of <2 weeks (odds ratio [OR] 9.67) and 2 to 8 weeks (OR 4.72), compared with age ≥6 months; birth weight <2.3 kg (5 pounds; OR 2.15), compared with ≥3.2 kg (7 pounds); caretaker report of previous apnea during this bronchiolitis episode (OR 3.63); preadmission respiratory rates of <30 (OR 4.05), 30 to 39 (OR 2.35) and >70 (OR 2.26), compared with 40 to 49; and having a preadmission room air oxygen saturation <90% (OR 1.60). Apnea risk was similar across the major viral pathogens. CONCLUSIONS: In this prospective, multicenter study of children hospitalized with bronchiolitis, inpatient apnea was associated with younger corrected age, lower birth weight, history of apnea, and preadmission clinical factors including low or high respiratory rates and low room air oxygen saturation. Several bronchiolitis pathogens were associated with apnea, with similar apnea risk across the major viral pathogens. PMID:24101759

Opportunistic Pathogenic Yeasts

NASA Astrophysics Data System (ADS)

Banerjee, Uma

Advances in medical research, made during the last few decades, have improved the prophylactic, diagnostic and therapeutic capabilities for variety of infections/diseases. However, many of the prophylactic and therapeutic procedures have been seen in many instances to exact a price of host-vulnerability to an expanding group of opportunistic pathogens and yeasts are one of the important members in it. Fortunately amongst the vast majority of yeasts present in nature only few are considered to have the capability to cause infections when certain opportunities predisposes and these are termed as ‘opportunistic pathogenic yeasts.’ However, the term ‘pathogenic’ is quite tricky, as it depends of various factors of the host, the ‘bug’ and the environment to manifest the clinical infection. The borderline is expanding. In the present century with unprecedented increase in number of immune-compromised host in various disciplines of health care settings, where any yeast, which has the capability to grow at 37 ° C (normal body temperature of human), can be pathogenic and cause infection in particular situation

The role of hyperparasitism in microbial pathogen ecology and evolution.

PubMed

Parratt, Steven R; Laine, Anna-Liisa

2016-08-01

Many micro-organisms employ a parasitic lifestyle and, through their antagonistic interactions with host populations, have major impacts on human, agricultural and natural ecosystems. Most pathogens are likely to host parasites of their own, that is, hyperparasites, but how nested chains of parasites impact on disease dynamics is grossly neglected in the ecological and evolutionary literature. In this minireview we argue that the diversity and dynamics of micro-hyperparasites are an important component of natural host-pathogen systems. We use the current literature from a handful of key systems to show that observed patterns of pathogen virulence and disease dynamics may well be influenced by hyperparasites. Exploring these factors will shed light on many aspects of microbial ecology and disease biology, including resistance-virulence evolution, apparent competition, epidemiology and ecosystem stability. Considering the importance of hyperparasites in natural populations will have applied consequences for the field of biological control and therapeutic science, where hyperparastism is employed as a control mechanism but not necessarily ecologically understood.

Climate change: effects on animal disease systems and implications for surveillance and control.

PubMed

de La Rocque, S; Rioux, J A; Slingenbergh, J

2008-08-01

Climate driven and other changes in landscape structure and texture, plus more general factors, may create favourable ecological niches for emerging diseases. Abiotic factors impact on vectors, reservoirs and pathogen bionomics and their ability to establish in new ecosystems. Changes in climatic patterns and in seasonal conditions may affect disease behaviour in terms of spread pattern, diffusion range, amplification and persistence in novel habitats. Pathogen invasion may result in the emergence of novel disease complexes, presenting major challenges for the sustainability of future animal agriculture at the global level. In this paper, some of the ecological mechanisms underlying the impact of climatic change on disease transmission and disease spread are further described. Potential effects of different climatic variables on pathogens and host population dynamics and distribution are complex to assess, and different approaches are used to describe the underlying epidemiological processes and the availability of ecological niches for pathogens and vectors. The invasion process can disrupt the long-term co-evolution of species. Pathogens adhering to an r-type strategy (e.g. RNA viruses) may be more inclined to encroach on a novel niche resulting from climate change. However, even when linkage between disease dynamics and climate change are relatively strong, there are other factors changing disease behaviour, and these should be accounted for as well. Overall vulnerability of a given ecosystem is a key variable in this regard. The impact of climate-driven changes varies in different parts of the world and in the different agro-climatic zones. Perhaps priority should go to those geographical areas where the integrity of the ecosystem is most severely affected and the adaptability, in terms of robustness and sustainability of response, relatively low.

Oxidative stress survival in a clinical Saccharomyces cerevisiae isolate is influenced by a major quantitative trait nucleotide.

PubMed

Diezmann, Stephanie; Dietrich, Fred S

2011-07-01

One of the major challenges in characterizing eukaryotic genetic diversity is the mapping of phenotypes that are the cumulative effect of multiple alleles. We have investigated tolerance of oxidative stress in the yeast Saccharomyces cerevisiae, a trait showing phenotypic variation in the population. Initial crosses identified that this is a quantitative trait. Microorganisms experience oxidative stress in many environments, including during infection of higher eukaryotes. Natural variation in oxidative stress tolerance is an important aspect of response to oxidative stress exerted by the human immune system and an important trait in microbial pathogens. A clinical isolate of the usually benign yeast S. cerevisiae was found to survive oxidative stress significantly better than the laboratory strain. We investigated the genetic basis of increased peroxide survival by crossing those strains, phenotyping 1500 segregants, and genotyping of high-survival segregants by hybridization of bulk and single segregant DNA to microarrays. This effort has led to the identification of an allele of the transcription factor Rds2 as contributing to stress response. Rds2 has not previously been associated with the survival of oxidative stress. The identification of its role in the oxidative stress response here is an example of a specific trait that appears to be beneficial to Saccharomyces cerevisiae when growing as a pathogen. Understanding the role of this fungal-specific transcription factor in pathogenicity will be important in deciphering how fungi infect and colonize the human host and could eventually lead to a novel drug target.

Community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus virulence toward Caenorhabditis elegans compared.

PubMed

Day, Shandra R; Moore, Christopher M; Kundzins, John R; Sifri, Costi D

2012-11-15

Community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as major human pathogens. CA-MRSA virulence appears to be distinct from healthcare-associated (HA) MRSA with several factors [α-hemolysin (Hla), Panton-Valentine leukocidin (PVL), α-type phenol soluble modulins (PSMα) and SCCmec IV] postulated to enhance virulence or fitness. Using the Caenorhabditis elegans infection model, we compared the virulence of clinical and laboratory isolates of CA-MRSA and HA-MRSA and explored the contribution of CA-MRSA associated virulence factors to nematode killing. All CA-MRSA strains were highly pathogenic to nematodes, while HA-MRSA strains demonstrated variable nematode killing. Nematode killing by isogenic mutants of hla or the loci for PVL, PSMα, PSMβ, PSMδ or SCCmec IV was not different than the parental strains. These results demonstrate that CA-MRSA is highly virulent, shows some strains of HA-MRSA are equally virulent toward nematodes and suggests CA-MRSA virulence in C. elegans is not linked to a single virulence factor.

Community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus virulence toward Caenorhabditis elegans compared

PubMed Central

Day, Shandra R.; Moore, Christopher M.; Kundzins, John R.; Sifri, Costi D.

2012-01-01

Community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as major human pathogens. CA-MRSA virulence appears to be distinct from healthcare-associated (HA) MRSA with several factors [α-hemolysin (Hla), Panton-Valentine leukocidin (PVL), α-type phenol soluble modulins (PSMα) and SCCmec IV] postulated to enhance virulence or fitness. Using the Caenorhabditis elegans infection model, we compared the virulence of clinical and laboratory isolates of CA-MRSA and HA-MRSA and explored the contribution of CA-MRSA associated virulence factors to nematode killing. All CA-MRSA strains were highly pathogenic to nematodes, while HA-MRSA strains demonstrated variable nematode killing. Nematode killing by isogenic mutants of hla or the loci for PVL, PSMα, PSMβ, PSMδ or SCCmec IV was not different than the parental strains. These results demonstrate that CA-MRSA is highly virulent, shows some strains of HA-MRSA are equally virulent toward nematodes and suggests CA-MRSA virulence in C. elegans is not linked to a single virulence factor. PMID:23076331

In vivo insertion pool sequencing identifies virulence factors in a complex fungal–host interaction

PubMed Central

Uhse, Simon; Pflug, Florian G.; Stirnberg, Alexandra; Ehrlinger, Klaus; von Haeseler, Arndt

2018-01-01

Large-scale insertional mutagenesis screens can be powerful genome-wide tools if they are streamlined with efficient downstream analysis, which is a serious bottleneck in complex biological systems. A major impediment to the success of next-generation sequencing (NGS)-based screens for virulence factors is that the genetic material of pathogens is often underrepresented within the eukaryotic host, making detection extremely challenging. We therefore established insertion Pool-Sequencing (iPool-Seq) on maize infected with the biotrophic fungus U. maydis. iPool-Seq features tagmentation, unique molecular barcodes, and affinity purification of pathogen insertion mutant DNA from in vivo-infected tissues. In a proof of concept using iPool-Seq, we identified 28 virulence factors, including 23 that were previously uncharacterized, from an initial pool of 195 candidate effector mutants. Because of its sensitivity and quantitative nature, iPool-Seq can be applied to any insertional mutagenesis library and is especially suitable for genetically complex setups like pooled infections of eukaryotic hosts. PMID:29684023

Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites.

PubMed

Badirzadeh, Alireza; Taheri, Tahereh; Taslimi, Yasaman; Abdossamadi, Zahra; Heidari-Kharaji, Maryam; Gholami, Elham; Sedaghat, Baharehsadat; Niyyati, Maryam; Rafati, Sima

2017-07-01

Proliferation of Leishmania (L.) parasites depends on polyamine availability, which can be generated by the L-arginine catabolism and the enzymatic activity of arginase (ARG) of the parasites and of the mammalian hosts. In the present study, we characterized and compared the arginase (arg) genes from pathogenic L. major and L. tropica and from non-pathogenic L. tarentolae. We quantified the level of the ARG activity in promastigotes and macrophages infected with pathogenic L. major and L. tropica and non-pathogenic L. tarentolae amastigotes. The ARG's amino acid sequences of the pathogenic and non-pathogenic Leishmania demonstrated virtually 98.6% and 88% identities with the reference L. major Friedlin ARG. Higher ARG activity was observed in all pathogenic promastigotes as compared to non-pathogenic L. tarentolae. In vitro infection of human macrophage cell line (THP1) with pathogenic and non-pathogenic Leishmania spp. resulted in increased ARG activities in the infected macrophages. The ARG activities present in vivo were assessed in susceptible BALB/c and resistant C57BL/6 mice infected with L. major, L. tropica and L. tarentolae. We demonstrated that during the development of the infection, ARG is induced in both strains of mice infected with pathogenic Leishmania. However, in L. major infected BALB/c mice, the induction of ARG and parasite load increased simultaneously according to the time course of infection, whereas in C57BL/6 mice, the enzyme is upregulated solely during the period of footpad swelling. In L. tropica infected mice, the footpads' swellings were slow to develop and demonstrated minimal cutaneous pathology and ARG activity. In contrast, ARG activity was undetectable in mice inoculated with the non-pathogenic L. tarentolae. Our data suggest that infection by Leishmania parasites can increase ARG activity of the host and provides essential polyamines for parasite salvage and its replication. Moreover, the ARG of Leishmania is vital for parasite proliferation and required for infection in mice. ARG activity can be used as one of the main marker of the disease severity.

Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites

PubMed Central

Badirzadeh, Alireza; Taheri, Tahereh; Taslimi, Yasaman; Abdossamadi, Zahra; Heidari-Kharaji, Maryam; Gholami, Elham; Sedaghat, Baharehsadat; Niyyati, Maryam

2017-01-01

Proliferation of Leishmania (L.) parasites depends on polyamine availability, which can be generated by the L-arginine catabolism and the enzymatic activity of arginase (ARG) of the parasites and of the mammalian hosts. In the present study, we characterized and compared the arginase (arg) genes from pathogenic L. major and L. tropica and from non-pathogenic L. tarentolae. We quantified the level of the ARG activity in promastigotes and macrophages infected with pathogenic L. major and L. tropica and non-pathogenic L. tarentolae amastigotes. The ARG's amino acid sequences of the pathogenic and non-pathogenic Leishmania demonstrated virtually 98.6% and 88% identities with the reference L. major Friedlin ARG. Higher ARG activity was observed in all pathogenic promastigotes as compared to non-pathogenic L. tarentolae. In vitro infection of human macrophage cell line (THP1) with pathogenic and non-pathogenic Leishmania spp. resulted in increased ARG activities in the infected macrophages. The ARG activities present in vivo were assessed in susceptible BALB/c and resistant C57BL/6 mice infected with L. major, L. tropica and L. tarentolae. We demonstrated that during the development of the infection, ARG is induced in both strains of mice infected with pathogenic Leishmania. However, in L. major infected BALB/c mice, the induction of ARG and parasite load increased simultaneously according to the time course of infection, whereas in C57BL/6 mice, the enzyme is upregulated solely during the period of footpad swelling. In L. tropica infected mice, the footpads' swellings were slow to develop and demonstrated minimal cutaneous pathology and ARG activity. In contrast, ARG activity was undetectable in mice inoculated with the non-pathogenic L. tarentolae. Our data suggest that infection by Leishmania parasites can increase ARG activity of the host and provides essential polyamines for parasite salvage and its replication. Moreover, the ARG of Leishmania is vital for parasite proliferation and required for infection in mice. ARG activity can be used as one of the main marker of the disease severity. PMID:28708893

Pathogen evolution and the immunological niche

PubMed Central

Cobey, Sarah

2014-01-01

Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible–infected–recovered (SIR) model. However, there is growing evidence that the complexity of many host–pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

Genomic characterisation of an endometrial pathogenic Escherichia coli strain reveals the acquisition of genetic elements associated with extra-intestinal pathogenicity.

PubMed

Goldstone, Robert J; Popat, Roman; Schuberth, Hans-Joachim; Sandra, Olivier; Sheldon, I Martin; Smith, David G E

2014-12-06

Strains of Escherichia coli cause a wide variety of intestinal and extra-intestinal diseases in both humans and animals, and are also often found in healthy individuals or the environment. Broadly, a strong phylogenetic relationship exists that distinguishes most E. coli causing intestinal disease from those that cause extra-intestinal disease, however, isolates within a recently described subclass of Extra-Intestinal Pathogenic E. coli (ExPEC), termed endometrial pathogenic E. coli, tend to be phylogenetically distant from the vast majority of characterised ExPECs, and more closely related to human intestinal pathogens. In this work, we investigate the genetic basis for ExPEC infection in the prototypic endometrial pathogenic E. coli strain MS499. By investigating the genome of MS499 in comparison with a range of other E. coli sequences, we have discovered that this bacterium has acquired substantial lengths of DNA which encode factors more usually associated with ExPECs and less frequently found in the phylogroup relatives of MS499. Many of these acquired factors, including several iron acquisition systems and a virulence plasmid similar to that found in several ExPECs such as APEC O1 and the neonatal meningitis E. coli S88, play characterised roles in a variety of typical ExPEC infections and appear to have been acquired recently by the evolutionary lineage leading to MS499. Taking advantage of the phylogenetic relationship we describe between MS499 and several other closely related E. coli isolates from across the globe, we propose a step-wise evolution of a novel clade of sequence type 453 ExPECs within phylogroup B1, involving the recruitment of ExPEC virulence factors into the genome of an ancestrally non-extraintestinal E. coli, which has repurposed this lineage with the capacity to cause extraintestinal disease. These data reveal the genetic components which may be involved in this phenotype switching, and argue that horizontal gene exchange may be a key factor in the emergence of novel lineages of ExPECs.

Molecular epidemiology of pathogenic Leptospira spp. among large ruminants in the Philippines.

PubMed

Villanueva, Marvin A; Mingala, Claro N; Balbin, Michelle M; Nakajima, Chie; Isoda, Norikazu; Suzuki, Yasuhiko; Koizumi, Nobuo

2016-12-01

The extent of Leptospira infection in large ruminants resulting to economic problems in livestock industry in a leptospirosis-endemic country like the Philippines has not been extensively explored. Therefore, we determined the prevalence and carrier status of leptospirosis in large ruminants using molecular techniques and assessed the risk factors of acquiring leptospirosis in these animals. Water buffalo and cattle urine samples (n=831) collected from 21 farms during 2013-2015 were subjected to flaB-nested PCR to detect pathogenic Leptospira spp. Leptospiral flaB was detected in both species with a detection rate of 16.1%. Leptospiral DNA was detected only in samples from animals managed in communal farms. Sequence analysis of Leptospira flaB in large ruminants revealed the formation of three major clusters with L. borgpetersenii or L. kirschneri. One farm contained Leptospira flaB sequences from all clusters identified in this study, suggesting this farm was the main source of leptospires for other farms. This study suggested that these large ruminants are infected with various pathogenic Leptospira species causing possible major economic loss in the livestock industry as well as potential Leptospira reservoirs that can transmit infection to humans and other animals in the Philippines.

A comprehensive review of non-enterica subspecies of Salmonella enterica.

PubMed

Lamas, Alexandre; Miranda, José Manuel; Regal, Patricia; Vázquez, Beatriz; Franco, Carlos Manuel; Cepeda, Alberto

2018-01-01

Salmonella is a major foodborne pathogen with a complex nomenclature. This genus is composed of two species, S. enterica and S. bongori. S. enterica is divided into six subspecies. S. enterica subspecies enterica is composed of more than 1500 serotypes with some of great importance, such as S. Typhimurium and S. Enteritidis. S. enterica subsp. enterica is responsible of more than 99% of human salmonellosis and therefore it is widely studied. However, the non-enterica subspecies of S. enterica have been little studied. These subspecies are considered to be related to cold-blooded animals and their pathogenicity is very limited. Phenotype and genotype information generated from different studies of non-enterica subspecies reveal poor ability to invade host cells and the absence or modification of important virulence factors. Also, the great majority of human infections due to non-enterica subspecies are related to a previous depressed immune system. Therefore, we propose to treat these subspecies only as opportunistic pathogens. For establish this premise, the present review evaluated, among other things, the genomic characteristics, prevalence, antimicrobial resistance and reported human cases of the non-enterica subspecies. Copyright © 2017 Elsevier GmbH. All rights reserved.

Arabidopsis Defense against Botrytis cinerea: Chronology and Regulation Deciphered by High-Resolution Temporal Transcriptomic Analysis[C][W

PubMed Central

Windram, Oliver; Madhou, Priyadharshini; McHattie, Stuart; Hill, Claire; Hickman, Richard; Cooke, Emma; Jenkins, Dafyd J.; Penfold, Christopher A.; Baxter, Laura; Breeze, Emily; Kiddle, Steven J.; Rhodes, Johanna; Atwell, Susanna; Kliebenstein, Daniel J.; Kim, Youn-sung; Stegle, Oliver; Borgwardt, Karsten; Zhang, Cunjin; Tabrett, Alex; Legaie, Roxane; Moore, Jonathan; Finkenstadt, Bärbel; Wild, David L.; Mead, Andrew; Rand, David; Beynon, Jim; Ott, Sascha; Buchanan-Wollaston, Vicky; Denby, Katherine J.

2012-01-01

Transcriptional reprogramming forms a major part of a plant’s response to pathogen infection. Many individual components and pathways operating during plant defense have been identified, but our knowledge of how these different components interact is still rudimentary. We generated a high-resolution time series of gene expression profiles from a single Arabidopsis thaliana leaf during infection by the necrotrophic fungal pathogen Botrytis cinerea. Approximately one-third of the Arabidopsis genome is differentially expressed during the first 48 h after infection, with the majority of changes in gene expression occurring before significant lesion development. We used computational tools to obtain a detailed chronology of the defense response against B. cinerea, highlighting the times at which signaling and metabolic processes change, and identify transcription factor families operating at different times after infection. Motif enrichment and network inference predicted regulatory interactions, and testing of one such prediction identified a role for TGA3 in defense against necrotrophic pathogens. These data provide an unprecedented level of detail about transcriptional changes during a defense response and are suited to systems biology analyses to generate predictive models of the gene regulatory networks mediating the Arabidopsis response to B. cinerea. PMID:23023172

Ultrastructural characterization of melanosomes of the human pathogenic fungus Fonsecaea pedrosoi.

PubMed

Franzen, Anderson J; Cunha, Marcel M L; Miranda, Kildare; Hentschel, Joachim; Plattner, Helmut; da Silva, Moises B; Salgado, Claudio G; de Souza, Wanderley; Rozental, Sonia

2008-04-01

Melanin is a complex polymer widely distributed in nature and has been described as an important virulence factor in pathogenic fungi. In the majority of fungi, the mechanism of melanin formation remains unclear. In Fonsecaea pedrosoi, the major etiologic agent of chromoblastomycosis, melanin is stored in intracellular vesicles, named melanosomes. This paper details the ultrastructural aspects of melanin formation, its storage and transportation to the cell wall in the human pathogenic fungus F. pedrosoi. In this fungus, melanin synthesis within melanosomes also begins with a fibrillar matrix formation, displaying morphological and structural features similar to melanosomes from amphibian and mammalian cells. Silver precipitation based on Fontana-Masson technique for melanin detection and immunocytochemistry showed that melanosome fuses with fungal cell membrane where the melanin is released and reaches the cell wall. Melanin deposition in the fungal cell wall occurs in concentric layers. Antibodies raised against F. pedrosoi melanin revealed the sites of melanin production and storage in the melanosomes. In addition, a preliminary description of the elemental composition of this organelle by X-ray microanalysis and elemental mapping revealed the presence of calcium, phosphorus and iron concentrated in its matrix, suggesting a new functional role for these organelles as iron storage compartments.

Benefits of Genomic Insights and CRISPR-Cas Signatures to Monitor Potential Pathogens across Drinking Water Production and Distribution Systems

PubMed Central

Zhang, Ya; Kitajima, Masaaki; Whittle, Andrew J.; Liu, Wen-Tso

2017-01-01

The occurrence of pathogenic bacteria in drinking water distribution systems (DWDSs) is a major health concern, and our current understanding is mostly related to pathogenic species such as Legionella pneumophila and Mycobacterium avium but not to bacterial species closely related to them. In this study, genomic-based approaches were used to characterize pathogen-related species in relation to their abundance, diversity, potential pathogenicity, genetic exchange, and distribution across an urban drinking water system. Nine draft genomes recovered from 10 metagenomes were identified as Legionella (4 draft genomes), Mycobacterium (3 draft genomes), Parachlamydia (1 draft genome), and Leptospira (1 draft genome). The pathogenicity potential of these genomes was examined by the presence/absence of virulence machinery, including genes belonging to Type III, IV, and VII secretion systems and their effectors. Several virulence factors known to pathogenic species were detected with these retrieved draft genomes except the Leptospira-related genome. Identical clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins (CRISPR-Cas) genetic signatures were observed in two draft genomes recovered at different stages of the studied system, suggesting that the spacers in CRISPR-Cas could potentially be used as a biomarker in the monitoring of Legionella related strains at an evolutionary scale of several years across different drinking water production and distribution systems. Overall, metagenomics approach was an effective and complementary tool of culturing techniques to gain insights into the pathogenic characteristics and the CRISPR-Cas signatures of pathogen-related species in DWDSs. PMID:29097994

Modeling the surface cross-contamination of Salmonella spp. on ready-to-eat meat via a slicing operation

USDA-ARS?s Scientific Manuscript database

Food pathogen cross-contamination occurring in the home or at retail food service or the production site is a major factor contributing to food-borne illness. Studies on Salmonella spp. surface transfer on ready-to-eat (RTE) deli meat and the slicer used for slicing RTE products are needed to ensur...

Mechanistic Insights into Elastin Degradation by Pseudolysin, the Major Virulence Factor of the Opportunistic Pathogen Pseudomonas aeruginosa

PubMed Central

Yang, Jie; Zhao, Hui-Lin; Ran, Li-Yuan; Li, Chun-Yang; Zhang, Xi-Ying; Su, Hai-Nan; Shi, Mei; Zhou, Bai-Cheng; Chen, Xiu-Lan; Zhang, Yu-Zhong

2015-01-01

Pseudolysin is the most abundant protease secreted by Pseudomonas aeruginosa and is the major extracellular virulence factor of this opportunistic human pathogen. Pseudolysin destroys human tissues by solubilizing elastin. However, the mechanisms by which pseudolysin binds to and degrades elastin remain elusive. In this study, we investigated the mechanism of action of pseudolysin on elastin binding and degradation by biochemical assay, microscopy and site-directed mutagenesis. Pseudolysin bound to bovine elastin fibers and preferred to attack peptide bonds with hydrophobic residues at the P1 and P1’ positions in the hydrophobic domains of elastin. The time-course degradation processes of both bovine elastin fibers and cross-linked human tropoelastin by pseudolysin were further investigated by microscopy. Altogether, the results indicate that elastin degradation by pseudolysin began with the hydrophobic domains on the fiber surface, followed by the progressive disassembly of macroscopic elastin fibers into primary structural elements. Moreover, our site-directed mutational results indicate that five hydrophobic residues in the S1-S1’ sub-sites played key roles in the binding of pseudolysin to elastin. This study sheds lights on the pathogenesis of P. aeruginosa infection. PMID:25905792

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa.

PubMed

Persat, Alexandre; Inclan, Yuki F; Engel, Joanne N; Stone, Howard A; Gitai, Zemer

2015-06-16

Bacteria have evolved a wide range of sensing systems to appropriately respond to environmental signals. Here we demonstrate that the opportunistic pathogen Pseudomonas aeruginosa detects contact with surfaces on short timescales using the mechanical activity of its type IV pili, a major surface adhesin. This signal transduction mechanism requires attachment of type IV pili to a solid surface, followed by pilus retraction and signal transduction through the Chp chemosensory system, a chemotaxis-like sensory system that regulates cAMP production and transcription of hundreds of genes, including key virulence factors. Like other chemotaxis pathways, pili-mediated surface sensing results in a transient response amplified by a positive feedback that increases type IV pili activity, thereby promoting long-term surface attachment that can stimulate additional virulence and biofilm-inducing pathways. The methyl-accepting chemotaxis protein-like chemosensor PilJ directly interacts with the major pilin subunit PilA. Our results thus support a mechanochemical model where a chemosensory system measures the mechanically induced conformational changes in stretched type IV pili. These findings demonstrate that P. aeruginosa not only uses type IV pili for surface-specific twitching motility, but also as a sensor regulating surface-induced gene expression and pathogenicity.

Inhibitory effect of totarol on exotoxin proteins hemolysin and enterotoxins secreted by Staphylococcus aureus.

PubMed

Shi, Ce; Zhao, Xingchen; Li, Wenli; Meng, Rizeng; Liu, Zonghui; Liu, Mingyuan; Guo, Na; Yu, Lu

2015-10-01

Staphylococcus aureus (S. aureus) causes a wide variety of infections, which are of major concern worldwide. S. aureus produces multiple virulence factors, resulting in food infection and poisoning. These virulence factors include hyaluronidases, proteases, coagulases, lipases, deoxyribonucleases and enterotoxins. Among the extracellular proteins produced by S. aureus that contribute to pathogenicity, the exotoxins α-hemolysin, staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) are thought to be of major significance. Totarol, a plant extract, has been revealed to inhibit the proliferation of several pathogens effectively. However, there are no reports on the effects of totarol on the production of α-hemolysin, SEA or SEB secreted by S. aureus. The aim of this study was to evaluate the effects of totarol on these three exotoxins. Hemolysis assay, western blotting and real-time reverse transcriptase-PCR assay were performed to identify the influence of graded subinhibitory concentrations of totarol on the production of α-hemolysin and the two major enterotoxins, SEA and SEB, by S. aureus in a dose-dependent manner. Moreover, an enzyme linked immunosorbent assay showed that the TNF-α production of RAW264.7 cells stimulated by S. aureus supernatants was inhibited by subinhibitory concentrations of totarol. Form the data, we propose that totarol could potentially be used as a promising natural compound in the food and pharmaceutical industries.

Factors associated with Anaplasma spp. seroprevalence among dogs in the United States.

PubMed

McMahan, Christopher S; Wang, Dongmei; Beall, Melissa J; Bowman, Dwight D; Little, Susan E; Pithua, Patrick O; Sharp, Julia L; Stich, Roger W; Yabsley, Michael J; Lund, Robert B

2016-03-22

Dogs in the United States are hosts to a diverse range of ticks and tick-borne pathogens, including A. phagocytophilum, an important emerging canine and human pathogen. Previously, a Companion Animal Parasite Council (CAPC)-sponsored workshop proposed factors purported to be associated with the infection risk for tick-transmitted pathogens in dogs in the United States, including climate conditions, socioeconomic characteristics, local topography, and vector distribution. Approximately four million test results from routine veterinary diagnostic tests from 2011-2013, which were collected on a county level across the contiguous United States, are statistically analyzed with the proposed factors via logistic regression and generalized estimating equations. Spatial prevalence maps of baseline Anaplasma spp. prevalence are constructed from Kriging and head-banging smoothing methods. All of the examined factors, with the exception of surface water coverage, were significantly associated with Anaplasma spp. prevalence. Overall, Anaplasma spp. prevalence increases with increasing precipitation and forestation coverage and decreases with increasing temperature, population density, relative humidity, and elevation. Interestingly, socioeconomic status and deer/vehicle collisions were positively and negatively correlated with canine Anaplasma seroprevalence, respectively. A spatial map of the canine Anaplasma hazard is an auxiliary product of the analysis. Anaplasma spp. prevalence is highest in New England and the Upper Midwest. The results from the two posited statistical models (one that contains an endemic areas assumption and one that does not) are in general agreement, with the major difference being that the endemic areas model estimates a larger prevalence in Western Texas, New Mexico, and Colorado. As A. phagocytophilum is zoonotic, the results of this analysis could also help predict areas of high risk for human exposure to this pathogen.

Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

PubMed Central

Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

2015-01-01

Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study reveals virulence factors and phenotypic characteristics of MPEC that may play a role in pathogenesis of E. coli mastitis. PMID:26327312

Isolation and purification of antigenic components of Cryptococcus.

PubMed

Wozniak, Karen L; Levitz, Stuart M

2009-01-01

The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are significant agents of life-threatening infections, particularly in persons with suppressed cell-mediated immunity. This chapter provides detailed methodology for the purification of two of the major antigen fractions of C. neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary component of the polysaccharide capsule, which is the major cryptococcal virulence factor. In contrast, MPs have been identified as key antigens that stimulate T-cell responses. Purification of GXM and MP should assist investigators studying the antigenic, biochemical, and virulence properties of Cryptococcus species.

Pathogen-group specific association between CXCR1 polymorphisms and subclinical mastitis in dairy heifers.

PubMed

Verbeke, Joren; Piepers, Sofie; Peelman, Luc; Van Poucke, Mario; De Vliegher, Sarne

2012-08-01

The chemokine (C-X-C motif) receptor 1 (CXCR1) gene encodes the homonymous receptor for interleukin 8 (IL8) on polymorphonuclear neutrophilic leucocytes (PMNL). Binding causes migration from blood to milk, activation and prolonged survival of PMNL, a crucial process in the innate immune defence of the bovine mammary gland against invading mastitis-causing pathogens. The main objective of this study was to screen the entire coding region of the CXCR1 gene for polymorphisms and to analyse their association with udder health of dairy heifers. One-hundred-and-forty Belgian Holstein heifers originating from 20 commercial dairy farms were genotyped by DNA sequencing. Detailed phenotypic data on udder health was available including quarter bacteriological culture results and somatic cell count (SCC) in early lactation and composite milk SCC during first lactation. In total, 16 polymorphisms (including 8 missense mutations) were detected. Polymorphism c.980A>G was associated with pathogen-group specific IMI: heifers with genotype AG were less likely to have an IMI due to major mastitis pathogens compared with heifers with genotype GG but did not have less IMI by coagulase-negative staphylococci, so-called minor pathogens. CXCR1 genotype was neither associated with quarter SCC in early lactation nor with composite SCC during lactation. Although mastitis susceptibility is influenced by many factors, some genetic polymorphisms potentially have major effects on udder health of heifers, as was shown here. These results trigger us to further study the relationship between CXCR1 polymorphisms and mastitis susceptibility in both observational and experimental trials.

Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line

PubMed Central

How, Kah Yan; Song, Keang Peng; Chan, Kok Gan

2016-01-01

Periodontal disease represents a group of oral inflammatory infections initiated by oral pathogens which exist as a complex biofilms on the tooth surface and cause destruction to tooth supporting tissues. The severity of this disease ranges from mild and reversible inflammation of the gingiva (gingivitis) to chronic destruction of connective tissues, the formation of periodontal pocket and ultimately result in loss of teeth. While human subgingival plaque harbors more than 500 bacterial species, considerable research has shown that Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is the major etiologic agent which contributes to chronic periodontitis. This black-pigmented bacterium produces a myriad of virulence factors that cause destruction to periodontal tissues either directly or indirectly by modulating the host inflammatory response. Here, this review provides an overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity. PMID:26903954

Anaplasma phagocytophilum Infection Subverts Carbohydrate Metabolic Pathways in the Tick Vector, Ixodes scapularis.

PubMed

Cabezas-Cruz, Alejandro; Alberdi, Pilar; Valdés, James J; Villar, Margarita; de la Fuente, José

2017-01-01

The obligate intracellular pathogen, Anaplasma phagocytophilum , is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. A. phagocytophilum has become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts. However, our current knowledge on how A. phagocytophilum affect these processes in the tick vector, Ixodes scapularis is limited. In this study, a genome-wide search for components of major carbohydrate metabolic pathways was performed in I. scapularis ticks for which the genome was recently published. The enzymes involved in the seven major carbohydrate metabolic pathways glycolysis, gluconeogenesis, pentose phosphate, tricarboxylic acid cycle (TCA), glyceroneogenesis, and mitochondrial oxidative phosphorylation and β-oxidation were identified. Then, the available transcriptomics and proteomics data was used to characterize the mRNA and protein levels of I. scapularis major carbohydrate metabolic pathway components in response to A. phagocytophilum infection of tick tissues and cultured cells. The results showed that major carbohydrate metabolic pathways are conserved in ticks. A. phagocytophilum infection inhibits gluconeogenesis and mitochondrial metabolism, but increases the expression of glycolytic genes. A model was proposed to explain how A. phagocytophilum could simultaneously control tick cell glucose metabolism and cytoskeleton organization, which may be achieved in part by up-regulating and stabilizing hypoxia inducible factor 1 alpha in a hypoxia-independent manner. The present work provides a more comprehensive view of the major carbohydrate metabolic pathways involved in the response to A. phagocytophilum infection in ticks, and provides the basis for further studies to develop novel strategies for the control of granulocytic anaplasmosis.

Leishmania major Infection Activates NF-κB and Interferon Regulatory Factors 1 and 8 in Human Dendritic Cells▿

PubMed Central

Jayakumar, Asha; Donovan, Michael J.; Tripathi, Vinita; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann

2008-01-01

The salient feature of dendritic cells (DC) is the initiation of appropriate adaptive immune responses by discriminating between pathogens. Using a prototypic model of intracellular infection, we previously showed that Leishmania major parasites prime human DC for efficient interleukin-12 (IL-12) secretion. L. major infection is associated with self-limiting cutaneous disease and powerful immunity. In stark contrast, the causative agent of visceral leishmaniasis, Leishmania donovani, does not prime human DC for IL-12 production. Here, we report that DC priming by L. major infection results in the early activation of NF-κB transcription factors and the up-regulation and nuclear translocation of interferon regulatory factor 1 (IRF-1) and IRF-8. The inhibition of NF-κB activation by the pretreatment of DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 expression. We further demonstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their consensus binding sites on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signaling cascade or induces an autocrine pathway that activates IRF-1 and IRF-8, ultimately resulting in IL-12 transcription. PMID:18316378

Population genomics of Fusarium graminearum reveals signatures of divergent evolution within a major cereal pathogen

USDA-ARS?s Scientific Manuscript database

The cereal pathogen Fusarium graminearum is the primary cause of Fusarium head blight (FHB) and a significant threat to food safety and crop production. To elucidate population structure and identify genomic targets of selection within major FHB pathogen populations in North America we sequenced the...

The Genome Biology of Effector Gene Evolution in Filamentous Plant Pathogens.

PubMed

Sánchez-Vallet, Andrea; Fouché, Simone; Fudal, Isabelle; Hartmann, Fanny E; Soyer, Jessica L; Tellier, Aurélien; Croll, Daniel

2018-05-16

Filamentous pathogens, including fungi and oomycetes, pose major threats to global food security. Crop pathogens cause damage by secreting effectors that manipulate the host to the pathogen's advantage. Genes encoding such effectors are among the most rapidly evolving genes in pathogen genomes. Here, we review how the major characteristics of the emergence, function, and regulation of effector genes are tightly linked to the genomic compartments where these genes are located in pathogen genomes. The presence of repetitive elements in these compartments is associated with elevated rates of point mutations and sequence rearrangements with a major impact on effector diversification. The expression of many effectors converges on an epigenetic control mediated by the presence of repetitive elements. Population genomics analyses showed that rapidly evolving pathogens show high rates of turnover at effector loci and display a mosaic in effector presence-absence polymorphism among strains. We conclude that effective pathogen containment strategies require a thorough understanding of the effector genome biology and the pathogen's potential for rapid adaptation. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Infection processes of xylem-colonizing pathogenic bacteria: possible explanations for the scarcity of qualitative disease resistance genes against them in crops.

PubMed

Bae, Chungyun; Han, Sang Wook; Song, Yu-Rim; Kim, Bo-Young; Lee, Hyung-Jin; Lee, Je-Min; Yeam, Inhwa; Heu, Sunggi; Oh, Chang-Sik

2015-07-01

Disease resistance against xylem-colonizing pathogenic bacteria in crops. Plant pathogenic bacteria cause destructive diseases in many commercially important crops. Among these bacteria, eight pathogens, Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, X. campestris pv. campestris, Erwinia amylovora, Pantoea stewartii subsp. stewartii, Clavibacter michiganensis subsp. michiganensis, Pseudomonas syringae pv. actinidiae, and Xylella fastidiosa, infect their host plants through different infection sites and paths and eventually colonize the xylem tissues of their host plants, resulting in wilting symptoms by blocking water flow or necrosis of xylem tissues. Noticeably, only a relatively small number of resistant cultivars in major crops against these vascular bacterial pathogens except X. oryzae pv. oryzae have been found or generated so far, although these pathogens threaten productivity of major crops. In this review, we summarize the lifestyles of major xylem-colonizing bacterial pathogens and then discuss the progress of current research on disease resistance controlled by qualitative disease resistance genes or quantitative trait loci against them. Finally, we propose infection processes of xylem-colonizing bacterial pathogens as one of possible reasons for why so few qualitative disease resistance genes against these pathogens have been developed or identified so far in crops.

An overview of calf diarrhea - infectious etiology, diagnosis, and intervention

PubMed Central

Cho, Yong-il

2014-01-01

Calf diarrhea is a commonly reported disease in young animals, and still a major cause of productivity and economic loss to cattle producers worldwide. In the report of the 2007 National Animal Health Monitoring System for U.S. dairy, half of the deaths among unweaned calves was attributed to diarrhea. Multiple pathogens are known or postulated to cause or contribute to calf diarrhea development. Other factors including both the environment and management practices influence disease severity or outcomes. The multifactorial nature of calf diarrhea makes this disease hard to control effectively in modern cow-calf operations. The purpose of this review is to provide a better understanding of a) the ecology and pathogenesis of well-known and potential bovine enteric pathogens implicated in calf diarrhea, b) describe diagnostic tests used to detect various enteric pathogens along with their pros and cons, and c) propose improved intervention strategies for treating calf diarrhea. PMID:24378583

Extra-corporeal membrane oxygenation-associated infections: implication of extra-intestinal pathogenic Escherichia coli clones.

PubMed

Messika, Jonathan; Clermont, Olivier; Landraud, Luce; Schmidt, Matthieu; Aubry, Alexandra; Sougakoff, Wladimir; Fernandes, Romain; Combes, Alain; Denamur, Erick; Ricard, Jean-Damien

2017-08-01

Extra-corporeal membrane oxygenation (ECMO) is a promising life-saving technique for critically ill patients. Bacterial infection is a frequent complication, and Escherichia coli the predominant causative pathogen, but little is known about the characteristics of E. coli strains in these infections. We therefore conducted a retrospective study of 33 E. coli strains responsible for 33 ECMO-related infections, in 30 subjects. Antimicrobial susceptibility, phylotyping, O-typing, clonal relatedness determination and the screening for four virulence factor genes were conducted. Polymicrobial infections were evidenced in 61.6 % of episodes, irrespective of E. coli characteristics. Extra-intestinal pathogenic strains represented the large majority (69.7 %) of all E. coli isolates. Their advantageous genetic background may explain their predominance in this context. The potential for targeted digestive decontamination should be investigated in these patients for whom infectious complications are a heavy burden.

Periodontal microbiology in Latin America.

PubMed

Contreras, Adolfo; Moreno, Sandra M; Jaramillo, Adriana; Pelaez, Melissa; Duque, Andres; Botero, Javier E; Slots, Jørgen

2015-02-01

This review article describes the microbiota associated with periodontal disease in Latin America. This vast territory includes 22 nations, which show great ethnic diversity, with large groups of White people, Black people, Mestizo people and Native people. Widespread poverty and limited access to education and health-care services, including periodontal care, are prominent predisposing factors for destructive periodontal disease in Latin America. Black people and Mestizo people seem to have particularly severe periodontal disease and are frequently colonized by the major periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The 'red complex' bacterial pathogens and A. actinomycetemcomitans predominate in chronic and aggressive periodontitis, but gram-negative enteric rods and herpesviruses can also play important periodontopathic roles in Latin America. The key to minimizing the risk of periodontal disease is control of the pathogens, and new low-cost periodontal treatments deserve serious consideration in Latin America. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Norepinephrine and dopamine increase motility, biofilm formation, and virulence of Vibrio harveyi

PubMed Central

Yang, Qian; Anh, Nguyen D. Q.; Bossier, Peter; Defoirdt, Tom

2014-01-01

Vibrio harveyi is one of the major pathogens of aquatic organisms, affecting both vertebrates and invertebrates, and causes important losses in the aquaculture industry. In order to develop novel methods to control disease caused by this pathogen, we need to obtain a better understanding of pathogenicity mechanisms. Sensing of catecholamines increases both growth and production of virulence-related factors in pathogens of terrestrial animals and humans. However, at this moment, knowledge on the impact of catecholamines on the virulence of pathogens of aquatic organisms is lacking. In the present study, we report that in V. harveyi, norepinephrine (NE) and dopamine (Dopa) increased growth in serum-supplemented medium, siderophore production, swimming motility, and expression of genes involved in flagellar motility, biofilm formation, and exopolysaccharide production. Consistent with this, pretreatment of V. harveyi with catecholamines prior to inoculation into the rearing water resulted in significantly decreased survival of gnotobiotic brine shrimp larvae, when compared to larvae challenged with untreated V. harveyi. Further, NE-induced effects could be neutralized by α-adrenergic antagonists or by the bacterial catecholamine receptor antagonist LED209, but not by β-adrenergic or dopaminergic antagonists. Dopa-induced effects could be neutralized by dopaminergic antagonists or LED209, but not by adrenergic antagonists. Together, our results indicate that catecholamine sensing increases the success of transmission of V. harveyi and that interfering with catecholamine sensing might be an interesting strategy to control vibriosis in aquaculture. We hypothesize that upon tissue and/or hemocyte damage during infection, pathogens come into contact with elevated catecholamine levels, and that this stimulates the expression of virulence factors that are required to colonize a new host. PMID:25414697

Transfer of plasmid DNA to clinical coagulase-negative staphylococcal pathogens by using a unique bacteriophage.

PubMed

Winstel, Volker; Kühner, Petra; Krismer, Bernhard; Peschel, Andreas; Rohde, Holger

2015-04-01

Genetic manipulation of emerging bacterial pathogens, such as coagulase-negative staphylococci (CoNS), is a major hurdle in clinical and basic microbiological research. Strong genetic barriers, such as restriction modification systems or clustered regularly interspaced short palindromic repeats (CRISPR), usually interfere with available techniques for DNA transformation and therefore complicate manipulation of CoNS or render it impossible. Thus, current knowledge of pathogenicity and virulence determinants of CoNS is very limited. Here, a rapid, efficient, and highly reliable technique is presented to transfer plasmid DNA essential for genetic engineering to important CoNS pathogens from a unique Staphylococcus aureus strain via a specific S. aureus bacteriophage, Φ187. Even strains refractory to electroporation can be transduced by this technique once donor and recipient strains share similar Φ187 receptor properties. As a proof of principle, this technique was used to delete the alternative transcription factor sigma B (SigB) via allelic replacement in nasal and clinical Staphylococcus epidermidis isolates at high efficiencies. The described approach will allow the genetic manipulation of a wide range of CoNS pathogens and might inspire research activities to manipulate other important pathogens in a similar fashion. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Targeted mutagenesis in pathogenic Leptospira species: disruption of the LigB gene does not affect virulence in animal models of leptospirosis.

PubMed

Croda, Julio; Figueira, Claudio Pereira; Wunder, Elsio A; Santos, Cleiton S; Reis, Mitermayer G; Ko, Albert I; Picardeau, Mathieu

2008-12-01

The pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenic Leptospira species. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putative Leptospira virulence factors. In this study, a ligB mutant was constructed by allelic exchange in L. interrogans; in this mutant a spectinomycin resistance (Spc(r)) gene replaced a portion of the ligB coding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with the ligB mutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenic Leptospira species. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization.

Targeted Mutagenesis in Pathogenic Leptospira Species: Disruption of the LigB Gene Does Not Affect Virulence in Animal Models of Leptospirosis▿

PubMed Central

Croda, Julio; Figueira, Claudio Pereira; Wunder, Elsio A.; Santos, Cleiton S.; Reis, Mitermayer G.; Ko, Albert I.; Picardeau, Mathieu

2008-01-01

The pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenic Leptospira species. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putative Leptospira virulence factors. In this study, a ligB mutant was constructed by allelic exchange in L. interrogans; in this mutant a spectinomycin resistance (Spcr) gene replaced a portion of the ligB coding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with the ligB mutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenic Leptospira species. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization. PMID:18809657

Targeting Host Factors to Treat West Nile and Dengue Viral Infections

PubMed Central

Krishnan, Manoj N.; Garcia-Blanco, Mariano A.

2014-01-01

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans. PMID:24517970

Targeting host factors to treat West Nile and dengue viral infections.

PubMed

Krishnan, Manoj N; Garcia-Blanco, Mariano A

2014-02-10

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

Transcriptome-wide analysis of WRKY transcription factors in wheat and their leaf rust responsive expression profiling.

PubMed

Satapathy, Lopamudra; Singh, Dharmendra; Ranjan, Prashant; Kumar, Dhananjay; Kumar, Manish; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2014-12-01

WRKY, a plant-specific transcription factor family, has important roles in pathogen defense, abiotic cues and phytohormone signaling, yet little is known about their roles and molecular mechanism of function in response to rust diseases in wheat. We identified 100 TaWRKY sequences using wheat Expressed Sequence Tag database of which 22 WRKY sequences were novel. Identified proteins were characterized based on their zinc finger motifs and phylogenetic analysis clustered them into six clades consisting of class IIc and class III WRKY proteins. Functional annotation revealed major functions in metabolic and cellular processes in control plants; whereas response to stimuli, signaling and defense in pathogen inoculated plants, their major molecular function being binding to DNA. Tag-based expression analysis of the identified genes revealed differential expression between mock and Puccinia triticina inoculated wheat near isogenic lines. Gene expression was also performed with six rust-related microarray experiments at Gene Expression Omnibus database. TaWRKY10, 15, 17 and 56 were common in both tag-based and microarray-based differential expression analysis and could be representing rust specific WRKY genes. The obtained results will bestow insight into the functional characterization of WRKY transcription factors responsive to leaf rust pathogenesis that can be used as candidate genes in molecular breeding programs to improve biotic stress tolerance in wheat.

De Novo Assembled Wheat Transcriptomes Delineate Differentially Expressed Host Genes in Response to Leaf Rust Infection.

PubMed

Chandra, Saket; Singh, Dharmendra; Pathak, Jyoti; Kumari, Supriya; Kumar, Manish; Poddar, Raju; Balyan, Harindra Singh; Gupta, Puspendra Kumar; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2016-01-01

Pathogens like Puccinia triticina, the causal organism for leaf rust, extensively damages wheat production. The interaction at molecular level between wheat and the pathogen is complex and less explored. The pathogen induced response was characterized using mock- or pathogen inoculated near-isogenic wheat lines (with or without seedling leaf rust resistance gene Lr28). Four Serial Analysis of Gene Expression libraries were prepared from mock- and pathogen inoculated plants and were subjected to Sequencing by Oligonucleotide Ligation and Detection, which generated a total of 165,767,777 reads, each 35 bases long. The reads were processed and multiple k-mers were attempted for de novo transcript assembly; 22 k-mers showed the best results. Altogether 21,345 contigs were generated and functionally characterized by gene ontology annotation, mining for transcription factors and resistance genes. Expression analysis among the four libraries showed extensive alterations in the transcriptome in response to pathogen infection, reflecting reorganizations in major biological processes and metabolic pathways. Role of auxin in determining pathogenesis in susceptible and resistant lines were imperative. The qPCR expression study of four LRR-RLK (Leucine-rich repeat receptor-like protein kinases) genes showed higher expression at 24 hrs after inoculation with pathogen. In summary, the conceptual model of induced resistance in wheat contributes insights on defense responses and imparts knowledge of Puccinia triticina-induced defense transcripts in wheat plants.

De Novo Assembled Wheat Transcriptomes Delineate Differentially Expressed Host Genes in Response to Leaf Rust Infection

PubMed Central

Pathak, Jyoti; Kumari, Supriya; Kumar, Manish; Poddar, Raju; Balyan, Harindra Singh; Gupta, Puspendra Kumar; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2016-01-01

Pathogens like Puccinia triticina, the causal organism for leaf rust, extensively damages wheat production. The interaction at molecular level between wheat and the pathogen is complex and less explored. The pathogen induced response was characterized using mock- or pathogen inoculated near-isogenic wheat lines (with or without seedling leaf rust resistance gene Lr28). Four Serial Analysis of Gene Expression libraries were prepared from mock- and pathogen inoculated plants and were subjected to Sequencing by Oligonucleotide Ligation and Detection, which generated a total of 165,767,777 reads, each 35 bases long. The reads were processed and multiple k-mers were attempted for de novo transcript assembly; 22 k-mers showed the best results. Altogether 21,345 contigs were generated and functionally characterized by gene ontology annotation, mining for transcription factors and resistance genes. Expression analysis among the four libraries showed extensive alterations in the transcriptome in response to pathogen infection, reflecting reorganizations in major biological processes and metabolic pathways. Role of auxin in determining pathogenesis in susceptible and resistant lines were imperative. The qPCR expression study of four LRR-RLK (Leucine-rich repeat receptor-like protein kinases) genes showed higher expression at 24 hrs after inoculation with pathogen. In summary, the conceptual model of induced resistance in wheat contributes insights on defense responses and imparts knowledge of Puccinia triticina-induced defense transcripts in wheat plants. PMID:26840746

Can mother-infant interaction produce vulnerability to schizophrenia?

PubMed

Brody, E B

1981-02-01

Schizophrenia is regarded as a final common behavioral syndrome which may be arrived at though a variety of routes. Even with a probably genotype, environmental influence seems necessary for the phenotype to appear. The problem concerns the likelihood of an early experience-induced sequence of events within the person of infant and later adult vs. a continuing pathogenic environment. Either may or may not interact with a continuing genic factor(s) as a source of vulnerability. Vulnerability is here, then, viewed as epigenetically evolving via individual-environment transactions throughout life (although with major impacts from conception through adolescence). At any point, therapeutic intervention may preclude or minimize the actualization of the pathogenic potential. It may begin during pregnancy, with attention to such factors as diet, drugs, physical stress, and illness, influencing fetal development and obstetrical manipulations and the birth process. All influence earliest mother-infant interaction from the point of view both of the infant's evocation of maternal behavior and maternal responsivity. Therapeutic interventions also include attention to the multigenerational context of earliest interaction, with special reference to a woman's relationships with her own mother. At every point, nonspecific protective or pathogenic factors such as social support or stressful precipitating events may become important. Socioeconomic status appears to have a powerful nonspecific influence as the core of a cluster of factors which exert an enduring influence from infancy to adulthood. A continuing specific factor may reside in distorted communicative reciprocity between parent an child rooted in the preverbal period of infant development. Context-mediated cerebral deficits may influence learning capacity, hedonic capacity, behavioral rigidity, and many other factors leading ultimately to impaired social competence and increased vulnerability.

Accounting for biotic spatial variability in fields: Case of resistance screening against sunflower Verticillium wilt

PubMed Central

Missonnier, Hélène; Jacques, Alban; Bang, JiSu; Daydé, Jean; Mirleau-Thebaud, Virginie

2017-01-01

In breeding for disease resistance, the magnitude of the genetic response is difficult to appreciate because of environmental stresses that interact with the plant genotype. We discuss herein the fundamental problems in breeding for disease resistance with the aim being to better understand the interactions between plant, pathogen, and spatial patterns. The goal of this study is to fine tune breeding decisions by incorporating spatial patterns of such biotic factors into the definition of disease-occurrence probability. We use a preexisting statistics method based on geostatistics for a descriptive analysis of biotic factors for trial quality control. The plant-population structure used for spatial-pattern analysis consists of two F1-hybrid cultivars, defined as symptomatic and asymptomatic controls with respect to the studied pathogen. The controls are inserted at specific locations to establish a grid arrangement over the field that include the F1-hybrid cultivars under evaluation. We characterize the spatial structure of the pathogen population and of the general plant environment—with undetermined but present abiotic constraints—not by using direct notation such as flower time or rainfall but by using plant behavior (i.e., leaf symptom severity, indirect notation). The analysis indicates areas with higher or lower risk of disease and reveals a correlation between the symptomatic control and the effective level of disease for sunflowers. This result suggests that the pathogen and/or abiotic components are major factors in determining the probability that a plant develops the disease, which could lead to a misinterpretation of plant resistance. PMID:28817567

Accounting for biotic spatial variability in fields: Case of resistance screening against sunflower Verticillium wilt.

PubMed

Missonnier, Hélène; Jacques, Alban; Bang, JiSu; Daydé, Jean; Mirleau-Thebaud, Virginie

2017-01-01

In breeding for disease resistance, the magnitude of the genetic response is difficult to appreciate because of environmental stresses that interact with the plant genotype. We discuss herein the fundamental problems in breeding for disease resistance with the aim being to better understand the interactions between plant, pathogen, and spatial patterns. The goal of this study is to fine tune breeding decisions by incorporating spatial patterns of such biotic factors into the definition of disease-occurrence probability. We use a preexisting statistics method based on geostatistics for a descriptive analysis of biotic factors for trial quality control. The plant-population structure used for spatial-pattern analysis consists of two F1-hybrid cultivars, defined as symptomatic and asymptomatic controls with respect to the studied pathogen. The controls are inserted at specific locations to establish a grid arrangement over the field that include the F1-hybrid cultivars under evaluation. We characterize the spatial structure of the pathogen population and of the general plant environment-with undetermined but present abiotic constraints-not by using direct notation such as flower time or rainfall but by using plant behavior (i.e., leaf symptom severity, indirect notation). The analysis indicates areas with higher or lower risk of disease and reveals a correlation between the symptomatic control and the effective level of disease for sunflowers. This result suggests that the pathogen and/or abiotic components are major factors in determining the probability that a plant develops the disease, which could lead to a misinterpretation of plant resistance.

Complete genome sequence analysis of the fish pathogen Flavobacterium columnare provides insights into antibiotic resistance and pathogenicity related genes.

PubMed

Zhang, Yulei; Zhao, Lijuan; Chen, Wenjie; Huang, Yunmao; Yang, Ling; Sarathbabu, V; Wu, Zaohe; Li, Jun; Nie, Pin; Lin, Li

2017-10-01

We analyzed here the complete genome sequences of a highly virulent Flavobacterium columnare Pf1 strain isolated in our laboratory. The complete genome consists of a 3,171,081 bp circular DNA with 2784 predicted protein-coding genes. Among these, 286 genes were predicted as antibiotic resistance genes, including 32 RND-type efflux pump related genes which were associated with the export of aminoglycosides, indicating inducible aminoglycosides resistances in F. columnare. On the other hand, 328 genes were predicted as pathogenicity related genes which could be classified as virulence factors, gliding motility proteins, adhesins, and many putative secreted proteases. These genes were probably involved in the colonization, invasion and destruction of fish tissues during the infection of F. columnare. Apparently, our obtained complete genome sequences provide the basis for the explanation of the interactions between the F. columnare and the infected fish. The predicted antibiotic resistance and pathogenicity related genes will shed a new light on the development of more efficient preventional strategies against the infection of F. columnare, which is a major worldwide fish pathogen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathogen evolution and the immunological niche.

PubMed

Cobey, Sarah

2014-07-01

Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible-infected-recovered (SIR) model. However, there is growing evidence that the complexity of many host-pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. © 2014 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Anaplasma phagocytophilum MSP4 and HSP70 Proteins Are Involved in Interactions with Host Cells during Pathogen Infection

PubMed Central

Contreras, Marinela; Alberdi, Pilar; Mateos-Hernández, Lourdes; Fernández de Mera, Isabel G.; García-Pérez, Ana L.; Vancová, Marie; Villar, Margarita; Ayllón, Nieves; Cabezas-Cruz, Alejandro; Valdés, James J.; Stuen, Snorre; Gortazar, Christian; de la Fuente, José

2017-01-01

Anaplasma phagocytophilum transmembrane and surface proteins play a role during infection and multiplication in host neutrophils and tick vector cells. Recently, A. phagocytophilum Major surface protein 4 (MSP4) and Heat shock protein 70 (HSP70) were shown to be localized on the bacterial membrane, with a possible role during pathogen infection in ticks. In this study, we hypothesized that A. phagocytophilum MSP4 and HSP70 have similar functions in tick-pathogen and host-pathogen interactions. To address this hypothesis, herein we characterized the role of these bacterial proteins in interaction and infection of vertebrate host cells. The results showed that A. phagocytophilum MSP4 and HSP70 are involved in host-pathogen interactions, with a role for HSP70 during pathogen infection. The analysis of the potential protective capacity of MSP4 and MSP4-HSP70 antigens in immunized sheep showed that MSP4-HSP70 was only partially protective against pathogen infection. This limited protection may be associated with several factors, including the recognition of non-protective epitopes by IgG in immunized lambs. Nevertheless, these antigens may be combined with other candidate protective antigens for the development of vaccines for the control of human and animal granulocytic anaplasmosis. Focusing on the characterization of host protective immune mechanisms and protein-protein interactions at the host-pathogen interface may lead to the discovery and design of new effective protective antigens. PMID:28725639

Anaplasma phagocytophilum MSP4 and HSP70 Proteins Are Involved in Interactions with Host Cells during Pathogen Infection.

PubMed

Contreras, Marinela; Alberdi, Pilar; Mateos-Hernández, Lourdes; Fernández de Mera, Isabel G; García-Pérez, Ana L; Vancová, Marie; Villar, Margarita; Ayllón, Nieves; Cabezas-Cruz, Alejandro; Valdés, James J; Stuen, Snorre; Gortazar, Christian; de la Fuente, José

2017-01-01

Anaplasma phagocytophilum transmembrane and surface proteins play a role during infection and multiplication in host neutrophils and tick vector cells. Recently, A. phagocytophilum Major surface protein 4 (MSP4) and Heat shock protein 70 (HSP70) were shown to be localized on the bacterial membrane, with a possible role during pathogen infection in ticks. In this study, we hypothesized that A. phagocytophilum MSP4 and HSP70 have similar functions in tick-pathogen and host-pathogen interactions. To address this hypothesis, herein we characterized the role of these bacterial proteins in interaction and infection of vertebrate host cells. The results showed that A. phagocytophilum MSP4 and HSP70 are involved in host-pathogen interactions, with a role for HSP70 during pathogen infection. The analysis of the potential protective capacity of MSP4 and MSP4-HSP70 antigens in immunized sheep showed that MSP4-HSP70 was only partially protective against pathogen infection. This limited protection may be associated with several factors, including the recognition of non-protective epitopes by IgG in immunized lambs. Nevertheless, these antigens may be combined with other candidate protective antigens for the development of vaccines for the control of human and animal granulocytic anaplasmosis. Focusing on the characterization of host protective immune mechanisms and protein-protein interactions at the host-pathogen interface may lead to the discovery and design of new effective protective antigens.

Development of a PCR-RFLP method based on the transcription elongation factor 1-a gene to differentiate Fusarium graminearum from other species within the Fusarium graminearum species complex

USDA-ARS?s Scientific Manuscript database

Fusarium head blight (FHB) is a destructive disease of cereals crops worldwide and a major food safety concern due to grain contamination with trichothecenes and other mycotoxins. Fusarium graminearum, a member of the Fusarium graminearum species complex (FGSC) is the dominant FHB pathogen in many p...

[Spread of nosocomial infection in obstetric hospitals].

PubMed

Adamyan, L V; Kuzmin, V N; Arslanyan, K N; Kharchenko, E I

2015-01-01

The paper highlights the topical problems of nosocomial infection in the practice of obstetrics and perinatology. It systematizes procedures for controlling the occurrence of nosocomial infection and preventing its spread, such as identification of risk groups and risk factors and prerequisites for complications of epidemiological surveillance, as well as specific diagnosis in pregnant women. Group B streptococcus, one of the major pathogens of nosocomial infection, is described.

Prosthetic Joint Infections

PubMed Central

Aslam, Saima; Darouiche, Rabih O.

2012-01-01

Prosthetic joint infections represent a major therapeutic challenge for both healthcare providers and patients. This paper reviews the predisposing factors, pathogenesis, microbiology, diagnosis, treatment and prophylaxis of prosthetic joint infection. The most optimal management strategy should be identified based on a number of considerations including type and duration of infection, antimicrobial susceptibility of the infecting pathogen, condition of infected tissues and bone stock, patient wishes and functional status. PMID:22847032

Multiplexed lateral flow microarray assay for detection of citrus pathogens Xylella fastidiosa and Xanthomonas axonopodis pv citri

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cary,; Bruce, R; Stubben, Christopher J

The invention provides highly sensitive and specific assays for the major citrus pathogens Xylella fastidiosa and Xanthomonas axonopodis, including a field deployable multiplexed assay capable of rapidly assaying for both pathogens simultaneously. The assays are directed at particular gene targets derived from pathogenic strains that specifically cause the major citrus diseases of citrus variegated chlorosis (Xylella fastidiosa 9a5c) and citrus canker (Xanthomonas axonopodis pv citri). The citrus pathogen assays of the invention offer femtomole sensitivity, excellent linear dynamic range, and rapid and specific detection.

Evolution of entomopathogenicity in fungi.

PubMed

Humber, Richard A

2008-07-01

The recent completions of publications presenting the results of a comprehensive study on the fungal phylogeny and a new classification reflecting that phylogeny form a new basis to examine questions about the origins and evolutionary implications of such major habits among fungi as the use of living arthropods or other invertebrates as the main source of nutrients. Because entomopathogenicity appears to have arisen or, indeed, have lost multiple times in many independent lines of fungal evolution, some of the factors that might either define or enable entomopathogenicity are examined. The constant proximity of populations of potential new hosts seem to have been a factor encouraging the acquisition or loss of entomopathogenicity by a very diverse range of fungi, particularly when involving gregarious and immobile host populations of scales, aphids, and cicadas (all in Hemiptera). An underlying theme within the vast complex of pathogenic and parasitic ascomycetes in the Clavicipitaceae (Hypocreales) affecting plants and insects seems to be for interkingdom host-jumping by these fungi from plants to arthropods and then back to the plant or on to fungal hosts. Some genera of Entomophthorales suggest that the associations between fungal pathogens and their insect hosts appear to be shifting away from pathogenicity and towards nonlethal parasitism.

Comparative analysis of the Photorhabdus luminescens and the Yersinia enterocolitica genomes: uncovering candidate genes involved in insect pathogenicity

PubMed Central

Heermann, Ralf; Fuchs, Thilo M

2008-01-01

Background Photorhabdus luminescens and Yersinia enterocolitica are both enteric bacteria which are associated with insects. P. luminescens lives in symbiosis with soil nematodes and is highly pathogenic towards insects but not to humans. In contrast, Y. enterocolitica is widely found in the environment and mainly known to cause gastroenteritis in men, but has only recently been shown to be also toxic for insects. It is expected that both pathogens share an overlap of genetic determinants that play a role within the insect host. Results A selective genome comparison was applied. Proteins belonging to the class of two-component regulatory systems, quorum sensing, universal stress proteins, and c-di-GMP signalling have been analysed. The interorganismic synopsis of selected regulatory systems uncovered common and distinct signalling mechanisms of both pathogens used for perception of signals within the insect host. Particularly, a new class of LuxR-like regulators was identified, which might be involved in detecting insect-specific molecules. In addition, the genetic overlap unravelled a two-component system that is unique for the genera Photorhabdus and Yersinia and is therefore suggested to play a major role in the pathogen-insect relationship. Our analysis also highlights factors of both pathogens that are expressed at low temperatures as encountered in insects in contrast to higher (body) temperature, providing evidence that temperature is a yet under-investigated environmental signal for bacterial adaptation to various hosts. Common degradative metabolic pathways are described that might be used to explore nutrients within the insect gut or hemolymph, thus enabling the proliferation of P. luminescens and Y. enterocolitica in their invertebrate hosts. A strikingly higher number of genes encoding insecticidal toxins and other virulence factors in P. luminescens compared to Y. enterocolitica correlates with the higher virulence of P. luminescens towards insects, and suggests a putative broader insect host spectrum of this pathogen. Conclusion A set of factors shared by the two pathogens was identified including those that are involved in the host infection process, in persistence within the insect, or in host exploitation. Some of them might have been selected during the association with insects and then adapted to pathogenesis in mammalian hosts. PMID:18221513

Analysis of Pathogen and Host Factors Related to Clinical Outcomes in Patients with Hospital-Acquired Pneumonia Due to Methicillin-Resistant Staphylococcus aureus

PubMed Central

Haque, Nadia Z.; Arshad, Samia; Peyrani, Paula; Ford, Kimbal D.; Perri, Mary B.; Jacobsen, Gordon; Reyes, Katherine; Scerpella, Ernesto G.; Ramirez, Julio A.

2012-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial pneumonia. To characterize pathogen-derived and host-related factors in intensive care unit (ICU) patients with MRSA pneumonia, we evaluated the Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) database. We performed multivariate regression analyses of 28-day mortality and clinical response using univariate analysis variables at a P level of <0.25. In isolates from 251 patients, the most common molecular characteristics were USA100 (55.0%) and USA300 (23.9%), SCCmec types II (64.1%) and IV (33.1%), and agr I (36.7%) and II (61.8%). Panton-Valentine leukocidin (PVL) was present in 21.9%, and vancomycin heteroresistance was present in 15.9%. Mortality occurred in 37.1% of patients; factors in the univariate analysis were age, APACHE II score, AIDS, cardiac disease, vascular disease, diabetes, SCCmec type II, PVL negativity, and higher vancomycin MIC (all P values were <0.05). In multivariate analysis, independent predictors were APACHE II score (odds ratio [OR], 1.090; 95% confidence interval [CI], 1.041 to 1.141; P < 0.001) and age (OR, 1.024; 95% CI, 1.003 to 1.046; P = 0.02). Clinical failure occurred in 36.8% of 201 evaluable patients; the only independent predictor was APACHE II score (OR, 1.082; 95% CI, 1.031 to 1.136; P = 0.002). In summary, APACHE II score (mortality, clinical failure) and age (mortality) were the only independent predictors, which is consistent with severity of illness in ICU patients with MRSA pneumonia. Interestingly, our univariate findings suggest that both pathogen and host factors influence outcomes. As the epidemiology of MRSA pneumonia continues to evolve, both pathogen- and host-related factors should be considered when describing epidemiological trends and outcomes of therapeutic interventions. PMID:22337980

DBSecSys: a database of Burkholderia mallei secretion systems.

PubMed

Memišević, Vesna; Kumar, Kamal; Cheng, Li; Zavaljevski, Nela; DeShazer, David; Wallqvist, Anders; Reifman, Jaques

2014-07-16

Bacterial pathogenicity represents a major public health concern worldwide. Secretion systems are a key component of bacterial pathogenicity, as they provide the means for bacterial proteins to penetrate host-cell membranes and insert themselves directly into the host cells' cytosol. Burkholderia mallei is a Gram-negative bacterium that uses multiple secretion systems during its host infection life cycle. To date, the identities of secretion system proteins for B. mallei are not well known, and their pathogenic mechanisms of action and host factors are largely uncharacterized. We present the Database of Burkholderia malleiSecretion Systems (DBSecSys), a compilation of manually curated and computationally predicted bacterial secretion system proteins and their host factors. Currently, DBSecSys contains comprehensive experimentally and computationally derived information about B. mallei strain ATCC 23344. The database includes 143 B. mallei proteins associated with five secretion systems, their 1,635 human and murine interacting targets, and the corresponding 2,400 host-B. mallei interactions. The database also includes information about 10 pathogenic mechanisms of action for B. mallei secretion system proteins inferred from the available literature. Additionally, DBSecSys provides details about 42 virulence attenuation experiments for 27 B. mallei secretion system proteins. Users interact with DBSecSys through a Web interface that allows for data browsing, querying, visualizing, and downloading. DBSecSys provides a comprehensive, systematically organized resource of experimental and computational data associated with B. mallei secretion systems. It provides the unique ability to study secretion systems not only through characterization of their corresponding pathogen proteins, but also through characterization of their host-interacting partners.The database is available at https://applications.bhsai.org/dbsecsys.

Birds Shed RNA-Viruses According to the Pareto Principle

PubMed Central

Jankowski, Mark D.; Williams, Christopher J.; Fair, Jeanne M.; Owen, Jennifer C.

2013-01-01

A major challenge in disease ecology is to understand the role of individual variation of infection load on disease transmission dynamics and how this influences the evolution of resistance or tolerance mechanisms. Such information will improve our capacity to understand, predict, and mitigate pathogen-associated disease in all organisms. In many host-pathogen systems, particularly macroparasites and sexually transmitted diseases, it has been found that approximately 20% of the population is responsible for approximately 80% of the transmission events. Although host contact rates can account for some of this pattern, pathogen transmission dynamics also depend upon host infectiousness, an area that has received relatively little attention. Therefore, we conducted a meta-analysis of pathogen shedding rates of 24 host (avian) – pathogen (RNA-virus) studies, including 17 bird species and five important zoonotic viruses. We determined that viral count data followed the Weibull distribution, the mean Gini coefficient (an index of inequality) was 0.687 (0.036 SEM), and that 22.0% (0.90 SEM) of the birds shed 80% of the virus across all studies, suggesting an adherence of viral shedding counts to the Pareto Principle. The relative position of a bird in a distribution of viral counts was affected by factors extrinsic to the host, such as exposure to corticosterone and to a lesser extent reduced food availability, but not to intrinsic host factors including age, sex, and migratory status. These data provide a quantitative view of heterogeneous virus shedding in birds that may be used to better parameterize epidemiological models and understand transmission dynamics. PMID:23991129

Bacterial size matters: Multiple mechanisms controlling septum cleavage and diplococcus formation are critical for the virulence of the opportunistic pathogen Enterococcus faecalis

PubMed Central

Salamaga, Bartłomiej; Prajsnar, Tomasz K.; Willemse, Joost; Bewley, Martin A.; Chau, Françoise

2017-01-01

Enterococcus faecalis is an opportunistic pathogen frequently isolated in clinical settings. This organism is intrinsically resistant to several clinically relevant antibiotics and can transfer resistance to other pathogens. Although E. faecalis has emerged as a major nosocomial pathogen, the mechanisms underlying the virulence of this organism remain elusive. We studied the regulation of daughter cell separation during growth and explored the impact of this process on pathogenesis. We demonstrate that the activity of the AtlA peptidoglycan hydrolase, an enzyme dedicated to septum cleavage, is controlled by several mechanisms, including glycosylation and recognition of the peptidoglycan substrate. We show that the long cell chains of E. faecalis mutants are more susceptible to phagocytosis and are no longer able to cause lethality in the zebrafish model of infection. Altogether, this work indicates that control of cell separation during division underpins the pathogenesis of E. faecalis infections and represents a novel enterococcal virulence factor. We propose that inhibition of septum cleavage during division represents an attractive therapeutic strategy to control infections. PMID:28742152

The prediction of a pathogenesis-related secretome of Puccinia helianthi through high-throughput transcriptome analysis.

PubMed

Jing, Lan; Guo, Dandan; Hu, Wenjie; Niu, Xiaofan

2017-03-11

Many plant pathogen secretory proteins are known to be elicitors or pathogenic factors,which play an important role in the host-pathogen interaction process. Bioinformatics approaches make possible the large scale prediction and analysis of secretory proteins from the Puccinia helianthi transcriptome. The internet-based software SignalP v4.1, TargetP v1.01, Big-PI predictor, TMHMM v2.0 and ProtComp v9.0 were utilized to predict the signal peptides and the signal peptide-dependent secreted proteins among the 35,286 ORFs of the P. helianthi transcriptome. 908 ORFs (accounting for 2.6% of the total proteins) were identified as putative secretory proteins containing signal peptides. The length of the majority of proteins ranged from 51 to 300 amino acids (aa), while the signal peptides were from 18 to 20 aa long. Signal peptidase I (SpI) cleavage sites were found in 463 of these putative secretory signal peptides. 55 proteins contained the lipoprotein signal peptide recognition site of signal peptidase II (SpII). Out of 908 secretory proteins, 581 (63.8%) have functions related to signal recognition and transduction, metabolism, transport and catabolism. Additionally, 143 putative secretory proteins were categorized into 27 functional groups based on Gene Ontology terms, including 14 groups in biological process, seven in cellular component, and six in molecular function. Gene ontology analysis of the secretory proteins revealed an enrichment of hydrolase activity. Pathway associations were established for 82 (9.0%) secretory proteins. A number of cell wall degrading enzymes and three homologous proteins specific to Phytophthora sojae effectors were also identified, which may be involved in the pathogenicity of the sunflower rust pathogen. This investigation proposes a new approach for identifying elicitors and pathogenic factors. The eventual identification and characterization of 908 extracellularly secreted proteins will advance our understanding of the molecular mechanisms of interactions between sunflower and rust pathogen and will enhance our ability to intervene in disease states.

Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

PubMed Central

Verbruggen, Bas; Bickley, Lisa K.; van Aerle, Ronny; Bateman, Kelly S.; Stentiford, Grant D.; Santos, Eduarda M.; Tyler, Charles R.

2016-01-01

Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment. PMID:26797629

A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis

PubMed Central

Cassat, James E.; Hammer, Neal D.; Campbell, J. Preston; Benson, Meredith A.; Perrien, Daniel S.; Mrak, Lara N.; Smeltzer, Mark S.; Torres, Victor J.; Skaar, Eric P.

2013-01-01

Summary Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection. Pathogen-induced bone destruction limits antimicrobial penetration to the infectious focus and compromises treatment of osteomyelitis. To investigate mechanisms of S. aureus-induced bone destruction, we developed a murine model of osteomyelitis. Micro-computed tomography of infected femurs revealed that S. aureus triggers profound alterations in bone turnover. The bacterial regulatory locus sae was found to be critical for osteomyelitis pathogenesis, as Sae-regulated factors promote pathologic bone remodeling and intraosseous bacterial survival. Exoproteome analyses revealed the Sae-regulated protease aureolysin as a major determinant of the S. aureus secretome and identified the phenol soluble modulins as aureolysin-degraded, osteolytic peptides that trigger osteoblast cell death and bone destruction. These studies establish a murine model for pathogen-induced bone remodeling, define Sae as critical for osteomyelitis pathogenesis, and identify protease-dependent exoproteome remodeling as a major determinant of the staphylococcal virulence repertoire. PMID:23768499

Essential Oil from Sweet Potato Vines, a Potential New Natural Preservative, and an Antioxidant on Sweet Potato Tubers: Assessment of the Activity and the Constitution.

PubMed

Yuan, Bo; Xue, Ling-Wei; Zhang, Qiu-Yue; Kong, Wan-Wan; Peng, Jun; Kou, Meng; Jiang, Ji-Hong

2016-10-12

Pathogenic fungi and oxidation are the major factors that cause the deterioration of sweet potatoes and also cause the loss of quality that makes consumption unsafe. In the present study, the in vitro results demonstrate that the essential oil from sweet potato vines exhibits significantly enhanced activity compared to that of the control. Furthermore, the essential oil can actively inhibit the growth of some common microorganisms inducing pathogenic bacteria and fungi (inhibition rates above 50% at low concentrations). A total of 31 constituents were identified using GC-MS and confirmed that linalool and p-hydroxybenzoic acid are the major active ingredients. The experiment involving actual tubers showed that the essential oil could retains its quality and effectiveness again the fungus disease. This suggests that it could be used in the food industry to increase the shelf life of stored produce (tubers) to ensure food safety without the use of additives or preservatives.

Bacterial community dynamics in a cooling tower with emphasis on pathogenic bacteria and Legionella species using universal and genus-specific deep sequencing.

PubMed

Pereira, Rui P A; Peplies, Jörg; Höfle, Manfred G; Brettar, Ingrid

2017-10-01

Cooling towers are the major source of outbreaks of legionellosis in Europe and worldwide. These outbreaks are mostly associated with Legionella species, primarily L. pneumophila, and its surveillance in cooling tower environments is of high relevance to public health. In this study, a combined NGS-based approach was used to study the whole bacterial community, specific waterborne and water-based bacterial pathogens, especially Legionella species, targeting the 16S rRNA gene. This approach was applied to water from a cooling tower obtained by monthly sampling during two years. The studied cooling tower was an open circuit cooling tower with lamellar cooling situated in Braunschweig, Germany. A highly diverse bacterial community was observed with 808 genera including 25 potentially pathogenic taxa using universal 16S rRNA primers. Sphingomonas and Legionella were the most abundant pathogenic genera. By applying genus-specific primers for Legionella, a diverse community with 85 phylotypes, and a representative core community with substantial temporal heterogeneity was observed. A high percentage of sequences (65%) could not be affiliated to an acknowledged species. L. pneumophila was part of the core community and the most abundant Legionella species reinforcing the importance of cooling towers as its environmental reservoir. Major temperature shifts (>10 °C) were the key environmental factor triggering the reduction or dominance of the Legionella species in the Legionella community dynamics. In addition, interventions by chlorine dioxide had a strong impact on the Legionella community composition but not on the whole bacterial community. Overall, the presented results demonstrated the value of a combined NGS approach for the molecular monitoring and surveillance of health related pathogens in man-made freshwater systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of biotic disturbances on forest carbon cycling in the United States and Canada

USGS Publications Warehouse

Vogelmann, James E.; Allen, Craig D.; Hicke, Jeffrey A.; Desai, Ankur R.; Dietze, Michael C.; Hall, Ronald J.; ,

2012-01-01

Forest insects and pathogens are major disturbance agents that have affected millions of hectares in North America in recent decades, implying significant impacts to the carbon (C) cycle. Here, we review and synthesize published studies of the effects of biotic disturbances on forest C cycling in the United States and Canada. Primary productivity in stands was reduced, sometimes considerably, immediately following insect or pathogen attack. After repeated growth reductions caused by some insects or pathogens or a single infestation by some bark beetle species, tree mortality occurred, altering productivity and decomposition. In the years following disturbance, primary productivity in some cases increased rapidly as a result of enhanced growth by surviving vegetation, and in other cases increased slowly because of lower forest regrowth. In the decades following tree mortality, decomposition increased as a result of the large amount of dead organic matter. Net ecosystem productivity decreased immediately following attack, with some studies reporting a switch to a C source to the atmosphere, and increased afterward as the forest regrew and dead organic matter decomposed. Large variability in C cycle responses arose from several factors, including type of insect or pathogen, time since disturbance, number of trees affected, and capacity of remaining vegetation to increase growth rates following outbreak. We identified significant knowledge gaps, including limited understanding of carbon cycle impacts among different biotic disturbance types (particularly pathogens), their impacts at landscape and regional scales, and limited capacity to predict disturbance events and their consequences for carbon cycling. We conclude that biotic disturbances can have major impacts on forest C stocks and fluxes and can be large enough to affect regional C cycling. However, additional research is needed to reduce the uncertainties associated with quantifying biotic disturbance effects on the North American C budget.

A hydrodynamics-based approach to evaluating the risk of waterborne pathogens entering drinking water intakes in a large, stratified lake.

PubMed

Hoyer, Andrea B; Schladow, S Geoffrey; Rueda, Francisco J

2015-10-15

Pathogen contamination of drinking water lakes and reservoirs is a severe threat to human health worldwide. A major source of pathogens in surface sources of drinking waters is from body-contact recreation in the water body. However, dispersion pathways of human waterborne pathogens from recreational beaches, where body-contact recreation is known to occur to drinking water intakes, and the associated risk of pathogens entering the drinking water supply remain largely undocumented. A high spatial resolution, three-dimensional hydrodynamic and particle tracking modeling approach has been developed to analyze the risk and mechanisms presented by pathogen dispersion. The pathogen model represents the processes of particle release, transport and survival. Here survival is a function of both water temperature and cumulative exposure to ultraviolet (UV) radiation. Pathogen transport is simulated using a novel and computationally efficient technique of tracking particle trajectories backwards, from a drinking water intake toward their source areas. The model has been applied to a large, alpine lake - Lake Tahoe, CA-NV (USA). The dispersion model results reveal that for this particular lake (1) the risk of human waterborne pathogens to enter drinking water intakes is low, but significant; (2) this risk is strongly related to the depth of the thermocline in relation to the depth of the intake; (3) the risk increases with the seasonal deepening of the surface mixed layer; and (4) the risk increases at night when the surface mixed layer deepens through convective mixing and inactivation by UV radiation is eliminated. While these risk factors will quantitatively vary in different lakes, these same mechanisms will govern the process of transport of pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Isolation and Purification of Antigenic Components of Cryptococcus

PubMed Central

Wozniak, Karen L.; Levitz, Stuart M.

2012-01-01

The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are significant agents of life-threatening infections, particularly in persons with suppressed cell-mediated immunity. This chapter provides detailed methodology for the purification of two of the major antigen fractions of C. neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary component of the polysaccharide capsule, which is the major cryptococcal virulence factor. In contrast, MPs have been identified as key antigens that stimulate T-cell responses. Purification of GXM and MP should assist investigators studying the antigenic, biochemical, and virulence properties of Cryptococcus species. PMID:19089377

A new pharmacological agent (AKB-4924) stabilizes hypoxia inducible factor-1 (HIF-1) and increases skin innate defenses against bacterial infection.

PubMed

Okumura, Cheryl Y M; Hollands, Andrew; Tran, Dan N; Olson, Joshua; Dahesh, Samira; von Köckritz-Blickwede, Maren; Thienphrapa, Wdee; Corle, Courtney; Jeung, Seung Nam; Kotsakis, Anna; Shalwitz, Robert A; Johnson, Randall S; Nizet, Victor

2012-09-01

Hypoxia inducible factor-1 (HIF-1) is a transcription factor that is a major regulator of energy homeostasis and cellular adaptation to low oxygen stress. HIF-1 is also activated in response to bacterial pathogens and supports the innate immune response of both phagocytes and keratinocytes. In this work, we show that a new pharmacological compound AKB-4924 increases HIF-1 levels and enhances the antibacterial activity of phagocytes and keratinocytes against both methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus in vitro. AKB-4924 is also effective in stimulating the killing capacity of keratinocytes against the important opportunistic skin pathogens Pseudomonas aeruginosa and Acinetobacter baumanii. The effect of AKB-4924 is mediated through the activity of host cells, as the compound exerts no direct antimicrobial activity. Administered locally as a single agent, AKB-4924 limits S. aureus proliferation and lesion formation in a mouse skin abscess model. This approach to pharmacologically boost the innate immune response via HIF-1 stabilization may serve as a useful adjunctive treatment for antibiotic-resistant bacterial infections.

A New Pharmacological Agent (AKB-4924) Stabilizes Hypoxia Inducible Factor (HIF) and Increases Skin Innate Defenses Against Bacterial Infection

PubMed Central

Okumura, Cheryl Y.M.; Hollands, Andrew; Tran, Dan N.; Olson, Joshua; Dahesh, Samira; von Köckritz-Blickwede, Maren; Thienphrapa, Wdee; Corle, Courtney; Jeung, Seung Nam; Kotsakis, Anna; Shalwitz, Robert A.; Johnson, Randall S.; Nizet, Victor

2013-01-01

Hypoxia inducible factor-1 (HIF-1) is a transcription factor that is a major regulator of energy homeostasis and cellular adaptation to low oxygen stress. HIF-1 is also activated in response to bacterial pathogens and supports the innate immune response of both phagocytes and keratinocytes. In this work, we show that a new pharmacological compound AKB-4924 (Akebia Therapeutics) increases HIF-1α levels and enhances the antibacterial activity of phagocytes and keratinocytes against both methicillin-sensitive and -resistant strains of Staphylococcus aureus in vitro. AKB-4924 is also effective in stimulating the killing capacity of keratinocytes against the important opportunistic skin pathogens Pseudomonas aeruginosa and Acinitobacter baumanii. The effect of AKB-4924 is mediated through the activity of host cells, as the compound exerts no direct antimicrobial activity. Administered locally as a single agent, AKB-4924 limits S. aureus proliferation and lesion formation in a mouse skin abscess model. This approach to pharmacologically boost the innate immune response via HIF-1 stabilization may serve as a useful adjunctive treatment for antibiotic-resistant bacterial infections. PMID:22371073

Tailoring the Immune Response via Customization of Pathogen Gene Expression.

PubMed

Runco, Lisa M; Stauft, Charles B; Coleman, J Robert

2014-01-01

The majority of studies focused on the construction and reengineering of bacterial pathogens have mainly relied on the knocking out of virulence factors or deletion/mutation of amino acid residues to then observe the microbe's phenotype and the resulting effect on the host immune response. These knockout bacterial strains have also been proposed as vaccines to combat bacterial disease. Theoretically, knockout strains would be unable to cause disease since their virulence factors have been removed, yet they could induce a protective memory response. While knockout strains have been valuable tools to discern the role of virulence factors in host immunity and bacterial pathogenesis, they have been unable to yield clinically relevant vaccines. The advent of synthetic biology and enhanced user-directed gene customization has altered this binary process of knockout, followed by observation. Recent studies have shown that a researcher can now tailor and customize a given microbe's gene expression to produce a desired immune response. In this commentary, we highlight these studies as a new avenue for controlling the inflammatory response as well as vaccine development.

Tailoring the Immune Response via Customization of Pathogen Gene Expression

PubMed Central

Runco, Lisa M.; Stauft, Charles B.

2014-01-01

The majority of studies focused on the construction and reengineering of bacterial pathogens have mainly relied on the knocking out of virulence factors or deletion/mutation of amino acid residues to then observe the microbe's phenotype and the resulting effect on the host immune response. These knockout bacterial strains have also been proposed as vaccines to combat bacterial disease. Theoretically, knockout strains would be unable to cause disease since their virulence factors have been removed, yet they could induce a protective memory response. While knockout strains have been valuable tools to discern the role of virulence factors in host immunity and bacterial pathogenesis, they have been unable to yield clinically relevant vaccines. The advent of synthetic biology and enhanced user-directed gene customization has altered this binary process of knockout, followed by observation. Recent studies have shown that a researcher can now tailor and customize a given microbe's gene expression to produce a desired immune response. In this commentary, we highlight these studies as a new avenue for controlling the inflammatory response as well as vaccine development. PMID:24719769

Multidrug-resistant pathogens in patients with pneumonia coming from the community.

PubMed

Sibila, Oriol; Rodrigo-Troyano, Ana; Shindo, Yuichiro; Aliberti, Stefano; Restrepo, Marcos I

2016-05-01

Identification of patients with multidrug-resistant (MDR) pathogens at initial diagnosis is essential for the appropriate selection of empiric treatment of patients with pneumonia coming from the community. The term Healthcare-Associated Pneumonia (HCAP) is controversial for this purpose. Our goal is to summarize and interpret the data addressing the association of MDR pathogens and community-onset pneumonia. Most recent clinical studies conclude that HCAP risk factor does not accurately identify resistant pathogens. Several risk factors related to MDR pathogens, including new ones that were not included in the original HCAP definition, have been described and different risk scores have been proposed. The present review focuses on the most recent literature assessing the importance of different risk factors for MDR pathogens in patients with pneumonia coming from the community. These included generally MDR risk factors, specific risk factors related to methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa and clinical scoring systems develop to assess the MDR risk factors and its application in clinical practice. Different MDR risk factors and prediction scores have been recently developed. However, further research is needed in order to help clinicians in distinguishing between different MDR pathogens causing pneumonia.

The pathogenesis, detection, and prevention of Vibrio parahaemolyticus

PubMed Central

Wang, Rongzhi; Zhong, Yanfang; Gu, Xiaosong; Yuan, Jun; Saeed, Abdullah F.; Wang, Shihua

2015-01-01

Vibrio parahaemolyticus, a Gram-negative motile bacterium that inhabits marine and estuarine environments throughout the world, is a major food-borne pathogen that causes life-threatening diseases in humans after the consumption of raw or undercooked seafood. The global occurrence of V. parahaemolyticus accentuates the importance of investigating its virulence factors and their effects on the human host. This review describes the virulence factors of V. parahaemolyticus reported to date, including hemolysin, urease, two type III secretion systems and two type VI secretion systems, which both cause both cytotoxicity in cultured cells and enterotoxicity in animal models. We describe various types of detection methods, based on virulence factors, that are used for quantitative detection of V. parahaemolyticus in seafood. We also discuss some useful preventive measures and therapeutic strategies for the diseases mediated by V. parahaemolyticus, which can reduce, to some extent, the damage to humans and aquatic animals attributable to V. parahaemolyticus. This review extends our understanding of the pathogenic mechanisms of V. parahaemolyticus mediated by virulence factors and the diseases it causes in its human host. It should provide new insights for the diagnosis, treatment, and prevention of V. parahaemolyticus infection. PMID:25798132

Major emerging and re-emerging zoonoses in China: a matter of global health and socioeconomic development for 1.3 billion.

PubMed

Liu, Quan; Cao, Lili; Zhu, Xing-Quan

2014-08-01

Emerging and re-emerging zoonoses are a significant public health concern and cause considerable socioeconomic problems globally. The emergence of severe acute respiratory syndrome (SARS), highly pathogenic avian influenza (HPAI) H5N1, avian influenza H7N9, and severe fever with thrombocytopenia syndrome (SFTS), and the re-emergence of rabies, brucellosis, and other zoonoses have had a significant effect on the national economy and public health in China, and have affected other countries. Contributing factors that continue to affect emerging and re-emerging zoonoses in China include social and environmental factors and microbial evolution, such as population growth, urbanization, deforestation, livestock production, food safety, climate change, and pathogen mutation. The Chinese government has devised new strategies and has taken measures to deal with the challenges of these diseases, including the issuing of laws and regulations, establishment of disease reporting systems, implementation of special projects for major infectious diseases, interdisciplinary and international cooperation, exotic disease surveillance, and health education. These strategies and measures can serve as models for the surveillance and response to continuing threats from emerging and re-emerging zoonoses in other countries. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Risk factors for drug-resistant pathogens in immunocompetent patients with pneumonia: Evaluation of PES pathogens.

PubMed

Ishida, Tadashi; Ito, Akihiro; Washio, Yasuyoshi; Yamazaki, Akio; Noyama, Maki; Tokioka, Fumiaki; Arita, Machiko

2017-01-01

The new acronym, PES pathogens (Pseudomonas aeruginosa, Enterobacteriaceae extended-spectrum beta-lactamase-positive, and methicillin-resistant Staphylococcus aureus), was recently proposed to identify drug-resistant pathogens associated with community-acquired pneumonia. To evaluate the risk factors for antimicrobial-resistant pathogens in immunocompetent patients with pneumonia and to validate the role of PES pathogens. A retrospective analysis of a prospective observational study of immunocompetent patients with pneumonia between March 2009 and June 2015 was conducted. We clarified the risk factors for PES pathogens. Of the total 1559 patients, an etiological diagnosis was made in 705 (45.2%) patients. PES pathogens were identified in 51 (7.2%) patients, with 53 PES pathogens (P. aeruginosa, 34; ESBL-positive Enterobacteriaceae, 6; and MRSA, 13). Patients with PES pathogens had tendencies toward initial treatment failure, readmission within 30 days, and a prolonged hospital stay. Using multivariate analysis, female sex (adjusted odds ratio [AOR] 1.998, 95% confidence interval [CI] 1.047-3.810), admission within 90 days (AOR 2.827, 95% CI 1.250-6.397), poor performance status (AOR 2.380, 95% CI 1.047-5.413), and enteral feeding (AOR 5.808, 95% CI 1.813-18.613) were independent risk factors for infection with PES pathogens. The area under the receiver operating characteristics curve for the risk factors was 0.66 (95% CI 0.577-0.744). We believe the definition of PES pathogens is an appropriate description of drug-resistant pathogens associated with pneumonia in immunocompetent patients. The frequency of PES pathogens is quite low. However, recognition is critical because they can cause refractory pneumonia and different antimicrobial treatment is required. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain.

PubMed

Kunsmann, Lisa; Rüter, Christian; Bauwens, Andreas; Greune, Lilo; Glüder, Malte; Kemper, Björn; Fruth, Angelika; Wai, Sun Nyunt; He, Xiaohua; Lloubes, Roland; Schmidt, M Alexander; Dobrindt, Ulrich; Mellmann, Alexander; Karch, Helge; Bielaszewska, Martina

2015-08-18

The highly virulent Escherichia coli O104:H4 that caused the large 2011 outbreak of diarrhoea and haemolytic uraemic syndrome secretes blended virulence factors of enterohaemorrhagic and enteroaggregative E. coli, but their secretion pathways are unknown. We demonstrate that the outbreak strain releases a cocktail of virulence factors via outer membrane vesicles (OMVs) shed during growth. The OMVs contain Shiga toxin (Stx) 2a, the major virulence factor of the strain, Shigella enterotoxin 1, H4 flagellin, and O104 lipopolysaccharide. The OMVs bind to and are internalised by human intestinal epithelial cells via dynamin-dependent and Stx2a-independent endocytosis, deliver the OMV-associated virulence factors intracellularly and induce caspase-9-mediated apoptosis and interleukin-8 secretion. Stx2a is the key OMV component responsible for the cytotoxicity, whereas flagellin and lipopolysaccharide are the major interleukin-8 inducers. The OMVs represent novel ways for the E. coli O104:H4 outbreak strain to deliver pathogenic cargoes and injure host cells.

The Impact of Recombination Hotspots on Genome Evolution of a Fungal Plant Pathogen

PubMed Central

Croll, Daniel; Lendenmann, Mark H.; Stewart, Ethan; McDonald, Bruce A.

2015-01-01

Recombination has an impact on genome evolution by maintaining chromosomal integrity, affecting the efficacy of selection, and increasing genetic variability in populations. Recombination rates are a key determinant of the coevolutionary dynamics between hosts and their pathogens. Historic recombination events created devastating new pathogens, but the impact of ongoing recombination in sexual pathogens is poorly understood. Many fungal pathogens of plants undergo regular sexual cycles, and sex is considered to be a major factor contributing to virulence. We generated a recombination map at kilobase-scale resolution for the haploid plant pathogenic fungus Zymoseptoria tritici. To account for intraspecific variation in recombination rates, we constructed genetic maps from two independent crosses. We localized a total of 10,287 crossover events in 441 progeny and found that recombination rates were highly heterogeneous within and among chromosomes. Recombination rates on large chromosomes were inversely correlated with chromosome length. Short accessory chromosomes often lacked evidence for crossovers between parental chromosomes. Recombination was concentrated in narrow hotspots that were preferentially located close to telomeres. Hotspots were only partially conserved between the two crosses, suggesting that hotspots are short-lived and may vary according to genomic background. Genes located in hotspot regions were enriched in genes encoding secreted proteins. Population resequencing showed that chromosomal regions with high recombination rates were strongly correlated with regions of low linkage disequilibrium. Hence, genes in pathogen recombination hotspots are likely to evolve faster in natural populations and may represent a greater threat to the host. PMID:26392286

Sequence diversity and evolution of antimicrobial peptides in invertebrates.

PubMed

Tassanakajon, Anchalee; Somboonwiwat, Kunlaya; Amparyup, Piti

2015-02-01

Antimicrobial peptides (AMPs) are evolutionarily ancient molecules that act as the key components in the invertebrate innate immunity against invading pathogens. Several AMPs have been identified and characterized in invertebrates, and found to display considerable diversity in their amino acid sequence, structure and biological activity. AMP genes appear to have rapidly evolved, which might have arisen from the co-evolutionary arms race between host and pathogens, and enabled organisms to survive in different microbial environments. Here, the sequence diversity of invertebrate AMPs (defensins, cecropins, crustins and anti-lipopolysaccharide factors) are presented to provide a better understanding of the evolution pattern of these peptides that play a major role in host defense mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two Types of Threonine-Tagged Lipopeptides Synergize in Host Colonization by Pathogenic Burkholderia Species.

PubMed

Thongkongkaew, Tawatchai; Ding, Wei; Bratovanov, Evgeni; Oueis, Emilia; Garcı A-Altares, Marı A; Zaburannyi, Nestor; Harmrolfs, Kirsten; Zhang, Youming; Scherlach, Kirstin; Müller, Rolf; Hertweck, Christian

2018-05-18

Bacterial infections of agriculturally important mushrooms and plants pose a major threat to human food sources worldwide. However, structures of chemical mediators required by the pathogen for host colonization and infection remain elusive in most cases. Here, we report two types of threonine-tagged lipopeptides conserved among mushroom and rice pathogenic Burkholderia species that facilitate bacterial infection of hosts. Genome mining, metabolic profiling of infected mushrooms, and heterologous expression of orphan gene clusters allowed the discovery of these unprecedented metabolites in the mushroom pathogen Burkholderia gladioli (haereogladin, burriogladin) and the plant pathogen Burkholderia glumae (haereoglumin and burrioglumin). Through targeted gene deletions, the molecular basis of lipopeptide biosynthesis by nonribosomal peptide synthetases was revealed. Surprisingly, both types of lipopeptides feature unusual threonine tags, which yield longer peptide backbones than one would expect based on the canonical colinearity of the NRPS assembly lines. Both peptides play an indirect role in host infection as biosurfactants that enable host colonization by mediating swarming and biofilm formation abilities. Moreover, MALDI imaging mass spectrometry was applied to investigate the biological role of the lipopeptides. Our results shed light on conserved mechanisms that mushroom and plant pathogenic bacteria utilize for host infection and expand current knowledge on bacterial virulence factors that may represent a new starting point for the targeted development of crop protection measures in the future.

Helicobacter pylori potentiates epithelial:mesenchymal transition in gastric cancer: links to soluble HB-EGF, gastrin and matrix metalloproteinase-7

PubMed Central

Yin, Yinfei; Grabowska, Anna M; Clarke, Philip A; Whelband, Elisabeth; Robinson, Karen; Argent, Richard H; Tobias, Amanda; Kumari, Rajendra; Atherton, John C

2010-01-01

Background and aims Helicobacter pylori (H pylori) infection is a major risk factor in the development of distal gastric adenocarcinoma. Development of the invasive phenotype is associated with the phenomenon of epithelial:mesenchymal transition (EMT). Soluble heparin-binding epidermal growth factor (HB-EGF) has been implicated in this process. A study was undertaken to investigate the possibility that matrix metalloproteinase (MMP)-7 is upregulated in H pylori infection as a result of hypergastrinaemia, which may enhance shedding of HB-EGF and contribute towards EMT in gastric adenocarcinoma cell lines. Methods Three gastric epithelial cell lines (AGS, MGLVA1 and ST16) were co-cultured with the pathogenic H pylori strain 60190 and non-pathogenic strain Tx30a in an in vitro infection model. Gene expression was quantified by real-time PCR, HB-EGF shedding by ELISA and protein expression by immunofluorescence or immunohistochemistry. The INS-GAS mouse, a transgenic mouse model of gastric carcinogenesis which overexpresses amidated gastrin, was used to investigate the in vivo relationship between HB-EGF, MMP-7, gastrin and EMT. Results The pathogenic strain of H pylori significantly upregulated EMT-associated genes Snail, Slug and vimentin in all three gastric cell lines to a greater degree than the non-pathogenic strain. Pathogenic H pylori also upregulated HB-EGF shedding, a factor implicated in EMT, which was partially dependent on both gastrin and MMP-7 expression. Gastrin and MMP-7 siRNAs and MMP-7 neutralising antibody significantly reduced upregulation of HB-EGF shedding in H pylori infected gastric cell lines and reduced EMT gene expression. The effect of H pylori on EMT was also reversed by gastrin siRNA. Neutralisation of gastrin in the INS-GAS mouse model reduced expression of MMP-7, HB-EGF and key EMT proteins. Conclusion The upregulation of MMP-7 by pathogenic H pylori is partially dependent on gastrin and may have a role in the development of gastric cancer, potentially through EMT, by indirectly increasing levels of soluble HB-EGF. PMID:20584780

Development and validation of a clinical risk score for predicting drug-resistant bacterial pneumonia in older Chinese patients.

PubMed

Ma, Hon Ming; Ip, Margaret; Woo, Jean; Hui, David S C

2014-05-01

Health care-associated pneumonia (HCAP) and drug-resistant bacterial pneumonia may not share identical risk factors. We have shown that bronchiectasis, recent hospitalization and severe pneumonia (confusion, blood urea level, respiratory rate, low blood pressure and 65 year old (CURB-65) score ≥ 3) were independent predictors of pneumonia caused by potentially drug-resistant (PDR) pathogens. This study aimed to develop and validate a clinical risk score for predicting drug-resistant bacterial pneumonia in older patients. We derived a risk score by assigning a weighting to each of these risk factors as follows: 14, bronchiectasis; 5, recent hospitalization; 2, severe pneumonia. A 0.5 point was defined for the presence of other risk factors for HCAP. We compared the areas under the receiver-operating characteristics curve (AUROC) of our risk score and the HCAP definition in predicting PDR pathogens in two cohorts of older patients hospitalized with non-nosocomial pneumonia. The derivation and validation cohorts consisted of 354 and 96 patients with bacterial pneumonia, respectively. PDR pathogens were isolated in 48 and 21 patients in the derivation and validation cohorts, respectively. The AUROCs of our risk score and the HCAP definition were 0.751 and 0.650, respectively, in the derivation cohort, and were 0.782 and 0.671, respectively, in the validation cohort. The differences between our risk score and the HCAP definition reached statistical significance. A score ≥ 2.5 had the best balance between sensitivity and specificity. Our risk score outperformed the HCAP definition to predict pneumonia caused by PDR pathogens. A history of bronchiectasis or recent hospitalization is the major indication of starting empirical broad-spectrum antibiotics. © 2014 Asian Pacific Society of Respirology.

OsMADS26 Negatively Regulates Resistance to Pathogens and Drought Tolerance in Rice1[OPEN

PubMed Central

Khong, Giang Ngan; Richaud, Frédérique; Parizot, Boris; Mai, Chung Duc; Bès, Martine; Bourrié, Isabelle; Meynard, Donaldo; Beeckman, Tom; Selvaraj, Michael Gomez; Manabu, Ishitani; Brugidou, Christophe; Nang Do, Vinh; Guiderdoni, Emmanuel; Morel, Jean-Benoit; Gantet, Pascal

2015-01-01

Functional analyses of MADS-box transcription factors in plants have unraveled their role in major developmental programs (e.g. flowering and floral organ identity) as well as stress-related developmental processes, such as abscission, fruit ripening, and senescence. Overexpression of the rice (Oryza sativa) MADS26 gene in rice has revealed a possible function related to stress response. Here, we show that OsMADS26-down-regulated plants exhibit enhanced resistance against two major rice pathogens: Magnaporthe oryzae and Xanthomonas oryzae. Despite this enhanced resistance to biotic stresses, OsMADS26-down-regulated plants also displayed enhanced tolerance to water deficit. These phenotypes were observed in both controlled and field conditions. Interestingly, alteration of OsMADS26 expression does not have a strong impact on plant development. Gene expression profiling revealed that a majority of genes misregulated in overexpresser and down-regulated OsMADS26 lines compared with control plants are associated to biotic or abiotic stress response. Altogether, our data indicate that OsMADS26 acts as an upstream regulator of stress-associated genes and thereby, a hub to modulate the response to various stresses in the rice plant. PMID:26424158

Comparative evaluation of aggressiveness traits in staphylococcal strains from severe infections versus nasopharyngeal carriage.

PubMed

Săndulescu, Oana; Bleotu, Coralia; Matei, Lilia; Streinu-Cercel, Anca; Oprea, Mihaela; Drăgulescu, Elena Carmina; Chifiriuc, Mariana Carmen; Rafila, Alexandru; Pirici, Daniel; Tălăpan, Daniela; Dorobăţ, Olga Mihaela; Neguţ, Alina Cristina; Oţelea, Dan; Berciu, Ioana; Ion, Daniela Adriana; Codiţă, Irina; Calistru, Petre Iacob; Streinu-Cercel, Adrian

2017-01-01

Despite their commensal status, staphylococci can become problematic pathogens expressing multiple and redundant virulence factors. This study aimed to evaluate aggressiveness markers comparatively in staphylococcal strains isolated from severe infections versus asymptomatic carriage in order to identify clinically relevant bacterial traits that could easily be detected in clinical practice and could be suggestive for particular host-pathogen interactions such as cyto-adhesion or biofilm formation, ultimately orienting the clinical decision-making process. We have used in vitro phenotypic methods to assess adhesion to and invasion of eukaryotic cells, biofilm development, and expression of soluble virulence factors in 92 Staphylococcus spp. strains. The adhesion index, invasion capacity, biofilm formation and expression of soluble factors did not differ significantly between clinical and commensal strains. The major bacterial traits we found to be significantly more prevalent in clinical staphylococci were the aggregative adhesion pattern (P = 0.012), cluster adhesion (P = 0.001) and tetrad morphology (P = 0.018). The aggregative adhesion pattern was correlated with higher cyto-adhesion (P < 0.001), higher invasion capacity (P = 0.003) and lower Carmeli scores (P = 0.002). Three major bacterial traits, namely tetrad morphology, aggregative adhesion pattern, and resistance to methicillin (acronym: TAM), can be used to compute an aggressiveness score (SAS) predictive of the staphylococcal strain's virulence and capacity to initiate and develop a biofilm-driven chronic infectious process versus a fulminant acute infection, in a susceptible host. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overexpression of BSR1 confers broad-spectrum resistance against two bacterial diseases and two major fungal diseases in rice

PubMed Central

Maeda, Satoru; Hayashi, Nagao; Sasaya, Takahide; Mori, Masaki

2016-01-01

Broad-spectrum disease resistance against two or more types of pathogen species is desirable for crop improvement. In rice, Xanthomonas oryzae pv. oryzae (Xoo), the causal bacteria of rice leaf blight, and Magnaporthe oryzae, the fungal pathogen causing rice blast, are two of the most devastating pathogens. We identified the rice BROAD-SPECTRUM RESISTANCE 1 (BSR1) gene for a BIK1-like receptor-like cytoplasmic kinase using the FOX hunting system, and demonstrated that BSR1-overexpressing (OX) rice showed strong resistance to the bacterial pathogen, Xoo and the fungal pathogen, M. oryzae. Here, we report that BSR1-OX rice showed extended resistance against two other different races of Xoo, and to at least one other race of M. oryzae. In addition, the rice showed resistance to another bacterial species, Burkholderia glumae, which causes bacterial seedling rot and bacterial grain rot, and to Cochliobolus miyabeanus, another fungal species causing brown spot. Furthermore, BSR1-OX rice showed slight resistance to rice stripe disease, a major viral disease caused by rice stripe virus. Thus, we demonstrated that BSR1-OX rice shows remarkable broad-spectrum resistance to at least two major bacterial species and two major fungal species, and slight resistance to one viral pathogen. PMID:27436950

Overexpression of BSR1 confers broad-spectrum resistance against two bacterial diseases and two major fungal diseases in rice.

PubMed

Maeda, Satoru; Hayashi, Nagao; Sasaya, Takahide; Mori, Masaki

2016-06-01

Broad-spectrum disease resistance against two or more types of pathogen species is desirable for crop improvement. In rice, Xanthomonas oryzae pv. oryzae (Xoo), the causal bacteria of rice leaf blight, and Magnaporthe oryzae, the fungal pathogen causing rice blast, are two of the most devastating pathogens. We identified the rice BROAD-SPECTRUM RESISTANCE 1 (BSR1) gene for a BIK1-like receptor-like cytoplasmic kinase using the FOX hunting system, and demonstrated that BSR1-overexpressing (OX) rice showed strong resistance to the bacterial pathogen, Xoo and the fungal pathogen, M. oryzae. Here, we report that BSR1-OX rice showed extended resistance against two other different races of Xoo, and to at least one other race of M. oryzae. In addition, the rice showed resistance to another bacterial species, Burkholderia glumae, which causes bacterial seedling rot and bacterial grain rot, and to Cochliobolus miyabeanus, another fungal species causing brown spot. Furthermore, BSR1-OX rice showed slight resistance to rice stripe disease, a major viral disease caused by rice stripe virus. Thus, we demonstrated that BSR1-OX rice shows remarkable broad-spectrum resistance to at least two major bacterial species and two major fungal species, and slight resistance to one viral pathogen.

Significance of Infectious Agents in Colorectal Cancer Development

PubMed Central

Antonic, Vlado; Stojadinovic, Alexander; Kester, Kent E.; Weina, Peter J; Brücher, Björn LDM; Protic, Mladjan; Avital, Itzhak; Izadjoo, Mina

2013-01-01

Colorectal cancer (CRC) is a major burden to healthcare systems worldwide accounting for approximately one million of new cancer cases worldwide. Even though, CRC mortality has decreased over the last 20 years, it remains the third most common cause of cancer-related mortality, accounting for approximately 600,000 deaths in 2008 worldwide. A multitude of risk factors have been linked to CRC, including hereditary factors, environmental factors and inflammatory syndromes affecting the gastrointestinal tract. Recently, various pathogens were added to the growing list of risk factors for a number of common epithelial cancers, but despite the multitude of correlative studies, only suggestions remain about the possible relationship between selected viruses and bacteria of interest and the CRC risk. United States military service members are exposed to various risk factors impacting the incidence of cancer development. These exposures are often different from that of many sectors of the civilian population. Thereby, cancer risk identification, screening and early detection are imperative for both the military health care beneficiaries and the population as a whole. In this review, we will focus on several pathogens and their potential roles in development of CRC, highlighting the clinical trials evaluating this correlation and provide our personal opinion about the importance of risk reduction, health promotion and disease prevention for military health care beneficiaries. PMID:23459622

Bacteria between protists and phages: from antipredation strategies to the evolution of pathogenicity.

PubMed

Brüssow, Harald

2007-08-01

Bacteriophages and protists are major causes of bacterial mortality. Genomics suggests that phages evolved well before eukaryotic protists. Bacteria were thus initially only confronted with phage predators. When protists evolved, bacteria were caught between two types of predators. One successful antigrazing strategy of bacteria was the elaboration of toxins that would kill the grazer. The released cell content would feed bystander bacteria. I suggest here that, to fight grazing protists, bacteria teamed up with those phage predators that concluded at least a temporary truce with them in the form of lysogeny. Lysogeny was perhaps initially a resource management strategy of phages that could not maintain infection chains. Subsequently, lysogeny might have evolved into a bacterium-prophage coalition attacking protists, which became a food source for them. When protists evolved into multicellular animals, the lysogenic bacteria tracked their evolving food source. This hypothesis could explain why a frequent scheme of bacterial pathogenicity is the survival in phagocytes, why a significant fraction of bacterial pathogens have prophage-encoded virulence genes, and why some virulence factors of animal pathogens are active against unicellular eukaryotes. Bacterial pathogenicity might thus be one playing option of the stone-scissor-paper game played between phages-bacteria-protists, with humans getting into the crossfire.

Host specific glycans are correlated with susceptibility to infection by lagoviruses, but not with their virulence.

PubMed

Lopes, Ana M; Breiman, Adrien; Lora, Mónica; Le Moullac-Vaidye, Béatrice; Galanina, Oxana; Nyström, Kristina; Marchandeau, Stephane; Le Gall-Reculé, Ghislaine; Strive, Tanja; Neimanis, Aleksija; Bovin, Nicolai V; Ruvoën-Clouet, Nathalie; Esteves, Pedro J; Abrantes, Joana; Le Pendu, Jacques

2017-11-29

The rabbit hemorrhagic disease virus (RHDV) and the European brown hare syndrome virus (EBHSV) are two lagoviruses from the family Caliciviridae that cause fatal diseases in two leporid genera, Oryctolagus and Lepus , respectively. In the last few years, several examples of host jumps of lagoviruses among leporids were recorded. In addition, a new pathogenic genotype of RHDV emerged and many non-pathogenic strains of lagoviruses have been described. The molecular mechanisms behind host shifts and the emergence of virulence are unknown. Since RHDV uses glycans of the histo-blood group antigen type as attachment factors to initiate infection, we studied if glycan specificities of the new pathogenic RHDV genotype, non-pathogenic lagoviruses and EBHSV potentially play a role in determining host range and virulence of lagoviruses. We observed binding to A, B or H antigens of the histo-blood group family for all strains known to primarily infect European rabbits ( Oryctolagus cuniculus ), that have recently been classified as GI strains. Yet, we could not explain the emergence of virulence since similar glycan specificities were found between several pathogenic and non-pathogenic strains. By contrast, EBHSV, recently classified as GII.1, bound to terminal β-linked N-acetylglucosamine residues of O-glycans. Expression of these attachment factors in the upper respiratory and digestive tracts in three lagomorph species ( Oryctolagus cuniculus, Lepus europaeus and Sylvilagus floridanus ) showed species-specific patterns regarding the susceptibility to infection by these viruses, indicating that species-specific glycan expression is likely a major contributor to lagoviruses host specificity and range. IMPORTANCE Lagoviruses constitute a genus of the Caliciviridae family, comprising highly pathogenic viruses, RHDV and EBHSV, which infect rabbits and hares, respectively. Recently, non-pathogenic strains were discovered and new pathogenic strains have emerged. In addition, host jumps between lagomorphs are observed. The mechanisms responsible for the emergence of pathogenicity and host-species range are unknown. Previous studies showed that RHDV strains attach to glycans expressed in the upper respiratory and digestive tracts of rabbits, the likely doors of virus entry. Here we studied the glycan-binding properties of novel pathogenic and non-pathogenic strains looking for a link between glycan-binding and virulence or between glycan specificity and host range. We found that glycan binding did not correlate with virulence. However, expression of glycan motifs in the upper respiratory and digestive tracts of lagomorphs revealed species-specific patterns associated with the host range of the virus strains, suggesting that glycan diversity contributes to lagoviruses' host range. Copyright © 2017 American Society for Microbiology.

The genetic basis of local adaptation for pathogenic fungi in agricultural ecosystems.

PubMed

Croll, Daniel; McDonald, Bruce A

2017-04-01

Local adaptation plays a key role in the evolutionary trajectory of host-pathogen interactions. However, the genetic architecture of local adaptation in host-pathogen systems is poorly understood. Fungal plant pathogens in agricultural ecosystems provide highly tractable models to quantify phenotypes and map traits to corresponding genomic loci. The outcome of crop-pathogen interactions is thought to be governed largely by gene-for-gene interactions. However, recent studies showed that virulence can be governed by quantitative trait loci and that many abiotic factors contribute to the outcome of the interaction. After introducing concepts of local adaptation and presenting examples from wild plant pathosystems, we focus this review on a major pathogen of wheat, Zymoseptoria tritici, to show how a multitude of traits can affect local adaptation. Zymoseptoria tritici adapted to different thermal environments across its distribution range, indicating that thermal adaptation may limit effective dispersal to different climates. The application of fungicides led to the rapid evolution of multiple, independent resistant populations. The degree of colony melanization showed strong pleiotropic effects with other traits, including trade-offs with colony growth rates and fungicide sensitivity. The success of the pathogen on its host can be assessed quantitatively by counting pathogen reproductive structures and measuring host damage based on necrotic lesions. Interestingly, these two traits can be weakly correlated and depend both on host and pathogen genotypes. Quantitative trait mapping studies showed that the genetic architecture of locally adapted traits varies from single loci with large effects to many loci with small individual effects. We discuss how local adaptation could hinder or accelerate the development of epidemics in agricultural ecosystems. © 2016 John Wiley & Sons Ltd.

Pathogenic agents in freshwater resources

NASA Astrophysics Data System (ADS)

Geldreich, Edwin E.

1996-02-01

Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

Function and Biosynthesis of Cell Wall α-1,3-Glucan in Fungi.

PubMed

Yoshimi, Akira; Miyazawa, Ken; Abe, Keietsu

2017-11-18

Although α-1,3-glucan is a major cell wall polysaccharide in filamentous fungi, its biological functions remain unclear, except that it acts as a virulence factor in animal and plant pathogenic fungi: it conceals cell wall β-glucan on the fungal cell surface to circumvent recognition by hosts. However, cell wall α-1,3-glucan is also present in many of non-pathogenic fungi. Recently, the universal function of α-1,3-glucan as an aggregation factor has been demonstrated. Applications of fungi with modified cell wall α-1,3-glucan in the fermentation industry and of in vitro enzymatically-synthesized α-1,3-glucan in bio-plastics have been developed. This review focuses on the recent progress in our understanding of the biological functions and biosynthetic mechanism of cell wall α-1,3-glucan in fungi. We briefly consider the history of studies on α-1,3-glucan, overview its biological functions and biosynthesis, and finally consider the industrial applications of fungi deficient in α-1,3-glucan.

Gut microbiota and malnutrition.

PubMed

Million, Matthieu; Diallo, Aldiouma; Raoult, Didier

2017-05-01

Malnutrition is the leading cause of death worldwide in children under the age of five, and is the focus of the first World Health Organization (WHO) Millennium Development Goal. Breastfeeding, food and water security are major protective factors against malnutrition and critical factors in the maturation of healthy gut microbiota, characterized by a transient bifidobacterial bloom before a global rise in anaerobes. Early depletion in gut Bifidobacterium longum, a typical maternal probiotic, known to inhibit pathogens, represents the first step in gut microbiota alteration associated with severe acute malnutrition (SAM). Later, the absence of the Healthy Mature Anaerobic Gut Microbiota (HMAGM) leads to deficient energy harvest, vitamin biosynthesis and immune protection, and is associated with diarrhea, malabsorption and systemic invasion by microbial pathogens. A therapeutic diet and infection treatment may be unable to restore bifidobacteria and HMAGM. Besides refeeding and antibiotics, future trials including non-toxic missing microbes and nutrients necessary to restore bifidobacteria and HMAGM, including prebiotics and antioxidants, are warranted in children with severe or refractory disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lethality of First Contact Dysentery Epidemics on Pacific Islands

PubMed Central

Shanks, G. Dennis

2016-01-01

Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen-induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history. PMID:27185765

Streptococcus agalactiae Non-Pilus, Cell Wall-Anchored Proteins: Involvement in Colonization and Pathogenesis and Potential as Vaccine Candidates

PubMed Central

Pietrocola, Giampiero; Arciola, Carla Renata; Rindi, Simonetta; Montanaro, Lucio; Speziale, Pietro

2018-01-01

Group B Streptococcus (GBS) remains an important etiological agent of several infectious diseases including neonatal septicemia, pneumonia, meningitis, and orthopedic device infections. This pathogenicity is due to a variety of virulence factors expressed by Streptococcus agalactiae. Single virulence factors are not sufficient to provoke a streptococcal infection, which is instead promoted by the coordinated activity of several pathogenicity factors. Such determinants, mostly cell wall-associated and secreted proteins, include adhesins that mediate binding of the pathogen to host extracellular matrix/plasma ligands and cell surfaces, proteins that cooperate in the invasion of and survival within host cells and factors that neutralize phagocytosis and/or modulate the immune response. The genome-based approaches and bioinformatics tools and the extensive use of biophysical and biochemical methods and animal model studies have provided a great wealth of information on the molecular structure and function of these virulence factors. In fact, a number of new GBS surface-exposed or secreted proteins have been identified (GBS immunogenic bacterial adhesion protein, leucine-rich repeat of GBS, serine-rich repeat proteins), the three-dimensional structures of known streptococcal proteins (αC protein, C5a peptidase) have been solved and an understanding of the pathogenetic role of “old” and new determinants has been better defined in recent years. Herein, we provide an update of our current understanding of the major surface cell wall-anchored proteins from GBS, with emphasis on their biochemical and structural properties and the pathogenetic roles they may have in the onset and progression of host infection. We also focus on the antigenic profile of these compounds and discuss them as targets for therapeutic intervention. PMID:29686667

Virulence Gene Pool Detected in Bovine Group C Streptococcus dysgalactiae subsp. dysgalactiae Isolates by Use of a Group A S. pyogenes Virulence Microarray ▿

PubMed Central

Rato, Márcia G.; Nerlich, Andreas; Bergmann, René; Bexiga, Ricardo; Nunes, Sandro F.; Vilela, Cristina L.; Santos-Sanches, Ilda; Chhatwal, Gursharan S.

2011-01-01

A custom-designed microarray containing 220 virulence genes of Streptococcus pyogenes (group A Streptococcus [GAS]) was used to test group C Streptococcus dysgalactiae subsp. dysgalactiae (GCS) field strains causing bovine mastitis and group C or group G Streptococcus dysgalactiae subsp. equisimilis (GCS/GGS) isolates from human infections, with the latter being used for comparative purposes, for the presence of virulence genes. All bovine and all human isolates carried a fraction of the 220 genes (23% and 39%, respectively). The virulence genes encoding streptolysin S, glyceraldehyde-3-phosphate dehydrogenase, the plasminogen-binding M-like protein PAM, and the collagen-like protein SclB were detected in the majority of both bovine and human isolates (94 to 100%). Virulence factors, usually carried by human beta-hemolytic streptococcal pathogens, such as streptokinase, laminin-binding protein, and the C5a peptidase precursor, were detected in all human isolates but not in bovine isolates. Additionally, GAS bacteriophage-associated virulence genes encoding superantigens, DNase, and/or streptodornase were detected in bovine isolates (72%) but not in the human isolates. Determinants located in non-bacteriophage-related mobile elements, such as the gene encoding R28, were detected in all bovine and human isolates. Several virulence genes, including genes of bacteriophage origin, were shown to be expressed by reverse transcriptase PCR (RT-PCR). Phylogenetic analysis of superantigen gene sequences revealed a high level (>98%) of identity among genes of bovine GCS, of the horse pathogen Streptococcus equi subsp. equi, and of the human pathogen GAS. Our findings indicate that alpha-hemolytic bovine GCS, an important mastitis pathogen and considered to be a nonhuman pathogen, carries important virulence factors responsible for virulence and pathogenesis in humans. PMID:21525223

Occurrence and Antibiotic Resistance of Vibrio parahaemolyticus from Shellfish in Selangor, Malaysia

PubMed Central

Letchumanan, Vengadesh; Pusparajah, Priyia; Tan, Loh Teng-Hern; Yin, Wai-Fong; Lee, Learn-Han; Chan, Kok-Gan

2015-01-01

High consumer demand for shellfish has led to the need for large-scale, reliable shellfish supply through aquaculture or shellfish farming. However, bacterial infections which can spread rapidly among shellfish poses a major threat to this industry. Shellfish farmers therefore often resort to extensive use of antibiotics, both prophylactically and therapeutically, in order to protect their stocks. The extensive use of antibiotics in aquaculture has been postulated to represent a major contributing factor in the rising incidence of antimicrobial resistant pathogenic bacteria in shellfish. This study aimed to investigate the incidence of pathogenic Vibrio parahaemolyticus and determine the antibiotic resistance profile as well as to perform plasmid curing in order to determine the antibiotic resistance mediation. Based on colony morphology, all 450 samples tested were positive for Vibrio sp; however, tox-R assay showed that only 44.4% (200/450) of these were V. parahaemolyticus. Out of these 200 samples, 6.5% (13/200) were trh-positive while none were tdh-positive. Antibiotic resistance was determined for all V. parahaemolyticus identified against 14 commonly used antibiotics and the multiple antibiotic resistance index (MAR) was calculated. The isolates demonstrated high resistance to several antibiotics tested- including second and third-line antibiotics- with 88% resistant to ampicillin, 81% to amikacin,70.5% to kanamycin, 73% to cefotaxime, and 51.5% to ceftazidime. The MAR index ranged from 0.00 to 0.79 with the majority of samples having an index of 0.36 (resistant to five antibiotics). Among the 13 trh-positive strains, almost 70% (9/13) demonstrated resistance to 4 or more antibiotics. Plasmid profiling for all V. parahaemolyticus isolates revealed that 86.5% (173/200) contained plasmids - ranging from 1 to 7 plasmids with DNA band sizes ranging from 1.2 kb to greater than 10 kb. 6/13 of the pathogenic V. pathogenic strains contained plasmid. After plasmid curing, the plasmid containing pathogenic strains isolated in our study have chromosomally mediated ampicillin resistance while the remaining resistance phenotypes are plasmid mediated. Overall, our results indicate that while the incidence of pathogenic V. parahaemolyticus in shellfish in Selangor still appears to be at relatively reassuring levels, antibiotic resistance is a real concern and warrants ongoing surveillance. PMID:26697003

Comparative genomics of the major fungal agents of human and animal Sporotrichosis: Sporothrix schenckii and Sporothrix brasiliensis.

PubMed

Teixeira, Marcus M; de Almeida, Luiz G P; Kubitschek-Barreira, Paula; Alves, Fernanda L; Kioshima, Erika S; Abadio, Ana K R; Fernandes, Larissa; Derengowski, Lorena S; Ferreira, Karen S; Souza, Rangel C; Ruiz, Jeronimo C; de Andrade, Nathalia C; Paes, Hugo C; Nicola, André M; Albuquerque, Patrícia; Gerber, Alexandra L; Martins, Vicente P; Peconick, Luisa D F; Neto, Alan Viggiano; Chaucanez, Claudia B; Silva, Patrícia A; Cunha, Oberdan L; de Oliveira, Fabiana F M; dos Santos, Tayná C; Barros, Amanda L N; Soares, Marco A; de Oliveira, Luciana M; Marini, Marjorie M; Villalobos-Duno, Héctor; Cunha, Marcel M L; de Hoog, Sybren; da Silveira, José F; Henrissat, Bernard; Niño-Vega, Gustavo A; Cisalpino, Patrícia S; Mora-Montes, Héctor M; Almeida, Sandro R; Stajich, Jason E; Lopes-Bezerra, Leila M; Vasconcelos, Ana T R; Felipe, Maria S S

2014-10-29

The fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on this comparative genomic study are: 1) to explore the presence of virulence factors in S. schenckii and S. brasiliensis; 2) to compare S. brasiliensis, which is cat-transmitted and infects both humans and cats with S. schenckii, mainly a human pathogen; 3) to compare these two species to other human pathogens (Onygenales) with similar thermo-dimorphic behavior and to other plant-associated Sordariomycetes. The genomes of S. schenckii and S. brasiliensis were pyrosequenced to 17x and 20x coverage comprising a total of 32.3 Mb and 33.2 Mb, respectively. Pair-wise genome alignments revealed that the two species are highly syntenic showing 97.5% average sequence identity. Phylogenomic analysis reveals that both species diverged about 3.8-4.9 MYA suggesting a recent event of speciation. Transposable elements comprise respectively 0.34% and 0.62% of the S. schenckii and S. brasiliensis genomes and expansions of Gypsy-like elements was observed reflecting the accumulation of repetitive elements in the S. brasiliensis genome. Mitochondrial genomic comparisons showed the presence of group-I intron encoding homing endonucleases (HE's) exclusively in S. brasiliensis. Analysis of protein family expansions and contractions in the Sporothrix lineage revealed expansion of LysM domain-containing proteins, small GTPases, PKS type1 and leucin-rich proteins. In contrast, a lack of polysaccharide lyase genes that are associated with decay of plants was observed when compared to other Sordariomycetes and dimorphic fungal pathogens, suggesting evolutionary adaptations from a plant pathogenic or saprobic to an animal pathogenic life style. Comparative genomic data suggest a unique ecological shift in the Sporothrix lineage from plant-association to mammalian parasitism, which contributes to the understanding of how environmental interactions may shape fungal virulence. . Moreover, the striking differences found in comparison with other dimorphic fungi revealed that dimorphism in these close relatives of plant-associated Sordariomycetes is a case of convergent evolution, stressing the importance of this morphogenetic change in fungal pathogenesis.

Intersections between immune responses and morphological regulation in plants.

PubMed

Uchida, Naoyuki; Tasaka, Masao

2010-06-01

Successful plant pathogens have developed strategies to interfere with the defence mechanisms of their host plants through evolution. Conversely, host plants have evolved systems to counteract pathogen attack. Some pathogens induce pathogenic symptoms on plants that include morphological changes in addition to interference with plant growth. Recent studies, based on molecular biology and genetics using Arabidopsis thaliana, have revealed that factors derived from pathogens can modulate host systems and/or host factors that play important roles in the morphological regulation of host plants. Other reports, meanwhile, have shown that factors known to have roles in plant morphology also function in plant immune responses. Evolutionary conservation of these factors and systems implies that host-pathogen interactions and the evolution they drive have yielded tight links between morphological processes and immune responses. In this review, recent findings about these topics are introduced and discussed.

Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans.

PubMed

Newburg, D S

2009-04-01

This review discusses the role of human milk glycans in protecting infants, but the conclusion that the human milk glycans constitute an innate immune system whereby the mother protects her offspring may have general applicability in all mammals, including species of commercial importance. Infants that are not breastfed have a greater incidence of severe diarrhea and respiratory diseases than those who are breastfed. In the past, this had been attributed primarily to human milk secretory antibodies. However, the oligosaccharides are major components of human milk, and milk is also rich in other glycans, including glycoproteins, mucins, glycosaminoglycans, and glycolipids. These milk glycans, especially the oligosaccharides, are composed of thousands of components. The milk factor that promotes gut colonization by Bifidobacterium bifidum was found to be a glycan, and such prebiotic characteristics may contribute to protection against infectious agents. However, the ability of human milk glycans to protect the neonate seems primarily to be due to their inhibition of pathogen binding to their host cell target ligands. Many such examples include specific fucosylated oligosaccharides and glycans that inhibit specific pathogens. Most human milk oligosaccharides are fucosylated, and their production depends on fucosyltransferase enzymes; mutations in these fucosyltransferase genes are common and underlie the various Lewis blood types in humans. Variable expression of specific fucosylated oligosaccharides in milk, also a function of these genes (and maternal Lewis blood type), is significantly associated with the risk of infectious disease in breastfed infants. Human milk also contains major quantities and large numbers of sialylated oligosaccharides, many of which are also present in bovine colostrum. These could similarly inhibit several common viral pathogens. Moreover, human milk oligosaccharides strongly attenuate inflammatory processes in the intestinal mucosa. These results support the hypothesis that oligosaccharides and other glycans are the major constituents of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit disease by mucosal pathogens in many species.

Enteric Pathogens and Coinfections in Foals with and without Diarrhea

PubMed Central

Olivo, Giovane; Lucas, Thays Mizuki; Borges, Alexandre Secorun; Silva, Rodrigo Otávio Silveira; Lobato, Francisco Carlos Faria; Siqueira, Amanda Keller; da Silva Leite, Domingos; Brandão, Paulo Eduardo; de Oliveira-Filho, José Paes

2016-01-01

Diarrhea is a major clinical problem affecting foals up to 3 months of age. The aim of this study was to identify enteric microorganisms involved in monoinfections and coinfections and the associated virulence factors in healthy and diarrheic foals. Diarrheic (D) (n = 56) and nondiarrheic (ND) foals (n = 60) up to three months of age were studied. Fecal samples were analyzed for identification of infectious agents (microbiological culturing, molecular techniques, and microscopic analyses). Escherichia coli fimH (30% versus 25%), Salmonella spp. (25% versus 7%), Strongyloides westeri (25% versus 25%), Clostridium perfringens type A (21% versus 10%), E. coli ag43 (20% versus 35%), Strongylus (11% versus 18%), and vapA-positive Rhodococcus equi (5% versus 2%) were the most frequent enteric pathogens detected in D and ND foals, respectively. The frequency of toxin A-positive C. perfringens was significantly increased in the D (p = 0.033) compared with the ND animals. R. equi strains harboring virulent plasmids were also identified (VapA 85-kb type I and VapA 87-kb type I) in D and ND foals. Coinfections were observed in 46% of the D and 33% of the ND foals. Our results demonstrate the great diversity of enteric pathogens, virulence factors, and coinfections involved in enteric infections of foals. PMID:28116290

A mutli-omic systems approach to elucidating Yersinia virulence mechanisms

PubMed Central

Ansong, Charles; Schrimpe-Rutledge, Alexandra C.; Mitchell, Hugh; Chauhan, Sadhana; Jones, Marcus B.; Kim, Young-Mo; McAteer, Kathleen; Deatherage Kaiser, Brooke L.; Dubois, Jennifer L.; Brewer, Heather M.; Frank, Bryan C.; McDermott, Jason E.; Metz, Thomas O.; Peterson, Scott N.; Smith, Richard D.; Motin, Vladimir L.; Adkins, Joshua N.

2012-01-01

The underlying mechanisms that lead to dramatic differences between closely related pathogens are not always readily apparent. For example, the genomes of Yersinia pestis (YP) the causative agent of plague with a high mortality rate and Yersinia pseudotuberculosis (YPT) an enteric pathogen with a modest mortality rate are highly similar with some species specific differences; however the molecular causes of their distinct clinical outcomes remain poorly understood. In this study, a temporal multi-omic analysis of YP and YPT at physiologically relevant temperatures was performed to gain insights into how an acute and highly lethal bacterial pathogen, YP, differs from its less virulent progenitor, YPT. This analysis revealed higher gene and protein expression levels of conserved major virulence factors in YP relative to YPT, including the Yop virulon and the pH6 antigen. This suggests that adaptation in the regulatory architecture, in addition to the presence of unique genetic material, may contribute to the increased pathogenenicity of YP relative to YPT. Additionally, global transcriptome and proteome responses of YP and YPT revealed conserved post-transcriptional control of metabolism and the translational machinery including the modulation of glutamate levels in Yersiniae. Finally, the omics data was coupled with a computational network analysis, allowing an efficient prediction of novel Yersinia virulence factors based on gene and protein expression patterns. PMID:23147219

Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection

PubMed Central

Sistrunk, Jeticia R.; Nickerson, Kourtney P.; Chanin, Rachael B.; Rasko, David A.

2016-01-01

SUMMARY Bacterial pathogens have coevolved with humans in order to efficiently infect, replicate within, and be transmitted to new hosts to ensure survival and a continual infection cycle. For enteric pathogens, the ability to adapt to numerous host factors under the harsh conditions of the gastrointestinal tract is critical for establishing infection. One such host factor readily encountered by enteric bacteria is bile, an innately antimicrobial detergent-like compound essential for digestion and nutrient absorption. Not only have enteric pathogens evolved to resist the bactericidal conditions of bile, but these bacteria also utilize bile as a signal to enhance virulence regulation for efficient infection. This review provides a comprehensive and up-to-date analysis of bile-related research with enteric pathogens. From common responses to the unique expression of specific virulence factors, each pathogen has overcome significant challenges to establish infection in the gastrointestinal tract. Utilization of bile as a signal to modulate virulence factor expression has led to important insights for our understanding of virulence mechanisms for many pathogens. Further research on enteric pathogens exposed to this in vivo signal will benefit therapeutic and vaccine development and ultimately enhance our success at combating such elite pathogens. PMID:27464994

Pathogenic Leptospira interrogans Exoproteins Are Primarily Involved in Heterotrophic Processes

PubMed Central

Eshghi, Azad; Pappalardo, Elisa; Hester, Svenja; Thomas, Benjamin; Pretre, Gabriela

2015-01-01

Leptospirosis is a life-threatening and emerging zoonotic disease with a worldwide annual occurrence of more than 1 million cases. Leptospirosis is caused by spirochetes belonging to the genus Leptospira. The mechanisms of disease manifestation in the host remain elusive, and the roles of leptospiral exoproteins in these processes have yet to be determined. Our aim in this study was to assess the composition and quantity of exoproteins of pathogenic Leptospira interrogans and to construe how these proteins contribute to disease pathogenesis. Label-free quantitative mass spectrometry of proteins obtained from Leptospira spirochetes cultured in vitro under conditions mimicking infection identified 325 exoproteins. The majority of these proteins are conserved in the nonpathogenic species Leptospira biflexa, and proteins involved in metabolism and energy-generating functions were overrepresented and displayed the highest relative abundance in culture supernatants. Conversely, proteins of unknown function, which represent the majority of pathogen-specific proteins (presumably involved in virulence mechanisms), were underrepresented. Characterization of various L. interrogans exoprotein mutants in the animal infection model revealed host mortality rates similar to those of hosts infected with wild-type L. interrogans. Collectively, these results indicate that pathogenic Leptospira exoproteins primarily function in heterotrophic processes (the processes by which organisms utilize organic substances as nutrient sources) to maintain the saprophytic lifestyle rather than the virulence of the bacteria. The underrepresentation of proteins homologous to known virulence factors, such as toxins and effectors in the exoproteome, also suggests that disease manifesting from Leptospira infection is likely caused by a combination of the primary and potentially moonlight functioning of exoproteins. PMID:25987703

Insights into virulence factors determining the pathogenicity of Cronobacter sakazakii.

PubMed

Singh, Niharika; Goel, Gunjan; Raghav, Mamta

2015-01-01

Cronobacter sakazakii is an opportunistic pathogen associated with outbreaks of life-threatening necrotizing enterocolitis, meningitis and sepsis in neonates and infants. The pathogen possesses an array of virulence factors which aid in tissue adhesion, invasion and host cell injury. Although the identification and validation of C. sakazakii virulence factors has been hindered by availability of suitable neonatal animal model, various studies has reported outer membrane protein A (ompA) as a potential virulence marker. Various other plasmid associated genes such as filamentous hemagglutinin (fhaBC), Cronobacter plasminogen activator (cpa) and genes responsible for iron acquisition (eitCBAD and iucABD/iutA) have been reported in different strains of C. sakazakii. Besides these proposed virulence factors, several biophysical growth factors such as formation of biofilms and resistance to various environmental stresses also contributes to the pathogenic potential of this pathogen. This review provides an update on virulence determinants associated with the pathogenesis of C. sakazakii. The potential reservoirs of the pathogen, mode of transmission and epidemiology are also discussed.

Insights into virulence factors determining the pathogenicity of Cronobacter sakazakii

PubMed Central

Singh, Niharika; Goel, Gunjan; Raghav, Mamta

2015-01-01

Cronobacter sakazakii is an opportunistic pathogen associated with outbreaks of life-threatening necrotizing enterocolitis, meningitis and sepsis in neonates and infants. The pathogen possesses an array of virulence factors which aid in tissue adhesion, invasion and host cell injury. Although the identification and validation of C. sakazakii virulence factors has been hindered by availability of suitable neonatal animal model, various studies has reported outer membrane protein A (ompA) as a potential virulence marker. Various other plasmid associated genes such as filamentous hemagglutinin (fhaBC), Cronobacter plasminogen activator (cpa) and genes responsible for iron acquisition (eitCBAD and iucABD/iutA) have been reported in different strains of C. sakazakii. Besides these proposed virulence factors, several biophysical growth factors such as formation of biofilms and resistance to various environmental stresses also contributes to the pathogenic potential of this pathogen. This review provides an update on virulence determinants associated with the pathogenesis of C. sakazakii. The potential reservoirs of the pathogen, mode of transmission and epidemiology are also discussed. PMID:25950947

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence.

PubMed

Ball, P; Baquero, F; Cars, O; File, T; Garau, J; Klugman, K; Low, D E; Rubinstein, E; Wise, R

2002-01-01

Widespread, increasing antibiotic resistance amongst the major respiratory pathogens has compromised traditional therapy of the major infective respiratory syndromes, including bacterial pneumonia and acute exacerbations of chronic bronchitis. Guidelines for antibiotic prescribing dating from the 1980s to 1990s, which attempted to address such problems, were commonly too prescriptive and difficult to apply, and took little account of end-user practice or locally prevalent resistance levels. Further confusion was caused by conflicting recommendations emanating from differing specialty groups. The evidence that such guidelines benefited either clinical outcomes or treatment costs has been disputed. They have probably had little effect on resistance emergence. We report the recommendations of an independent, multi-national, inter-disciplinary group, which met to identify principles underlying prescribing and guideline formulation in an age of increasing bacterial resistance. Unnecessary prescribing was recognized as the major factor in influencing resistance and costs. Antibiotic therapy must be limited to syndromes in which bacterial infection is the predominant cause and should attempt maximal reduction in bacterial load, with the ultimate aim of bacterial eradication. It should be appropriate in type and context of local resistance prevalence, and optimal in dosage for the pathogen(s) involved. Prescribing should be based on pharmacodynamic principles that predict efficacy, bacterial eradication and prevention of resistance emergence. Pharmacoeconomic analyses confirm that bacteriologically more effective antibiotics can reduce overall management costs, particularly with respect to consequential morbidity and hospital admission. Application of these principles should positively benefit therapeutic outcomes, resistance avoidance and management costs and will more accurately guide antibiotic choices by both individuals and formulary/guideline committees.

Factors affecting host range in a generalist seed pathogen of semi-arid shrublands

Treesearch

Julie Beckstead; Susan E. Meyer; Kurt O. Reinhart; Kellene M. Bergen; Sandra R. Holden; Heather F. Boekweg

2014-01-01

Generalist pathogens can exhibit differential success on different hosts, resulting in complex host range patterns. Several factors operate to reduce realized host range relative to potential host range, particularly under field conditions. We explored factors influencing host range of the naturally occurring generalist ascomycete grass seed pathogen Pyrenophora...

Divergent and convergent modes of interaction between wheat and Puccinia graminis f. sp. tritici isolates revealed by the comparative gene co-expression network and genome analyses.

PubMed

Rutter, William B; Salcedo, Andres; Akhunova, Alina; He, Fei; Wang, Shichen; Liang, Hanquan; Bowden, Robert L; Akhunov, Eduard

2017-04-12

Two opposing evolutionary constraints exert pressure on plant pathogens: one to diversify virulence factors in order to evade plant defenses, and the other to retain virulence factors critical for maintaining a compatible interaction with the plant host. To better understand how the diversified arsenals of fungal genes promote interaction with the same compatible wheat line, we performed a comparative genomic analysis of two North American isolates of Puccinia graminis f. sp. tritici (Pgt). The patterns of inter-isolate divergence in the secreted candidate effector genes were compared with the levels of conservation and divergence of plant-pathogen gene co-expression networks (GCN) developed for each isolate. Comprative genomic analyses revealed substantial level of interisolate divergence in effector gene complement and sequence divergence. Gene Ontology (GO) analyses of the conserved and unique parts of the isolate-specific GCNs identified a number of conserved host pathways targeted by both isolates. Interestingly, the degree of inter-isolate sub-network conservation varied widely for the different host pathways and was positively associated with the proportion of conserved effector candidates associated with each sub-network. While different Pgt isolates tended to exploit similar wheat pathways for infection, the mode of plant-pathogen interaction varied for different pathways with some pathways being associated with the conserved set of effectors and others being linked with the diverged or isolate-specific effectors. Our data suggest that at the intra-species level pathogen populations likely maintain divergent sets of effectors capable of targeting the same plant host pathways. This functional redundancy may play an important role in the dynamic of the "arms-race" between host and pathogen serving as the basis for diverse virulence strategies and creating conditions where mutations in certain effector groups will not have a major effect on the pathogen's ability to infect the host.

Pathogen-driven selection in the human genome.

PubMed

Cagliani, Rachele; Sironi, Manuela

2013-01-01

Infectious diseases and epidemics have always accompanied and characterized human history, representing one of the main causes of death. Even today, despite progress in sanitation and medical research, infections are estimated to account for about 15% of deaths. The hypothesis whereby infectious diseases have been acting as a powerful selective pressure was formulated long ago, but it was not until the availability of large-scale genetic data and the development of novel methods to study molecular evolution that we could assess how pervasively infectious agents have shaped human genetic diversity. Indeed, recent evidences indicated that among the diverse environmental factors that acted as selective pressures during the evolution of our species, pathogen load had the strongest influence. Beside the textbook example of the major histocompatibility complex, selection signatures left by pathogen-exerted pressure can be identified at several human loci, including genes not directly involved in immune response. In the future, high-throughput technologies and the availability of genetic data from different populations are likely to provide novel insights into the evolutionary relationships between the human host and its pathogens. Hopefully, this will help identify the genetic determinants modulating the susceptibility to infectious diseases and will translate into new treatment strategies.

Dissemination of Clostridium difficile in food and the environment: Significant sources of C. difficile community-acquired infection?

PubMed

Warriner, K; Xu, C; Habash, M; Sultan, S; Weese, S J

2017-03-01

Clostridium difficile is a significant pathogen with over 300 000 cases reported in North America annually. Previously, it was thought that C. difficile was primarily a clinically associated infection. However, through the use of whole genome sequencing it has been revealed that the majority of cases are community acquired. The source of community-acquired C. difficile infections (CDI) is open to debate with foodborne being one route considered. Clostridium difficile fits the criteria of a foodborne pathogen with respect to being commonly encountered in a diverse range of foods that includes meat, seafood and fresh produce. However, no foodborne illness outbreaks have been directly linked to C. difficile there is also no conclusive evidence that its spores can germinate in food matrices. This does not exclude food as a potential vehicle but it is likely that the pathogen is also acquired through zoonosis and the environment. The most significant factor that defines susceptibility to CDI is the host microbiome and functioning immune system. In this respect, effective control can be exercised by reducing the environmental burden of C. difficile along with boosting the host defences against the virulent enteric pathogen. © 2016 The Society for Applied Microbiology.

Pesticide exposure in honey bees results in increased levels of the gut pathogen Nosema

NASA Astrophysics Data System (ADS)

Pettis, Jeffery S.; Vanengelsdorp, Dennis; Johnson, Josephine; Dively, Galen

2012-02-01

Global pollinator declines have been attributed to habitat destruction, pesticide use, and climate change or some combination of these factors, and managed honey bees, Apis mellifera, are part of worldwide pollinator declines. Here we exposed honey bee colonies during three brood generations to sub-lethal doses of a widely used pesticide, imidacloprid, and then subsequently challenged newly emerged bees with the gut parasite, Nosema spp. The pesticide dosages used were below levels demonstrated to cause effects on longevity or foraging in adult honey bees. Nosema infections increased significantly in the bees from pesticide-treated hives when compared to bees from control hives demonstrating an indirect effect of pesticides on pathogen growth in honey bees. We clearly demonstrate an increase in pathogen growth within individual bees reared in colonies exposed to one of the most widely used pesticides worldwide, imidacloprid, at below levels considered harmful to bees. The finding that individual bees with undetectable levels of the target pesticide, after being reared in a sub-lethal pesticide environment within the colony, had higher Nosema is significant. Interactions between pesticides and pathogens could be a major contributor to increased mortality of honey bee colonies, including colony collapse disorder, and other pollinator declines worldwide.

Combining Selective Pressures to Enhance the Durability of Disease Resistance Genes.

PubMed

2016-01-01

The efficacy of disease resistance genes in plants decreases over time because of the selection of virulent pathogen genotypes. A key goal of crop protection programs is to increase the durability of the resistance conferred by these genes. The spatial and temporal deployment of plant disease resistance genes is considered to be a major factor determining their durability. In the literature, four principal strategies combining resistance genes over time and space have been considered to delay the evolution of virulent pathogen genotypes. We reviewed this literature with the aim of determining which deployment strategy results in the greatest durability of resistance genes. Although theoretical and empirical studies comparing deployment strategies of more than one resistance gene are very scarce, they suggest that the overall durability of disease resistance genes can be increased by combining their presence in the same plant (pyramiding). Retrospective analyses of field monitoring data also suggest that the pyramiding of disease resistance genes within a plant is the most durable strategy. By extension, we suggest that the combination of disease resistance genes with other practices for pathogen control (pesticides, farming practices) may be a relevant management strategy to slow down the evolution of virulent pathogen genotypes.

Common themes in microbial pathogenicity revisited.

PubMed Central

Finlay, B B; Falkow, S

1997-01-01

Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics. PMID:9184008

Environmental Factors and Zoonotic Pathogen Ecology in Urban Exploiter Species.

PubMed

Rothenburger, Jamie L; Himsworth, Chelsea H; Nemeth, Nicole M; Pearl, David L; Jardine, Claire M

2017-09-01

Knowledge of pathogen ecology, including the impacts of environmental factors on pathogen and host dynamics, is essential for determining the risk that zoonotic pathogens pose to people. This review synthesizes the scientific literature on environmental factors that influence the ecology and epidemiology of zoonotic microparasites (bacteria, viruses and protozoa) in globally invasive urban exploiter wildlife species (i.e., rock doves [Columba livia domestica], European starlings [Sturnus vulgaris], house sparrows [Passer domesticus], Norway rats [Rattus norvegicus], black rats [R. rattus] and house mice [Mus musculus]). Pathogen ecology, including prevalence and pathogen characteristics, is influenced by geographical location, habitat, season and weather. The prevalence of zoonotic pathogens in mice and rats varies markedly over short geographical distances, but tends to be highest in ports, disadvantaged (e.g., low income) and residential areas. Future research should use epidemiological approaches, including random sampling and robust statistical analyses, to evaluate a range of biotic and abiotic environmental factors at spatial scales suitable for host home range sizes. Moving beyond descriptive studies to uncover the causal factors contributing to uneven pathogen distribution among wildlife hosts in urban environments may lead to targeted surveillance and intervention strategies. Application of this knowledge to urban maintenance and planning may reduce the potential impacts of urban wildlife-associated zoonotic diseases on people.

Host-pathogen interactions: A cholera surveillance system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, Aaron T.

2016-02-22

Bacterial pathogen-secreted proteases may play a key role in inhibiting a potentially widespread host-pathogen interaction. Activity-based protein profiling enabled the identification of a major Vibrio cholerae serine protease that limits the ability of a host-derived intestinal lectin to bind to the bacterial pathogen in vivo.

Detection of hepatitis E virus and other livestock-related pathogens in Iowa streams

USDA-ARS?s Scientific Manuscript database

Manure application is a major source of pathogens to the environment. Through overland runoff and tile drainage, these pathogens contaminate surface water and stream bed sediment. Some of these pathogens are zoonotic that can potentially affect both animal and human health. This study examined the p...

Genomic insights into strategies used by Xanthomonas albilineans with its reduced artillery to spread within sugarcane xylem vessels.

PubMed

Pieretti, Isabelle; Royer, Monique; Barbe, Valérie; Carrere, Sébastien; Koebnik, Ralf; Couloux, Arnaud; Darrasse, Armelle; Gouzy, Jérôme; Jacques, Marie-Agnès; Lauber, Emmanuelle; Manceau, Charles; Mangenot, Sophie; Poussier, Stéphane; Segurens, Béatrice; Szurek, Boris; Verdier, Valérie; Arlat, Matthieu; Gabriel, Dean W; Rott, Philippe; Cociancich, Stéphane

2012-11-21

Xanthomonas albilineans causes leaf scald, a lethal disease of sugarcane. X. albilineans exhibits distinctive pathogenic mechanisms, ecology and taxonomy compared to other species of Xanthomonas. For example, this species produces a potent DNA gyrase inhibitor called albicidin that is largely responsible for inducing disease symptoms; its habitat is limited to xylem; and the species exhibits large variability. A first manuscript on the complete genome sequence of the highly pathogenic X. albilineans strain GPE PC73 focused exclusively on distinctive genomic features shared with Xylella fastidiosa-another xylem-limited Xanthomonadaceae. The present manuscript on the same genome sequence aims to describe all other pathogenicity-related genomic features of X. albilineans, and to compare, using suppression subtractive hybridization (SSH), genomic features of two strains differing in pathogenicity. Comparative genomic analyses showed that most of the known pathogenicity factors from other Xanthomonas species are conserved in X. albilineans, with the notable absence of two major determinants of the "artillery" of other plant pathogenic species of Xanthomonas: the xanthan gum biosynthesis gene cluster, and the type III secretion system Hrp (hypersensitive response and pathogenicity). Genomic features specific to X. albilineans that may contribute to specific adaptation of this pathogen to sugarcane xylem vessels were also revealed. SSH experiments led to the identification of 20 genes common to three highly pathogenic strains but missing in a less pathogenic strain. These 20 genes, which include four ABC transporter genes, a methyl-accepting chemotaxis protein gene and an oxidoreductase gene, could play a key role in pathogenicity. With the exception of hypothetical proteins revealed by our comparative genomic analyses and SSH experiments, no genes potentially involved in any offensive or counter-defensive mechanism specific to X. albilineans were identified, supposing that X. albilineans has a reduced artillery compared to other pathogenic Xanthomonas species. Particular attention has therefore been given to genomic features specific to X. albilineans making it more capable of evading sugarcane surveillance systems or resisting sugarcane defense systems. This study confirms that X. albilineans is a highly distinctive species within the genus Xanthomonas, and opens new perpectives towards a greater understanding of the pathogenicity of this destructive sugarcane pathogen.

Porphyromonas gingivalis: Major Periodontopathic Pathogen Overview

PubMed Central

Mysak, Jaroslav; Podzimek, Stepan; Sommerova, Pavla; Lyuya-Mi, Yelena; Bartova, Jirina; Janatova, Tatjana; Prochazkova, Jarmila; Duskova, Jana

2014-01-01

Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis and is a member of more than 500 bacterial species that live in the oral cavity. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions: this is attributed to its arsenal of specialized virulence factors. The purpose of this review is to provide an overview of one of the main periodontal pathogens—Porphyromonas gingivalis. This bacterium, along with Treponema denticola and Tannerella forsythia, constitute the “red complex,” a prototype polybacterial pathogenic consortium in periodontitis. This review outlines Porphyromonas gingivalis structure, its metabolism, its ability to colonize the epithelial cells, and its influence upon the host immunity. PMID:24741603

Biological and Physicochemical Wastewater Treatment Processes Reduce the Prevalence of Virulent Escherichia coli

PubMed Central

Biswal, Basanta Kumar; Mazza, Alberto; Masson, Luke; Gehr, Ronald

2013-01-01

Effluents discharged from wastewater treatment plants are possible sources of pathogenic bacteria, including Escherichia coli, in the freshwater environment, and determining the possible selection of pathogens is important. This study evaluated the impact of activated sludge and physicochemical wastewater treatment processes on the prevalence of potentially virulent E. coli. A total of 719 E. coli isolates collected from four municipal plants in Québec before and after treatment were characterized by using a customized DNA microarray to determine the impact of treatment processes on the frequency of specific pathotypes and virulence genes. The percentages of potentially pathogenic E. coli isolates in the plant influents varied between 26 and 51%, and in the effluents, the percentages were 14 to 31%, for a reduction observed at all plants ranging between 14 and 45%. Pathotypes associated with extraintestinal pathogenic E. coli (ExPEC) were the most abundant at three of the four plants and represented 24% of all isolates, while intestinal pathogenic E. coli pathotypes (IPEC) represented 10% of the isolates. At the plant where ExPEC isolates were not the most abundant, a large number of isolates were classified as both ExPEC and IPEC; overall, 6% of the isolates were classified in both groups, with the majority being from the same plant. The reduction of the proportion of pathogenic E. coli could not be explained by the preferential loss of one virulence gene or one type of virulence factor; however, the quinolone resistance gene (qnrS) appears to enhance the loss of virulence genes, suggesting a mechanism involving the loss of pathogenicity islands. PMID:23160132

The Impact of Recombination Hotspots on Genome Evolution of a Fungal Plant Pathogen.

PubMed

Croll, Daniel; Lendenmann, Mark H; Stewart, Ethan; McDonald, Bruce A

2015-11-01

Recombination has an impact on genome evolution by maintaining chromosomal integrity, affecting the efficacy of selection, and increasing genetic variability in populations. Recombination rates are a key determinant of the coevolutionary dynamics between hosts and their pathogens. Historic recombination events created devastating new pathogens, but the impact of ongoing recombination in sexual pathogens is poorly understood. Many fungal pathogens of plants undergo regular sexual cycles, and sex is considered to be a major factor contributing to virulence. We generated a recombination map at kilobase-scale resolution for the haploid plant pathogenic fungus Zymoseptoria tritici. To account for intraspecific variation in recombination rates, we constructed genetic maps from two independent crosses. We localized a total of 10,287 crossover events in 441 progeny and found that recombination rates were highly heterogeneous within and among chromosomes. Recombination rates on large chromosomes were inversely correlated with chromosome length. Short accessory chromosomes often lacked evidence for crossovers between parental chromosomes. Recombination was concentrated in narrow hotspots that were preferentially located close to telomeres. Hotspots were only partially conserved between the two crosses, suggesting that hotspots are short-lived and may vary according to genomic background. Genes located in hotspot regions were enriched in genes encoding secreted proteins. Population resequencing showed that chromosomal regions with high recombination rates were strongly correlated with regions of low linkage disequilibrium. Hence, genes in pathogen recombination hotspots are likely to evolve faster in natural populations and may represent a greater threat to the host. Copyright © 2015 by the Genetics Society of America.

A Multiple Decrement Life Table Reveals That Host Plant Resistance and Parasitism Are Major Causes of Mortality for the Wheat Stem Sawfly.

PubMed

Buteler, Micaela; Peterson, Robert K D; Hofland, Megan L; Weaver, David K

2015-12-01

This study investigated the dynamics of parasitism, host plant resistance, pathogens, and predation on the demography of wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), developing in susceptible (hollow stem) and resistant (solid stem) wheat hosts. This study is also the first to investigate the prevalence and impact of cannibalism on wheat stem sawfly mortality. Wheat stem sawflies were sampled in two commercial wheat fields over 4 yr from the egg stage through adult emergence, and multiple decrement life tables were constructed and analyzed. Cannibalism, host plant resistance, or unknown factors were the most prevalent factors causing egg mortality. Summer mortality of prediapause larvae ranged from 28 to 84%, mainly due to parasitism by Bracon cephi (Gahan) and Bracon lissogaster Muesebeck, cannibalism, and host plant resistance. Winter mortality ranged from 6 to 54% of the overwintering larvae, mainly due to unknown factors or pathogens. Cannibalism is a major cause of irreplaceable mortality because it is absolute, with only a single survivor in every multiple infested stem. Subsequent to obligate cannibalism, mortality of feeding larvae due to host plant resistance was lower in hollow stem wheat than in solid stem wheat. Mortality from host plant resistance was largely irreplaceable. Irreplaceable mortality due to parasitoids was greater in hollow stem wheat than in solid stem wheat. Host plant resistance due to stem solidness and parasitism in hollow stems cause substantial mortality in populations of actively feeding larvae responsible for all crop losses. Therefore, enhancing these mortality factors is vital to effective integrated pest management of wheat stem sawfly. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Interaction of the tick immune system with transmitted pathogens

PubMed Central

Hajdušek, Ondřej; Šíma, Radek; Ayllón, Nieves; Jalovecká, Marie; Perner, Jan; de la Fuente, José; Kopáček, Petr

2013-01-01

Ticks are hematophagous arachnids transmitting a wide variety of pathogens including viruses, bacteria, and protozoans to their vertebrate hosts. The tick vector competence has to be intimately linked to the ability of transmitted pathogens to evade tick defense mechanisms encountered on their route through the tick body comprising midgut, hemolymph, salivary glands or ovaries. Tick innate immunity is, like in other invertebrates, based on an orchestrated action of humoral and cellular immune responses. The direct antimicrobial defense in ticks is accomplished by a variety of small molecules such as defensins, lysozymes or by tick-specific antimicrobial compounds such as microplusin/hebraein or 5.3-kDa family proteins. Phagocytosis of the invading microbes by tick hemocytes is likely mediated by the primordial complement-like system composed of thioester-containing proteins, fibrinogen-related lectins and convertase-like factors. Moreover, an important role in survival of the ingested microbes seems to be played by host proteins and redox balance maintenance in the tick midgut. Here, we summarize recent knowledge about the major components of tick immune system and focus on their interaction with the relevant tick-transmitted pathogens, represented by spirochetes (Borrelia), rickettsiae (Anaplasma), and protozoans (Babesia). Availability of the tick genomic database and feasibility of functional genomics based on RNA interference greatly contribute to the understanding of molecular and cellular interplay at the tick-pathogen interface and may provide new targets for blocking the transmission of tick pathogens. PMID:23875177

Prophenoloxidase system and its role in shrimp immune responses against major pathogens.

PubMed

Amparyup, Piti; Charoensapsri, Walaiporn; Tassanakajon, Anchalee

2013-04-01

The global shrimp industry still faces various serious disease-related problems that are mainly caused by pathogenic bacteria and viruses. Understanding the host defense mechanisms is likely to be beneficial in designing and implementing effective strategies to solve the current and future pathogen-related problems. Melanization, which is performed by phenoloxidase (PO) and controlled by the prophenoloxidase (proPO) activation cascade, plays an important role in the invertebrate immune system in allowing a rapid response to pathogen infection. The activation of the proPO system, by the specific recognition of microorganisms by pattern-recognition proteins (PRPs), triggers a serine proteinase cascade, eventually leading to the cleavage of the inactive proPO to the active PO that functions to produce the melanin and toxic reactive intermediates against invading pathogens. This review highlights the recent discoveries of the critical roles of the proPO system in the shrimp immune responses against major pathogens, and emphasizes the functional characterizations of four major groups of genes and proteins in the proPO cascade in penaeid shrimp, that is the PRPs, serine proteinases, proPO and inhibitors. Copyright © 2012 Elsevier Ltd. All rights reserved.

BACTERIAL WATERBORNE PATHOGENS

EPA Science Inventory

Bacterial pathogens are examples of classical etiological agents of waterborne disease. While these agents no longer serve as major threats to U.S. water supplies, they are still important pathogens in areas with substandard sanitation and poor water treatment facilities. In th...

Emerging foodborne pathogens

USDA-ARS?s Scientific Manuscript database

The emergence of new foodborne pathogens is due to a number of factors. An important factor is the globalization of the food supply with the possibility of the introduction of foodborne pathogens from other countries. Animal husbandry, food production, food processing, and food distribution system...

Congopain from Trypanosoma congolense: drug target and vaccine candidate.

PubMed

Lalmanach, Gilles; Boulangé, Alain; Serveau, Carole; Lecaille, Fabien; Scharfstein, Julio; Gauthier, Francis; Authié, Edith

2002-05-01

Trypanosomes are the etiological agents of human sleeping sickness and livestock trypanosomosis (nagana), which are major diseases in Africa. Their cysteine proteases (CPs), which are members of the papain family, are expressed during the infective stages of the parasites' life cycle. They are suspected to act as pathogenic factors in the mammalian host, where they also trigger prominent immune responses. Trypanosoma congolense, a major pathogenic species in livestock, possesses at least two families of closely related CPs, named CP1 and CP2. Congopain, a CP2-type of enzyme, shares structural and functional resemblances with cruzipain from T. cruzi and with mammalian cathepsin L. Like CPs from other Trypanosomatids, congopain might be an attractive target for trypanocidal drugs. Here we summarise the current knowledge in the two main areas of research on congopain: first, the biochemical properties of congopain were characterised and its substrate specificity was determined, as a first step towards drug design; second, the possibility was being explored that inhibition of congopain by host-specific antibodies may mitigate the pathology associated with trypanosome infection.

Shifting Prevalence of Major Diarrheal Pathogens in Patients Seeking Hospital Care during Floods in 1998, 2004, and 2007 in Dhaka, Bangladesh

PubMed Central

Harris, Aaron M.; Chowdhury, Fahima; Begum, Yasmin Ara; Khan, Ashraful Islam; Faruque, Abu S. G.; Svennerholm, Ann-Mari; Harris, Jason B.; Ryan, Edward T.; Cravioto, Alejandro; Calderwood, Stephen B.; Qadri, Firdausi

2009-01-01

Bangladesh experienced severe flooding and diarrheal epidemics in 2007. We compared flood data from 2007 with 2004 and 1998 for diarrheal patients attending the ICDDR,B hospital in Dhaka. In 2007, Vibrio cholerae O1 (33%), rotavirus (12%), and enterotoxigenic Escherichia coli (ETEC) (12%) were most prevalent. More severe dehydration was seen in 2007 compared with 2004 and 1998 (P < 0.001). In 2007, V. cholerae O1 Inaba (52%) and Ogawa (48%) were seen, whereas in 2004 and 1998 it was primarily Inaba and the Ogawa types, respectively (P < 0.001). In 2007, 51% of ETEC produced the heat labile toxin (LT) (P < 0.001 compared with 2004), 22% expressed the heat stable (ST) (P < 0.001), and 27% were ST/LT positive (P = 0.231). The CS7 colonization factor (CF) was the most prevalent in 2007 (20% compared with 6% in 2004; P = 0.05). Our findings demonstrate alterations in clinical features and phenotypic changes of major bacterial pathogens in the recent Bangladesh flood. PMID:18981509

Natural killer cells as a therapeutic tool for infectious diseases – current status and future perspectives

PubMed Central

Schmidt, Stanislaw; Tramsen, Lars; Rais, Bushra; Ullrich, Evelyn; Lehrnbecher, Thomas

2018-01-01

Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells. To date, relatively little is known about the potential of adoptively transferring NK cells in immunocompromised patients with infectious complications, although the anti-cancer property of NK cells is already being investigated in the clinical setting. This review will focus on the antimicrobial properties of NK cells and the current standing and future perspectives of generating and using NK cells as immunotherapy in patients with infectious complications, an approach which is promising and might have an important clinical impact in the future. PMID:29755697

Wildlife as Source of Zoonotic Infections

PubMed Central

Kirkemo, Anne-Mette; Handeland, Kjell

2004-01-01

Zoonoses with a wildlife reservoir represent a major public health problem, affecting all continents. Hundreds of pathogens and many different transmission modes are involved, and many factors influence the epidemiology of the various zoonoses. The importance and recognition of wildlife as a reservoir of zoonoses are increasing. Cost-effective prevention and control of these zoonoses necessitate an interdisciplinary and holistic approach and international cooperation. Surveillance, laboratory capability, research, training and education, and communication are key elements. PMID:15663840

[Innate immunity in neuroimmunological disorders].

PubMed

Miyake, Sachiko

2013-05-01

Exogeneous pathogen-associated molecular patterns and endogenous danger signals bind to pattern recognition receptors and activate innate immunity cells, leading to proinflammatory cytokine production and activation of acquired immue cells. These are important factors in the pathogenesis of autoimmune-mediated neuroimmunological disorders such as multiple sclerosis. Furthermore, recent advances in the study of innate immunity revealed that innate immunity is a major players in the pathogenesis of some neuroimmunological diseases such as Behçet's disease and herpes simplex virus encephalitis.

Queen Quality and the Impact of Honey Bee Diseases on Queen Health: Potential for Interactions between Two Major Threats to Colony Health.

PubMed

Amiri, Esmaeil; Strand, Micheline K; Rueppell, Olav; Tarpy, David R

2017-05-08

Western honey bees, Apis mellifera , live in highly eusocial colonies that are each typically headed by a single queen. The queen is the sole reproductive female in a healthy colony, and because long-term colony survival depends on her ability to produce a large number of offspring, queen health is essential for colony success. Honey bees have recently been experiencing considerable declines in colony health. Among a number of biotic and abiotic factors known to impact colony health, disease and queen failure are repeatedly reported as important factors underlying colony losses. Surprisingly, there are relatively few studies on the relationship and interaction between honey bee diseases and queen quality. It is critical to understand the negative impacts of pests and pathogens on queen health, how queen problems might enable disease, and how both factors influence colony health. Here, we review the current literature on queen reproductive potential and the impacts of honey bee parasites and pathogens on queens. We conclude by highlighting gaps in our knowledge on the combination of disease and queen failure to provide a perspective and prioritize further research to mitigate disease, improve queen quality, and ensure colony health.

Environmental factors influencing the development and spread of antibiotic resistance

PubMed Central

Kristiansson, Erik; Larsson, D G Joakim

2017-01-01

Abstract Antibiotic resistance and its wider implications present us with a growing healthcare crisis. Recent research points to the environment as an important component for the transmission of resistant bacteria and in the emergence of resistant pathogens. However, a deeper understanding of the evolutionary and ecological processes that lead to clinical appearance of resistance genes is still lacking, as is knowledge of environmental dispersal barriers. This calls for better models of how resistance genes evolve, are mobilized, transferred and disseminated in the environment. Here, we attempt to define the ecological and evolutionary environmental factors that contribute to resistance development and transmission. Although mobilization of resistance genes likely occurs continuously, the great majority of such genetic events do not lead to the establishment of novel resistance factors in bacterial populations, unless there is a selection pressure for maintaining them or their fitness costs are negligible. To enable preventative measures it is therefore critical to investigate under what conditions and to what extent environmental selection for resistance takes place. In addition, understanding dispersal barriers is not only key to evaluate risks, but also to prevent resistant pathogens, as well as novel resistance genes, from reaching humans. PMID:29069382

Tendinopathy in diabetes mellitus patients-Epidemiology, pathogenesis, and management.

PubMed

Lui, P P Y

2017-08-01

Chronic tendinopathy is a frequent and disabling musculo-skeletal problem affecting the athletic and general populations. The affected tendon is presented with local tenderness, swelling, and pain which restrict the activity of the individual. Tendon degeneration reduces the mechanical strength and predisposes it to rupture. The pathogenic mechanisms of chronic tendinopathy are not fully understood and several major non-mutually exclusive hypotheses including activation of the hypoxia-apoptosis-pro-inflammatory cytokines cascade, neurovascular ingrowth, increased production of neuromediators, and erroneous stem cell differentiation have been proposed. Many intrinsic and extrinsic risk/causative factors can predispose to the development of tendinopathy. Among them, diabetes mellitus is an important risk/causative factor. This review aims to appraise the current literature on the epidemiology and pathology of tendinopathy in diabetic patients. Systematic reviews were done to summarize the literature on (a) the association between diabetes mellitus and tendinopathy/tendon tears, (b) the pathological changes in tendon under diabetic or hyperglycemic conditions, and (c) the effects of diabetes mellitus or hyperglycemia on the outcomes of tendon healing. The potential mechanisms of diabetes mellitus in causing and exacerbating tendinopathy with reference to the major non-mutually exclusive hypotheses of the pathogenic mechanisms of chronic tendinopathy as reported in the literature are also discussed. Potential strategies for the management of tendinopathy in diabetic patients are presented. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantitative Differences in Salivary Pathogen Load during Tick Transmission Underlie Strain-Specific Variation in Transmission Efficiency of Anaplasma marginale

USDA-ARS?s Scientific Manuscript database

The relative fitness of arthropod-borne pathogens within the vector can be a major determinant of pathogen prevalence within the mammalian host population. Strains of the tick-borne rickettsia Anaplasma marginale differ markedly in transmission efficiency with consequent impact on pathogen strain st...

Amoeba provide insight into the origin of virulence in pathogenic fungi.

PubMed

Casadevall, Arturo

2012-01-01

Why are some fungi pathogenic while the majority poses no threat to humans or other hosts? Of the more than 1.5 million fungal species only about 150-300 are pathogenic for humans, and of these, only 10-15 are relatively common pathogens. In contrast, fungi are major pathogens for plants and insects. These facts pose several fundamental questions including the mechanisms responsible for the origin of virulence among the few pathogenic species and the high resistance of mammals to fungal diseases. This essay explores the origin of virulences among environmental fungi with no obvious requirement for animal association and proposes that selection pressures by amoeboid predators led to the emergence of traits that can also promote survival in mammalian hosts. In this regard, analysis of the interactions between the human pathogenic funges Cryptococcus neoformans and amoeba have shown a remarkable similarity with the interaction of this fungus with macrophages. Hence the virulence of environmental pathogenic fungi is proposed to originate from a combination of selection by amoeboid predators and perhaps other soil organism with thermal tolerance sufficient to allow survival in mammalian hosts.

Laboratory colonization stabilizes the naturally dynamic microbiome composition of field collected dermacentor andersoni ticks

USDA-ARS?s Scientific Manuscript database

Nearly a quarter of emerging infectious diseases in the last century were transmitted by arthropods. Although ticks and insects can carry pathogenic microorganisms, non-pathogenic microbes make up the majority of the microbial community. Currently, the majority of tick microbiome research has had a ...

The Extracellular Metalloprotease of Vibrio tubiashii Is a Major Virulence Factor for Pacific Oyster (Crassostrea gigas) Larvae▿

PubMed Central

Hasegawa, Hiroaki; Lind, Erin J.; Boin, Markus A.; Häse, Claudia C.

2008-01-01

Vibrio tubiashii is a recently reemerging pathogen of larval bivalve mollusks, causing both toxigenic and invasive disease. Marine Vibrio spp. produce an array of extracellular products as potential pathogenicity factors. Culture supernatants of V. tubiashii have been shown to be toxic to oyster larvae and were reported to contain a metalloprotease and a cytolysin/hemolysin. However, the structural genes responsible for these proteins have yet to be identified, and it is uncertain which extracellular products play a role in pathogenicity. We investigated the effects of the metalloprotease and hemolysin secreted by V. tubiashii on its ability to kill Pacific oyster (Crassostrea gigas) larvae. While V. tubiashii supernatants treated with metalloprotease inhibitors severely reduced the toxicity to oyster larvae, inhibition of the hemolytic activity did not affect larval toxicity. We identified structural genes of V. tubiashii encoding a metalloprotease (vtpA) and a hemolysin (vthA). Sequence analyses revealed that VtpA shared high homology with metalloproteases from a variety of Vibrio species, while VthA showed high homology only to the cytolysin/hemolysin of Vibrio vulnificus. Compared to the wild-type strain, a VtpA mutant of V. tubiashii not only produced reduced amounts of protease but also showed decreased toxicity to C. gigas larvae. Vibrio cholerae strains carrying the vtpA or vthA gene successfully secreted the heterologous protein. Culture supernatants of V. cholerae carrying vtpA but not vthA were highly toxic to Pacific oyster larvae. Together, these results suggest that the V. tubiashii extracellular metalloprotease is important in its pathogenicity to C. gigas larvae. PMID:18456850

Estimates of Foodborne Illness in the United States -- Burden of Foodborne Illness: Findings

MedlinePlus

... Pathogens causing the most foodborne illnesses, hospitalizations, and deaths each year Eight known pathogens are estimated to ... majority of domestically acquired foodborne illnesses, hospitalizations, and deaths. The tables below list the top five pathogens ...

Fungi in the cystic fibrosis lung: bystanders or pathogens?

PubMed

Chotirmall, Sanjay H; McElvaney, Noel G

2014-07-01

Improvement to the life expectancy of people with cystic fibrosis (PWCF) brings about novel challenges including the need for evaluation of the role of fungi in the cystic fibrosis (CF) lung. To determine if such organisms represent bystanders or pathogens affecting clinical outcomes we review the existing knowledge from a clinical, biochemical, inflammatory and immunological perspective. The prevalence and importance of fungi in the CF airway has likely been underestimated with the most frequently isolated filamentous fungi being Aspergillus fumigatus and Scedosporium apiospermum and the major yeast Candida albicans. Developing non-culture based microbiological methods for fungal detection has improved both our classification and understanding of their clinical consequences including localized, allergic and systemic infections. Cross-kingdom interaction between bacteria and fungi are discussed as is the role of biofilms further affecting clinical outcome. A combination of host and pathogen-derived factors determines if a particular fungus represents a commensal, colonizer or pathogen in the setting of CF. The underlying immune state, disease severity and treatment burden represent key host variables whilst fungal type, form, chronicity and virulence including the ability to evade immune recognition determines the pathogenic potential of a specific fungus at a particular point in time. Further research in this emerging field is warranted to fully elucidate the spectrum of disease conferred by the presence of fungi in the CF airway and the indications for therapeutic interventions. Copyright © 2014. Published by Elsevier Ltd.

An operon for production of bioactive gibberellin A4 phytohormone with wide distribution in the bacterial rice leaf streak pathogen Xanthomonas oryzae pv. oryzicola.

PubMed

Nagel, Raimund; Turrini, Paula C G; Nett, Ryan S; Leach, Jan E; Verdier, Valérie; Van Sluys, Marie-Anne; Peters, Reuben J

2017-05-01

Phytopathogens have developed elaborate mechanisms to attenuate the defense response of their host plants, including convergent evolution of complex pathways for production of the GA phytohormones, which were actually first isolated from the rice fungal pathogen Gibberella fujikuroi. The rice bacterial pathogen Xanthomonas oryzae pv. oryzicola (Xoc) has been demonstrated to contain a biosynthetic operon with cyclases capable of producing the universal GA precursor ent-kaurene. Genetic (knock-out) studies indicate that the derived diterpenoid serves as a virulence factor for this rice leaf streak pathogen, serving to reduce the jasmonic acid-mediated defense response. Here the functions of the remaining genes in the Xoc operon are elucidated and the distribution of the operon in X. oryzae is investigated in over 100 isolates. The Xoc operon leads to production of the bioactive GA 4 , an additional step beyond production of the penultimate precursor GA 9 mediated by the homologous operons recently characterized from rhizobia. Moreover, this GA biosynthetic operon was found to be widespread in Xoc (> 90%), but absent in the other major X. oryzae pathovar. These results indicate selective pressure for production of GA 4 in the distinct lifestyle of Xoc, and the importance of GA to both fungal and bacterial pathogens of rice. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

An operon for production of bioactive gibberellin A4 phytohormone with wide distribution in the bacterial rice leaf streak pathogen Xanthomonas oryzae pv. oryzicola

PubMed Central

Nagel, Raimund; Turrini, Paula C. G.; Nett, Ryan S.; Leach, Jan E.; Verdier, Valérie; Van Sluys, Marie-Anne; Peters, Reuben J.

2016-01-01

Summary Phytopathogens have developed elaborate mechanisms to attenuate the defense response of their host plants, including convergent evolution of complex pathways for production of the gibberellin (GA) phytohormones, which were actually first isolated from the rice fungal pathogen Gibberella fujikuroi. The rice bacterial pathogen Xanthomonas oryzae pv. oryzicola (Xoc) has been demonstrated to contain a biosynthetic operon with cyclases capable of producing the universal GA precursor ent-kaurene. Genetic (knock-out) studies indicate that the derived diterpenoid serves as a virulence factor for this rice leaf streak pathogen, serving to reduce the jasmonic acid (JA) mediated defense response.Here the function of the remaining genes in the Xoc operon are elucidated and the distribution of the operon in X. oryzae investigated in over 100 isolates.The Xoc operon leads to production of the bioactive GA4, an additional step beyond production of the penultimate precursor GA9 mediated by the homologous operons recently characterized from rhizobia. Moreover, this GA biosynthetic operon was found to be widespread in Xoc (>90%), but absent in the other major oryzae pathovar.These results indicate selective pressure for production of GA4 in the distinct lifestyle of Xoc, and the importance of GA to both fungal and bacterial pathogens of rice. PMID:28134995

Understanding the contribution of environmental factors in the spread of antimicrobial resistance.

PubMed

Fletcher, Stephanie

2015-07-01

The overuse and abuse of antibiotics have contributed to the global epidemic of antibiotic resistance. Current evidence suggests that widespread dependency on antibiotics and complex interactions between human health, animal husbandry and veterinary medicine, have contributed to the propagation and spread of resistant organisms. The lack of information on pathogens of major public health importance, limited surveillance, and paucity of standards for a harmonised and coordinated approach, further complicates the issue. Despite the widespread nature of antimicrobial resistance, limited focus has been placed on the role of environmental factors in propagating resistance. There are limited studies that examine the role of the environment, specifically water, sanitation and hygiene factors that contribute to the development of resistant pathogens. Understanding these elements is necessary to identify any modifiable interactions to reduce or interrupt the spread of resistance from the environment into clinical settings. This paper discusses some environmental issues that contribute to antimicrobial resistance, including soil related factors, animal husbandry and waste management, potable and wastewater, and food safety, with examples drawn mainly from the Asian region. The discussion concludes that some of the common issues are often overlooked and whilst there are numerous opportunities for environmental factors to contribute to the growing burden of antimicrobial resistance, a renewed focus on innovative and traditional environmental approaches is needed to tackle the problem.

Stratifying risk factors for multidrug-resistant pathogens in hospitalized patients coming from the community with pneumonia.

PubMed

Aliberti, Stefano; Di Pasquale, Marta; Zanaboni, Anna Maria; Cosentini, Roberto; Brambilla, Anna Maria; Seghezzi, Sonia; Tarsia, Paolo; Mantero, Marco; Blasi, Francesco

2012-02-15

 Not all risk factors for acquiring multidrug-resistant (MDR) organisms are equivalent in predicting pneumonia caused by resistant pathogens in the community. We evaluated risk factors for acquiring MDR bacteria in patients coming from the community who were hospitalized with pneumonia. Our evaluation was based on actual infection with a resistant pathogen and clinical outcome during hospitalization.  An observational, prospective study was conducted on consecutive patients coming from the community who were hospitalized with pneumonia. Data on admission and during hospitalization were collected. Logistic regression models were used to evaluate risk factors for acquiring MDR bacteria independently associated with the actual presence of a resistant pathogen and in-hospital mortality.  Among the 935 patients enrolled in the study, 473 (51%) had at least 1 risk factor for acquiring MDR bacteria on admission. Of all risk factors, hospitalization in the preceding 90 days (odds ratio [OR], 4.87 95% confidence interval {CI}, 1.90-12.4]; P = .001) and residency in a nursing home (OR, 3.55 [95% CI, 1.12-11.24]; P = .031) were independent predictors for an actual infection with a resistant pathogen. A score able to predict pneumonia caused by a resistant pathogen was computed, including comorbidities and risk factors for MDR. Hospitalization in the preceding 90 days and residency in a nursing home were also independent predictors for in-hospital mortality.  Risk factors for acquiring MDR bacteria should be weighted differently, and a probabilistic approach to identifying resistant pathogens among patients coming from the community with pneumonia should be embraced.

Inactivation of the Major Hemolysin Gene Influences Expression of the Nonribosomal Peptide Synthetase Gene swrA in the Insect Pathogen Serratia sp. Strain SCBI

PubMed Central

Petersen, Lauren M.; LaCourse, Kaitlyn; Schöner, Tim A.; Bode, Helge

2017-01-01

ABSTRACT Hemolysins are important virulence factors for many bacterial pathogens, including Serratia marcescens. The role of the major hemolysin gene in the insect pathogen Serratia sp. strain SCBI was investigated using both forward and reverse-genetics approaches. Introduction of the major hemolysin gene into Escherichia coli resulted in a gain of both virulence and hemolytic activity. Inactivation of this hemolysin in Serratia sp. SCBI resulted in a loss of hemolysis but did not attenuate insecticidal activity. Unexpectedly, inactivation of the hemolysin gene in Serratia sp. SCBI resulted in significantly increased motility and increased antimicrobial activity. Reverse transcription-quantitative PCR (qRT-PCR) analysis of mutants with a disrupted hemolysin gene showed a dramatic increase in mRNA levels of a nonribosomal peptide synthetase gene, swrA, which produces the surfactant serrawettin W2. Mutation of the swrA gene in Serratia sp. SCBI resulted in highly varied antibiotic activity, motility, virulence, and hemolysis phenotypes that were dependent on the site of disruption within this 17.75-kb gene. When introduced into E. coli, swrA increases rates of motility and confers antimicrobial activity. While it is unclear how inactivation of the major hemolysin gene influences the expression of swrA, these results suggest that swrA plays an important role in motility and antimicrobial activity in Serratia sp. SCBI. IMPORTANCE The opportunistic Gram-negative bacteria of the genus Serratia are widespread in the environment and can cause human illness. A comparative genomics analysis between Serratia marcescens and a new Serratia species from South Africa, termed Serratia sp. strain SCBI, shows that these two organisms are closely related but differ in pathogenesis. S. marcescens kills Caenorhabditis nematodes, while Serratia sp. SCBI is not harmful and forms a beneficial association with them. This distinction presented the opportunity to investigate potential differences in regulation of common virulence mechanisms between these two species. With the emergence of antibiotic-resistant microorganisms, there is a widespread need to understand the regulation of pathogenesis. The significance of this study is the presentation of evidence for cross-pathway regulation of virulence factors and how the elimination of one mechanism may be compensated for by the upregulation of others. PMID:28784817

Inactivation of the Major Hemolysin Gene Influences Expression of the Nonribosomal Peptide Synthetase Gene swrA in the Insect Pathogen Serratia sp. Strain SCBI.

PubMed

Petersen, Lauren M; LaCourse, Kaitlyn; Schöner, Tim A; Bode, Helge; Tisa, Louis S

2017-11-01

Hemolysins are important virulence factors for many bacterial pathogens, including Serratia marcescens The role of the major hemolysin gene in the insect pathogen Serratia sp. strain SCBI was investigated using both forward and reverse-genetics approaches. Introduction of the major hemolysin gene into Escherichia coli resulted in a gain of both virulence and hemolytic activity. Inactivation of this hemolysin in Serratia sp. SCBI resulted in a loss of hemolysis but did not attenuate insecticidal activity. Unexpectedly, inactivation of the hemolysin gene in Serratia sp. SCBI resulted in significantly increased motility and increased antimicrobial activity. Reverse transcription-quantitative PCR (qRT-PCR) analysis of mutants with a disrupted hemolysin gene showed a dramatic increase in mRNA levels of a nonribosomal peptide synthetase gene, swrA , which produces the surfactant serrawettin W2. Mutation of the swrA gene in Serratia sp. SCBI resulted in highly varied antibiotic activity, motility, virulence, and hemolysis phenotypes that were dependent on the site of disruption within this 17.75-kb gene. When introduced into E. coli , swrA increases rates of motility and confers antimicrobial activity. While it is unclear how inactivation of the major hemolysin gene influences the expression of swrA , these results suggest that swrA plays an important role in motility and antimicrobial activity in Serratia sp. SCBI. IMPORTANCE The opportunistic Gram-negative bacteria of the genus Serratia are widespread in the environment and can cause human illness. A comparative genomics analysis between Serratia marcescens and a new Serratia species from South Africa, termed Serratia sp. strain SCBI, shows that these two organisms are closely related but differ in pathogenesis. S. marcescens kills Caenorhabditis nematodes, while Serratia sp. SCBI is not harmful and forms a beneficial association with them. This distinction presented the opportunity to investigate potential differences in regulation of common virulence mechanisms between these two species. With the emergence of antibiotic-resistant microorganisms, there is a widespread need to understand the regulation of pathogenesis. The significance of this study is the presentation of evidence for cross-pathway regulation of virulence factors and how the elimination of one mechanism may be compensated for by the upregulation of others. Copyright © 2017 American Society for Microbiology.

Methods to study legionella transcriptome in vitro and in vivo.

PubMed

Faucher, Sebastien P; Shuman, Howard A

2013-01-01

The study of transcriptome responses can provide insight into the regulatory pathways and genetic factors that contribute to a specific phenotype. For bacterial pathogens, it can identify putative new virulence systems and shed light on the mechanisms underlying the regulation of virulence factors. Microarrays have been previously used to study gene regulation in Legionella pneumophila. In the past few years a sharp reduction of the costs associated with microarray experiments together with the availability of relatively inexpensive custom-designed commercial microarrays has made microarray technology an accessible tool for the majority of researchers. Here we describe the methodologies to conduct microarray experiments from in vitro and in vivo samples.

Cross-reactive acquired immunity influences transmission success of the Lyme disease pathogen, Borrelia afzelii.

PubMed

Jacquet, Maxime; Durand, Jonas; Rais, Olivier; Voordouw, Maarten J

2015-12-01

Cross-reactive acquired immunity in the vertebrate host induces indirect competition between strains of a given pathogen species and is critical for understanding the ecology of mixed infections. In vector-borne diseases, cross-reactive antibodies can reduce pathogen transmission at the vector-to-host and the host-to-vector lifecycle transition. The highly polymorphic, immunodominant, outer surface protein C (OspC) of the tick-borne spirochete bacterium Borrelia afzelii induces a strong antibody response in the vertebrate host. To test how cross-immunity in the vertebrate host influences tick-to-host and host-to-tick transmission, mice were immunized with one of two strain-specific recombinant OspC proteins (A3, A10), challenged via tick bite with one of the two B. afzelii ospC strains (A3, A10), and infested with xenodiagnostic ticks. Immunization with a given rOspC antigen protected mice against homologous strains carrying the same major ospC group allele but provided little or no cross-protection against heterologous strains carrying a different major ospC group allele. There were cross-immunity effects on the tick spirochete load but not on the probability of host-to-tick transmission. The spirochete load in ticks that had fed on mice with cross-immune experience was reduced by a factor of two compared to ticks that had fed on naive control mice. In addition, strain-specific differences in mouse spirochete load, host-to-tick transmission, tick spirochete load, and the OspC-specific IgG response revealed the mechanisms that determine variation in transmission success between strains of B. afzelii. This study shows that cross-immunity in infected vertebrate hosts can reduce pathogen load in the arthropod vector with potential consequences for vector-to-host pathogen transmission. Copyright © 2015 Elsevier B.V. All rights reserved.

Streptococcus suis: a re-emerging pathogen associated with occupational exposure to pigs or pork products. Part II - Pathogenesis.

PubMed

Dutkiewicz, Jacek; Zając, Violetta; Sroka, Jacek; Wasiński, Bernard; Cisak, Ewa; Sawczyn, Anna; Kloc, Anna; Wójcik-Fatla, Angelina

2018-03-14

Streptococcus suis is a re-emerging zoonotic pathogen that may cause severe disease, mostly meningitis, in pigs and in humans having occupational contact with pigs and pork, such as farmers, slaughterhose workers and butchers. The first stage of the pathogenic process, similar in pigs and humans, is adherence to and colonisation of mucosal and/or epithelial surface(s) of the host. The second stage is invasion into deeper tissue and extracellular translocation of bacterium in the bloodstream, either free in circulation or attached to the surface of monocytes. If S. suis present in blood fails to cause fatal septicaemia, it is able to progress into the third stage comprising penetration into host's organs, mostly by crossing the blood-brain barrier and/or blood-cerebrospinal fluid barrier to gain access to the central nervous system (CNS) and cause meningitis. The fourth stage is inflammation that plays a key role in the pathogen esis of both systemic and CNS infections caused by S. suis. The pathogen may induce the overproduction of pro-inflammatory cytokines that cause septic shock and/or the recruitment and activation of different leukocyte populations, causing acute inflammation of the CNS. Streptococcus suis can also evoke - through activation of microglial cells, astrocytes and possibly other cell types - a fulminant inflammatory reaction of the brain which leads to intracranial complications, including brain oedema, increased intracranial pressure, cerebrovascular insults, and deafness, as a result of cochlear sepsis. In all stages of the pathogenic process, S. suis interacts with many types of immunocompetent host's cells, such as polymorphonuclear leukocytes, mononuclear macrophages, lymphocytes, dendritic cells and microglia, using a range of versatile virulence factors for evasion of the innate and adaptive immune defence of the host, and for overcoming environmental stress. It is estimated that S. suis produces more than 100 different virulence factors that could be classified into 4 groups: surface components or secreted elements, enzymes, transcription factors or regulatory systems and transporter factors or secretion systems. A major virulence factor is capsular polysaccharide (CPS) that protects bacteria from phagocytosis. However, it hampers adhesion to and invasion of host's cells, release of inflammatory cytokines and formation of the resistant biofilm which, in many cases, is vital for the persistence of bacteria. It has been demonstrated that the arising by mutation unencapsulated S. suis clones, which are more successful in penetration to and propagation within the host's cells, may coexist in the organism of a single host together with those that are encapsulated. Both 'complementary' clones assist each other in the successful colonization of host's tissues and persistence therein. S. suis has an open pan-genome characterized by a frequent gene transfer and a large diversity. Of the genetic determinants of S. suis pathogenicity, the most important are pathogenicity islands (PAI), in particular, a novel DNA segment of 89 kb length with evident pathogenic traits that has been designated as 89K PAI. It has been estimated that more than one-third of the S. suis virulence factors is associated with this PAI. It has been proved that the virulent S. suis strains possess smaller genomes, compared to avirulent ones, but more genes associated with virulence. Overall, the evolution of the species most probably aims towards increased pathogenicity, and hence the most significant task of the current research is an elaboration of a vaccine, efficient both for humans and pigs.

Development of a qualitative pathogen risk-assessment methodology for municipal-sludge landfilling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1988-04-01

This report addresses potential risks from microbiological pathogens present in municipal sludge disposal in landfills. Municipal sludges contain a wide variety of bacteria, viruses, protozoa, helminths, and fungi. Survival characteristics of pathogens are critical factors in assessing the risks associated with potential transport of microorganisms from the sludge-soil matrix to the ground-water environment of landfills. Various models are discussed for predicting microbial die-off. The order of persistence in the environment from longest to shortest survival time appears to be helminth eggs > viruses > bacteria > protozoan cysts. Whether or not a pathogen reaches ground-water and is transported to drinking-watermore » wells depends on a number of factors, including initial concentration of the pathogen, survival of the pathogen, number of pathogens that reach the sludge-soil interface, degree of removal through the unsaturated and saturated-soil zones, and the hydraulic gradient. The degree to which each of these factors will influence the probability of pathogens entering ground-water cannot be determined precisely. Information on the fate of pathogens at existing landfills is sorely lacking. Additional laboratory and field studies are needed to determine the degree of pathogen leaching, survival and transport in ground-water in order to estimate potential risks from pathogens at sludge landfills with reasonable validity.« less

DEVELOPMENT OF HUMAN BIOMARKERS OF EXPOSURE TO WATERBORNE PATHOGENS

EPA Science Inventory

Contaminated drinking water is major source of waterborne diseases. EPA has published a drinking water contaminant candidate list (CCL) that contains a number of pathogens that potentially could be regulated in drinking water. Studies indicate that certain viral pathogens (adenov...

Influence of oak woodland composition and structure on infection by Phytophthora ramorum

Treesearch

Nathan Rank; Hall Cushman; Brian Anacker; David Rizzo; Ross Meentemeyer

2008-01-01

Introduced plant pathogens have major ecological impacts in many parts of the world. While the spread of pathogens can be strongly mediated by the composition and structure of local host plant communities, little is known about effects of plant community structure on invasion dynamics of introduced pathogens. The progress of infection by the invasive pathogen ...

Oligo-DNA Custom Macroarray for Monitoring Major Pathogenic and Non-Pathogenic Fungi and Bacteria in the Phyllosphere of Apple Trees

PubMed Central

He, Ying-Hong; Isono, Sayaka; Shibuya, Makoto; Tsuji, Masaharu; Adkar Purushothama, Charith-Raj; Tanaka, Kazuaki; Sano, Teruo

2012-01-01

Background To monitor the richness in microbial inhabitants in the phyllosphere of apple trees cultivated under various cultural and environmental conditions, we developed an oligo-DNA macroarray for major pathogenic and non-pathogenic fungi and bacteria inhabiting the phyllosphere of apple trees. Methods and Findings First, we isolated culturable fungi and bacteria from apple orchards by an agar-plate culture method, and detected 32 fungal and 34 bacterial species. Alternaria, Aureobasidium, Cladosporium, Rhodotorula, Cystofilobasidium, and Epicoccum genera were predominant among the fungi, and Bacillus, Pseudomonas, Sphingomonas, Methylobacterium, and Pantoea genera were predominant among the bacteria. Based on the data, we selected 29 major non-pathogenic and 12 phytopathogenic fungi and bacteria as the targets of macroarray. Forty-one species-specific 40-base pair long oligo-DNA sequences were selected from the nucleotide sequences of rDNA-internal transcribed spacer region for fungi and 16S rDNA for bacteria. The oligo-DNAs were fixed on nylon membrane and hybridized with digoxigenin-labeled cRNA probes prepared for each species. All arrays except those for Alternaria, Bacillus, and their related species, were specifically hybridized. The array was sensitive enough to detect 103 CFU for Aureobasidium pullulans and Bacillus cereus. Nucleotide sequencing of 100 each of independent fungal rDNA-ITS and bacterial 16S-rDNA sequences from apple tree was in agreement with the macroarray data obtained using the same sample. Finally, we analyzed the richness in the microbial inhabitants in the samples collected from apple trees in four orchards. Major apple pathogens that cause scab, Alternaria blotch, and Marssonina blotch were detected along with several non-phytopathogenic fungal and bacterial inhabitants. Conclusions The macroarray technique presented here is a strong tool to monitor the major microbial species and the community structures in the phyllosphere of apple trees and identify key species antagonistic, supportive or co-operative to specific pathogens in the orchard managed under different environmental conditions. PMID:22479577

Oligo-DNA custom macroarray for monitoring major pathogenic and non-pathogenic fungi and bacteria in the phyllosphere of apple trees.

PubMed

He, Ying-Hong; Isono, Sayaka; Shibuya, Makoto; Tsuji, Masaharu; Adkar Purushothama, Charith-Raj; Tanaka, Kazuaki; Sano, Teruo

2012-01-01

To monitor the richness in microbial inhabitants in the phyllosphere of apple trees cultivated under various cultural and environmental conditions, we developed an oligo-DNA macroarray for major pathogenic and non-pathogenic fungi and bacteria inhabiting the phyllosphere of apple trees. First, we isolated culturable fungi and bacteria from apple orchards by an agar-plate culture method, and detected 32 fungal and 34 bacterial species. Alternaria, Aureobasidium, Cladosporium, Rhodotorula, Cystofilobasidium, and Epicoccum genera were predominant among the fungi, and Bacillus, Pseudomonas, Sphingomonas, Methylobacterium, and Pantoea genera were predominant among the bacteria. Based on the data, we selected 29 major non-pathogenic and 12 phytopathogenic fungi and bacteria as the targets of macroarray. Forty-one species-specific 40-base pair long oligo-DNA sequences were selected from the nucleotide sequences of rDNA-internal transcribed spacer region for fungi and 16S rDNA for bacteria. The oligo-DNAs were fixed on nylon membrane and hybridized with digoxigenin-labeled cRNA probes prepared for each species. All arrays except those for Alternaria, Bacillus, and their related species, were specifically hybridized. The array was sensitive enough to detect 10(3) CFU for Aureobasidium pullulans and Bacillus cereus. Nucleotide sequencing of 100 each of independent fungal rDNA-ITS and bacterial 16S-rDNA sequences from apple tree was in agreement with the macroarray data obtained using the same sample. Finally, we analyzed the richness in the microbial inhabitants in the samples collected from apple trees in four orchards. Major apple pathogens that cause scab, Alternaria blotch, and Marssonina blotch were detected along with several non-phytopathogenic fungal and bacterial inhabitants. The macroarray technique presented here is a strong tool to monitor the major microbial species and the community structures in the phyllosphere of apple trees and identify key species antagonistic, supportive or co-operative to specific pathogens in the orchard managed under different environmental conditions.

Comparative Profiling of Ubiquitin Proteasome System Interplay with Influenza A Virus PB2 Polymerase Protein Recapitulating Virus Evolution in Humans.

PubMed

Biquand, Elise; Poirson, Juline; Karim, Marwah; Declercq, Marion; Malausse, Nicolas; Cassonnet, Patricia; Barbezange, Cyril; Straub, Marie-Laure; Jones, Louis; Munier, Sandie; Naffakh, Nadia; van der Werf, Sylvie; Jacob, Yves; Masson, Murielle; Demeret, Caroline

2017-01-01

The optimized exploitation of cell resources is one cornerstone of a successful infection. Differential mapping of host-pathogen protein-protein interactions (PPIs) on the basis of comparative interactomics of multiple strains is an effective strategy to highlight correlations between host proteome hijacking and biological or pathogenic traits. Here, we developed an interactomic pipeline to deliver high-confidence comparative maps of PPIs between a given pathogen and the human ubiquitin proteasome system (UPS). This subarray of the human proteome represents a range of essential cellular functions and promiscuous targets for many viruses. The screening pipeline was applied to the influenza A virus (IAV) PB2 polymerase proteins of five strains representing different levels of virulence in humans. An extensive PB2-UPS interplay has been detected that recapitulates the evolution of IAVs in humans. Functional validation with several IAV strains, including the seasonal H1N1 pdm09 and H3N2 viruses, confirmed the biological relevance of most identified UPS factors and revealed strain-independent and strain-specific effects of UPS factor invalidation on IAV infection. This strategy is applicable to proteins from any other virus or pathogen, providing a valuable resource with which to explore the UPS-pathogen interplay and its relationship with pathogenicity. IMPORTANCE Influenza A viruses (IAVs) are responsible for mild-to-severe seasonal respiratory illness of public health concern worldwide, and the risk of avian strain outbreaks in humans is a constant threat. Elucidating the requisites of IAV adaptation to humans is thus of prime importance. In this study, we explored how PB2 replication proteins of IAV strains with different levels of virulence in humans hijack a major protein modification pathway of the human host cell, the ubiquitin proteasome system (UPS). We found that the PB2 protein engages in an extended interplay with the UPS that evolved along with the virus's adaptation to humans. This suggests that UPS hijacking underlies the efficient infection of humans and can be used as an indicator for evaluation of the potential of avian IAVs to infect humans. Several UPS factors were found to be necessary for infection with circulating IAV strains, pointing to potential targets for therapeutic approaches.

The mating type-like loci of Candida glabrata.

PubMed

Yáñez-Carrillo, Patricia; Robledo-Márquez, Karina A; Ramírez-Zavaleta, Candy Y; De Las Peñas, Alejandro; Castaño, Irene

2014-01-01

Candida glabrata, a haploid and opportunistic fungal pathogen that has not known sexual cycle, has conserved the majority of the genes required for mating and cell type identity. The C. glabrata genome contains three mating-type-like loci called MTL1, MTL2 and MTL3. The three loci encode putative transcription factors, a1, α1 and α2 that regulate cell type identity and sexual reproduction in other fungi like the closely related Saccharomyces cerevisiae. MTL1 can contain either a or α information. MTL2, which contains a information and MTL3 with α information, are relatively close to two telomeres. MTL1 and MTL2 are transcriptionally active, while MTL3 is subject to an incomplete silencing nucleated at the telomere that depends on the silencing proteins Sir2, Sir3, Sir4, yKu70/80, Rif1, Rap1 and Sum1. C. glabrata does not seem to maintain cell type identity, as cell type-specific genes are expressed regardless of the type (or even absence) of mating information. These data highlight important differences in the control of mating and cell type identity between the non-pathogenic yeast S. cerevisiae and C. glabrata, which might explain the absence of a sexual cycle in C. glabrata. The fact that C. glabrata has conserved the vast majority of the genes involved in mating might suggest that some of these genes perhaps have been rewired to control other processes important for the survival inside the host as a commensal or as a human pathogen. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Emergence and Prevalence of Human Vector-Borne Diseases in Sink Vector Populations

PubMed Central

Rascalou, Guilhem; Pontier, Dominique; Menu, Frédéric; Gourbière, Sébastien

2012-01-01

Vector-borne diseases represent a major public health concern in most tropical and subtropical areas, and an emerging threat for more developed countries. Our understanding of the ecology, evolution and control of these diseases relies predominantly on theory and data on pathogen transmission in large self-sustaining ‘source’ populations of vectors representative of highly endemic areas. However, there are numerous places where environmental conditions are less favourable to vector populations, but where immigration allows them to persist. We built an epidemiological model to investigate the dynamics of six major human vector borne-diseases in such non self-sustaining ‘sink’ vector populations. The model was parameterized through a review of the literature, and we performed extensive sensitivity analysis to look at the emergence and prevalence of the pathogen that could be encountered in these populations. Despite the low vector abundance in typical sink populations, all six human diseases were able to spread in 15–55% of cases after accidental introduction. The rate of spread was much more strongly influenced by vector longevity, immigration and feeding rates, than by transmission and virulence of the pathogen. Prevalence in humans remained lower than 5% for dengue, leishmaniasis and Japanese encephalitis, but substantially higher for diseases with longer duration of infection; malaria and the American and African trypanosomiasis. Vector-related parameters were again the key factors, although their influence was lower than on pathogen emergence. Our results emphasize the need for ecology and evolution to be thought in the context of metapopulations made of a mosaic of sink and source habitats, and to design vector control program not only targeting areas of high vector density, but working at a larger spatial scale. PMID:22629337

Aging and the Pathogenic Response to Burn

PubMed Central

Rani, Meenakshi; Schwacha, Martin G.

2012-01-01

Aging is an important and critical factor that contributes to the clinical outcome of burn patients. The very young and the elderly are more likely to succumb after major burn as compared to their adult counterparts. With the aging population, improved understanding of the mechanisms underlying age-associated complications after burns becomes even more demanding. It is widely accepted that elderly burn patients have significantly increased morbidity and mortality. Irrespective of the type of burn injury, the aged population shows slower recoveries and suffers more complications. Age-associated immune dysfunction, immunosenescence, may predispose the elderly burn patients to more infections, slower healing and/or to other complications. Furthermore, pre-existing, age-related medical conditions such as, pulmonary/cardiovascular dysfunctions and diabetes in the elderly are other important factors that contribute to their poorer outcomes after major burn. The present review describes the impact of aging on burn patients outcomes. PMID:22724078

Microbial Hub Taxa Link Host and Abiotic Factors to Plant Microbiome Variation

PubMed Central

Agler, Matthew T.; Ruhe, Jonas; Kroll, Samuel; Morhenn, Constanze; Kim, Sang-Tae; Weigel, Detlef; Kemen, Eric M.

2016-01-01

Plant-associated microorganisms have been shown to critically affect host physiology and performance, suggesting that evolution and ecology of plants and animals can only be understood in a holobiont (host and its associated organisms) context. Host-associated microbial community structures are affected by abiotic and host factors, and increased attention is given to the role of the microbiome in interactions such as pathogen inhibition. However, little is known about how these factors act on the microbial community, and especially what role microbe–microbe interaction dynamics play. We have begun to address this knowledge gap for phyllosphere microbiomes of plants by simultaneously studying three major groups of Arabidopsis thaliana symbionts (bacteria, fungi and oomycetes) using a systems biology approach. We evaluated multiple potential factors of microbial community control: we sampled various wild A. thaliana populations at different times, performed field plantings with different host genotypes, and implemented successive host colonization experiments under lab conditions where abiotic factors, host genotype, and pathogen colonization was manipulated. Our results indicate that both abiotic factors and host genotype interact to affect plant colonization by all three groups of microbes. Considering microbe–microbe interactions, however, uncovered a network of interkingdom interactions with significant contributions to community structure. As in other scale-free networks, a small number of taxa, which we call microbial “hubs,” are strongly interconnected and have a severe effect on communities. By documenting these microbe–microbe interactions, we uncover an important mechanism explaining how abiotic factors and host genotypic signatures control microbial communities. In short, they act directly on “hub” microbes, which, via microbe–microbe interactions, transmit the effects to the microbial community. We analyzed two “hub” microbes (the obligate biotrophic oomycete pathogen Albugo and the basidiomycete yeast fungus Dioszegia) more closely. Albugo had strong effects on epiphytic and endophytic bacterial colonization. Specifically, alpha diversity decreased and beta diversity stabilized in the presence of Albugo infection, whereas they otherwise varied between plants. Dioszegia, on the other hand, provided evidence for direct hub interaction with phyllosphere bacteria. The identification of microbial “hubs” and their importance in phyllosphere microbiome structuring has crucial implications for plant–pathogen and microbe–microbe research and opens new entry points for ecosystem management and future targeted biocontrol. The revelation that effects can cascade through communities via “hub” microbes is important to understand community structure perturbations in parallel fields including human microbiomes and bioprocesses. In particular, parallels to human microbiome “keystone” pathogens and microbes open new avenues of interdisciplinary research that promise to better our understanding of functions of host-associated microbiomes. PMID:26788878

[Factors of persistence and (or) pathogenicity in vibrios and aeromonads belonging to different ecotopes].

PubMed

Bukharin, O V; Boĭko, A V; Zhuravleva, L A

1998-01-01

Factors of persistence and/or pathogenicity in Vibrio parahaemolyticus and Aeromonas hydrophila (hemolytic, lipase, lecithin, DNAase, RNAase, antilysozyme, "anti-interferon", anticomplementary activities and capacity for absorbing Congo red) were studied. The study revealed the interspecific and subpopulation (hospital and extraorganismal parts of the population) differences in the activity of the manifestation of these factors. Strong dependence of the whole complex of persistence and pathogenicity factors of their belonging to the hostal part of Vibrio and Aeromonas populations was shown.

Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test.

PubMed

Monteiro, Rejane A C; de Freitas, Mariana L; Vianna, Gabrielle S; de Oliveira, Valdirene T; Pietra, Rafaella X; Ferreira, Luana C A; Rocha, Patrícia P O; da S Gonçalves, Michele; da C César, Giovana; de S Lima, Joziele; Medeiros, Paula F V; Mazzeu, Juliana F; Jehee, Fernanda S

2017-08-01

Congenital heart disease (CHD) is the most common congenital disorder among live births. When associated with extracardiac abnormalities, it is characterized as a syndromic heart disease (syndromic CHD) and corresponds to 25% of all liveborn infants with a heart defect. The etiology in about 65% of the cases still remains unknown, and in about 35% of the patients, it is associated with genetic factors. In the present study, MLPA and SNP-array techniques were used to investigate a group of 47 patients with syndromic CHD. In total, 16 defects (34%) were identified, of which 12 (25.5%) were classified as pathogenic or probably pathogenic. The most frequent abnormalities were 22q11.2 deletion (22q11.2 deletion syndrome) and 7q11.23 deletion (Williams-Beuren syndrome). We also show that rarer malformations may be associated with syndromic CHD, such as 14q32.33 deletion as well as 17q25.3, 15q11.2 (BP1-BP2), 22q13.31, and 12p13.31 ( SLC2A3 ) duplications. The present study demonstrates that CNVs are important causal factors and should be studied in patients with syndromic CHD. Furthermore, the use of MLPA as a first screening test was appropriate, as this less expensive technology detected 11 of the 12 pathogenic abnormalities (91.6%).

Bacillus anthracis Interacts with Plasmin(ogen) to Evade C3b-Dependent Innate Immunity

PubMed Central

Chung, Myung-Chul; Tonry, Jessica H.; Narayanan, Aarthi; Manes, Nathan P.; Mackie, Ryan S.; Gutting, Bradford; Mukherjee, Dhritiman V.; Popova, Taissia G.; Kashanchi, Fatah; Bailey, Charles L.; Popov, Serguei G.

2011-01-01

The causative agent of anthrax, Bacillus anthracis, is capable of circumventing the humoral and innate immune defense of the host and modulating the blood chemistry in circulation to initiate a productive infection. It has been shown that the pathogen employs a number of strategies against immune cells using secreted pathogenic factors such as toxins. However, interference of B. anthracis with the innate immune system through specific interaction of the spore surface with host proteins such as the complement system has heretofore attracted little attention. In order to assess the mechanisms by which B. anthracis evades the defense system, we employed a proteomic analysis to identify human serum proteins interacting with B. anthracis spores, and found that plasminogen (PLG) is a major surface-bound protein. PLG efficiently bound to spores in a lysine- and exosporium-dependent manner. We identified α-enolase and elongation factor tu as PLG receptors. PLG-bound spores were capable of exhibiting anti-opsonic properties by cleaving C3b molecules in vitro and in rabbit bronchoalveolar lavage fluid, resulting in a decrease in macrophage phagocytosis. Our findings represent a step forward in understanding the mechanisms involved in the evasion of innate immunity by B. anthracis through recruitment of PLG resulting in the enhancement of anti-complement and anti-opsonization properties of the pathogen. PMID:21464960

The Transcription Factor Rbf1 Is the Master Regulator for b-Mating Type Controlled Pathogenic Development in Ustilago maydis

PubMed Central

Vranes, Miroslav; Wahl, Ramon; Pothiratana, Chetsada; Schuler, David; Vincon, Volker; Finkernagel, Florian; Flor-Parra, Ignacio; Kämper, Jörg

2010-01-01

In the phytopathogenic basidiomycete Ustilago maydis, sexual and pathogenic development are tightly connected and controlled by the heterodimeric bE/bW transcription factor complex encoded by the b-mating type locus. The formation of the active bE/bW heterodimer leads to the formation of filaments, induces a G2 cell cycle arrest, and triggers pathogenicity. Here, we identify a set of 345 bE/bW responsive genes which show altered expression during these developmental changes; several of these genes are associated with cell cycle coordination, morphogenesis and pathogenicity. 90% of the genes that show altered expression upon bE/bW-activation require the zinc finger transcription factor Rbf1, one of the few factors directly regulated by the bE/bW heterodimer. Rbf1 is a novel master regulator in a multilayered network of transcription factors that facilitates the complex regulatory traits of sexual and pathogenic development. PMID:20700446

Campylobacter jejuni—An Emerging Foodborne Pathogen

PubMed Central

Stern, Norman J.; Fields, Patricia I.; Swerdlow, David L.

1999-01-01

Campylobacter jejuni is the most commonly reported bacterial cause of foodborne infection in the United States. Adding to the human and economic costs are chronic sequelae associated with C. jejuni infection—Guillian-Barré syndrome and reactive arthritis. In addition, an increasing proportion of human infections caused by C. jejuni are resistant to antimicrobial therapy. Mishandling of raw poultry and consumption of undercooked poultry are the major risk factors for human campylobacteriosis. Efforts to prevent human illness are needed throughout each link in the food chain. PMID:10081669

Campylobacter jejuni--an emerging foodborne pathogen.

PubMed

Altekruse, S F; Stern, N J; Fields, P I; Swerdlow, D L

1999-01-01

Campylobacter jejuni is the most commonly reported bacterial cause of foodborne infection in the United States. Adding to the human and economic costs are chronic sequelae associated with C. jejuni infection--Guillian-Barré syndrome and reactive arthritis. In addition, an increasing proportion of human infections caused by C. jejuni are resistant to antimicrobial therapy. Mishandling of raw poultry and consumption of undercooked poultry are the major risk factors for human campylobacteriosis. Efforts to prevent human illness are needed throughout each link in the food chain.

Antimicrobial Peptides from Fish

PubMed Central

Masso-Silva, Jorge A.; Diamond, Gill

2014-01-01

Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture. PMID:24594555

Multiplex identification of sepsis-causing Gram-negative pathogens from the plasma of infected blood.

PubMed

Chung, Boram; Park, Chulmin; Cho, Sung-Yeon; Shin, Juyoun; Shin, Sun; Yim, Seon-Hee; Lee, Dong-Gun; Chung, Yeun-Jung

2018-02-01

Early and accurate detection of bacterial pathogens in the blood is the most crucial step for sepsis management. Gram-negative bacteria are the most common organisms causing severe sepsis and responsible for high morbidity and mortality. We aimed to develop a method for rapid multiplex identification of clinically important Gram-negative pathogens and also validated whether our system can identify Gram-negative pathogens with the cell-free plasm DNA from infected blood. We designed five MLPA probe sets targeting the genes specific to major Gram-negative pathogens (uidA and lacY for E. coli, ompA for A. baumannii, phoE for K. pneumoniae, and ecfX for P. aeruginosa) and one set targeting the CTX-M group 1 to identify the ESBL producing Gram-negative pathogens. All six target-specific peaks were clearly separated without any non-specific peaks in a multiplex reaction condition. The minimum detection limit was 100 fg of pathogen DNA. When we tested 28 Gram-negative clinical isolates, all of them were successfully identified without any non-specific peaks. To evaluate the clinical applicability, we tested seven blood samples from febrile patients. Three blood culture positive cases showed E. coli specific peaks, while no peak was detected in the other four culture negative samples. This technology can be useful for detection of major sepsis-causing, drug-resistant Gram-negative pathogens and also the major ESBL producing Gram-negatives from the blood of sepsis patients in a clinical setting. This system can help early initiation of effective antimicrobial treatment against Gram-negative pathogens for sepsis patients, which is very crucial for better treatment outcomes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Deceptive chemical signals induced by a plant virus attract insect vectors to inferior hosts.

PubMed

Mauck, Kerry E; De Moraes, Consuelo M; Mescher, Mark C

2010-02-23

Previous studies have shown that vector-borne pathogens can alter the phenotypes of their hosts and vectors in ways that influence the frequency and nature of interactions between them, with significant implications for the transmission and spread of disease. For insect-borne pathogens, host odors are particularly likely targets for manipulation, because both plant- and animal-feeding insects use volatile compounds derived from their hosts as key foraging cues. Here, we document the effects of a widespread plant pathogen, Cucumber mosaic virus (CMV), on the quality and attractiveness of one of its host plants (Cucurbita pepo cv. Dixie) for two aphid vectors, Myzus persicae and Aphis gossypii. Our results indicate that CMV greatly reduces host-plant quality-aphids performed poorly on infected plants and rapidly emigrated from them-but increases the attractiveness of infected plants to aphids by inducing elevated emissions of a plant volatile blend otherwise similar to that emitted by healthy plants. Thus, CMV appears to attract vectors deceptively to infected plants from which they then disperse rapidly, a pattern highly conducive to the nonpersistent transmission mechanism employed by CMV and very different from the pattern previously reported for persistently transmitted viruses that require sustained aphid feeding for transmission. In addition to providing a documented example of a pathogen inducing a deceptive signal of host-plant quality to vectors, our results suggest that the transmission mechanism is a major factor shaping pathogen-induced changes in host-plant phenotypes. Furthermore, our findings yield a general hypothesis that, when vector-borne plant or animal pathogens reduce host quality for vectors, pathogen-induced changes in host phenotypes that enhance vector attraction frequently will involve the exaggeration of existing host-location cues.

Deceptive chemical signals induced by a plant virus attract insect vectors to inferior hosts

PubMed Central

Mauck, Kerry E.; De Moraes, Consuelo M.; Mescher, Mark C.

2010-01-01

Previous studies have shown that vector-borne pathogens can alter the phenotypes of their hosts and vectors in ways that influence the frequency and nature of interactions between them, with significant implications for the transmission and spread of disease. For insect-borne pathogens, host odors are particularly likely targets for manipulation, because both plant- and animal-feeding insects use volatile compounds derived from their hosts as key foraging cues. Here, we document the effects of a widespread plant pathogen, Cucumber mosaic virus (CMV), on the quality and attractiveness of one of its host plants (Cucurbita pepo cv. Dixie) for two aphid vectors, Myzus persicae and Aphis gossypii. Our results indicate that CMV greatly reduces host-plant quality—aphids performed poorly on infected plants and rapidly emigrated from them—but increases the attractiveness of infected plants to aphids by inducing elevated emissions of a plant volatile blend otherwise similar to that emitted by healthy plants. Thus, CMV appears to attract vectors deceptively to infected plants from which they then disperse rapidly, a pattern highly conducive to the nonpersistent transmission mechanism employed by CMV and very different from the pattern previously reported for persistently transmitted viruses that require sustained aphid feeding for transmission. In addition to providing a documented example of a pathogen inducing a deceptive signal of host-plant quality to vectors, our results suggest that the transmission mechanism is a major factor shaping pathogen-induced changes in host-plant phenotypes. Furthermore, our findings yield a general hypothesis that, when vector-borne plant or animal pathogens reduce host quality for vectors, pathogen-induced changes in host phenotypes that enhance vector attraction frequently will involve the exaggeration of existing host-location cues. PMID:20133719

Function and Biosynthesis of Cell Wall α-1,3-Glucan in Fungi

PubMed Central

Yoshimi, Akira; Miyazawa, Ken; Abe, Keietsu

2017-01-01

Although α-1,3-glucan is a major cell wall polysaccharide in filamentous fungi, its biological functions remain unclear, except that it acts as a virulence factor in animal and plant pathogenic fungi: it conceals cell wall β-glucan on the fungal cell surface to circumvent recognition by hosts. However, cell wall α-1,3-glucan is also present in many of non-pathogenic fungi. Recently, the universal function of α-1,3-glucan as an aggregation factor has been demonstrated. Applications of fungi with modified cell wall α-1,3-glucan in the fermentation industry and of in vitro enzymatically-synthesized α-1,3-glucan in bio-plastics have been developed. This review focuses on the recent progress in our understanding of the biological functions and biosynthetic mechanism of cell wall α-1,3-glucan in fungi. We briefly consider the history of studies on α-1,3-glucan, overview its biological functions and biosynthesis, and finally consider the industrial applications of fungi deficient in α-1,3-glucan. PMID:29371579

Lethality of First Contact Dysentery Epidemics on Pacific Islands.

PubMed

Shanks, G Dennis

2016-08-03

Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen-induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history. © The American Society of Tropical Medicine and Hygiene.

Contamination with bacterial zoonotic pathogen genes in U.S. streams influenced by varying types of animal agriculture.

PubMed

Haack, Sheridan K; Duris, Joseph W; Kolpin, Dana W; Focazio, Michael J; Meyer, Michael T; Johnson, Heather E; Oster, Ryan J; Foreman, William T

2016-09-01

Animal waste, stream water, and streambed sediment from 19 small (<32km(2)) watersheds in 12U.S. states having either no major animal agriculture (control, n=4), or predominantly beef (n=4), dairy (n=3), swine (n=5), or poultry (n=3) were tested for: 1) cholesterol, coprostanol, estrone, and fecal indicator bacteria (FIB) concentrations, and 2) shiga-toxin producing and enterotoxigenic Escherichia coli, Salmonella, Campylobacter, and pathogenic and vancomycin-resistant enterococci by polymerase chain reaction (PCR) on enrichments, and/or direct quantitative PCR. Pathogen genes were most frequently detected in dairy wastes, followed by beef, swine and poultry wastes in that order; there was only one detection of an animal-source-specific pathogen gene (stx1) in any water or sediment sample in any control watershed. Post-rainfall pathogen gene numbers in stream water were significantly correlated with FIB, cholesterol and coprostanol concentrations, and were most highly correlated in dairy watershed samples collected from 3 different states. Although collected across multiple states and ecoregions, animal-waste gene profiles were distinctive via discriminant analysis. Stream water gene profiles could also be discriminated by the watershed animal type. Although pathogen genes were not abundant in stream water or streambed samples, PCR on enrichments indicated that many genes were from viable organisms, including several (shiga-toxin producing or enterotoxigenic E. coli, Salmonella, vancomycin-resistant enterococci) that could potentially affect either human or animal health. Pathogen gene numbers and types in stream water samples were influenced most by animal type, by local factors such as whether animals had stream access, and by the amount of local rainfall, and not by studied watershed soil or physical characteristics. Our results indicated that stream water in small agricultural U.S. watersheds was susceptible to pathogen gene inputs under typical agricultural practices and environmental conditions. Pathogen gene profiles may offer the potential to address both source of, and risks associated with, fecal pollution. Published by Elsevier B.V.

Chromosomal features of Escherichia coli serotype O2:K2, an avian pathogenic E. coli.

PubMed

Jørgensen, Steffen L; Kudirkiene, Egle; Li, Lili; Christensen, Jens P; Olsen, John E; Nolan, Lisa; Olsen, Rikke H

2017-01-01

Escherichia coli causing infection outside the gastrointestinal system are referred to as extra-intestinal pathogenic E. coli. Avian pathogenic E. coli is a subgroup of extra-intestinal pathogenic E. coli and infections due to avian pathogenic E. coli have major impact on poultry production economy and welfare worldwide. An almost defining characteristic of avian pathogenic E. coli is the carriage of plasmids, which may encode virulence factors and antibiotic resistance determinates. For the same reason, plasmids of avian pathogenic E. coli have been intensively studied. However, genes encoded by the chromosome may also be important for disease manifestation and antimicrobial resistance. For the E. coli strain APEC_O2 the plasmids have been sequenced and analyzed in several studies, and E. coli APEC_O2 may therefore serve as a reference strain in future studies. Here we describe the chromosomal features of E. coli APEC_O2. E. coli APEC_O2 is a sequence type ST135, has a chromosome of 4,908,820 bp (plasmid removed), comprising 4672 protein-coding genes, 110 RNA genes, and 156 pseudogenes, with an average G + C content of 50.69%. We identified 82 insertion sequences as well as 4672 protein coding sequences, 12 predicated genomic islands, three prophage-related sequences, and two clustered regularly interspaced short palindromic repeats regions on the chromosome, suggesting the possible occurrence of horizontal gene transfer in this strain. The wildtype strain of E. coli APEC_O2 is resistant towards multiple antimicrobials, however, no (complete) antibiotic resistance genes were present on the chromosome, but a number of genes associated with extra-intestinal disease were identified. Together, the information provided here on E. coli APEC_O2 will assist in future studies of avian pathogenic E. coli strains, in particular regarding strain of E. coli APEC_O2, and aid in the general understanding of the pathogenesis of avian pathogenic E. coli .

Transcription Factors Involved in Plant Resistance to Pathogens.

PubMed

Amorim, Lidiane L B; da Fonseca Dos Santos, Romulo; Neto, Joao Pacífico Bezerra; Guida-Santos, Mauro; Crovella, Sergio; Benko-Iseppon, Ana Maria

2017-01-01

Phytopathogenic microorganisms have a significant influence on survival and productivity of several crop plants. Transcription factors (TFs) are important players in the response to biotic stresses, as insect attack and pathogen infection. In face of such adversities many TFs families have been previously reported as differentially expressed in plants as a reaction to bacterial, fungal and viral infection. This review highlights recent progresses in understanding the structure, function, signal regulation and interaction of transcription factors with other proteins in response to pathogens. Hence, we focus on three families of transcription factors: ERF, bZIP and WRKY, due to their abundance, importance and the availability of functionally well-characterized members in response to pathogen attack. Their roles and the possibilities related to the use of this knowledge for engineering pathogen resistance in crop plants are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A phage display-selected peptide inhibitor of Agrobacterium vitis polygalacturonase.

PubMed

Warren, Jeremy G; Kasun, George W; Leonard, Takara; Kirkpatrick, Bruce C

2016-05-01

Agrobacterium vitis, the causal agent of crown gall of grapevine, is a threat to viticulture worldwide. A major virulence factor of this pathogen is polygalacturonase, an enzyme that degrades pectin components of the xylem cell wall. A single gene encodes for the polygalacturonase gene. Disruption of the polygalacturonase gene results in a mutant that is less pathogenic and produces significantly fewer root lesions on grapevines. Thus, the identification of peptides or proteins that could inhibit the activity of polygalacturonase could be part of a strategy for the protection of plants against this pathogen. A phage-displayed combinatorial peptide library was used to isolate peptides with a high binding affinity to A. vitis polygalacturonase. These peptides showed sequence similarity to regions of Oryza sativa (EMS66324, Japonica) and Triticum urartu (NP_001054402, wild wheat) polygalacturonase-inhibiting proteins (PGIPs). Furthermore, these panning experiments identified a peptide, SVTIHHLGGGS, which was able to reduce A. vitis polygalacturonase activity by 35% in vitro. Truncation studies showed that the IHHL motif alone is sufficient to inhibit A. vitis polygalacturonase activity. © 2015 BSPP AND JOHN WILEY & SONS LTD.

Role of quorum sensing in bacterial infections

PubMed Central

Castillo-Juárez, Israel; Maeda, Toshinari; Mandujano-Tinoco, Edna Ayerim; Tomás, María; Pérez-Eretza, Berenice; García-Contreras, Silvia Julieta; Wood, Thomas K; García-Contreras, Rodolfo

2015-01-01

Quorum sensing (QS) is cell communication that is widely used by bacterial pathogens to coordinate the expression of several collective traits, including the production of multiple virulence factors, biofilm formation, and swarming motility once a population threshold is reached. Several lines of evidence indicate that QS enhances virulence of bacterial pathogens in animal models as well as in human infections; however, its relative importance for bacterial pathogenesis is still incomplete. In this review, we discuss the present evidence from in vitro and in vivo experiments in animal models, as well as from clinical studies, that link QS systems with human infections. We focus on two major QS bacterial models, the opportunistic Gram negative bacteria Pseudomonas aeruginosa and the Gram positive Staphylococcus aureus, which are also two of the main agents responsible of nosocomial and wound infections. In addition, QS communication systems in other bacterial, eukaryotic pathogens, and even immune and cancer cells are also reviewed, and finally, the new approaches proposed to combat bacterial infections by the attenuation of their QS communication systems and virulence are also discussed. PMID:26244150

Tick-borne infections in human and animal population worldwide

PubMed Central

Brites-Neto, José; Duarte, Keila Maria Roncato; Martins, Thiago Fernandes

2015-01-01

The abundance and activity of ectoparasites and its hosts are affected by various abiotic factors, such as climate and other organisms (predators, pathogens and competitors) presenting thus multiples forms of association (obligate to facultative, permanent to intermittent and superficial to subcutaneous) developed during long co-evolving processes. Ticks are ectoparasites widespread globally and its eco epidemiology are closely related to the environmental conditions. They are obligatory hematophagous ectoparasites and responsible as vectors or reservoirs at the transmission of pathogenic fungi, protozoa, viruses, rickettsia and others bacteria during their feeding process on the hosts. Ticks constitute the second vector group that transmit the major number of pathogens to humans and play a role primary for animals in the process of diseases transmission. Many studies on bioecology of ticks, considering the information related to their population dynamics, to the host and the environment, comes possible the application and efficiency of tick control measures in the prevention programs of vector-borne diseases. In this review were considered some taxonomic, morphological, epidemiological and clinical fundamental aspects related to the tick-borne infections that affect human and animal populations. PMID:27047089

Haemophilus ducreyi Hfq contributes to virulence gene regulation as cells enter stationary phase.

PubMed

Gangaiah, Dharanesh; Labandeira-Rey, Maria; Zhang, Xinjun; Fortney, Kate R; Ellinger, Sheila; Zwickl, Beth; Baker, Beth; Liu, Yunlong; Janowicz, Diane M; Katz, Barry P; Brautigam, Chad A; Munson, Robert S; Hansen, Eric J; Spinola, Stanley M

2014-02-11

To adapt to stresses encountered in stationary phase, Gram-negative bacteria utilize the alternative sigma factor RpoS. However, some species lack RpoS; thus, it is unclear how stationary-phase adaptation is regulated in these organisms. Here we defined the growth-phase-dependent transcriptomes of Haemophilus ducreyi, which lacks an RpoS homolog. Compared to mid-log-phase organisms, cells harvested from the stationary phase upregulated genes encoding several virulence determinants and a homolog of hfq. Insertional inactivation of hfq altered the expression of ~16% of the H. ducreyi genes. Importantly, there were a significant overlap and an inverse correlation in the transcript levels of genes differentially expressed in the hfq inactivation mutant relative to its parent and the genes differentially expressed in stationary phase relative to mid-log phase in the parent. Inactivation of hfq downregulated genes in the flp-tad and lspB-lspA2 operons, which encode several virulence determinants. To comply with FDA guidelines for human inoculation experiments, an unmarked hfq deletion mutant was constructed and was fully attenuated for virulence in humans. Inactivation or deletion of hfq downregulated Flp1 and impaired the ability of H. ducreyi to form microcolonies, downregulated DsrA and rendered H. ducreyi serum susceptible, and downregulated LspB and LspA2, which allow H. ducreyi to resist phagocytosis. We propose that, in the absence of an RpoS homolog, Hfq serves as a major contributor of H. ducreyi stationary-phase and virulence gene regulation. The contribution of Hfq to stationary-phase gene regulation may have broad implications for other organisms that lack an RpoS homolog. Pathogenic bacteria encounter a wide range of stresses in their hosts, including nutrient limitation; the ability to sense and respond to such stresses is crucial for bacterial pathogens to successfully establish an infection. Gram-negative bacteria frequently utilize the alternative sigma factor RpoS to adapt to stresses and stationary phase. However, homologs of RpoS are absent in some bacterial pathogens, including Haemophilus ducreyi, which causes chancroid and facilitates the acquisition and transmission of HIV-1. Here, we provide evidence that, in the absence of an RpoS homolog, Hfq serves as a major contributor of stationary-phase gene regulation and that Hfq is required for H. ducreyi to infect humans. To our knowledge, this is the first study describing Hfq as a major contributor of stationary-phase gene regulation in bacteria and the requirement of Hfq for the virulence of a bacterial pathogen in humans.

Test characteristics of milk amyloid A ELISA, somatic cell count, and bacteriological culture for detection of intramammary pathogens that cause subclinical mastitis.

PubMed

Jaeger, S; Virchow, F; Torgerson, P R; Bischoff, M; Biner, B; Hartnack, S; Rüegg, S R

2017-09-01

Bovine mastitis is an important disease in the dairy industry, causing economic losses as a result of withheld milk and treatment costs. Several studies have suggested milk amyloid A (MAA) as a promising biomarker in the diagnosis of mastitis. In the absence of a gold standard for diagnosis of subclinical mastitis, we estimated the diagnostic test accuracy of a commercial MAA-ELISA, somatic cell count (SCC), and bacteriological culture using Bayesian latent class modeling. We divided intramammary infections into 2 classes: those caused by major pathogens (e.g., Escherichia coli, Staphylococcus aureus, streptococci, and lacto-/enterococci) and those caused by all pathogens (major pathogens plus Corynebacterium bovis, coagulase-negative staphylococci, Bacillus spp., Streptomyces spp.). We applied the 3 diagnostic tests to all samples. Of 433 composite milk samples included in this study, 275 (63.5%) contained at least 1 colony of any bacterial species; of those, 56 contained major pathogens and 219 contained minor pathogens. The remaining 158 samples (36.5%) were sterile. We determined 2 different thresholds for the MAA-ELISA using Bayesian latent class modeling: 3.9 µg/mL to detect mastitis caused by major pathogens and 1.6 µg/mL to detect mastitis caused by all pathogens. The optimal SCC threshold for identification of subclinical mastitis was 150,000 cells/mL; this threshold led to higher specificity (Sp) than 100,000 cells/mL. Test accuracy for major-pathogen intramammary infections was as follows: SCC, sensitivity (Se) 92.6% and Sp 72.9%; MAA-ELISA, Se 81.4% and Sp 93.4%; bacteriological culture, Se 23.8% and Sp 95.2%. Test accuracy for all-pathogen intramammary infections was as follows: SCC, sensitivity 90.3% and Sp 71.8%; MAA-ELISA, Se 88.0% and Sp 65.2%; bacteriological culture, Se 83.8% and Sp 54.8%. We suggest the use of SCC and MAA-ELISA as a combined screening procedure for situations such as a Staphylococcus aureus control program. With Bayesian latent class analysis, we were able to identify a more differentiated use of the 3 diagnostic tools. The MAA-ELISA is a valuable addition to existing tools for the diagnosis of subclinical mastitis. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Oral Microbial Ecology and the Role of Salivary Immunoglobulin A

PubMed Central

Marcotte, Harold; Lavoie, Marc C.

1998-01-01

In the oral cavity, indigenous bacteria are often associated with two major oral diseases, caries and periodontal diseases. These diseases seem to appear following an inbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. To define the process involved in caries and periodontal diseases, it is necessary to understand the ecology of the oral cavity and to identify the factors responsible for the transition of the oral microbiota from a commensal to a pathogenic relationship with the host. The regulatory forces influencing the oral ecosystem can be divided into three major categories: host related, microbe related, and external factors. Among host factors, secretory immunoglobulin A (SIgA) constitutes the main specific immune defense mechanism in saliva and may play an important role in the homeostasis of the oral microbiota. Naturally occurring SIgA antibodies that are reactive against a variety of indigenous bacteria are detectable in saliva. These antibodies may control the oral microbiota by reducing the adherence of bacteria to the oral mucosa and teeth. It is thought that protection against bacterial etiologic agents of caries and periodontal diseases could be conferred by the induction of SIgA antibodies via the stimulation of the mucosal immune system. However, elucidation of the role of the SIgA immune system in controlling the oral indigenous microbiota is a prerequisite for the development of effective vaccines against these diseases. The role of SIgA antibodies in the acquisition and the regulation of the indigenous microbiota is still controversial. Our review discusses the importance of SIgA among the multiple factors that control the oral microbiota. It describes the oral ecosystems, the principal factors that may control the oral microbiota, a basic knowledge of the secretory immune system, the biological functions of SIgA, and, finally, experiments related to the role of SIgA in oral microbial ecology. PMID:9529888

The extracellular adherence protein (Eap) of Staphylococcus aureus acts as a proliferation and migration repressing factor that alters the cell morphology of keratinocytes.

PubMed

Eisenbeis, Janina; Peisker, Henrik; Backes, Christian S; Bur, Stephanie; Hölters, Sebastian; Thewes, Nicolas; Greiner, Markus; Junker, Christian; Schwarz, Eva C; Hoth, Markus; Junker, Kerstin; Preissner, Klaus T; Jacobs, Karin; Herrmann, Mathias; Bischoff, Markus

2017-02-01

Staphyloccocus aureus is a major human pathogen and a common cause for superficial and deep seated wound infections. The pathogen is equipped with a large arsenal of virulence factors, which facilitate attachment to various eukaryotic cell structures and modulate the host immune response. One of these factors is the extracellular adherence protein Eap, a member of the "secretable expanded repertoire adhesive molecules" (SERAM) protein family that possesses adhesive and immune modulatory properties. The secreted protein was previously shown to impair wound healing by interfering with host defense and neovascularization. However, its impact on keratinocyte proliferation and migration, two major steps in the re-epithelialization process of wounds, is not known. Here, we report that Eap affects the proliferation and migration capacities of keratinocytes by altering their morphology and adhesive properties. In particular, treatment of non-confluent HaCaT cell cultures with Eap resulted in cell morphology changes as well as a significant reduction in cell proliferation and migration. Eap-treated HaCaT cells changed their appearance from an oblong via a trapezoid to an astral-like shape, accompanied by decreases in cell volume and cell stiffness, and exhibited significantly increased cell adhesion. Eap had a similar influence on endothelial and cancer cells, indicative for a general effect of Eap on eukaryotic cell morphology and functions. Specifically, Eap was found to interfere with growth factor-stimulated activation of the mitogen-activated protein kinase (MAPK) pathway that is known to be responsible for cell shape modulation, induction of proliferation and migration of epithelial cells. Western blot analyses revealed that Eap blocked the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2) in keratinocyte growth factor (KGF)-stimulated HaCaT cells. Together, these data add another antagonistic mechanism of Eap in wound healing, whereby the bacterial protein interferes with keratinocyte migration and proliferation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Risk factors for exposure to feline pathogens in California mountain lions (Puma concolor).

PubMed

Foley, Janet E; Swift, Pamela; Fleer, Katryna A; Torres, Steve; Girard, Yvette A; Johnson, Christine K

2013-04-01

The primary challenge to mountain lion population viability in California is habitat loss and fragmentation. These habitat impacts could enhance disease risk by increasing contact with domestic animals and by altering patterns of exposure to other wild felids. We performed a serologic survey for feline pathogens in California mountain lions (Puma concolor) using 490 samples from 45 counties collected from 1990 to 2008. Most mountain lions sampled were killed because of depredation or public safety concerns and 75% were adults. Pathogens detected by serosurvey in sampled mountain lions included feline panleukopenia virus (39.0%), feline calicivirus (33.0%), feline coronavirus (FCoV, 15.1%), feline herpesvirus (13.0%), heartworm (12.4%), feline leukemia virus (5.4%), and canine distemper virus (3%). An outbreak of heartworm exposure occurred from 1995 to 2003 and higher than expected levels of FCoV-antibody-positive mountain lions were observed from 2005 to 2008, with foci in southern Mendocino and eastern Lake counties. We show that the majority of mountain lions were exposed to feline pathogens and may be at risk of illness or fatality, particularly kittens. Combined with other stressors, such as ongoing habitat loss, infectious disease deserves recognition for potential negative impact on mountain lion health and population viability.

Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri.

PubMed

Zysset-Burri, Denise C; Müller, Norbert; Beuret, Christian; Heller, Manfred; Schürch, Nadia; Gottstein, Bruno; Wittwer, Matthias

2014-06-19

The free-living amoeba Naegleria fowleri is the causative agent of the rapidly progressing and typically fatal primary amoebic meningoencephalitis (PAM) in humans. Despite the devastating nature of this disease, which results in > 97% mortality, knowledge of the pathogenic mechanisms of the amoeba is incomplete. This work presents a comparative proteomic approach based on an experimental model in which the pathogenic potential of N. fowleri trophozoites is influenced by the compositions of different media. As a scaffold for proteomic analysis, we sequenced the genome and transcriptome of N. fowleri. Since the sequence similarity of the recently published genome of Naegleria gruberi was far lower than the close taxonomic relationship of these species would suggest, a de novo sequencing approach was chosen. After excluding cell regulatory mechanisms originating from different media compositions, we identified 22 proteins with a potential role in the pathogenesis of PAM. Functional annotation of these proteins revealed, that the membrane is the major location where the amoeba exerts its pathogenic potential, possibly involving actin-dependent processes such as intracellular trafficking via vesicles. This study describes for the first time the 30 Mb-genome and the transcriptome sequence of N. fowleri and provides the basis for the further definition of effective intervention strategies against the rare but highly fatal form of amoebic meningoencephalitis.

Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System

PubMed Central

Mott, G. Adam; Wilson, Raymond; Fernando, Anuruddika; Robinson, Ailie; MacGregor, Paula; Kennedy, David; Schaap, Dick; Matthews, Jacqueline B.; Matthews, Keith R.

2011-01-01

Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis. PMID:22046137

Canadian National Dairy Study: Herd-level milk quality.

PubMed

Bauman, C A; Barkema, H W; Dubuc, J; Keefe, G P; Kelton, D F

2018-03-01

The objective of this study was to estimate Canadian national milk quality parameters and estimate the bulk tank milk (BTM) prevalence of 4 mastitis pathogens, Staphylococcus aureus, Streptococcus agalactiae, Mycoplasma bovis, and Prototheca spp., on Canadian dairy farms. A questionnaire was sent to all Canadian dairy producers. Of the 1,062 producers who completed the questionnaire, 374 producers from across the country were visited and milking hygiene was assessed. Farm-level milk quality data for all Canadian dairy producers was collected from the provincial marketing boards and combined with the questionnaire and farm visit data. In addition, a BTM sample was collected either during the farm visit or by the marketing board in November of 2015 and was tested for 4 major mastitis pathogens using the PathoProof Mastitis Major 4 PCR Assay (Thermo Fisher Scientific Inc., Waltham, MA). Apparent herd-level prevalence was 46% for S. aureus, 6% for Prototheca spp., 0% for M. bovis, and 0% for Strep. agalactiae. Due to the low prevalence of M. bovis and Strep. agalactiae and a lack of significant factors associated with farms testing positive for Prototheca spp., an association analysis could only be carried out for Staph. aureus-positive farms. Factors associated with Staph. aureus-positive farms were not fore-stripping cows before milking (odds ratio = 1.87), milking with a pipeline system (odds ratio = 2.21), and stall bases made of a rubberized surface (mats and mattresses), whereas protective factors were using blanket dry cow therapy (odds ratio = 0.49) and applying a tag or visible mark on cows known to have chronic mastitis infections (odds ratio = 0.45). The Canadian national production-weighted geometric mean somatic cell count was determined to be 208,000 cells/mL. This is the first national dairy study conducted in Canada. Participating farms had higher milk yield; were more likely to have a loose housing system, parlor, or automated milking system; and had lower weighted mean BTM somatic cell count than the national level. Sampling larger farms with better milk quality means the apparent prevalence of the 4 mastitis pathogens likely underestimates the true levels. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

An Enterotoxin-Bearing Pathogenicity Island in Staphylococcus epidermidis▿†

PubMed Central

Madhusoodanan, Jyoti; Seo, Keun Seok; Remortel, Brian; Park, Joo Youn; Hwang, Sun Young; Fox, Lawrence K.; Park, Yong Ho; Deobald, Claudia F.; Wang, Dan; Liu, Song; Daugherty, Sean C.; Gill, Ann Lindley; Bohach, Gregory A.; Gill, Steven R.

2011-01-01

Cocolonization of human mucosal surfaces causes frequent encounters between various staphylococcal species, creating opportunities for the horizontal acquisition of mobile genetic elements. The majority of Staphylococcus aureus toxins and virulence factors are encoded on S. aureus pathogenicity islands (SaPIs). Horizontal movement of SaPIs between S. aureus strains plays a role in the evolution of virulent clinical isolates. Although there have been reports of the production of toxic shock syndrome toxin 1 (TSST-1), enterotoxin, and other superantigens by coagulase-negative staphylococci, no associated pathogenicity islands have been found in the genome of Staphylococcus epidermidis, a generally less virulent relative of S. aureus. We show here the first evidence of a composite S. epidermidis pathogenicity island (SePI), the product of multiple insertions in the genome of a clinical isolate. The taxonomic placement of S. epidermidis strain FRI909 was confirmed by a number of biochemical tests and multilocus sequence typing. The genome sequence of this strain was analyzed for other unique gene clusters and their locations. This pathogenicity island encodes and expresses staphylococcal enterotoxin C3 (SEC3) and staphylococcal enterotoxin-like toxin L (SElL), as confirmed by quantitative reverse transcription-PCR (qRT-PCR) and immunoblotting. We present here an initial characterization of this novel pathogenicity island, and we establish that it is stable, expresses enterotoxins, and is not obviously transmissible by phage transduction. We also describe the genome sequence, excision, replication, and packaging of a novel bacteriophage in S. epidermidis FRI909, as well as attempts to mobilize the SePI element by this phage. PMID:21317317

Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens

PubMed Central

Cywes-Bentley, Colette; Skurnik, David; Zaidi, Tanweer; Roux, Damien; DeOliveira, Rosane B.; Garrett, Wendy S.; Lu, Xi; O’Malley, Jennifer; Kinzel, Kathryn; Zaidi, Tauqeer; Rey, Astrid; Perrin, Christophe; Fichorova, Raina N.; Kayatani, Alexander K. K.; Maira-Litràn, Tomas; Gening, Marina L.; Tsvetkov, Yury E.; Nifantiev, Nikolay E.; Bakaletz, Lauren O.; Pelton, Stephen I.; Golenbock, Douglas T.; Pier, Gerald B.

2013-01-01

Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)–linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology. PMID:23716675

QTL mapping and candidate gene discovery in potato for resistance to the Verticillium wilt pathogen Verticillium dahliae

USDA-ARS?s Scientific Manuscript database

Verticillium wilt (VW) of potato (Solanum tuberosum), caused by fungal pathogens, Verticillium dahliae and V. albo atrum, is a disease of major significance throughout the potato growing regions in the world. In the past, researchers have focused on the Ve gene, which is a major dominant gene that c...

Approaches to understanding the impact of life-history features on plant-pathogen co-evolutionary dynamics

Treesearch

Jeremy J. Burdon; Peter H. Thrall; Adnane Nemri

2012-01-01

Natural plant-pathogen associations are complex interactions in which the interplay of environment, host, and pathogen factors results in spatially heterogeneous ecological and epidemiological dynamics. The evolutionary patterns that result from the interaction of these factors are still relatively poorly understood. Recently, integration of the appropriate spatial and...

Global Warming Will Bring New Fungal Diseases for Mammals

PubMed Central

Garcia-Solache, Monica A.; Casadevall, Arturo

2010-01-01

ABSTRACT Fungi are major pathogens of plants, other fungi, rotifers, insects, and amphibians, but relatively few cause disease in mammals. Fungi became important human pathogens only in the late 20th century, primarily in hosts with impaired immunity as a consequence of medical interventions or HIV infection. The relatively high resistance of mammals has been attributed to a combination of a complex immune system and endothermy. Mammals maintain high body temperatures relative to environmental temperatures, creating a thermally restrictive ambient for the majority of fungi. According to this view, protection given by endothermy requires a temperature gradient between those of mammals and the environment. We hypothesize that global warming will increase the prevalence of fungal diseases in mammals by two mechanisms: (i) increasing the geographic range of currently pathogenic species and (ii) selecting for adaptive thermotolerance for species with significant pathogenic potential but currently not pathogenic by virtue of being restricted by mammalian temperatures. PMID:20689745

Forthcoming therapeutic perspectives for infections due to multidrug-resistant Gram-positive pathogens.

PubMed

Cornaglia, G; Rossolini, G M

2009-03-01

Multidrug resistance in Gram-positive pathogens emerged as a major therapeutic challenge over two decades ago. The worldwide spread of methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci and other resistant Gram-positive pathogens had a major impact on antibiotic policies, and prompted the discovery and development of new antibiotics to combat difficult-to-treat infections caused by such pathogens. Several new antibiotics active against multidrug-resistant Gram-positive pathogens have recently been introduced into clinical practice, and the antibiotic pipeline contains additional anti-Gram-positive drugs at an advanced stage of development, including new glycopeptides (dalbavancin, oritavancin, and telavancin), new anti-MRSA beta-lactams (ceftobiprole), and new diaminopyrimidines (iclaprim). This article provides a brief overview of these upcoming agents, partially based on the material presented at the ESCMID Conference entitled 'Fighting infections due to multidrug-resistant Gram-positives' (Venice, Italy, 29-31 May 2008) and on the most recent literature.

A genomic island integrated into recA of Vibrio cholerae contains a divergent recA and provides multi-pathway protection from DNA damage.

PubMed

Rapa, Rita A; Islam, Atiqul; Monahan, Leigh G; Mutreja, Ankur; Thomson, Nicholas; Charles, Ian G; Stokes, Harold W; Labbate, Maurizio

2015-04-01

Lateral gene transfer (LGT) has been crucial in the evolution of the cholera pathogen, Vibrio cholerae. The two major virulence factors are present on two different mobile genetic elements, a bacteriophage containing the cholera toxin genes and a genomic island (GI) containing the intestinal adhesin genes. Non-toxigenic V. cholerae in the aquatic environment are a major source of novel DNA that allows the pathogen to morph via LGT. In this study, we report a novel GI from a non-toxigenic V. cholerae strain containing multiple genes involved in DNA repair including the recombination repair gene recA that is 23% divergent from the indigenous recA and genes involved in the translesion synthesis pathway. This is the first report of a GI containing the critical gene recA and the first report of a GI that targets insertion into a specific site within recA. We show that possession of the island in Escherichia coli is protective against DNA damage induced by UV-irradiation and DNA targeting antibiotics. This study highlights the importance of genetic elements such as GIs in the evolution of V. cholerae and emphasizes the importance of environmental strains as a source of novel DNA that can influence the pathogenicity of toxigenic strains. © 2014 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter

PubMed Central

2012-01-01

Background Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. Results Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R2 = 0.2, p < 0.05) existed between the transcriptomic and proteomics datasets for all time points. The lack of correlation between some transcript levels and their subsequent protein levels suggests another regulatory layer of the hypoxia response in A. fumigatus. Conclusions Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major components of the hypoxia response in this pathogenic mold. In addition, a significant induction of the transcripts involved in ergosterol biosynthesis is consistent with previous observations in the pathogenic yeasts Candida albicans and Cryptococcus neoformans indicating conservation of this response to hypoxia in pathogenic fungi. Because ergosterol biosynthesis enzymes also require iron as a co-factor, the increase in iron uptake transcripts is consistent with an increased need for iron under hypoxia. However, unlike C. albicans and C. neoformans, the GABA shunt appears to play an important role in reducing NADH levels in response to hypoxia in A. fumigatus and it will be intriguing to determine whether this is critical for fungal virulence. Overall, regulatory mechanisms of the A. fumigatus hypoxia response appear to involve both transcriptional and post-transcriptional control of transcript and protein levels and thus provide candidate genes for future analysis of their role in hypoxia adaptation and fungal virulence. PMID:22309491

Investigation of infectious reproductive pathogens of large ruminants: Are neosporosis, brucellosis, leptospirosis and BVDV of relevance in Lao PDR?

PubMed

Olmo, L; Dye, M T; Reichel, M P; Young, J R; Nampanya, S; Khounsy, S; Thomson, P C; Windsor, P A; Bush, R D

2018-01-01

N. caninum, bovine viral diarrhoea virus, Brucella abortus and Leptospira interrogans serovar Hardjo are globally significant reproductive pathogens that cause abortion and reproductive loss in large ruminants. Prevalence information is lacking in Lao People's Democratic Republic (Laos) despite the poor reproductive performance of cattle and buffalo. Serological examination of frozen cattle (n=90) and buffalo (n=61) sera by commercially available enzyme-linked immunosorbent assays provided the first reported screening of some of these pathogens in Laos. Seroprevalence differed amongst these large ruminant species, with N. caninum, BVDV and L. interrogans serovar Hardjo antibodies found in 68.9% (95% CI±11.6), 4.9% (95% CI±5.4) and 3.3% (95% CI±4.5) of buffalo sera, respectively, and in 7.8% (95% CI±5.5), 10.0% (95% CI±6.2) and 22.2% (95% CI±8.6) of cattle sera, respectively. Buffalo sera had a significantly higher seroprevalence of N. caninum compared to cattle (p<0.001) and cattle sera had a significantly higher seroprevalence of L. interrogans serovar Hardjo compared to buffalo (p=0.003). Variability was also observed across provinces for N. caninum in buffalo (p=0.007) and for L. interrogans serovar Hardjo in cattle (p=0.071), suggesting provincial risk factors conducive to pathogen transmission. BVDV and N. caninum seropositivity were negatively associated in buffalo (p=0.018) and cattle (p=0.003). In buffalo, L. interrogans serovar Hardjo and BVDV seropositivity were associated (p=0.035, p=0.039). The identification of antibodies against three major abortifacient pathogens in Laos prompts further research to determine if infection is associated with low reproductive efficiency and the risk factors for infection. This is needed for the development of evidence based prevention strategies for improved large ruminant reproductive management among smallholders in Laos. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute diarrhea during army field exercise in southern China

PubMed Central

Bai, Yang; Dai, Ying-Chun; Li, Jian-Dong; Nie, Jun; Chen, Qing; Wang, Hong; Rui, Yong-Yu; Zhang, Ya-Li; Yu, Shou-Yi

2004-01-01

AIM: During emergency period, infectious diseases can be a major threat to military forces. During field training in southern China, diarrhea is the main cause of nonbattle injury. To evaluate the causes of and risk factors for diarrhea in emergency period, we collected clinical and epidemiological data from the People’s Liberation Army (PLA) during field training in southern China. METHODS: From September 25 to October 2 1997, 2636 military personnel were investigated. Fecal sample cultures for lapactic pathogens were obtained from 103 military personnel with diarrhea. In addition, a questionnaire was administered to 103 cases and 206 controls to evaluate the association between illness and potential risk factors. At the same time, another questionnaire of 1:4 case-case control was administered to 22 severe cases (each severe case paired 4 mild cases). RESULTS: The training troop’s diarrhea incidence rate was significantly higher than that of garrison. The diarrhea incidence rate of officers was significantly lower than that of soldiers. A lapactic pathogen was identified in 63.1% (65/103) of the troops with diarrhea. Enterotoxigenic Escherichia coli (35.0%) and plesiomona shigelloides (16.5%) were the most common bacterial pathogens. All bacterial isolates were sensitive to norfloxacin and ceftazidine. However, almost all of them were resistant to sulfamethoxazole, trimethoprim-sulfamethoxazole, oxytetracycline, doxycycline, furazolidone, ampicillin and cloromycetin to a different degree. Risk factors associated with diarrhea included drinking raw water, eating outside, contacting diarrhea patients, lacking sanitation, depression, lacking sleep, which were established by multiple-factor logistic regression analysis. In addition, the unit incidence rate was associated with the density of flies and the average daily boiled water available by regression and discriminate analysis. CONCLUSION: A series of risk factors are associated with the incidence rate of diarrhea. Our results may provide a useful basis for prevention and cure of diarrhea in emergency period of PLA. PMID:14695783

Chemical, microbial and antibiotic susceptibility analyses of groundwater after a major flood event in Chennai

PubMed Central

Gowrisankar, Ganesan; Chelliah, Ramachandran; Ramakrishnan, Sudha Rani; Elumalai, Vetrimurugan; Dhanamadhavan, Saravanan; Brindha, Karthikeyan; Antony, Usha; Elango, Lakshmanan

2017-01-01

During floods, human exposure to pathogens through contaminated water leads to the outbreak of epidemic diseases. This research presents the first extensive assessment of surface and groundwater samples collected immediately after a flood (December 2015) and post-flood (April 2016) from the Adyar River of Chennai, a major city in India, for major ions, trace metals, bacterial population, and pathogens. Severe rains in a short period of time resulted in flooding which inundated the wells, allowing the entry of sewage contaminated river water into the groundwater zone. This has led to bacterial counts and chemical ions exceeding Bureau of Indian Standard’s recommended limits in most flood affected areas. Pathogens isolated from the groundwater showed resistance to antibiotics, namely ceftriaxone, doxycycline and nalidixic acid. However, they were sensitive to chloramphenicol, ciprofloxacin, norfloxacin, and tetracycline. Determining the antibiotic susceptibility of pathogens will help in the treatment of humans affected by contaminated water through an appropriate selection of prescribed medication. PMID:28994821

Does the Host Contribute to Modulation of Mycotoxin Production by Fruit Pathogens?

PubMed Central

Kumar, Dilip; Barad, Shiri; Sionov, Edward; Prusky, Dov B.

2017-01-01

Storage of freshly harvested fruit is a key factor in modulating their supply for several months after harvest; however, their quality can be reduced by pathogen attack. Fruit pathogens may infect their host through damaged surfaces, such as mechanical injuries occurring during growing, harvesting, and packing, leading to increased colonization as the fruit ripens. Of particular concern are fungal pathogens that not only macerate the host tissue but also secrete significant amounts of mycotoxins. Many studies have described the importance of physiological factors, including stage of fruit development, biochemical factors (ripening, C and N content), and environmental factors (humidity, temperature, water deficit) on the occurrence of mycotoxins. However, those factors usually show a correlative effect on fungal growth and mycotoxin accumulation. Recent reports have suggested that host factors can induce fungal metabolism, leading to the synthesis and accumulation of mycotoxins. This review describes the new vision of host-factor impact on the regulation of mycotoxin biosynthetic gene clusters underlying the complex regulation of mycotoxin accumulation in ripening fruit. PMID:28895896

Regulation of H2O2 stress-responsive genes through a novel transcription factor in the protozoan pathogen Entamoeba histolytica.

PubMed

Pearson, Richard J; Morf, Laura; Singh, Upinder

2013-02-08

Outcome of infection depends upon complex interactions between the invading pathogen and the host. As part of the host's innate immune response, the release of reactive oxygen and nitrogen species by phagocytes represents a major obstacle to the establishment of infection. The ability of the human parasite Entamoeba histolytica to survive reactive oxygen and nitrogen species is central to its pathogenic potential and contributes to disease outcome. In order to define the transcriptional network associated with oxidative stress, we utilized the MEME and MAST programs to analyze the promoter regions of 57 amoebic genes that had increased expression specifically in response to H(2)O(2) exposure. We functionally characterized an H(2)O(2)-regulatory motif (HRM) ((1)AAACCTCAATGAAGA(15)), which was enriched in these promoters and specifically bound amoebic nuclear protein(s). Assays with promoter-luciferase fusions established the importance of key residues and that the HRM motif directly impacted the ability of H(2)O(2)-responsive promoters to drive gene expression. DNA affinity chromatography and mass spectrometry identified EHI_108720 as an HRM DNA-binding protein. Overexpression and down-regulation of EHI_108720 demonstrated the specificity of EHI_108720 protein binding to the HRM, and overexpression increased basal expression from an H(2)O(2)-responsive wild-type promoter but not from its mutant counterpart. Thus, EHI_108720, or HRM-binding protein, represents a new stress-responsive transcription factor in E. histolytica that controls a transcriptional regulatory network associated with oxidative stress. Overexpression of EHI_108720 increased parasite virulence. Insight into how E. histolytica responds to oxidative stress increases our understanding of how this important human pathogen establishes invasive disease.

Regulation of H2O2 Stress-responsive Genes through a Novel Transcription Factor in the Protozoan Pathogen Entamoeba histolytica*

PubMed Central

Pearson, Richard J.; Morf, Laura; Singh, Upinder

2013-01-01

Outcome of infection depends upon complex interactions between the invading pathogen and the host. As part of the host's innate immune response, the release of reactive oxygen and nitrogen species by phagocytes represents a major obstacle to the establishment of infection. The ability of the human parasite Entamoeba histolytica to survive reactive oxygen and nitrogen species is central to its pathogenic potential and contributes to disease outcome. In order to define the transcriptional network associated with oxidative stress, we utilized the MEME and MAST programs to analyze the promoter regions of 57 amoebic genes that had increased expression specifically in response to H2O2 exposure. We functionally characterized an H2O2-regulatory motif (HRM) (1AAACCTCAATGAAGA15), which was enriched in these promoters and specifically bound amoebic nuclear protein(s). Assays with promoter-luciferase fusions established the importance of key residues and that the HRM motif directly impacted the ability of H2O2-responsive promoters to drive gene expression. DNA affinity chromatography and mass spectrometry identified EHI_108720 as an HRM DNA-binding protein. Overexpression and down-regulation of EHI_108720 demonstrated the specificity of EHI_108720 protein binding to the HRM, and overexpression increased basal expression from an H2O2-responsive wild-type promoter but not from its mutant counterpart. Thus, EHI_108720, or HRM-binding protein, represents a new stress-responsive transcription factor in E. histolytica that controls a transcriptional regulatory network associated with oxidative stress. Overexpression of EHI_108720 increased parasite virulence. Insight into how E. histolytica responds to oxidative stress increases our understanding of how this important human pathogen establishes invasive disease. PMID:23250742

Identification of diverse mycoviruses through metatranscriptomics characterization of the viromes of five major fungal plant pathogens

USDA-ARS?s Scientific Manuscript database

Infection of plant pathogenic fungi by mycoviruses can attenuate their virulence on plants and vigor in culture. In this study, we described the viromes of 275 isolates of five widely dispersed plant pathogenic fungal species (Colletotrichum truncatum, Macrophomina phaseolina, Phomopsis longicolla, ...

A Spectral Mapping Signature for the Rapid Ohia Death (ROD) Pathogen in Hawaiian Forests

USDA-ARS?s Scientific Manuscript database

Pathogenic invasions are a major disruptive source of change in both agricultural and natural ecosystems. In forests, fungal pathogens can kill habitat-generating plant species such as canopy trees, but methods for remote detection, mapping and monitoring of such outbreaks are poorly developed. Cera...

Optimal strategies for the eradication of Asiatic citrus canker in heterogeneous host landscapes

USDA-ARS?s Scientific Manuscript database

The eradication of non-native plant pathogens is a key challenge in plant disease epidemiology. Asiatic citrus canker is an economically significant disease of citrus caused by the bacterial plant pathogen Xanthomonas citri subsp. citri. The pathogen is a major exotic disease problem in many citru...

Comparative population genomics of Fusarium graminearum reveals adaptive divergence among cereal head blight pathogens

USDA-ARS?s Scientific Manuscript database

In this study we sequenced the genomes of 60 Fusarium graminearum, the major fungal pathogen responsible for Fusarium head blight (FHB) in cereal crops world-wide. To investigate adaptive evolution of FHB pathogens, we performed population-level analyses to characterize genomic structure, signatures...

Dual effectiveness of ascorbic acid and ethanol combined treatment to inhibit browning and inactivate pathogens on fresh-cut apples

USDA-ARS?s Scientific Manuscript database

Commercially-produced apple wedges have recently been associated with several recalls due to foodborne pathogen contamination. The fresh-cut industry faces a major technical challenge due to the incompatibility between chemicals used to control spoilage and pathogenic microorganisms (usually oxidize...

Aspergillus flavus infection triggered immune responses and host-pathogen cross-talks in groundnut during in-vitro seed colonization

USDA-ARS?s Scientific Manuscript database

Aflatoxin contamination, caused by fungal pathogen Aspergillus flavus, is a major quality and health problem delimiting the trade and consumption of groundnut (Arachis hypogaea L.) worldwide. RNA-seq approach was deployed to understand the host-pathogen interaction by identifying differentially expr...

A diagnostic guide for Fusarium Root Rot of pea

USDA-ARS?s Scientific Manuscript database

Fusarium root rot, caused by Fusarium solani f. sp. pisi, is a major root rot pathogen in pea production areas worldwide. Here we provide a diagnostic guide that describes: the taxonomy of the pathogen, signs and symptoms of the pathogen, host range, geographic distribution, methods used to isolate ...

Legionella - (re-)awakening to the Amoeba-based Pathogens of Distribution System Biofilm

EPA Science Inventory

Fecal pathogens have long been the focus of concern in the distribution of drinking waters. Yet today, with distribution system ‘failures’ accounting for the majority of waterborne outbreaks in the USA, there is growing realization that pathogens endemic to aquatic biofilms may a...

Global genetic structure of the fungal grapevine pathogen Eutypa lata

USDA-ARS?s Scientific Manuscript database

The ascomycete fungus Eutypa lata is a trunk pathogen of cultivated grapevine (Vitis vinifera) in all major grape-growing regions of the world. Throughout its geographic range, it is considered a generalist pathogen that can complete its life cycle on a broad range of hosts. To decipher the cosmopol...

Early Salmonella Typhimurium infection in pigs disrupts Microbiome composition and functionality principally at the ileum mucosa.

PubMed

Argüello, Héctor; Estellé, Jordi; Zaldívar-López, Sara; Jiménez-Marín, Ángeles; Carvajal, Ana; López-Bascón, Mª Asunción; Crispie, Fiona; O'Sullivan, Orla; Cotter, Paul D; Priego-Capote, Feliciano; Morera, Luis; Garrido, Juan J

2018-05-17

Salmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors which it uses to colonise and persist within the host. The host microbiota may play a role in resistance to, and may also be indirectly responsible from some of the consequences of, Salmonella infection. To investigate this, we used 16S rRNA metagenomic sequencing to determine the changes in the gut microbiota of pigs in response to infection by Salmonella Typhimurium at three locations: ileum mucosa, ileum content and faeces. Early infection (2 days post-infection) impacted on the microbiome diversity at the mucosa, reflected in a decrease in representatives of the generally regarded as desirable genera (i.e., Bifidobacterium and Lactobacillus). Severe damage in the epithelium of the ileum mucosa correlated with an increase in synergistic (with respect to Salmonella infection; Akkermansia) or opportunistically pathogenic bacteria (Citrobacter) and a depletion in anaerobic bacteria (Clostridium spp., Ruminococcus, or Dialliser). Predictive functional analysis, together with metabolomic analysis revealed changes in glucose and lipid metabolism in infected pigs. The observed changes in commensal healthy microbiota, including the growth of synergistic or potentially pathogenic bacteria and depletion of beneficial or competing bacteria, could contribute to the pathogen's ability to colonize the gut successfully. The findings from this study could be used to form the basis for further research aimed at creating intervention strategies to mitigate the effects of Salmonella infection.

Morphometrics of the Southern Green Stink Bug [Nezara viridula (L.) (Hemiptera: Pentatomidae)] Stylet Bundle.

PubMed

Esquivel, J F; Droleskey, R E; Ward, L A; Harvey, R B

2018-03-29

The southern green stink bug, Nezara viridula (L.) (Hemiptera: Pentatomidae), is a cosmopolitan pest of high-value cash crops, including cotton (Gossypium hirsutum L.; Malvales: Malvaceae). The pest can ingest and transmit disease-causing bacterial and fungal pathogens of cotton. We hypothesized that the size of the food canal may contribute to selective transmission, as observed in previous reports. The objective of this study was to examine food canal size and other morphometric parameters of the southern green stink bug stylet bundle at two locations (labium and head) to improve our understanding of factors that may contribute to pathogen transmission. For the food canal, females possessed significantly larger canals than males, major axes were significantly longer than minor axes, and canal sizes were numerically higher at the labium compared with the head. For salivary canal, mean axes lengths were similar between sexes and the head and labium. For both food and salivary canals, axes lengths were longer and area was larger at the labium compared with the head. These findings indicate the presence of a "funnel effect" with canals becoming narrower proximally. Sex and location significantly affected the size of the intact stylet bundle. Results indicate the food canal size was not a factor affecting previously observed selective passive transmission. Major and minor axes measurements, coupled with morphological observations of canal shapes and observed "funnel effect" in the food and salivary canals, improve our understanding of the hemipteran stylet bundle and its relationship with the insect's internal morphology.

The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes": Study protocol.

PubMed

Barchetta, I; Capoccia, D; Baroni, M G; Buzzetti, R; Cavallo, M G; De Cosmo, S; Leonetti, F; Leotta, S; Morano, S; Morviducci, L; Prudente, S; Pugliese, G; Trischitta, V

2016-02-01

The rate of mortality in diabetic patients, especially of cardiovascular origin, is about twice as much that of nondiabetic individuals. Thus, the pathogenic factors shaping the risk of mortality in such patients must be unraveled in order to target intensive prevention and treatment strategies. The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with type 2 diabetes mellitus (T2DM). The "SUMMER study in diabetes" is an observational, prospective, and collaborative study conducted on at least 5000 consecutive patients with T2DM, recruited from several diabetes clinics of Central-Southern Italy and followed up for a minimum of 5 years. The primary outcome is all-cause mortality; the secondary outcomes are cardiovascular mortality, acute myocardial infarction, stroke, and dialysis. A biobank will be created for genomic, transcriptomic, and metabolomic analysis, in order to unravel new molecular predictors of mortality and vascular morbidity. The "SUMMER study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with T2DM. These novel pathogenic factors will most likely be instrumental in unraveling new pathways underlying such dramatic events. In addition, they will also be used as additional markers to increase the performance of the already existing risk-scoring models for predicting the above-mentioned outcomes in T2DM, as well as for setting up new preventive and treatment strategies, possibly tailored to specific pathogenic backgrounds. ClinicalTrials.gov, NCT02311244; URL https://clinicaltrials.gov/ct2/show/NCT02311244?term=SUMMER&rank=5. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

The effect of deletion of the edema factor on Bacillus anthracis pathogenicity in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Glinert, Itai; Sittner, Assa; Kobiler, David

2012-01-01

Bacillus anthracis secretes three major components, which assemble into two bipartite toxins: lethal toxin (LT), composed of lethal factor (LF) and protective antigen (PA) and edema toxin (ET), composed of edema factor (EF) and PA. EF is a potent calmodulin-dependent adenylate cyclase, which is internalized into the target cell following PA binding. Once inside the cell, EF elevates cAMP levels, interrupting intracellular signaling. Effects of ET were demonstrated on monocytes, neutrophils and T-cells. In an earlier work we demonstrated that a deletion of LF in a fully virulent strain had no effect in guinea pigs and a significant, but not major, effect in the rabbit model. These results suggested that EF might play an important role in the development of infection and mortality following exposure to B. anthracis spores. To evaluate the role of EF in B. anthracis pathogenicity we deleted the cya gene, which encodes the EF protein, in the fully virulent Vollum strain. The Δcya mutant was fully virulent in the guinea pig model as determined by LD(50) experiments. In the rabbit model, when infected subcutaneously, the absence of EF had no effect on the virulence of the mutant. However an increase of two orders of magnitude in the LD(50) was demonstrated when the rabbits were infected by intranasal instillation accompanied with partial mortality and increased mean time to death. These results argue that in the guinea pig model the presence of one of the toxins, ET or LT is sufficient for the development of the infection. In the rabbit model ET plays a role in respiratory infection, most probably mediating the early steps of host colonization. Copyright © 2011 Elsevier Ltd. All rights reserved.

Role of major surface structures of Escherichia coli O157:H7 in initial attachment to biotic and abiotic surfaces

USDA-ARS?s Scientific Manuscript database

Infection by human pathogens through fresh, minimally processed produce and solid plant-derived foods is a major concern of U.S. and global food industry and public health services. The enterohemorrhagic Escherichia coli O157:H7 is a frequent and potent food borne pathogen that causes severe disease...

Correlates of virulence in a frog-killing fungal pathogen: evidence from a California amphibian decline

Treesearch

Jonah Piovia-Scott; Karen Pope; S. Joy Worth; Erica Bree Rosenblum; Dean Simon; Gordon Warburton; Louise A. Rollins-Smith; Laura K. Reinert; Heather L. Wells; Dan Rejmanek; Sharon Lawler; Janet Foley

2015-01-01

The fungal pathogen Batrachochytrium dendrobatidis (Bd) has caused declines and extinctions in amphibians worldwide, and there is increasing evidence that some strains of this pathogen are more virulent than others. While a number of putative virulence factors have been identified, few studies link these factors to specific epizootic events. We...

Identification of the haemolytic activity of Malassezia species.

PubMed

Juntachai, Weerapong; Kummasook, Aksarakorn; Mekaprateep, Malee; Kajiwara, Susumu

2014-03-01

Malassezia species are part of the normal skin flora and are associated with a number of human and animal skin diseases. However, the mechanisms that mediate infection and host-fungal interactions are poorly understood. The haemolytic activity of several microorganisms is considered a factor that contributes to pathogenicity of the organism to humans and animals. This virulence factor was previously identified in several pathogenic fungi that cause systemic mycoses, such as Aspergillus and Candida. In this study, the haemolytic activity of six major Malassezia species, including M. furfur, M. globosa, M. pachydermatis, M. restricta, M. slooffiae and M. sympodialis, was investigated. The haemolytic activity of these species was tested on tryptone soya agar with 5% sheep blood. All the examined Malassezia species produced a halo zone of complete haemolysis. A quantitative analysis of the haemolytic activity was performed by incubating sheep erythrocytes with the extraction from culture of each Malassezia species. Interestingly, M. globosa and M. restricta showed significantly high haemolytic activity compared with the other Malassezia species. In addition, M. globosa also exhibited stable haemolytic activity after treatment at 100 °C and in the presence of some proteases, indicating that this haemolytic factor is different from those of other fungi. © 2013 Blackwell Verlag GmbH.

The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background

PubMed Central

Marsh, Sharon; Hu, Junbo; Feng, Wenke

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression. PMID:27247565

Effect of Environment and Sugar Beet Genotype on Root Rot Development and Pathogen Profile During Storage.

PubMed

Liebe, Sebastian; Varrelmann, Mark

2016-01-01

Storage rots represent an economically important factor impairing the storability of sugar beet by increasing sucrose losses and invert sugar content. Understanding the development of disease management strategies, knowledge about major storage pathogens, and factors influencing their occurrence is crucial. In comprehensive storage trials conducted under controlled conditions, the effects of environment and genotype on rot development and associated quality changes were investigated. Prevalent species involved in rot development were identified by a newly developed microarray. The strongest effect on rot development was assigned to environment factors followed by genotypic effects. Despite large variation in rot severity (sample range 0 to 84%), the spectrum of microorganisms colonizing sugar beet remained fairly constant across all treatments with dominant species belonging to the fungal genera Botrytis, Fusarium, and Penicillium. The intensity of microbial tissue necrotization was strongly correlated with sucrose losses (R² = 0.79 to 0.91) and invert sugar accumulation (R² = 0.91 to 0.95). A storage rot resistance bioassay was developed that could successfully reproduce the genotype ranking observed in storage trials. Quantification of fungal biomass indicates that genetic resistance is based on a quantitative mechanism. Further work is required to understand the large environmental influence on rot development in sugar beet.

Queen Quality and the Impact of Honey Bee Diseases on Queen Health: Potential for Interactions between Two Major Threats to Colony Health

PubMed Central

Amiri, Esmaeil; Strand, Micheline K.; Rueppell, Olav; Tarpy, David R.

2017-01-01

Western honey bees, Apis mellifera, live in highly eusocial colonies that are each typically headed by a single queen. The queen is the sole reproductive female in a healthy colony, and because long-term colony survival depends on her ability to produce a large number of offspring, queen health is essential for colony success. Honey bees have recently been experiencing considerable declines in colony health. Among a number of biotic and abiotic factors known to impact colony health, disease and queen failure are repeatedly reported as important factors underlying colony losses. Surprisingly, there are relatively few studies on the relationship and interaction between honey bee diseases and queen quality. It is critical to understand the negative impacts of pests and pathogens on queen health, how queen problems might enable disease, and how both factors influence colony health. Here, we review the current literature on queen reproductive potential and the impacts of honey bee parasites and pathogens on queens. We conclude by highlighting gaps in our knowledge on the combination of disease and queen failure to provide a perspective and prioritize further research to mitigate disease, improve queen quality, and ensure colony health. PMID:28481294

Direct Transmembrane Interaction between Actin and the Pore-Competent, Cholesterol-Dependent Cytolysin Pneumolysin

PubMed Central

Hupp, Sabrina; Förtsch, Christina; Wippel, Carolin; Ma, Jiangtao; Mitchell, Timothy J.; Iliev, Asparouh I.

2013-01-01

The eukaryotic actin cytoskeleton is an evolutionarily well-established pathogen target, as a large number of bacterial factors disturb its dynamics to alter the function of the host cells. These pathogenic factors modulate or mimic actin effector proteins or they modify actin directly, leading to an imbalance of the precisely regulated actin turnover. Here, we show that the pore-forming, cholesterol-dependent cytolysin pneumolysin (PLY), a major neurotoxin of Streptococcus pneumoniae, has the capacity to bind actin directly and to enhance actin polymerisation in vitro. In cells, the toxin co-localised with F-actin shortly after exposure, and this direct interaction was verified by Förster resonance energy transfer. PLY was capable of exerting its effect on actin through the lipid bilayer of giant unilamellar vesicles, but only when its pore competence was preserved. The dissociation constant of G-actin binding to PLY in a biochemical environment was 170–190 nM, which is indicative of a high-affinity interaction, comparable to the affinity of other intracellular actin-binding factors. Our results demonstrate the first example of a direct interaction of a pore-forming toxin with cytoskeletal components, suggesting that the cross talk between pore-forming cytolysins and cells is more complex than previously thought. PMID:23219469

Economic costs of protistan and metazoan parasites to global mariculture.

PubMed

Shinn, A P; Pratoomyot, J; Bron, J E; Paladini, G; Brooker, E E; Brooker, A J

2015-01-01

Parasites have a major impact on global finfish and shellfish aquaculture, having significant effects on farm production, sustainability and economic viability. Parasite infections and impacts can, according to pathogen and context, be considered to be either unpredictable/sporadic or predictable/regular. Although both types of infection may result in the loss of stock and incur costs associated with the control and management of infection, predictable infections can also lead to costs associated with prophylaxis and related activities. The estimation of the economic cost of a parasite event is frequently complicated by the complex interplay of numerous factors associated with a specific incident, which may range from direct production losses to downstream socio-economic impacts on livelihoods and satellite industries associated with the primary producer. In this study, we examine the world's major marine and brackish water aquaculture production industries and provide estimates of the potential economic costs attributable to a range of key parasite pathogens using 498 specific events for the purposes of illustration and estimation of costs. This study provides a baseline resource for risk assessment and the development of more robust biosecurity practices, which can in turn help mitigate against and/or minimise the potential impacts of parasite-mediated disease in aquaculture.

Antimicrobial activity of zinc and titanium dioxide nanoparticles against biofilm-producing methicillin-resistant Staphylococcus aureus

NASA Astrophysics Data System (ADS)

Jesline, A.; John, Neetu P.; Narayanan, P. M.; Vani, C.; Murugan, Sevanan

2015-02-01

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major nosocomial pathogens responsible for a wide spectrum of infections and the emergence of bacterial resistance to antibiotics has lead to treatment drawbacks towards large number of drugs. Formation of biofilms is the main contributing factor to antibiotic resistance. The development of reliable processes for the synthesis of zinc oxide nanoparticles is an important aspect of nanotechnology today. Zinc oxide and titanium dioxide nanoparticles comprise well-known inhibitory and bactericidal effects. Emergence of antimicrobial resistance by pathogenic bacteria is a major health problem in recent years. This study was designed to determine the efficacy of zinc and titanium dioxide nanoparticles against biofilm producing methicillin-resistant S. aureus. Biofilm production was detected by tissue culture plate method. Out of 30 MRSA isolates, 22 isolates showed strong biofilm production and 2 showed weak and moderate biofilm formation. Two strong and weak biofilm-producing methicillin-resistant S. aureus isolates were subjected to antimicrobial activity using commercially available zinc and titanium dioxide nanoparticles. Thus, the nanoparticles showed considerably good activity against the isolates, and it can be concluded that they may act as promising, antibacterial agents in the coming years.

LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis

PubMed Central

Vrieling, Manouk; Boerhout, Eveline M.; van Wigcheren, Glenn F.; Koymans, Kirsten J.; Mols-Vorstermans, Tanja G.; de Haas, Carla J. C.; Aerts, Piet C.; Daemen, Ineke J. J. M.; van Kessel, Kok P. M.; Koets, Ad P.; Rutten, Victor P. M. G.; Nuijten, Piet J.M.; van Strijp, Jos A. G.; Benedictus, Lindert

2016-01-01

Staphylococcus aureus is a major human and animal pathogen and a common cause of mastitis in cattle. S. aureus secretes several leukocidins that target bovine neutrophils, crucial effector cells in the defence against bacterial pathogens. In this study, we investigated the role of staphylococcal leukocidins in the pathogenesis of bovine S. aureus disease. We show that LukAB, in contrast to the γ-hemolysins, LukED, and LukMF′, was unable to kill bovine neutrophils, and identified CXCR2 as a bovine receptor for HlgAB and LukED. Furthermore, we assessed functional leukocidin secretion by bovine mastitis isolates and observed that, although leukocidin production was strain dependent, LukMF′ was most abundantly secreted and the major toxin killing bovine neutrophils. To determine the role of LukMF′ in bovine mastitis, cattle were challenged with high (S1444) or intermediate (S1449, S1463) LukMF′-producing isolates. Only animals infected with S1444 developed severe clinical symptoms. Importantly, LukM was produced in vivo during the course of infection and levels in milk were associated with the severity of mastitis. Altogether, these findings underline the importance of LukMF′ as a virulence factor and support the development of therapeutic approaches targeting LukMF′ to control S. aureus mastitis in cattle. PMID:27886237

Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion*

PubMed Central

Wurm, Philipp; Spindelboeck, Walter; Krause, Robert; Plank, Johannes; Fuchs, Gottfried; Bashir, Mina; Petritsch, Wolfgang; Halwachs, Bettina; Langner, Cord; Högenauer, Christoph

2017-01-01

Objective: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. Patients: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth. Interventions: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis. Conclusions: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition. PMID:28333760

Titin Mutations in iPS cells Define Sarcomere Insufficiency as a Cause of Dilated Cardiomyopathy

PubMed Central

Hinson, John T.; Chopra, Anant; Nafissi, Navid; Polacheck, William J.; Benson, Craig C.; Swist, Sandra; Gorham, Joshua; Yang, Luhan; Schafer, Sebastian; Sheng, Calvin C.; Haghighi, Alireza; Homsy, Jason; Hubner, Norbert; Church, George; Cook, Stuart A.; Linke, Wolfgang A.; Chen, Christopher S.; Seidman, J. G.; Seidman, Christine E.

2015-01-01

Human mutations that truncate the massive sarcomere protein titin (TTNtv) are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtv, diminish contractile performance and are pathogenic. By combining functional analyses with RNAseq, we explain why truncations in the A-band domain of TTN cause DCM while truncations in the I-band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS-cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodelling. PMID:26315439

Host-parasite coevolution: genetic variation in a virus population and the interaction with a host gene.

PubMed

Wilfert, L; Jiggins, F M

2010-07-01

Host-parasite coevolution is considered to be an important factor in maintaining genetic variation in resistance to pathogens. Drosophila melanogaster is naturally infected by the sigma virus, a vertically transmitted and host-specific pathogen. In fly populations, there is a large amount of genetic variation in the transmission rate from parent to offspring, much of which is caused by major-effect resistance polymorphisms. We have found that there are similarly high levels of genetic variation in the rate of paternal transmission among 95 different isolates of the virus as in the host. However, when we examined a transmission-blocking gene in the host, we found that it was effective across virus isolates. Therefore, the high levels of genetic variation observed in this system do not appear to be maintained because of coevolution resulting from interactions between this host gene and parasite genes.

Invasive mold infections: virulence and pathogenesis of mucorales.

PubMed

Morace, Giulia; Borghi, Elisa

2012-01-01

Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the order Mucorales are responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to the Mucoraceae family. Mucorales are able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses.

Dermatological infectiology--Quo vadis? Symposium, Ruhr-University, September 29-30, 2000. Abstracts.

PubMed

2000-11-30

Infectious diseases remain a major cause of morbidity and mortality in the year 2000. 17 million deaths per year or roughly a third of all deaths are caused by infections. Infectious diseases also pose a serious economic threat. While many well-established pathogens have not been contained several new infectious agents have been discovered within the past 27 years which include rotavirus, legionella, HIV, ebola, campylobacter, helicobacter, nipah, HHV8, hepatitis C, and many others. Additionally many new pathogens have emerged as serious threats to the ever-growing number of immuno-compromised patients. Infectious etiologies have been found for many common diseases (certain leukemias, duodenal ulcers, etcetera). It is likely that infections are at least co-factors for many other diseases (transplant-associated atherosclerosis). Only specialized care and multi-disciplinary collaboration will enable us to cope with current problems and the inevitable emergence of new infectious diseases.

Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen Pneumocystis

PubMed Central

Ma, Liang; Wei Huang, Da; Khil, Pavel P.; Dekker, John P.; Kutty, Geetha; Bishop, Lisa; Liu, Yueqin; Deng, Xilong; Pagni, Marco; Hirsch, Vanessa; Lempicki, Richard A.

2018-01-01

ABSTRACT Pneumocystis species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable in vitro. Human Pneumocystis infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of Pneumocystis infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that Pneumocystis species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of Pneumocystis populations during their spread across mammals. PMID:29739910

Pathobiology and Immunobiology of Acanthamoeba Keratitis: Insights from Animal Models
.

PubMed

Neelam, Sudha; Niederkorn, Jerry Y

2017-06-01

Acanthamoeba keratitis (AK) is a rare but sight-threatening disease caused by pathogenic species of Acanthamoeba . Despite its ubiquitous nature, the incidence of AK is relatively low compared to other forms of infectious keratitis. Although contact lens wear is a major risk factor, exposure to contaminated water and ocular trauma are also associated with AK. Once a patient develops AK the prognosis is very poor unless an aggressive treatment regimen is initiated early. Some of the intriguing features of AK are the lack of immunological memory, resistance of the dormant cyst form to treatment, differences between the pathogenic strains and soil isolates of Acanthamoeba and the unique role of the innate immune system in controlling this disease. Understanding the series of steps involved in the pathogenesis of the disease and the host immune response against Acanthamoeba antigens is crucial for developing effective therapeutic strategies targeting the disease.

Frontiers for research on the ecology of plant-pathogenic bacteria: fundamentals for sustainability: Challenges in Bacterial Molecular Plant Pathology.

PubMed

Morris, Cindy E; Barny, Marie-Anne; Berge, Odile; Kinkel, Linda L; Lacroix, Christelle

2017-02-01

Methods to ensure the health of crops owe their efficacy to the extent to which we understand the ecology and biology of environmental microorganisms and the conditions under which their interactions with plants lead to losses in crop quality or yield. However, in the pursuit of this knowledge, notions of the ecology of plant-pathogenic microorganisms have been reduced to a plant-centric and agro-centric focus. With increasing global change, i.e. changes that encompass not only climate, but also biodiversity, the geographical distribution of biomes, human demographic and socio-economic adaptations and land use, new plant health problems will emerge via a range of processes influenced by these changes. Hence, knowledge of the ecology of plant pathogens will play an increasingly important role in the anticipation and response to disease emergence. Here, we present our opinion on the major challenges facing the study of the ecology of plant-pathogenic bacteria. We argue that the discovery of markedly novel insights into the ecology of plant-pathogenic bacteria is most likely to happen within a framework of more extensive scales of space, time and biotic interactions than those that currently guide much of the research on these bacteria. This will set a context that is more propitious for the discovery of unsuspected drivers of the survival and diversification of plant-pathogenic bacteria and of the factors most critical for disease emergence, and will set the foundation for new approaches to the sustainable management of plant health. We describe the contextual background of, justification for and specific research questions with regard to the following challenges: Development of terminology to describe plant-bacterial relationships in terms of bacterial fitness. Definition of the full scope of the environments in which plant-pathogenic bacteria reside or survive. Delineation of pertinent phylogenetic contours of plant-pathogenic bacteria and naming of strains independent of their presumed life style. Assessment of how traits of plant-pathogenic bacteria evolve within the overall framework of their life history. Exploration of possible beneficial ecosystem services contributed to by plant-pathogenic bacteria. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns.

PubMed

Cilloniz, Catia; Martin-Loeches, Ignacio; Garcia-Vidal, Carolina; San Jose, Alicia; Torres, Antoni

2016-12-16

Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason for the increased global mortality is the impact of pneumonia on chronic diseases, along with the increasing age of the population and the virulence factors of the causative microorganism. The increasing number of multidrug-resistant bacteria, difficult-to-treat microorganisms, and the emergence of new pathogens are a major problem for clinicians when deciding antimicrobial therapy. A key factor for managing and effectively guiding appropriate antimicrobial therapy is an understanding of the role of the different causative microorganisms in the etiology of pneumonia, since it has been shown that the adequacy of initial antimicrobial therapy is a key factor for prognosis in pneumonia. Furthermore, broad-spectrum antibiotic therapies are sometimes given until microbiological results are available and de-escalation cannot be performed quickly. This review provides an overview of microbial etiology, resistance patterns, epidemiology and microbial diagnosis of pneumonia.

Assessing the durability and efficiency of landscape-based strategies to deploy plant resistance to pathogens

PubMed Central

Rey, Jean-François; Barrett, Luke G.; Thrall, Peter H.

2018-01-01

Genetically-controlled plant resistance can reduce the damage caused by pathogens. However, pathogens have the ability to evolve and overcome such resistance. This often occurs quickly after resistance is deployed, resulting in significant crop losses and a continuing need to develop new resistant cultivars. To tackle this issue, several strategies have been proposed to constrain the evolution of pathogen populations and thus increase genetic resistance durability. These strategies mainly rely on varying different combinations of resistance sources across time (crop rotations) and space. The spatial scale of deployment can vary from multiple resistance sources occurring in a single cultivar (pyramiding), in different cultivars within the same field (cultivar mixtures) or in different fields (mosaics). However, experimental comparison of the efficiency (i.e. ability to reduce disease impact) and durability (i.e. ability to limit pathogen evolution and delay resistance breakdown) of landscape-scale deployment strategies presents major logistical challenges. Therefore, we developed a spatially explicit stochastic model able to assess the epidemiological and evolutionary outcomes of the four major deployment options described above, including both qualitative resistance (i.e. major genes) and quantitative resistance traits against several components of pathogen aggressiveness: infection rate, latent period duration, propagule production rate, and infectious period duration. This model, implemented in the R package landsepi, provides a new and useful tool to assess the performance of a wide range of deployment options, and helps investigate the effect of landscape, epidemiological and evolutionary parameters. This article describes the model and its parameterisation for rust diseases of cereal crops, caused by fungi of the genus Puccinia. To illustrate the model, we use it to assess the epidemiological and evolutionary potential of the combination of a major gene and different traits of quantitative resistance. The comparison of the four major deployment strategies described above will be the objective of future studies. PMID:29649208

Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.

PubMed

Arts, Isabelle S; Ball, Geneviève; Leverrier, Pauline; Garvis, Steven; Nicolaes, Valérie; Vertommen, Didier; Ize, Bérengère; Tamu Dufe, Veronica; Messens, Joris; Voulhoux, Romé; Collet, Jean-François

2013-12-10

Disulfide bond formation is required for the folding of many bacterial virulence factors. However, whereas the Escherichia coli disulfide bond-forming system is well characterized, not much is known on the pathways that oxidatively fold proteins in pathogenic bacteria. Here, we report the detailed unraveling of the pathway that introduces disulfide bonds in the periplasm of the human pathogen Pseudomonas aeruginosa. The genome of P. aeruginosa uniquely encodes two DsbA proteins (P. aeruginosa DsbA1 [PaDsbA1] and PaDsbA2) and two DsbB proteins (PaDsbB1 and PaDsbB2). We found that PaDsbA1, the primary donor of disulfide bonds to secreted proteins, is maintained oxidized in vivo by both PaDsbB1 and PaDsbB2. In vitro reconstitution of the pathway confirms that both PaDsbB1 and PaDsbB2 shuttle electrons from PaDsbA1 to membrane-bound quinones. Accordingly, deletion of both P. aeruginosa dsbB1 (PadsbB1) and PadsbB2 is required to prevent the folding of several P. aeruginosa virulence factors and to lead to a significant decrease in pathogenicity. Using a high-throughput proteomic approach, we also analyzed the impact of PadsbA1 deletion on the global periplasmic proteome of P. aeruginosa, which allowed us to identify more than 20 new potential substrates of this major oxidoreductase. Finally, we report the biochemical and structural characterization of PaDsbA2, a highly oxidizing oxidoreductase, which seems to be expressed under specific conditions. By fully dissecting the machinery that introduces disulfide bonds in P. aeruginosa, our work opens the way to the design of novel antibacterial molecules able to disarm this pathogen by preventing the proper assembly of its arsenal of virulence factors. The human pathogen Pseudomonas aeruginosa causes life-threatening infections in immunodepressed and cystic fibrosis patients. The emergence of P. aeruginosa strains resistant to all of the available antibacterial agents calls for the urgent development of new antibiotics active against this bacterium. The pathogenic power of P. aeruginosa is mediated by an arsenal of extracellular virulence factors, most of which are stabilized by disulfide bonds. Thus, targeting the machinery that introduces disulfide bonds appears to be a promising strategy to combat P. aeruginosa. Here, we unraveled the oxidative protein folding system of P. aeruginosa in full detail. The system uniquely consists of two membrane proteins that generate disulfide bonds de novo to deliver them to P. aeruginosa DsbA1 (PaDsbA1), a soluble oxidoreductase. PaDsbA1 in turn donates disulfide bonds to secreted proteins, including virulence factors. Disruption of the disulfide bond formation machinery dramatically decreases P. aeruginosa virulence, confirming that disulfide formation systems are valid targets for the design of antimicrobial drugs.

Mapping of SnTox3-Snn3 as a major determinant of field susceptibility to Septoria nodorum leaf blotch in the SHA3/CBRD x Naxos population

USDA-ARS?s Scientific Manuscript database

Parastagonospora nodorum is a necrotrophic pathogen of wheat, causing Septoria nodorum blotch (SNB) affecting both the leaf and glume. P. nodorum is the major leaf blotch pathogen on spring wheat in Norway. Resistance to the disease is quantitative, but several host-specific interactions between nec...

Nutritional modulators of ulcerative colitis: Clinical efficacies and mechanistic view

PubMed Central

Sung, Mi-Kyung; Park, Mi-Young

2013-01-01

Ulcerative colitis (UC) is an inflammation-associated disease of the colon and rectum. The onset and progress of the disease are directly influenced by the nature of the intestinal microflora, the intestinal barrier function, and the immunological responses of the host. The epithelial invasion of pathogenic bacteria due to excess contact and/or barrier dysfunction is related to inflammation mediated by intestinal immune responses. Although the etiology of UC is not clearly understood, recent studies have shown a rising incidence of UC worldwide, and this phenomenon is more prominent in Asian countries and in Asian immigrants in Western countries. The increased prevalence of UC also contributes to an increased risk of developing colorectal cancer. Environmental factors, including changes in dietary habits, have been suggested as major risk factors of UC. A systematic review showed a negative association between UC risk and vegetable intake, whereas total fat, omega-6 fatty acids and meat intake were positively associated with an increased risk of UC. Individual dietary factors and energy balance have been suggested as having important roles in inducing changes in the microbial population and intestinal barrier integrity and in regulating inflammatory immune responses, directly or indirectly. Excess energy intake is now known to increase pathogenic microbial populations. Likewise, the application of appropriate probiotics may reverse the pathogenic progression of the disease. In the meantime, dietary anti-inflammatory compounds, including omega-3 fatty acids and other phytochemicals, may directly suppress inflammatory responses in the course of UC development. In this review, the increased prevalence of UC and its management are interpreted from the standpoint of nutritional modulation to regulate the intestinal microflora population, intestinal epithelium permeability, and inflammatory responses. PMID:23467687

Nutritional modulators of ulcerative colitis: clinical efficacies and mechanistic view.

PubMed

Sung, Mi-Kyung; Park, Mi-Young

2013-02-21

Ulcerative colitis (UC) is an inflammation-associated disease of the colon and rectum. The onset and progress of the disease are directly influenced by the nature of the intestinal microflora, the intestinal barrier function, and the immunological responses of the host. The epithelial invasion of pathogenic bacteria due to excess contact and/or barrier dysfunction is related to inflammation mediated by intestinal immune responses. Although the etiology of UC is not clearly understood, recent studies have shown a rising incidence of UC worldwide, and this phenomenon is more prominent in Asian countries and in Asian immigrants in Western countries. The increased prevalence of UC also contributes to an increased risk of developing colorectal cancer. Environmental factors, including changes in dietary habits, have been suggested as major risk factors of UC. A systematic review showed a negative association between UC risk and vegetable intake, whereas total fat, omega-6 fatty acids and meat intake were positively associated with an increased risk of UC. Individual dietary factors and energy balance have been suggested as having important roles in inducing changes in the microbial population and intestinal barrier integrity and in regulating inflammatory immune responses, directly or indirectly. Excess energy intake is now known to increase pathogenic microbial populations. Likewise, the application of appropriate probiotics may reverse the pathogenic progression of the disease. In the meantime, dietary anti-inflammatory compounds, including omega-3 fatty acids and other phytochemicals, may directly suppress inflammatory responses in the course of UC development. In this review, the increased prevalence of UC and its management are interpreted from the standpoint of nutritional modulation to regulate the intestinal microflora population, intestinal epithelium permeability, and inflammatory responses.

Etiology of Genital Ulcer Disease in Male Patients Attending a Sexually Transmitted Diseases Clinic: First Assessment in Cuba.

PubMed

Noda, Angel A; Blanco, Orestes; Correa, Consuelo; Pérez, Lissette; Kourí, Vivian; Rodríguez, Islay

2016-08-01

Sexually transmitted diseases (STDs) and in particular genital ulcer disease (GUD) have a major impact on morbidity and mortality in developing countries. The World Health Organization recommends the use of syndromic guidelines for the treatment of sexually transmitted infections (STIs) in resource-constrained countries. Surveillance of autochthonous etiologies provides epidemiological information contributing to the prevention and treatment of STIs. We investigated the etiology and factors associated with GUD among male patients attending a STD clinic in Havana, Cuba. Swabs from genital ulcers of 113 male patients, collected from May 2012 to June 2015, were analyzed using PCR for herpes simplex virus types 1 and 2, Treponema pallidum, Haemophilus ducreyi, and Chlamydia trachomatis. We also investigated the clinical and epidemiological characteristics associated with the presence of these pathogens in GUD. At least one of the pathogens was detected in 70% of patients. The occurrence of the pathogens was herpes simplex virus type 2 (HSV-2) (51.3%), T. pallidum (29.2%), and C. trachomatis (1.8%). Co-infections occurred as follows: T. pallidum-HSV-2 (10.6%), C. trachomatis-HSV-2 (0.9%) and C. trachomatis-T. pallidum (0.9%). Herpes simplex virus type 1 and H. ducreyi were not detected. Ages 15 to 40 years, HIV-positive serostatus, and no condom use were significant risk factors for the presence of HSV-2 in genital ulcers. Our preliminary results highlight the predominance of HSV-2 and T. pallidum as the leading GUD etiologies in the study population and identified risk factors associated with HSV-2. This information should help to inform guidelines for better management of GUD in Havana, Cuba.

Using a common commensal bacterium in endangered Takahe as a model to explore pathogen dynamics in isolated wildlife populations.

PubMed

Grange, Zoe L; Gartrell, Brett D; Biggs, Patrick J; Nelson, Nicola J; Marshall, Jonathan C; Howe, Laryssa; Balm, Matthew G M; French, Nigel P

2015-10-01

Predicting and preventing outbreaks of infectious disease in endangered wildlife is problematic without an understanding of the biotic and abiotic factors that influence pathogen transmission and the genetic variation of microorganisms within and between these highly modified host communities. We used a common commensal bacterium, Campylobacter spp., in endangered Takahe (Porphyrio hochstetteri) populations to develop a model with which to study pathogen dynamics in isolated wildlife populations connected through ongoing translocations. Takahe are endemic to New Zealand, where their total population is approximately 230 individuals. Takahe were translocated from a single remnant wild population to multiple offshore and mainland reserves. Several fragmented subpopulations are maintained and connected through regular translocations. We tested 118 Takahe from 8 locations for fecal Campylobacter spp. via culture and DNA extraction and used PCR for species assignment. Factors relating to population connectivity and host life history were explored using multivariate analytical methods to determine associations between host variables and bacterial prevalence. The apparent prevalence of Campylobacter spp. in Takahe was 99%, one of the highest reported in avian populations. Variation in prevalence was evident among Campylobacter species identified. C. sp. nova 1 (90%) colonized the majority of Takahe tested. Prevalence of C. jejuni (38%) and C. coli (24%) was different between Takahe subpopulations, and this difference was associated with factors related to population management, captivity, rearing environment, and the presence of agricultural practices in the location in which birds were sampled. Modeling results of Campylobacter spp. in Takahe metapopulations suggest that anthropogenic management of endangered species within altered environments may have unforeseen effects on microbial exposure, carriage, and disease risk. Translocation of wildlife between locations could have unpredictable consequences including the spread of novel microbes between isolated populations. © 2015 Society for Conservation Biology.

Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-induced oxidation of the Cap1 transcription factor and macrophage escape.

PubMed

Patterson, Miranda J; McKenzie, Christopher G; Smith, Deborah A; da Silva Dantas, Alessandra; Sherston, Sam; Veal, Elizabeth A; Morgan, Brian A; MacCallum, Donna M; Erwig, Lars-Peter; Quinn, Janet

2013-12-20

As Candida albicans is the major fungal pathogen of humans, there is an urgent need to understand how this pathogen evades toxic reactive oxygen species (ROS) generated by the host immune system. A key regulator of antioxidant gene expression, and thus ROS resistance, in C. albicans is the AP-1-like transcription factor Cap1. Despite this, little is known regarding the intracellular signaling mechanisms that underlie the oxidation and activation of Cap1. Therefore, the aims of this study were; (i) to identify the regulatory proteins that govern Cap1 oxidation, and (ii) to investigate the importance of Cap1 oxidation in C. albicans pathogenesis. In response to hydrogen peroxide (H2O2), but not glutathione-depleting/modifying oxidants, Cap1 oxidation, nuclear accumulation, phosphorylation, and Cap1-dependent gene expression, is mediated by a glutathione peroxidase-like enzyme, which we name Gpx3, and an orthologue of the Saccharomyces cerevisiae Yap1 binding protein, Ybp1. In addition, Ybp1 also functions to stabilise Cap1 and this novel function is conserved in S. cerevisiae. C. albicans cells lacking Cap1, Ybp1, or Gpx3, are unable to filament and thus, escape from murine macrophages after phagocytosis, and also display defective virulence in the Galleria mellonella infection model. Ybp1 is required to promote the stability of fungal AP-1-like transcription factors, and Ybp1 and Gpx3 mediated Cap1-dependent oxidative stress responses are essential for the effective killing of macrophages by C. albicans. Activation of Cap1, specifically by H2O2, is a prerequisite for the subsequent filamentation and escape of this fungal pathogen from the macrophage.

Pathogen Decontamination of Food Crop Soil: A Review.

PubMed

Gurtler, Joshua B

2017-09-01

The purpose of this review is to delineate means of decontaminating soil. This information might be used to mitigate soil-associated risks of foodborne pathogens. The majority of the research in the published literature involves inactivation of plant pathogens in soil, i.e., those pathogens harmful to fruit and vegetable production and ornamental plants. Very little has been published regarding the inactivation of foodborne human pathogens in crop soil. Nevertheless, because decontamination techniques for plant pathogens might also be useful methods for eliminating foodborne pathogens, this review also includes inactivation of plant pathogens, with appropriate discussion and comparisons, in the hopes that these methods may one day be validated against foodborne pathogens. Some of the major soil decontamination methods that have been investigated and are covered include chemical decontamination (chemigation), solarization, steaming, biofumigation, bacterial competitive exclusion, torch flaming, microwave treatment, and amendment with biochar. Other innovative means of inactivating foodborne pathogens in soils may be discovered and explored in the future, provided that these techniques are economically feasible in terms of chemicals, equipment, and labor. Food microbiology and food safety researchers should reach out to soil scientists and plant pathologists to create links where they do not currently exist and strengthen relationships where they do exist to take advantage of multidisciplinary skills. In time, agricultural output and the demand for fresh produce will increase. With advances in the sensitivity of pathogen testing and epidemiological tracebacks, the need to mitigate preharvest bacterial contamination of fresh produce will become paramount. Hence, soil decontamination technologies may become more economically feasible and practical in light of increasing the microbial safety of fresh produce.

The Global Acetylome of the Human Pathogen Vibrio cholerae V52 Reveals Lysine Acetylation of Major Transcriptional Regulators

PubMed Central

Jers, Carsten; Ravikumar, Vaishnavi; Lezyk, Mateusz; Sultan, Abida; Sjöling, Åsa; Wai, Sun N.; Mijakovic, Ivan

2018-01-01

Protein lysine acetylation is recognized as an important reversible post translational modification in all domains of life. While its primary roles appear to reside in metabolic processes, lysine acetylation has also been implicated in regulating pathogenesis in bacteria. Several global lysine acetylome analyses have been carried out in various bacteria, but thus far there have been no reports of lysine acetylation taking place in the important human pathogen Vibrio cholerae. In this study, we analyzed the lysine acetylproteome of the human pathogen V. cholerae V52. By applying a combination of immuno-enrichment of acetylated peptides and high resolution mass spectrometry, we identified 3,402 acetylation sites on 1,240 proteins. Of the acetylated proteins, more than half were acetylated on two or more sites. As reported for other bacteria, we observed that many of the acetylated proteins were involved in metabolic and cellular processes and there was an over-representation of acetylated proteins involved in protein synthesis. Of interest, we demonstrated that many global transcription factors such as CRP, H-NS, IHF, Lrp and RpoN as well as transcription factors AphB, TcpP, and PhoB involved in direct regulation of virulence in V. cholerae were acetylated. In conclusion, this is the first global protein lysine acetylome analysis of V. cholerae and should constitute a valuable resource for in-depth studies of the impact of lysine acetylation in pathogenesis and other cellular processes. PMID:29376036

Descriptive epidemiology of infectious gastrointestinal illnesses in Sydney, Australia, 2007-2010.

PubMed

Fletcher, Stephanie; Sibbritt, David; Stark, Damien; Harkness, John; Rawlinson, William; Andresen, David; Van Hal, Sebastian; Merif, Juan; Ellis, John

2015-01-01

There is a lack of information about the prevalence of gastrointestinal illnesses in Australia. Current disease surveillance systems capture only a few pathogens. The aim of this study is to describe the epidemiology of infectious gastrointestinal illnesses in Sydney, Australia. A retrospective cross-sectional study of patients with gastrointestinal symptoms who visited tertiary public hospitals in Sydney was conducted between 2007 and 2010. Patients with diarrhoea or loose stools with an enteric pathogen detected were identified. Demographic, clinical and potential risk factor data were collected from their medical records. Measures of association, descriptive and inferential statistics were analysed. In total, 1722 patients were included in this study. Campylobacter (22.0%) and Clostridium difficile (19.2%) were the most frequently detected pathogens. Stratified analysis showed that rotavirus (22.4%), norovirus (20.7%) and adenovirus (18.1%) mainly affected children under 5 years; older children (5-12 years) were frequently infected with Campylobacter spp. (29.8%) and non-typhoid Salmonella spp. (24.4%); infections with C. difficile increased with age.Campylobacter and non-typhoid Salmonella spp. showed increased incidence in summer months (December to February), while rotavirus infections peaked in the cooler months (June to November). This study revealed that gastrointestinal illness remains a major public health issue in Sydney. Improvement of current disease surveillance and prevention and control measures are required. This study emphasizes the importance of laboratory diagnosis of enteric infections and the need for better clinical data collection to improve management of disease risk factors in the community.

Analysis of host-pathogen modulators of autophagy during Mycobacterium Tuberculosis infection and therapeutic repercussions.

PubMed

Khan, Arshad; Jagannath, Chinnaswamy

2017-09-03

Mycobacterium tuberculosis is one of the most deadly human pathogens known today in modern world, responsible for about 1.5 million deaths annually. Development of TB disease occurs only in 1 out of 10 individuals exposed to the pathogen which indicates that the competent host defense mechanisms exist in majority of the hosts to control the infection. In the last decade, autophagy has emerged as a key host immune defense mechanism against intracellular M. tuberculosis infection. Autophagy has been demonstrated not only as an effective antimicrobial mechanism for the clearance of M. tuberculosis, but the process has also been suggested to prevent excessive inflammation to avoid the adverse effects of infection on host. Nevertheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to compromise the optimal functioning of host autophagic machinery. This review describes an overview of the various host signaling pathways such as pattern recognition receptors, cytokines, nutrient starvation and other cellular stress that have been implicated in induction of autophagy during M. tuberculosis infection. The review also chalk out the complex interplay of several bacterial factors of M. tuberculosis that are known to be involved in compromising autophagy mediated defense of the host. A comprehensive understanding of the interaction of bacterial and host factors at the intersections of autophagic pathways could provide integrative insights for the development of autophagy-based prophylactics and novel therapeutic interventions for TB.

Scoping the Impact of Changes in Population Age-Structure on the Future Burden of Foodborne Disease in The Netherlands, 2020–2060

PubMed Central

Bouwknegt, Martijn; van Pelt, Wilfrid; Havelaar, Arie H.

2013-01-01

A demographic shift towards a larger proportion of elderly in the Dutch population in the coming decades might change foodborne disease incidence and mortality. In the current study we focused on the age-specific changes in the occurrence of foodborne pathogens by combining age-specific demographic forecasts for 10-year periods between 2020 and 2060 with current age-specific infection probabilities for Campylobacter spp., non-typhoidal Salmonella, hepatitis A virus, acquired Toxoplasma gondii and Listeria monocytogenes. Disease incidence rates for the former three pathogens were estimated to change marginally, because increases and decreases in specific age groups cancelled out over all ages. Estimated incidence of reported cases per 100,000 for 2060 mounted to 12 (Salmonella), 51 (Campylobacter), 1.1 (hepatitis A virus) and 2.1 (Toxoplasma). For L. monocytogenes, incidence increased by 45% from 0.41 per 100,000 in 2011 to 0.60 per 100,000. Estimated mortality rates increased two-fold for Salmonella and Campylobacter to 0.5 and 0.7 per 100,000, and increased by 25% for Listeria from 0.06 to 0.08. This straightforward scoping effort does not suggest major changes in incidence and mortality for these food borne pathogens based on changes in de population age-structure as independent factor. Other factors, such as changes in health care systems, social clustering and food processing and preparation, could not be included in the estimates. PMID:23851976

Scoping the impact of changes in population age-structure on the future burden of foodborne disease in the Netherlands, 2020-2060.

PubMed

Bouwknegt, Martijn; van Pelt, Wilfrid; Havelaar, Arie H

2013-07-11

A demographic shift towards a larger proportion of elderly in the Dutch population in the coming decades might change foodborne disease incidence and mortality. In the current study we focused on the age-specific changes in the occurrence of foodborne pathogens by combining age-specific demographic forecasts for 10-year periods between 2020 and 2060 with current age-specific infection probabilities for Campylobacter spp., non-typhoidal Salmonella, hepatitis A virus, acquired Toxoplasma gondii and Listeria monocytogenes. Disease incidence rates for the former three pathogens were estimated to change marginally, because increases and decreases in specific age groups cancelled out over all ages. Estimated incidence of reported cases per 100,000 for 2060 mounted to 12 (Salmonella), 51 (Campylobacter), 1.1 (hepatitis A virus) and 2.1 (Toxoplasma). For L. monocytogenes, incidence increased by 45% from 0.41 per 100,000 in 2011 to 0.60 per 100,000. Estimated mortality rates increased two-fold for Salmonella and Campylobacter to 0.5 and 0.7 per 100,000, and increased by 25% for Listeria from 0.06 to 0.08. This straightforward scoping effort does not suggest major changes in incidence and mortality for these food borne pathogens based on changes in de population age-structure as independent factor. Other factors, such as changes in health care systems, social clustering and food processing and preparation, could not be included in the estimates.

Transmission of foodborne zoonotic pathogens to riparian areas by grazing sheep

PubMed Central

Sutherland, Sara J.; Gray, Jeffrey T.; Menzies, Paula I.; Hook, Sarah E.; Millman, Suzanne T.

2009-01-01

The objective of this study was to determine if sheep grazing near riparian areas on pasture in Ontario are an important risk factor for the contamination of water with specific foodborne pathogens. Ten Ontario sheep farms were visited weekly for 12 wk during the summer of 2005. Samples of feces, soil, and water were collected and analyzed for the presence of Escherichia coli O157:H7, Salmonella spp., Campylobacter jejuni and C. coli, and Yersinia enterocolitica, by bacteriological identification and polymerase chain reaction (PCR). The data was analyzed as repeated measures over time using mixed models. No samples were positive for Salmonella, and no samples were confirmed positive for E. coli O157:H7 after PCR. Levels of Campylobacter were highest in the soil, but did not differ between soil where sheep grazed or camped and roadside soil that had never been grazed (P = 0.85). Levels of Yersinia were highest in water samples and were higher in soil where sheep had access (P = 0.01). The prevalence of positive Campylobacter and Yersinia samples were not associated with locations where sheep spent more time (Campylobacter P = 0.46, Yersinia P = 0.99). There was no effect of stocking density on the prevalence of Campylobacter (P = 0.30), but as the stocking density increased the levels of Yersinia increased (P = 0.04). It was concluded that although sheep transmit Yersinia to their environment, pastured sheep flocks are not major risk factors for the transmission of zoonotic pathogens into water. PMID:19436581

The role and regulation of catalase in respiratory tract opportunistic bacterial pathogens.

PubMed

Eason, Mia M; Fan, Xin

2014-09-01

Respiratory tract bacterial pathogens are the etiologic agents of a variety of illnesses. The ability of these bacteria to cause disease is imparted through survival within the host and avoidance of pathogen clearance by the immune system. Respiratory tract pathogens are continually bombarded by reactive oxygen species (ROS), which may be produced by competing bacteria, normal metabolic function, or host immunological responses. In order to survive and proliferate, bacteria have adapted defense mechanisms to circumvent the effects of ROS. Bacteria employ the use of anti-oxidant enzymes, catalases and catalase-peroxidases, to relieve the effects of the oxidative stressors to which they are continually exposed. The decomposition of ROS has been shown to provide favorable conditions in which respiratory tract opportunistic bacterial pathogens such as Haemophilus influenzae, Mycobacterium tuberculosis, Legionella pneumophila, and Neisseria meningitidis are able to withstand exposure to highly reactive molecules and yet survive. Bacteria possessing mutations in the catalase gene have a decreased survival rate, yet may be able to compensate for the lack of catalatic activity if peroxidatic activity is present. An incomplete knowledge of the mechanisms by which catalase and catalase-peroxidases are regulated still persists, however, in some bacterial species, a regulatory factor known as OxyR has been shown to either up-regulate or down-regulate catalase gene expression. Yet, more research is still needed to increase the knowledge base in relation to this enzyme class. As with this review, we focus on major respiratory tract opportunistic bacterial pathogens in order to elucidate the function and regulation of catalases. The importance of the research could lead to the development of novel treatments against respiratory bacterial infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prevalence, characteristics and correlates of enteric pathogenic protozoa in drinking water sources in Molyko and Bomaka, Cameroon: a cross-sectional study.

PubMed

Nsoh, Fuh Anold; Wung, Buh Amos; Atashili, Julius; Benjamin, Pokam Thumamo; Marvlyn, Eba; Ivo, Keumami Katte; Nguedia, Assob Jules Clément

2016-11-08

Access to potable water remains a major challenge particularly in resource-limited settings. Although the potential contaminants of water are varied, enteric pathogenic protozoa are known to cause waterborne diseases greatly. This study aimed at investigating the prevalence, characteristics and correlates of enteric pathogenic protozoa in drinking water sources in Buea, Cameroon. A cross-sectional study was conducted using 155 water samples collected from various drinking sources (boreholes, springs, taps and wells). Each sample was subjected to physicochemical examinations (pH, turbidity, odour and sliminess) and parasitological analysis (wet mount, modified Ziehl-Neelsen stain) to determine the presence of enteric pathogenic protozoa. A data collection tool was used to note characteristics of collected samples and the data was analysed using EPI-INFO Version 3.5.3. The overall prevalence of enteric pathogenic protozoa in water sources was 62.6 %. Eight species of enteric protozoa were observed with Cryptosporidium parvum being the most predominant (45.8 %). Spring water was the most contaminated source with enteric protozoa (85.7 %) while pipe borne water had all eight species of protozoa identified. A pH of 6 was the only significant factor associated with the prevalence of these pathogens in water sources. The prevalence of enteric protozoa in water sources in Molyko and Bomaka is high, spring water is the most contaminated water source and Cryptosporidium parvum is the most common protozoa contaminating water. A water pH of 6 is associated to the prevalence of protozoa. Community members need to be educated to treat water before drinking to avoid infection by enteric protozoa in water and further studies with larger samples of water need to be conducted to find other correlates of the presence of protozoa in water.

The Relationship between the Structure of the Tick-Borne Encephalitis Virus Strains and Their Pathogenic Properties

PubMed Central

Belikov, Sergei I.; Kondratov, Ilya G.; Potapova, Ulyana V.; Leonova, Galina N.

2014-01-01

Tick-borne encephalitis virus (TBEV) is transmitted to vertebrates by taiga or forest ticks through bites, inducing disease of variable severity. The reasons underlying these differences in the severity of the disease are unknown. In order to identify genetic factors affecting the pathogenicity of virus strains, we have sequenced and compared the complete genomes of 34 Far-Eastern subtype (FE) TBEV strains isolated from patients with different disease severity (Primorye, the Russian Far East). We analyzed the complete genomes of 11 human pathogenic strains isolated from the brains of dead patients with the encephalitic form of the disease (Efd), 4 strains from the blood of patients with the febrile form of TBE (Ffd), and 19 strains from patients with the subclinical form of TBE (Sfd). On the phylogenetic tree, pathogenic Efd strains formed two clusters containing the prototype strains, Senzhang and Sofjin, respectively. Sfd strains formed a third separate cluster, including the Oshima strain. The strains that caused the febrile form of the disease did not form a separate cluster. In the viral proteins, we found 198 positions with at least one amino acid residue substitution, of which only 17 amino acid residue substitutions were correlated with the variable pathogenicity of these strains in humans and they authentically differed between the groups. We considered the role of each amino acid substitution and assumed that the deletion of 111 amino acids in the capsid protein in combination with the amino acid substitutions R16K and S45F in the NS3 protease may affect the budding process of viral particles. These changes may be the major reason for the diminished pathogenicity of TBEV strains. We recommend Sfd strains for testing as attenuation vaccine candidates. PMID:24740396

Risks Posed by Reston, the Forgotten Ebolavirus

PubMed Central

Cantoni, Diego; Hamlet, Arran; Michaelis, Martin; Wass, Mark N.

2016-01-01

ABSTRACT Out of the five members of the Ebolavirus family, four cause life-threatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans. Amino acid sequence differences between RESTV and the other Ebolaviruses are found in all nine Ebolavirus proteins, though no one residue appears sufficient to confer pathogenicity. Changes in the glycoprotein contribute to differences in Ebolavirus pathogenicity but are not sufficient to confer pathogenicity on their own. Similarly, differences in VP24 and VP35 affect viral immune evasion and are associated with changes in human pathogenicity. A recent in silico analysis systematically determined the functional consequences of sequence variations between RESTV and human-pathogenic Ebolaviruses. Multiple positions in VP24 were differently conserved between RESTV and the other Ebolaviruses and may alter human pathogenicity. In conclusion, the factors that determine the pathogenicity of Ebolaviruses in humans remain insufficiently understood. An improved understanding of these pathogenicity-determining factors is of crucial importance for disease prevention and for the early detection of emergent and potentially human-pathogenic RESTVs. PMID:28066813

Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

DOE PAGES

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; ...

2015-10-12

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

PubMed Central

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; Cabelli, Diane E.; Bruns, Cami K.; Belzer, Carol A.; Gorringe, Andrew R.; Langford, Paul R.; Tabatabai, Louisa B.; Kroll, J. Simon; Tainer, John A.

2015-01-01

ABSTRACT Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. PMID:26459556

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus.

PubMed

Pratt, Ashley J; DiDonato, Michael; Shin, David S; Cabelli, Diane E; Bruns, Cami K; Belzer, Carol A; Gorringe, Andrew R; Langford, Paul R; Tabatabai, Louisa B; Kroll, J Simon; Tainer, John A; Getzoff, Elizabeth D

2015-12-01

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

Integrated proteomics, genomics, metabolomics approaches reveal oxalic acid as pathogenicity factor in Tilletia indica inciting Karnal bunt disease of wheat.

PubMed

Pandey, Vishakha; Singh, Manoj; Pandey, Dinesh; Kumar, Anil

2018-05-18

Tilletia indica incites Karnal bunt (KB) disease in wheat. To date, no KB resistant wheat cultivar could be developed due to non-availability of potential biomarkers related to pathogenicity/virulence for screening of resistant wheat genotypes. The present study was carried out to compare the proteomes of T. indica highly (TiK) and low (TiP) virulent isolates. Twenty one protein spots consistently observed as up-regulated/differential in the TiK proteome were selected for identification by MALDI-TOF/TOF. Identified sequences showed homology with fungal proteins playing essential role in plant infection and pathogen survival, including stress response, adhesion, fungal penetration, invasion, colonization, degradation of host cell wall, signal transduction pathway. These results were integrated with T. indica genome sequence for identification of homologs of candidate pathogenicity/virulence related proteins. Protein identified in TiK isolate as malate dehydrogenase that converts malate to oxaloacetate which is precursor of oxalic acid. Oxalic acid is key pathogenicity factor in phytopathogenic fungi. These results were validated by GC-MS based metabolic profiling of T. indica isolates indicating that oxalic acid was exclusively identified in TiK isolate. Thus, integrated omics approaches leads to identification of pathogenicity/virulence factor(s) that would provide insights into pathogenic mechanisms of fungi and aid in devising effective disease management strategies.

PATHOGENIC MICROORGANISMS AND THEIR FATE ON/IN THE ENVIRONMENT

EPA Science Inventory

Major sources of human and animal pathogens in the environment originate from animal feeding operations, decentralized wastewater treatment systems (e.g., septic tanks), wastewater treatment plants, and sewage sludges (biosolids).

Single-molecule analysis of the major glycopolymers of pathogenic and non-pathogenic yeast cells

NASA Astrophysics Data System (ADS)

El-Kirat-Chatel, Sofiane; Beaussart, Audrey; Alsteens, David; Sarazin, Aurore; Jouault, Thierry; Dufrêne, Yves F.

2013-05-01

Most microbes are coated with carbohydrates that show remarkable structural variability and play a crucial role in mediating microbial-host interactions. Understanding the functions of cell wall glycoconjugates requires detailed knowledge of their molecular organization, diversity and heterogeneity. Here we use atomic force microscopy (AFM) with tips bearing specific probes (lectins, antibodies) to analyze the major glycopolymers of pathogenic and non-pathogenic yeast cells at molecular resolution. We show that non-ubiquitous β-1,2-mannans are largely exposed on the surface of native cells from pathogenic Candida albicans and C. glabrata, the former species displaying the highest glycopolymer density and extensions. We also find that chitin, a major component of the inner layer of the yeast cell wall, is much more abundant in C. albicans. These differences in molecular properties, further supported by flow cytometry measurements, may play an important role in strengthening cell wall mechanics and immune interactions. This study demonstrates that single-molecule AFM, combined with immunological and fluorescence methods, is a powerful platform in fungal glycobiology for probing the density, distribution and extension of specific cell wall glycoconjugates. In nanomedicine, we anticipate that this new form of AFM-based nanoglycobiology will contribute to the development of sugar-based drugs, immunotherapeutics, vaccines and diagnostics.

Establishment of Stable, Cell-Mediated Immunity that Makes "Susceptible" Mice Resistant to Leishmania major

NASA Astrophysics Data System (ADS)

Bretscher, Peter A.; Wei, Guojian; Menon, Juthika N.; Bielefeldt-Ohmann, Helle

1992-07-01

Cell-mediated, but not antibody-mediated, immune responses protect humans against certain pathogens that produce chronic diseases such as leishmaniasis. Effective vaccination against such pathogens must therefore produce an immunological "imprint" so that stable, cell-mediated immunity is induced in all individuals after natural infection. BALB/c mice "innately susceptible" to Leishmania major produce antibodies after substantial infection. In the present study, "susceptible" mice injected with a small number of parasites mounted a cell-mediated response and acquired resistance to a larger, normally pathogenic, challenge. This vaccination strategy may be applicable in diseases in which protection is dependent on cell-mediated immunity.

Network biology discovers pathogen contact points in host protein-protein interactomes.

PubMed

Ahmed, Hadia; Howton, T C; Sun, Yali; Weinberger, Natascha; Belkhadir, Youssef; Mukhtar, M Shahid

2018-06-13

In all organisms, major biological processes are controlled by complex protein-protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1 MAIN ). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1 MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSI LRR ) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.

[Risk factors for Pseudomonas aeruginosa infections, resistant to carbapenem].

PubMed

Ghibu, Laura; Miftode, Egidia; Teodor, Andra; Bejan, Codrina; Dorobăţ, Carmen Mihaela

2010-01-01

Since their introduction in clinical practice,carbapenems have been among the most powerful antibiotics for treating serious infections cased by Gram-negative nosocomial pathogens, including Pseudomonas aeruginosa. The emergence of betalactamases with carbapenem-hydrolyzing activity is of major clinical concern. Pseudomonas aeruginosa is a leading cause of nosocomial infection. Risk factors for colonization with carbapenems-resistant Pseudomonas in hospital are: history of P. aeruginosa infection or colonization within the previous year, (length of hospital stay, being bedridden or in the ICU, mechanical ventilation, malignant disease, and history of chronic obstructive pulmonary disease have all been identified as independent risk factors for MDR P. aeruginosa infection. Long-term-care facilities are also reservoirs of resistant bacteria. Risk factors for colonization of LTCF residents with resistant bacteria included age > 86 years, antibiotic treatment in the previous 3 months, indwelling devices, chronic obstructive pulmonary disease, physical disability, and the particular LTCF unit.

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

PubMed Central

Menon, S.; Timms, P.; Allan, J. A.; Alexander, K.; Rombauts, L.; Horner, P.; Keltz, M.; Hocking, J.

2015-01-01

SUMMARY Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden. PMID:26310245

Pathogen prevalence and abundance in honey bee colonies involved in almond pollination.

PubMed

Cavigli, Ian; Daughenbaugh, Katie F; Martin, Madison; Lerch, Michael; Banner, Katie; Garcia, Emma; Brutscher, Laura M; Flenniken, Michelle L

Honey bees are important pollinators of agricultural crops. Since 2006, US beekeepers have experienced high annual honey bee colony losses, which may be attributed to multiple abiotic and biotic factors, including pathogens. However, the relative importance of these factors has not been fully elucidated. To identify the most prevalent pathogens and investigate the relationship between colony strength and health, we assessed pathogen occurrence, prevalence, and abundance in Western US honey bee colonies involved in almond pollination. The most prevalent pathogens were Black queen cell virus (BQCV), Lake Sinai virus 2 (LSV2), Sacbrood virus (SBV), Nosema ceranae , and trypanosomatids. Our results indicated that pathogen prevalence and abundance were associated with both sampling date and beekeeping operation, that prevalence was highest in honey bee samples obtained immediately after almond pollination, and that weak colonies had a greater mean pathogen prevalence than strong colonies.

Parameter estimation and sensitivity analysis in an agent-based model of Leishmania major infection

PubMed Central

Jones, Douglas E.; Dorman, Karin S.

2009-01-01

Computer models of disease take a systems biology approach toward understanding host-pathogen interactions. In particular, data driven computer model calibration is the basis for inference of immunological and pathogen parameters, assessment of model validity, and comparison between alternative models of immune or pathogen behavior. In this paper we describe the calibration and analysis of an agent-based model of Leishmania major infection. A model of macrophage loss following uptake of necrotic tissue is proposed to explain macrophage depletion following peak infection. Using Gaussian processes to approximate the computer code, we perform a sensitivity analysis to identify important parameters and to characterize their influence on the simulated infection. The analysis indicates that increasing growth rate can favor or suppress pathogen loads, depending on the infection stage and the pathogen’s ability to avoid detection. Subsequent calibration of the model against previously published biological observations suggests that L. major has a relatively slow growth rate and can replicate for an extended period of time before damaging the host cell. PMID:19837088

Screening of In Vivo Activated Genes in Enterococcus faecalis during Insect and Mouse Infections and Growth in Urine

PubMed Central

Hanin, Aurelie; Sava, Irina; Bao, YinYin; Huebner, Johannes; Hartke, Axel; Auffray, Yanick; Sauvageot, Nicolas

2010-01-01

Enterococcus faecalis is part of the commensal microbiota of humans and its main habitat is the gastrointestinal tract. Although harmless in healthy individuals, E. faecalis has emerged as a major cause of nosocomial infections. In order to better understand the transformation of a harmless commensal into a life-threatening pathogen, we developed a Recombination-based In Vivo Expression Technology for E. faecalis. Two R-IVET systems with different levels of sensitivity have been constructed in a E. faecalis V583 derivative strain and tested in the insect model Galleria mellonella, during growth in urine, in a mouse bacteremia and in a mouse peritonitis model. Our combined results led to the identification of 81 in vivo activated genes. Among them, the ef_3196/7 operon was shown to be strongly induced in the insect host model. Deletion of this operonic structure demonstrated that this two-component system was essential to the E. faecalis pathogenic potential in Galleria. Gene ef_0377, induced in insect and mammalian models, has also been further analyzed and it has been demonstrated that this ankyrin-encoding gene was also involved in E. faecalis virulence. Thus these R-IVET screenings led to the identification of new E. faecalis factors implied in in vivo persistence and pathogenic potential of this opportunistic pathogen. PMID:20686694

Sorption of pathogens during sub-surface drip irrigation with wastewater

NASA Astrophysics Data System (ADS)

Levi, Laillach; Gillerman Gillerman, Leonid; Kalavrouziotis, Ioannis; Oron, Gideon

2017-04-01

Water scarcity continues to be one of the major threats to human survival in many regions worldwide, such as Africa, the Mediterranean Basin, the State of California in the US. Due to a mixture of factors such as population growth, reduction in water resources availability and higher demand for high quality waters in these regions these countries face water shortage issues that stem from overuse, extensive extraction of groundwater, and frequent drought events. In addition, there are increases in environmental and health awareness that have led to intensive efforts in the treatment and reuse of nonconventional water sources, mainly wastewater and greywater. One approach to water shortages issues is to use wastewater as means to close the gap between supply and demand. However, the need to treat wastewater and to disinfect it forces additional economic burden on the users, primarily for agricultural irrigation. A possible solution might be to use the soil as a sorbent for the contained pathogens. Under sub-surface drip irrigation, not allowing the wastewater to reach the soil surface, the pathogens will remain in the soil. It was as well shown in field experiments that the opening size of roots will not allow pathogens to penetrate into the plants. Additional advantages such as water saving, protection of the pipe systems and others are also important. Field experiments in commercial fields just emphasize the main advantages of sub-surface drip irrigation.

Isolation and Identification of Putative Protein Substrates of the AAA+ Molecular Chaperone ClpB from the Pathogenic Spirochaete Leptospira interrogans.

PubMed

Krajewska, Joanna; Arent, Zbigniew; Zolkiewski, Michal; Kędzierska-Mieszkowska, Sabina

2018-04-18

Bacterial ClpB is an ATP-dependent Hsp100 chaperone that reactivates aggregated proteins in cooperation with the DnaK chaperone system and promotes survival of bacteria under stress conditions. A large number of publications also indicate that ClpB supports the virulence of bacteria, including a pathogenic spirochaete Leptospira interrogans responsible for leptospirosis in both animals and humans. However, the exact role of ClpB in bacterial pathogenicity remains poorly characterized. It can be assumed that ClpB, due to its role as the molecular chaperone, mediates refolding of essential bacterial proteins, including the known virulence factors, which may become prone to aggregation under infection-induced stresses. In this study, we identified putative substrates of ClpB from L. interrogans (ClpB Li ). For this purpose, we used a proteomic approach combining the ClpB-Trap affinity pull-down assays, Liquid chromatography-tandem mass spectrometry (LC-MS-MS/MS), and bioinformatics analyses. Most of the identified proteins were enzymes predominantly associated with major metabolic pathways like the tricarboxylic acid (TCA) cycle, glycolysis–gluconeogenesis and amino acid and fatty acid metabolism. Based on our proteomic study, we suggest that ClpB can support the virulence of L. interrogans by protecting the conformational integrity and catalytic activity of multiple metabolic enzymes, thus maintaining energy homeostasis in pathogen cells.

Disturbance in forest ecosystems caused by pathogens and insects

Treesearch

Philip M. Wargo; Philip M. Wargo

1995-01-01

Pathogens and insects are major driving forces of processes in forested ecosystems. Disturbances caused by them are as intimately involved in ecosystem dynamics as the more sudden and obvious abiotic disturbances, for example, those caused by wind or fire. However, because pathogens and insects are selective and may affect only one or several related species of...

Bacteremias in liver transplant recipients: shift toward gram-negative bacteria as predominant pathogens.

PubMed

Singh, Nina; Wagener, Marilyn M; Obman, Asia; Cacciarelli, Thomas V; de Vera, Michael E; Gayowski, Timothy

2004-07-01

During the 1990s, gram-positive bacteria emerged as major pathogens after liver transplantation. We sought to determine whether the pathogens associated with bacteremias in liver transplant recipients have changed. Patients included 233 liver transplant recipients transplanted between 1989 and 2003. The proportion of all infections due to bacteremias increased significantly over time (P <.0001). Of other major infections, a trend toward a decrease in fungal infections (P =.089) and a significant decrease in cytomegalovirus (CMV) disease (P =.0004) were documented. Whereas the proportion of bacteremias due to gram-negatives increased from 25% in the period of 1989-1993 to 51.8% in 1998-03, that of gram-positive bacteria decreased from 75% in the period of 1989-93 to 48.2% in the period of 1998-2003. Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent pathogens in bacteremic patients. The incidence of bacteremias due to MRSA and Pseudomonas aeruginosa has remained unchanged (P <.20); however, that due to enteric gram-negative bacteria, particularly Klebsiella pneumoniae has increased (P =.02). Klebsiella pneumoniae isolates in the current quartile were not clonally related. In conclusion, bacteremias as a proportion of all infections in liver transplant recipients have increased significantly over time, due in part to a decline in infections due to other major pathogens, e.g., fungi, primarily Candida species, and CMV. Gram-negative bacteria have emerged as predominant pathogens in bacteremic liver transplant recipients.

Tropical environments, human activities, and the transmission of infectious diseases.

PubMed

Sattenspiel, L

2000-01-01

Throughout recent history, the tropical regions of the world have been affected more severely by infectious diseases than the temperate world. Much of the success of infectious diseases in that region is due to both biological and environmental factors that encourage high levels of biodiversity in hosts, vectors, and pathogens, and social factors that compromise efforts to control diseases. Several of these factors are described. Discussion then shifts to specific types of host-pathogen relationships. The most important of these in the tropics is the relationship between humans, a pathogen, and a vector that carries the pathogen from one human to another. Mosquitoes are the vector responsible for the transmission of many vector-borne human diseases. Characteristics of mosquito-human interactions are described, including cultural behaviors humans have developed that both increase the chances of transmission and help to limit that transmission. The transmission of water-borne diseases, fecal-oral transmission, zoonotic diseases, respiratory illnesses, and sexually transmitted diseases are also discussed. Attention is paid to how diseases with these modes of transmission differ in characteristics and importance in tropical human populations compared to those in temperate regions. Following this general discussion, three case studies are presented in some detail. The diseases chosen for the case studies include cholera, lymphatic filariasis, and dracunculiasis (guinea worm). These three case studies taken together provide examples of the diversity of human host-pathogen interactions as well as ways that human activities have both promoted their spread and helped to control them. The transmission of all three diseases is related to the nature and quality of water sources. The transmission of cholera, a water-borne disease, is related to sanitation practices, physical characteristics of the environment such as temperature and humidity, and modern shipping practices. Lymphatic filariasis, a mosquito-borne disease, has increased in frequency in parts of Africa in recent decades as a consequence of large-scale agricultural development projects that have shifted the nature and quantity of water sources and potential mosquito breeding sites. Dracunculiasis is transmitted by a small crustacean that contaminates sources of drinking water. Because its transmission can be prevented by a simple change in human behavior, filtering all water with a small piece of cloth before using it, dracunculiasis has been the focus of a major eradication effort that is near success.

RNA-seq Transcriptome Response of Flax (Linum usitatissimum L.) to the Pathogenic Fungus Fusarium oxysporum f. sp. lini

PubMed Central

Galindo-González, Leonardo; Deyholos, Michael K.

2016-01-01

Fusarium oxysporum f. sp. lini is a hemibiotrophic fungus that causes wilt in flax. Along with rust, fusarium wilt has become an important factor in flax production worldwide. Resistant flax cultivars have been used to manage the disease, but the resistance varies, depending on the interactions between specific cultivars and isolates of the pathogen. This interaction has a strong molecular basis, but no genomic information is available on how the plant responds to attempted infection, to inform breeding programs on potential candidate genes to evaluate or improve resistance across cultivars. In the current study, disease progression in two flax cultivars [Crop Development Center (CDC) Bethune and Lutea], showed earlier disease symptoms and higher susceptibility in the later cultivar. Chitinase gene expression was also divergent and demonstrated and earlier molecular response in Lutea. The most resistant cultivar (CDC Bethune) was used for a full RNA-seq transcriptome study through a time course at 2, 4, 8, and 18 days post-inoculation (DPI). While over 100 genes were significantly differentially expressed at both 4 and 8 DPI, the broadest deployment of plant defense responses was evident at 18 DPI with transcripts of more than 1,000 genes responding to the treatment. These genes evidenced a reception and transduction of pathogen signals, a large transcriptional reprogramming, induction of hormone signaling, activation of pathogenesis-related genes, and changes in secondary metabolism. Among these, several key genes that consistently appear in studies of plant-pathogen interactions, had increased transcript abundance in our study, and constitute suitable candidates for resistance breeding programs. These included: an induced RPMI-induced protein kinase; transcription factors WRKY3, WRKY70, WRKY75, MYB113, and MYB108; the ethylene response factors ERF1 and ERF14; two genes involved in auxin/glucosinolate precursor synthesis (CYP79B2 and CYP79B3); the flavonoid-related enzymes chalcone synthase, dihydroflavonol reductase and multiple anthocyanidin synthases; and a peroxidase implicated in lignin formation (PRX52). Additionally, regulation of some genes indicated potential pathogen manipulation to facilitate infection; these included four disease resistance proteins that were repressed, indole acetic acid amido/amino hydrolases which were upregulated, activated expansins and glucanases, amino acid transporters and aquaporins, and finally, repression of major latex proteins. PMID:27933082

A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System

PubMed Central

Coudray-Meunier, Coralie; Fraisse, Audrey; Martin-Latil, Sandra; Delannoy, Sabine; Fach, Patrick; Perelle, Sylvie

2016-01-01

Human enteric viruses are recognized as the main causes of food- and waterborne diseases worldwide. Sensitive and quantitative detection of human enteric viruses is typically achieved through quantitative RT-PCR (RT-qPCR). A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The performance of high-throughput PCR methods was investigated for detecting 19 human pathogenic viruses and two main process controls used in food virology. The conventional real-time PCR system was compared to the RT-dPCR and RT-qPCR array. Based on the number of genome copies calculated by spectrophotometry, sensitivity was found to be slightly better with RT-qPCR than with RT-dPCR for 14 viruses by a factor range of from 0.3 to 1.6 log10. Conversely, sensitivity was better with RT-dPCR than with RT-qPCR for seven viruses by a factor range of from 0.10 to 1.40 log10. Interestingly, the number of genome copies determined by RT-dPCR was always from 1 to 2 log10 lower than the expected copy number calculated by RT-qPCR standard curve. The sensitivity of the RT-qPCR and RT-qPCR array assays was found to be similar for two viruses, and better with RT-qPCR than with RT-qPCR array for eighteen viruses by a factor range of from 0.7 to 3.0 log10. Conversely, sensitivity was only 0.30 log10 better with the RT-qPCR array than with conventional RT-qPCR assays for norovirus GIV detection. Finally, the RT-qPCR array and RT-dPCR assays were successfully used together to screen clinical samples and quantify pathogenic viruses. Additionally, this method made it possible to identify co-infection in clinical samples. In conclusion, given the rapidity and potential for large numbers of viral targets, this nanofluidic RT-qPCR assay should have a major impact on human pathogenic virus surveillance and outbreak investigations and is likely to be of benefit to public health. PMID:26824897

RNA-seq Transcriptome Response of Flax (Linum usitatissimum L.) to the Pathogenic Fungus Fusarium oxysporum f. sp. lini.

PubMed

Galindo-González, Leonardo; Deyholos, Michael K

2016-01-01

Fusarium oxysporum f. sp. lini is a hemibiotrophic fungus that causes wilt in flax. Along with rust, fusarium wilt has become an important factor in flax production worldwide. Resistant flax cultivars have been used to manage the disease, but the resistance varies, depending on the interactions between specific cultivars and isolates of the pathogen. This interaction has a strong molecular basis, but no genomic information is available on how the plant responds to attempted infection, to inform breeding programs on potential candidate genes to evaluate or improve resistance across cultivars. In the current study, disease progression in two flax cultivars [Crop Development Center (CDC) Bethune and Lutea], showed earlier disease symptoms and higher susceptibility in the later cultivar. Chitinase gene expression was also divergent and demonstrated and earlier molecular response in Lutea. The most resistant cultivar (CDC Bethune) was used for a full RNA-seq transcriptome study through a time course at 2, 4, 8, and 18 days post-inoculation (DPI). While over 100 genes were significantly differentially expressed at both 4 and 8 DPI, the broadest deployment of plant defense responses was evident at 18 DPI with transcripts of more than 1,000 genes responding to the treatment. These genes evidenced a reception and transduction of pathogen signals, a large transcriptional reprogramming, induction of hormone signaling, activation of pathogenesis-related genes, and changes in secondary metabolism. Among these, several key genes that consistently appear in studies of plant-pathogen interactions, had increased transcript abundance in our study, and constitute suitable candidates for resistance breeding programs. These included: an induced R PMI-induced protein kinase; transcription factors WRKY3, WRKY70, WRKY75, MYB113 , and MYB108 ; the ethylene response factors ERF1 and ERF14 ; two genes involved in auxin/glucosinolate precursor synthesis ( CYP79B2 and CYP79B3 ); the flavonoid-related enzymes chalcone synthase, dihydroflavonol reductase and multiple anthocyanidin synthases; and a peroxidase implicated in lignin formation ( PRX52 ). Additionally, regulation of some genes indicated potential pathogen manipulation to facilitate infection; these included four disease resistance proteins that were repressed, indole acetic acid amido/amino hydrolases which were upregulated, activated expansins and glucanases, amino acid transporters and aquaporins, and finally, repression of major latex proteins.

The graphene oxide contradictory effects against human pathogens

NASA Astrophysics Data System (ADS)

Palmieri, Valentina; Carmela Lauriola, Maria; Ciasca, Gabriele; Conti, Claudio; De Spirito, Marco; Papi, Massimiliano

2017-04-01

Standing out as the new wonder bidimensional material, graphene oxide (GO) has aroused an exceptional interest in biomedical research by holding promise for being the antibacterial of future. First, GO possesses a specific interaction with microorganisms combined with a mild toxicity for human cells. Additionally, its antibacterial action seems to be directed to multiple targets in pathogens, causing both membranes mechanical injury and oxidative stress. Lastly, compared to other carbon materials, GO has easy and low-cost processing and is environment-friendly. This remarkable specificity and multi-targeting antibacterial activity come at a time when antibiotic resistance represents the major health challenge. Unfortunately, a comprehensive framework to understand how to effectively utilize this material against microorganisms is still lacking. In the last decade, several groups tried to define the mechanisms of interaction between GO flakes and pathogens but conflicting results have been reported. This review is focused on all the contradictions of GO antimicrobial properties in solution. Flake size, incubation protocol, time of exposure and species considered are examples of factors influencing results. These parameters will be summarized and analyzed with the aim of defining the causes of contradictions, to allow fast GO clinical application.

Identification of an antibacterial compound, benzylideneacetone, from Xenorhabdus nematophila against major plant-pathogenic bacteria.

PubMed

Ji, Dongjin; Yi, Youngkeun; Kang, Ga-Hwa; Choi, Yong-Hwa; Kim, Pankyung; Baek, Nam-In; Kim, Yonggyun

2004-10-15

An entomopathogenic bacterium, Xenorhabdus nematophila, is known to have potent antibiotic activities to maintain monoxenic condition in its insect host for effective pathogenesis and ultimately for optimal development of its nematode symbiont, Steinernema carpocapsae. In this study we assess its antibacterial activity against plant-pathogenic bacteria and identify its unknown antibiotics. The bacterial culture broth had significant antibacterial activity that increased with development of the bacteria and reached its maximum at the stationary growth phase. The antibiotic activities were significant against five plant-pathogenic bacterial strains: Agrobacterium vitis, Pectobacterium carotovorum subsp. atrosepticum, P. carotovorum subsp. carotovorum, Pseudomonas syringae pv. tabaci, and Ralstonia solanacearum. The antibacterial factors were extracted with butanol and fractionated using column chromatography with the eluents of different hydrophobic intensities. Two active antibacterial subfractions were purified, and the higher active fraction was further fractionated and identified as a single compound of benzylideneacetone (trans-4-phenyl-3-buten-2-one). With heat stability, the synthetic compound showed equivalent antibiotic activity and spectrum to the purified compound. This study reports a new antibiotic compound synthesized by X. nematophila, which is a monoterpenoid compound and active against some Gram-negative bacteria.

Metacommunity and phylogenetic structure determine wildlife and zoonotic infectious disease patterns in time and space.

PubMed

Suzán, Gerardo; García-Peña, Gabriel E; Castro-Arellano, Ivan; Rico, Oscar; Rubio, André V; Tolsá, María J; Roche, Benjamin; Hosseini, Parviez R; Rizzoli, Annapaola; Murray, Kris A; Zambrana-Torrelio, Carlos; Vittecoq, Marion; Bailly, Xavier; Aguirre, A Alonso; Daszak, Peter; Prieur-Richard, Anne-Helene; Mills, James N; Guégan, Jean-Francois

2015-02-01

The potential for disease transmission at the interface of wildlife, domestic animals and humans has become a major concern for public health and conservation biology. Research in this subject is commonly conducted at local scales while the regional context is neglected. We argue that prevalence of infection at local and regional levels is influenced by three mechanisms occurring at the landscape level in a metacommunity context. First, (1) dispersal, colonization, and extinction of pathogens, reservoir or vector hosts, and nonreservoir hosts, may be due to stochastic and niche-based processes, thus determining distribution of all species, and then their potential interactions, across local communities (metacommunity structure). Second, (2) anthropogenic processes may drive environmental filtering of hosts, nonhosts, and pathogens. Finally, (3) phylogenetic diversity relative to reservoir or vector host(s), within and between local communities may facilitate pathogen persistence and circulation. Using a metacommunity approach, public heath scientists may better evaluate the factors that predispose certain times and places for the origin and emergence of infectious diseases. The multidisciplinary approach we describe fits within a comprehensive One Health and Ecohealth framework addressing zoonotic infectious disease outbreaks and their relationship to their hosts, other animals, humans, and the environment.

Environmental Attributes to Respiratory Diseases of Small Ruminants

PubMed Central

Rahal, Anu; Ahmad, Abul Hasan; Prakash, Atul; Mandil, Rajesh; Kumar, Aruna T.

2014-01-01

Respiratory diseases are the major disease crisis in small ruminants. A number of pathogenic microorganisms have been implicated in the development of respiratory disease but the importance of environmental factors in the initiation and progress of disease can never be overemphasized. They irritate the respiratory tree producing stress in the microenvironment causing a decline in the immune status of the small ruminants and thereby assisting bacterial, viral, and parasitic infections to break down the tissue defense barriers. Environmental pollutants cause acute or chronic reactions as they deposit on the alveolar surface which are characterized by inflammation or fibrosis and the formation of transitory or persistent tissue manifestation. Some of the effects of exposures may be immediate, whereas others may not be evident for many decades. Although the disease development can be portrayed as three sets of two-way communications (pathogen-environment, host-environment, and host-pathogen), the interactions are highly variable. Moreover, the environmental scenario is never static; new compounds are introduced daily making a precise evaluation of the disease burden almost impossible. The present review presents a detailed overview of these interactions and the ultimate effect on the respiratory health of sheep and goat. PMID:24782941

Characterization of a novel NADP+-dependent D-arabitol dehydrogenase from the plant pathogen Uromyces fabae

PubMed Central

2005-01-01

We have identified and characterized a novel NADP+-dependent D-arabitol dehydrogenase and the corresponding gene from the rust fungus Uromyces fabae, a biotrophic plant pathogen on broad bean (Vicia faba). The new enzyme was termed ARD1p (D-arabitol dehydrogenase 1). It recognizes D-arabitol and mannitol as substrates in the forward reaction, and D-xylulose, D-ribulose and D-fructose as substrates in the reverse reaction. Co-factor specificity was restricted to NADP(H). Kinetic data for the major substrates and co-factors are presented. A detailed analysis of the organization and expression pattern of the ARD1 gene are also given. Immunocytological data indicate a localization of the gene product predominantly in haustoria, the feeding structures of these fungi. Analyses of metabolite levels during pathogenesis indicate that the D-arabitol concentration rises dramatically as infection progresses, and D-arabitol was shown in an in vitro system to be capable of quenching reactive oxygen species involved in host plant defence reactions. ARD1p may therefore play an important role in carbohydrate metabolism and in establishing and/or maintaining the biotrophic interaction in U. fabae. PMID:15796718

Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in mice.

PubMed

Sun, Hongmin; Xu, Yuanxi; Sitkiewicz, Izabela; Ma, Yibao; Wang, Xixi; Yestrepsky, Bryan D; Huang, Yuping; Lapadatescu, Martian C; Larsen, Martha J; Larsen, Scott D; Musser, James M; Ginsburg, David

2012-02-28

The widespread occurrence of antibiotic resistance among human pathogens is a major public health problem. Conventional antibiotics typically target bacterial killing or growth inhibition, resulting in strong selection for the development of antibiotic resistance. Alternative therapeutic approaches targeting microbial pathogenicity without inhibiting growth might minimize selection for resistant organisms. Compounds inhibiting gene expression of streptokinase (SK), a critical group A streptococcal (GAS) virulence factor, were identified through a high-throughput, growth-based screen on a library of 55,000 small molecules. The lead compound [Center for Chemical Genomics 2979 (CCG-2979)] and an analog (CCG-102487) were confirmed to also inhibit the production of active SK protein. Microarray analysis of GAS grown in the presence of CCG-102487 showed down-regulation of a number of important virulence factors in addition to SK, suggesting disruption of a general virulence gene regulatory network. CCG-2979 and CCG-102487 both enhanced granulocyte phagocytosis and killing of GAS in an in vitro assay, and CCG-2979 also protected mice from GAS-induced mortality in vivo. These data suggest that the class of compounds represented by CCG-2979 may be of therapeutic value for the treatment of GAS and potentially other gram-positive infections in humans.

Proteins, pathogens, and failure at the composite-tooth interface.

PubMed

Spencer, P; Ye, Q; Misra, A; Goncalves, S E P; Laurence, J S

2014-12-01

In the United States, composites accounted for nearly 70% of the 173.2 million composite and amalgam restorations placed in 2006 (Kingman et al., 2012), and it is likely that the use of composite will continue to increase as dentists phase out dental amalgam. This trend is not, however, without consequences. The failure rate of composite restorations is double that of amalgam (Ferracane, 2013). Composite restorations accumulate more biofilm, experience more secondary decay, and require more frequent replacement. In vivo biodegradation of the adhesive bond at the composite-tooth interface is a major contributor to the cascade of events leading to restoration failure. Binding by proteins, particularly gp340, from the salivary pellicle leads to biofilm attachment, which accelerates degradation of the interfacial bond and demineralization of the tooth by recruiting the pioneer bacterium Streptococcus mutans to the surface. Bacterial production of lactic acid lowers the pH of the oral microenvironment, erodes hydroxyapatite in enamel and dentin, and promotes hydrolysis of the adhesive. Secreted esterases further hydrolyze the adhesive polymer, exposing the soft underlying collagenous dentinal matrix and allowing further infiltration by the pathogenic biofilm. Manifold approaches are being pursued to increase the longevity of composite dental restorations based on the major contributing factors responsible for degradation. The key material and biological components and the interactions involved in the destructive processes, including recent advances in understanding the structural and molecular basis of biofilm recruitment, are described in this review. Innovative strategies to mitigate these pathogenic effects and slow deterioration are discussed. © International & American Associations for Dental Research.

Relationship between Salmonella infection, shedding and serology in fattening pigs in low-moderate prevalence areas.

PubMed

San Román, B; Garrido, V; Sánchez, S; Martínez-Ballesteros, I; Garaizar, J; Mainar-Jaime, R C; Migura-Garcia, L; Grilló, M J

2018-04-27

Salmonella is a major foodborne pathogen causing important zoonosis worldwide. Pigs asymptomatically infected in mesenteric lymph nodes (MLN) can be intermittent shedders of the pathogen through faeces, being considered a major source of human infections. European baseline studies of fattening pig salmonellosis are based on Salmonella detection in MLN. This work studies the relationship between Salmonella infection in MLN and intestinal content (IC) shedding at slaughter and the relationship between the presence of the pathogen and the serologic status at farm level. Mean Salmonella prevalence in the selected pigs (vertically integrated production system of Navarra, Spain) was 7.2% in MLN, 8.4% in IC and 9.6% in serum samples. In this low-moderate prevalence context, poor concordance was found between MLN infection and shedding at slaughter and between bacteriology and serology. In fact, most of shedders were found uninfected in MLN (83%) or carrying different Salmonella strains in MLN and in IC (90%). The most prevalent Salmonellae were Typhimurium resistant to ACSSuT ± Nx or ASSuT antibiotic families, more frequently found invading the MLN (70%) than in IC (33.9%). Multivariable analysis revealed that risk factors associated with the presence of Salmonella in MLN or in IC were different, mainly related either to good hygiene practices or to water and feed control, respectively. Overall, in this prevalence context, detection of Salmonella in MLN is an unreliable predictor of faecal shedding at abattoir, indicating that subclinical infections in fattening pigs MLN could have limited relevance in the IC shedding. © 2018 Blackwell Verlag GmbH.

Design and Simulation of a MEMS Structure for Electrophoretic and Dielectrophoretic Separation of Particles by Contactless Electrodes

NASA Technical Reports Server (NTRS)

Shaw, Harry C.

2007-01-01

Rapid identification of pathogenic bacterial species is an important factor in combating public health problems such as E. coli contamination. Food and waterborne pathogens account for sickness in 76 million people annually (CDC). Diarrheagenic E. coli is a major source of gastrointestinal illness. Severe sepsis and Septicemia within the hospital environment are also major problems. 75 1,000 cases annually with a 30-50% mortality rate (Crit Care Med, July '01, Vol. 29, 1303-10). Patient risks run the continuum from fever to organ failure and death. Misdiagnosis or inappropriate treatment increases mortality. There exists a need for rapid screening of samples for identification of pathogenic species (Certain E. coli strains are essential for health). Critical to the identification process is the ability to isolate analytes of interest rapidly. This poster discusses novel devices for the separation of particles on the basis of the dielectric properties, mass and surface charge characteristics is presented. Existing designs involve contact between electrode surfaces and analyte medium resulting in contamination of the electrode bearing elements Two different device designs using different bulk micromachining MEMS processes (PolyMUMPS and a PyrexBIGold electrode design) are presented. These designs cover a range of particle sizes from small molecules through eucaryotic cells. The application of separation of bacteria is discussed in detail. Simulation data for electrostatic and microfluidic characteristics are provided. Detailed design characteristics and physical features of the as fabricated PolyMUMPS design are provided. Analysis of the simulation data relative to the expected performance of the devices will be provided and subsequent conclusions discussed.

Listeria monocytogenes endophthalmitis - case report and review of risk factors and treatment outcomes.

PubMed

Bajor, Anna; Luhr, Anke; Brockmann, Dorothee; Suerbaum, Sebastian; Framme, Carsten; Sedlacek, Ludwig

2016-07-16

The majority of cases of endophthalmitis are caused by exogenous pathogens; only 5-10 % are of endogenous origin. One cause of these rare cases of endogenous endophthalmitis is Listeria monocytogenes. Twenty-six cases of endophthalmitis due to this pathogen have been published over the last twenty years. The aim of this review is to summarize the main risk factors and common clinical findings of endogenous endophthalmitis due to Listeria monocytogenes. We report on a 62-year-old female presenting with a sterile hypopyon iritis with secondary glaucoma and an underlying rheumatoid disease. In microbiological analysis we identified Listeria monocytogenes. Further we searched through all published cases for typical signs, risk factors, details of medical and surgical treatment and outcome of endogenous endophthalmitis due to this rare pathogen. Ocular symptoms in almost all of these published cases included pain, redness of the eye, and decreased vision. Main clinical features included elevated intraocular pressure and fibrinous anterior chamber reaction, as well as a dark hypopyon. While the infection is typically spread endogenously, neither an exogenous nor endogenous source of infection could be identified in most cases. Immunocompromised patients are at higher risk of being infected than immunocompetent patients. The clinical course of endophthalmitis caused by Listeria monocytogenes had different visual outcomes. In some cases, the infection led to enucleation, blindness, or strong visual loss, whereas most patients showed a tendency of visual improvement during therapy. Early diagnosis and treatment initiation are crucial factors in the outcome of endogenous endophthalmitis caused by Listeria monocytogenes. This possible differential diagnosis should be kept in mind while treating patients with presumable sterile hypopyon and anterior uveitis having a high intraocular pressure. A bacterial source should be considered with a prompt initiation of systemic antibiotic treatment, mainly in immunocompromised patients, who develop endogenous anterior uveitis. An appropriate microbiological sampling is essential to detect atypical microorganisms and to choose an effective antibiotic treatment.

Clinical and epidemiological profiles including meteorological factors of low respiratory tract infection due to human rhinovirus in hospitalized children.

PubMed

Yan, Yongdong; Huang, Li; Wang, Meijuan; Wang, Yuqing; Ji, Wei; Zhu, Canhong; Chen, Zhengrong

2017-03-07

Lower respiratory tract infection (LRTI) is a major cause of morbidity and mortality in children. Human rhinovirus (HRV) is confirmed to be associated with pediatric lower respiratory tract infection. Seasonal and meteorological factors may play a key role in the epidemiology of HRV. The purposes of this study were to investigate the frequency, seasonal distribution, and clinical characteristics of hospitalized children with LRTI caused by HRVs. In addition, associations between incidence of HRVs and meteorological factors in a subtropical region of China were discussed. Hospitalized children <14 years old admitted to the Respiratory Department of the Children's Hospital, which is affiliated to Soochow University, between January 1, 2013 and December 31, 2015, were enrolled in this study. Multi-pathogens were detected in nasopharyngeal aspirate samples. Meanwhile, meteorological factors were recorded. The average incidence of HRVs infection was 11.4% (707/6194) and 240 cases of which were co-infection cases with other pathogens. Children with co-infection presented more frequent fever and tachypnea compared to children infected with HRVs only (both P < 0.05). Among 707 HRV positive children, the mean age was 23.2 months (range 1 to 140 months). Among all respiratory infections, the highest incidence of HRVs cases occurred in children age 13-36 months old (15.1%, 203/1341). Of all 228 HRV cases in 2014, 85 cases (37.3%) were HRV-C positive. HRVs and HRV-C infection occurred throughout the year during the study period, although a higher incidence was observed in summer and autumn seasons. HRVs or HRV-C incidence in hospitalized children with LRTI was associated with the monthly mean temperature (both P < 0.05). HRV was one of the most common viral pathogen detected in hospitalized children with LRTI at the Children's Hospital of Suzhou, China, and had its own seasonal distribution including HRV-C, which was partly caused by temperature.

Contamination with bacterial zoonotic pathogen genes in U.S. streams influenced by varying types of animal agriculture

USGS Publications Warehouse

Haack, Sheridan K.; Duris, Joseph W.; Kolpin, Dana W.; Focazio, Michael J.; Meyer, Michael T.; Johnson, Heather E.; Oster, Ryan J.; Foreman, William T.

2016-01-01

Animal waste, stream water, and streambed sediment from 19 small (< 32 km2) watersheds in 12 U.S. states having either no major animal agriculture (control, n = 4), or predominantly beef (n = 4), dairy (n = 3), swine (n = 5), or poultry (n = 3) were tested for: 1) cholesterol, coprostanol, estrone, and fecal indicator bacteria (FIB) concentrations, and 2) shiga-toxin producing and enterotoxigenic Escherichia coli, Salmonella, Campylobacter, and pathogenic and vancomycin-resistant enterococci by polymerase chain reaction (PCR) on enrichments, and/or direct quantitative PCR. Pathogen genes were most frequently detected in dairy wastes, followed by beef, swine and poultry wastes in that order; there was only one detection of an animal-source-specific pathogen gene (stx1) in any water or sediment sample in any control watershed. Post-rainfall pathogen gene numbers in stream water were significantly correlated with FIB, cholesterol and coprostanol concentrations, and were most highly correlated in dairy watershed samples collected from 3 different states. Although collected across multiple states and ecoregions, animal-waste gene profiles were distinctive via discriminant analysis. Stream water gene profiles could also be discriminated by the watershed animal type. Although pathogen genes were not abundant in stream water or streambed samples, PCR on enrichments indicated that many genes were from viable organisms, including several (shiga-toxin producing or enterotoxigenic E. coli, Salmonella, vancomycin-resistant enterococci) that could potentially affect either human or animal health. Pathogen gene numbers and types in stream water samples were influenced most by animal type, by local factors such as whether animals had stream access, and by the amount of local rainfall, and not by studied watershed soil or physical characteristics. Our results indicated that stream water in small agricultural U.S. watersheds was susceptible to pathogen gene inputs under typical agricultural practices and environmental conditions. Pathogen gene profiles may offer the potential to address both source of, and risks associated with, fecal pollution.

Species-specific chitin-binding module 18 expansion in the amphibian pathogen Batrachochytrium dendrobatidis.

PubMed

Abramyan, John; Stajich, Jason E

2012-01-01

Batrachochytrium dendrobatidis is the causative agent of chytridiomycosis, which is considered one of the driving forces behind the worldwide decline in populations of amphibians. As a member of the phylum Chytridiomycota, B. dendrobatidis has diverged significantly to emerge as the only pathogen of adult vertebrates. Such shifts in lifestyle are generally accompanied by various degrees of genomic modifications, yet neither its mode of pathogenicity nor any factors associated with it have ever been identified. Presented here is the identification and characterization of a unique expansion of the carbohydrate-binding module family 18 (CBM18), specific to B. dendrobatidis. CBM (chitin-binding module) expansions have been likened to the evolution of pathogenicity in a variety of fungus species, making this expanded group a prime candidate for the identification of potential pathogenicity factors. Furthermore, the CBM18 expansions are confined to three categories of genes, each having been previously implicated in host-pathogen interactions. These correlations highlight this specific domain expansion as a potential key player in the mode of pathogenicity in this unique fungus. The expansion of CBM18 in B. dendrobatidis is exceptional in its size and diversity compared to other pathogenic species of fungi, making this genomic feature unique in an evolutionary context as well as in pathogenicity. Amphibian populations are declining worldwide at an unprecedented rate. Although various factors are thought to contribute to this phenomenon, chytridiomycosis has been identified as one of the leading causes. This deadly fungal disease is cause by Batrachochytrium dendrobatidis, a chytrid fungus species unique in its pathogenicity and, furthermore, its specificity to amphibians. Despite more than two decades of research, the biology of this fungus species and its deadly interaction with amphibians had been notoriously difficult to unravel. Due to the alarming rate of worldwide spread and associated decline in amphibian populations, it is imperative to incorporate novel genomic and genetic techniques into the study of this species. In this study, we present the first reported potential pathogenicity factors in B. dendrobatidis. In silico studies such as this allow us to identify putative targets for more specific molecular analyses, furthering our hope for the control of this pathogen.

Repression of fungal plant pathogens and fungal-related contaminants: Selected ecosystem services by soil fauna communities in agroecosystems

NASA Astrophysics Data System (ADS)

Meyer-Wolfarth, Friederike; Schrader, Stefan; Oldenburg, Elisabeth; Brunotte, Joachim; Weinert, Joachim

2017-04-01

In agroecosystems soil-borne fungal plant diseases are major yield-limiting factors which are difficult to control. Fungal plant pathogens, like Fusarium species, survive as a saprophyte in infected tissue like crop residues and endanger the health of the following crop by increasing the infection risk for specific plant diseases. In infected plant organs, these pathogens are able to produce mycotoxins. Mycotoxins like deoxynivalenol (DON) persist during storage, are heat resistant and of major concern for human and animal health after consumption of contaminated food and feed, respectively. Among fungivorous soil organisms, there are representatives of the soil fauna which are obviously antagonistic to a Fusarium infection and the contamination with mycotoxins. Specific members of the soil macro-, meso-, and microfauna provide a wide range of ecosystem services including the stimulation of decomposition processes which may result in the regulation of plant pathogens and the degradation of environmental contaminants. Investigations under laboratory conditions and in field were conducted to assess the functional linkage between soil faunal communities and plant pathogenic fungi (Fusarium culmorum). The aim was to examine if Fusarium biomass and the content of its mycotoxin DON decrease substantially in the presence of soil fauna (earthworms: Lumbricus terrestris, collembolans: Folsomia candida and nematodes: Aphelenchoides saprophilus) in a commercial cropping system managed with conservation tillage located in Northern Germany. The results of our investigations pointed out that the degradation performance of the introduced soil fauna must be considered as an important contribution to the biodegradation of fungal plant diseases and fungal-related contaminants. Different size classes within functional groups and the traits of keystone species appear to be significant for soil function and the provision of ecosystem services as in particular L. terrestris revealed to be the driver of the degradation process. Thus, earthworms contribute to a sustainable control of fungal pathogens like Fusarium and its mycotoxins in wheat straw by reducing the risk of plant diseases and environmental pollution as ecosystem services. Further studies are planned within the EU-project SoilMan under the BiodivERsA network. In context of the suppression of fungal plant pathogens and the detoxification of their mycotoxins by soil organisms in agroecosystems it is hypothesised that (1) processes related to services or disservices are induced and directed by abundance and activity of functional groups of soil biota; (2) dynamics and interaction in the soil biota community control ecosystem function and services.

ORD/NERL CURRENT VRARS RESEARCH

EPA Science Inventory

Virulence is the degree of pathogenicity of a microorganism and virulence factors are the components of an organism that contribute to virulence. Identifying microorganisms using known virulence factors is one method used by microbiologists to distinguish pathogenic isolates fro...

Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species.

PubMed

Zhong, Zhenhui; Norvienyeku, Justice; Chen, Meilian; Bao, Jiandong; Lin, Lianyu; Chen, Liqiong; Lin, Yahong; Wu, Xiaoxian; Cai, Zena; Zhang, Qi; Lin, Xiaoye; Hong, Yonghe; Huang, Jun; Xu, Linghong; Zhang, Honghong; Chen, Long; Tang, Wei; Zheng, Huakun; Chen, Xiaofeng; Wang, Yanli; Lian, Bi; Zhang, Liangsheng; Tang, Haibao; Lu, Guodong; Ebbole, Daniel J; Wang, Baohua; Wang, Zonghua

2016-05-06

One major threat to global food security that requires immediate attention, is the increasing incidence of host shift and host expansion in growing number of pathogenic fungi and emergence of new pathogens. The threat is more alarming because, yield quality and quantity improvement efforts are encouraging the cultivation of uniform plants with low genetic diversity that are increasingly susceptible to emerging pathogens. However, the influence of host genome differentiation on pathogen genome differentiation and its contribution to emergence and adaptability is still obscure. Here, we compared genome sequence of 6 isolates of Magnaporthe species obtained from three different host plants. We demonstrated the evolutionary relationship between Magnaporthe species and the influence of host differentiation on pathogens. Phylogenetic analysis showed that evolution of pathogen directly corresponds with host divergence, suggesting that host-pathogen interaction has led to co-evolution. Furthermore, we identified an asymmetric selection pressure on Magnaporthe species. Oryza sativa-infecting isolates showed higher directional selection from host and subsequently tends to lower the genetic diversity in its genome. We concluded that, frequent gene loss or gain, new transposon acquisition and sequence divergence are host adaptability mechanisms for Magnaporthe species, and this coevolution processes is greatly driven by directional selection from host plants.

Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species

PubMed Central

Zhong, Zhenhui; Norvienyeku, Justice; Chen, Meilian; Bao, Jiandong; Lin, Lianyu; Chen, Liqiong; Lin, Yahong; Wu, Xiaoxian; Cai, Zena; Zhang, Qi; Lin, Xiaoye; Hong, Yonghe; Huang, Jun; Xu, Linghong; Zhang, Honghong; Chen, Long; Tang, Wei; Zheng, Huakun; Chen, Xiaofeng; Wang, Yanli; Lian, Bi; Zhang, Liangsheng; Tang, Haibao; Lu, Guodong; Ebbole, Daniel J.; Wang, Baohua; Wang, Zonghua

2016-01-01

One major threat to global food security that requires immediate attention, is the increasing incidence of host shift and host expansion in growing number of pathogenic fungi and emergence of new pathogens. The threat is more alarming because, yield quality and quantity improvement efforts are encouraging the cultivation of uniform plants with low genetic diversity that are increasingly susceptible to emerging pathogens. However, the influence of host genome differentiation on pathogen genome differentiation and its contribution to emergence and adaptability is still obscure. Here, we compared genome sequence of 6 isolates of Magnaporthe species obtained from three different host plants. We demonstrated the evolutionary relationship between Magnaporthe species and the influence of host differentiation on pathogens. Phylogenetic analysis showed that evolution of pathogen directly corresponds with host divergence, suggesting that host-pathogen interaction has led to co-evolution. Furthermore, we identified an asymmetric selection pressure on Magnaporthe species. Oryza sativa-infecting isolates showed higher directional selection from host and subsequently tends to lower the genetic diversity in its genome. We concluded that, frequent gene loss or gain, new transposon acquisition and sequence divergence are host adaptability mechanisms for Magnaporthe species, and this coevolution processes is greatly driven by directional selection from host plants. PMID:27151494

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens.

PubMed

Storisteanu, Daniel M L; Pocock, Joanna M; Cowburn, Andrew S; Juss, Jatinder K; Nadesalingam, Angalee; Nizet, Victor; Chilvers, Edwin R

2017-04-01

The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone- and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that "NET evasion" might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion-inhibition, degradation, and resistance-with particular reference to common respiratory pathogens.

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens

PubMed Central

Storisteanu, Daniel M. L.; Pocock, Joanna M.; Cowburn, Andrew S.; Juss, Jatinder K.; Nadesalingam, Angalee; Nizet, Victor

2017-01-01

The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone- and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that “NET evasion” might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion—inhibition, degradation, and resistance—with particular reference to common respiratory pathogens. PMID:27854516

Arabidopsis PECTIN METHYLESTERASEs Contribute to Immunity against Pseudomonas syringae1[C][W][OPEN

PubMed Central

Bethke, Gerit; Grundman, Rachael E.; Sreekanta, Suma; Truman, William; Katagiri, Fumiaki; Glazebrook, Jane

2014-01-01

Pectins, major components of dicot cell walls, are synthesized in a heavily methylesterified form in the Golgi and are partially deesterified by pectin methylesterases (PMEs) upon export to the cell wall. PME activity is important for the virulence of the necrotrophic fungal pathogen Botrytis cinerea. Here, the roles of Arabidopsis PMEs in pattern-triggered immunity and immune responses to the necrotrophic fungus Alternaria brassicicola and the bacterial hemibiotroph Pseudomonas syringae pv maculicola ES4326 (Pma ES4326) were studied. Plant PME activity increased during pattern-triggered immunity and after inoculation with either pathogen. The increase of PME activity in response to pathogen treatment was concomitant with a decrease in pectin methylesterification. The pathogen-induced PME activity did not require salicylic acid or ethylene signaling, but was dependent on jasmonic acid signaling. In the case of induction by A. brassicicola, the ethylene response factor, but not the MYC2 branch of jasmonic acid signaling, contributed to induction of PME activity, whereas in the case of induction by Pma ES4326, both branches contributed. There are 66 PME genes in Arabidopsis, suggesting extensive genetic redundancy. Nevertheless, selected pme single, double, triple and quadruple mutants allowed significantly more growth of Pma ES4326 than wild-type plants, indicating a role of PMEs in resistance to this pathogen. No decreases in total PME activity were detected in these pme mutants, suggesting that the determinant of immunity is not total PME activity; rather, it is some specific effect of PMEs such as changes in the pattern of pectin methylesterification. PMID:24367018

Rhamnolipids from non-pathogenic Burkholderia thailandensis E264: Physicochemical characterization, antimicrobial and antibiofilm efficacy against oral hygiene related pathogens.

PubMed

Elshikh, Mohamed; Funston, Scott; Chebbi, Alif; Ahmed, Syed; Marchant, Roger; Banat, Ibrahim M

2017-05-25

Biosurfactants are naturally occurring surface active compounds that have mainly been exploited for environmental applications and consumer products, with their biomedical efficacy an emerging area of research. Rhamnolipids area major group of biosurfactants that have been reported for their antimicrobial and antibiofilm efficacy. One of the main limiting factors for scaled up production and downstream applications of rhamnolipids is the fact that they are predominantly produced from the opportunistic pathogen Pseudomonas aeruginosa. In this article, we have reported the production and characterisation of long chain rhamnolipids from non-pathogenic Burkholderia thailandensis E264 (ATCC 700388). We have also investigated the antibacterial and antibiofilm properties of these rhamnolipids against some oral pathogens (Streptococcus oralis, Actinomyces naeslundii, Neisseria mucosa and Streptococcus sanguinis), important for oral health and hygiene. Treating these bacteria with different concentrations of long chain rhamnolipids resulted in a reduction of 3-4 log of bacterial viability, placing these rhamnolipids close to being classified as biocidal. Investigating long chain rhamnolipid efficacy as antibiofilm agents for prospective oral-related applications revealed good potency against oral-bacteria biofilms in a co-incubation experiments, in a pre-coated surface format, in disrupting immature biofilms and has shown excellent combination effect with Lauryl Sodium Sulphate which resulted in a drastic decrease in its minimal inhibitory concentration against different bacteria. Investigating the rhamnolipid permeabilization effect along with their ability to induce the formation of reactive oxygen species has shed light on the mechanism through which inhibition/killing of bacteria may occur. Copyright © 2017 Elsevier B.V. All rights reserved.

A Unique Set of the Burkholderia Collagen-Like Proteins Provides Insight into Pathogenesis, Genome Evolution and Niche Adaptation, and Infection Detection.

PubMed

Bachert, Beth A; Choi, Soo J; Snyder, Anna K; Rio, Rita V M; Durney, Brandon C; Holland, Lisa A; Amemiya, Kei; Welkos, Susan L; Bozue, Joel A; Cote, Christopher K; Berisio, Rita; Lukomski, Slawomir

2015-01-01

Burkholderia pseudomallei and Burkholderia mallei, classified as category B priority pathogens, are significant human and animal pathogens that are highly infectious and broad-spectrum antibiotic resistant. Currently, the pathogenicity mechanisms utilized by Burkholderia are not fully understood, and correct diagnosis of B. pseudomallei and B. mallei infection remains a challenge due to limited detection methods. Here, we provide a comprehensive analysis of a set of 13 novel Burkholderia collagen-like proteins (Bucl) that were identified among B. pseudomallei and B. mallei select agents. We infer that several Bucl proteins participate in pathogenesis based on their noncollagenous domains that are associated with the components of a type III secretion apparatus and membrane transport systems. Homology modeling of the outer membrane efflux domain of Bucl8 points to a role in multi-drug resistance. We determined that bucl genes are widespread in B. pseudomallei and B. mallei; Fischer's exact test and Cramer's V2 values indicate that the majority of bucl genes are highly associated with these pathogenic species versus nonpathogenic B. thailandensis. We designed a bucl-based quantitative PCR assay which was able to detect B. pseudomallei infection in a mouse with a detection limit of 50 CFU. Finally, chromosomal mapping and phylogenetic analysis of bucl loci revealed considerable genomic plasticity and adaptation of Burkholderia spp. to host and environmental niches. In this study, we identified a large set of phylogenetically unrelated bucl genes commonly found in Burkholderia select agents, encoding predicted pathogenicity factors, detection targets, and vaccine candidates.

A Unique Set of the Burkholderia Collagen-Like Proteins Provides Insight into Pathogenesis, Genome Evolution and Niche Adaptation, and Infection Detection

PubMed Central

Bachert, Beth A.; Choi, Soo J.; Snyder, Anna K.; Rio, Rita V. M.; Durney, Brandon C.; Holland, Lisa A.; Amemiya, Kei; Welkos, Susan L.; Bozue, Joel A.; Cote, Christopher K.; Berisio, Rita; Lukomski, Slawomir

2015-01-01

Burkholderia pseudomallei and Burkholderia mallei, classified as category B priority pathogens, are significant human and animal pathogens that are highly infectious and broad-spectrum antibiotic resistant. Currently, the pathogenicity mechanisms utilized by Burkholderia are not fully understood, and correct diagnosis of B. pseudomallei and B. mallei infection remains a challenge due to limited detection methods. Here, we provide a comprehensive analysis of a set of 13 novel Burkholderia collagen-like proteins (Bucl) that were identified among B. pseudomallei and B. mallei select agents. We infer that several Bucl proteins participate in pathogenesis based on their noncollagenous domains that are associated with the components of a type III secretion apparatus and membrane transport systems. Homology modeling of the outer membrane efflux domain of Bucl8 points to a role in multi-drug resistance. We determined that bucl genes are widespread in B. pseudomallei and B. mallei; Fischer’s exact test and Cramer’s V2 values indicate that the majority of bucl genes are highly associated with these pathogenic species versus nonpathogenic B. thailandensis. We designed a bucl-based quantitative PCR assay which was able to detect B. pseudomallei infection in a mouse with a detection limit of 50 CFU. Finally, chromosomal mapping and phylogenetic analysis of bucl loci revealed considerable genomic plasticity and adaptation of Burkholderia spp. to host and environmental niches. In this study, we identified a large set of phylogenetically unrelated bucl genes commonly found in Burkholderia select agents, encoding predicted pathogenicity factors, detection targets, and vaccine candidates. PMID:26356298

The development of pathogen resistance in Daphnia magna: implications for disease spread in age-structured populations.

PubMed

Garbutt, Jennie S; O'Donoghue, Anna J P; McTaggart, Seanna J; Wilson, Philip J; Little, Tom J

2014-11-01

Immunity in vertebrates is well established to develop with time, but the ontogeny of defence in invertebrates is markedly less studied. Yet, age-specific capacity for defence against pathogens, coupled with age structure in populations, has widespread implications for disease spread. Thus, we sought to determine the susceptibility of hosts of different ages in an experimental invertebrate host-pathogen system. In a series of experiments, we show that the ability of Daphnia magna to resist its natural bacterial pathogen Pasteuria ramosa changes with host age. Clonal differences make it difficult to draw general conclusions, but the majority of observations indicate that resistance increases early in the life of D. magna, consistent with the idea that the defence system develops with time. Immediately following this, at about the time when a daphnid would be most heavily investing in reproduction, resistance tends to decline. Because many ecological factors influence the age structure of Daphnia populations, our results highlight a broad mechanism by which ecological context can affect disease epidemiology. We also show that a previously observed protective effect of restricted maternal food persists throughout the entire juvenile period, and that the protective effect of prior treatment with a small dose of the pathogen ('priming') persists for 7 days, observations that reinforce the idea that immunity in D. magna can change over time. Together, our experiments lead us to conclude that invertebrate defence capabilities have an ontogeny that merits consideration with respect to both their immune systems and the epidemic spread of infection. © 2014. Published by The Company of Biologists Ltd.

The development of pathogen resistance in Daphnia magna: implications for disease spread in age-structured populations

PubMed Central

Garbutt, Jennie S.; O'Donoghue, Anna J. P.; McTaggart, Seanna J.; Wilson, Philip J.; Little, Tom J.

2014-01-01

Immunity in vertebrates is well established to develop with time, but the ontogeny of defence in invertebrates is markedly less studied. Yet, age-specific capacity for defence against pathogens, coupled with age structure in populations, has widespread implications for disease spread. Thus, we sought to determine the susceptibility of hosts of different ages in an experimental invertebrate host–pathogen system. In a series of experiments, we show that the ability of Daphnia magna to resist its natural bacterial pathogen Pasteuria ramosa changes with host age. Clonal differences make it difficult to draw general conclusions, but the majority of observations indicate that resistance increases early in the life of D. magna, consistent with the idea that the defence system develops with time. Immediately following this, at about the time when a daphnid would be most heavily investing in reproduction, resistance tends to decline. Because many ecological factors influence the age structure of Daphnia populations, our results highlight a broad mechanism by which ecological context can affect disease epidemiology. We also show that a previously observed protective effect of restricted maternal food persists throughout the entire juvenile period, and that the protective effect of prior treatment with a small dose of the pathogen (‘priming’) persists for 7 days, observations that reinforce the idea that immunity in D. magna can change over time. Together, our experiments lead us to conclude that invertebrate defence capabilities have an ontogeny that merits consideration with respect to both their immune systems and the epidemic spread of infection. PMID:25214486

A systematic review and meta-analysis of the epidemiology of pathogenic Escherichia coli of calves and the role of calves as reservoirs for human pathogenic E. coli.

PubMed

Kolenda, Rafał; Burdukiewicz, Michał; Schierack, Peter

2015-01-01

Escherichia coli bacteria are the most common causes of diarrhea and septicemia in calves. Moreover, calves form a major reservoir for transmission of pathogenic E. coli to humans. Systematic reviews and meta-analyses of publications on E. coli as calf pathogens and the role of calves as reservoir have not been done so far. We reviewed studies between 1951 and 2013 reporting the presence of virulence associated factors (VAFs) in calf E. coli and extracted the following information: year(s) and country of sampling, animal number, health status, isolate number, VAF prevalence, serotypes, diagnostic methods, and biological assays. The prevalence of VAFs or E. coli pathotypes was compared between healthy and diarrheic animals and was analyzed for time courses. Together, 106 papers with 25,982 E. coli isolates from 27 countries tested for VAFs were included. F5, F17, and F41 fimbriae and heat-stable enterotoxin (ST) - VAFs of enterotoxigenic E. coli (ETEC) were significantly associated with calf diarrhea. On the contrary, ETEC VAF F4 fimbriae and heat-labile enterotoxin as well as enteropathogenic (EPEC), Shiga toxin-producing (STEC), and enterohemorrhagic E. coli (EHEC) were not associated with diarrhea. The prevalence increased overtime for ST-positive isolates, but decreased for F5- and STEC-positive isolates. Our study provides useful information about the history of scientific investigations performed in this domain so far, and helps to define etiological agents of calf disease, and to evaluate calves as reservoir hosts for human pathogenic E. coli.

Inhibition of Cronobacter sakazakii Virulence Factors by Citral.

PubMed

Shi, Chao; Sun, Yi; Liu, Zhiyuan; Guo, Du; Sun, Huihui; Sun, Zheng; Chen, Shan; Zhang, Wenting; Wen, Qiwu; Peng, Xiaoli; Xia, Xiaodong

2017-02-24

Cronobacter sakazakii is a foodborne pathogen associated with fatal forms of necrotizing enterocolitis, meningitis and sepsis in neonates and infants. The aim of this study was to determine whether citral, a major component of lemongrass oil, could suppress putative virulence factors of C. sakazakii that contribute to infection. Sub-inhibitory concentrations of citral significantly decreased motility, quorum sensing, biofilm formation and endotoxin production. Citral substantially reduced the adhesion and invasion of C. sakazakii to Caco-2 cells and decreased bacterial survival and replication within the RAW 264.7 macrophage cells. Citral also repressed the expression of eighteen genes involved in the virulence. These findings suggest that citral has potential to be developed as an alternative or supplemental agent to mitigate the infections caused by C. sakazakii.

Oral Health and Erectile Dysfunction.

PubMed

Singh, Vijendra P; Nettemu, Sunil K; Nettem, Sowmya; Hosadurga, Rajesh; Nayak, Sangeeta U

2017-01-01

Ample evidence strongly supports the fact that periodontal disease is a major risk factor for various systemic diseases namely cardio-vascular disease, diabetes mellitus, etc. Recently, investigators focussed on exploring the link between chronic periodontitis (CP) and erectile dysfunction (ED) by contributing to the endothelial dysfunction. Both the diseases share common risk factors. Various studies conducted in different parts of the world in recent years reported the evidence linking this relationship as well as improvement in ED with periodontal treatment. Systemic exposure to the periodontal pathogen and periodontal infection-induced systemic inflammation was thought to associate with these conditions. The objective of this review was to highlight the evidence of the link between CP and ED and the importance of oral health in preventing the systemic conditions.

Oral Health and Erectile Dysfunction

PubMed Central

Singh, Vijendra P.; Nettemu, Sunil K.; Nettem, Sowmya; Hosadurga, Rajesh; Nayak, Sangeeta U.

2017-01-01

Ample evidence strongly supports the fact that periodontal disease is a major risk factor for various systemic diseases namely cardio-vascular disease, diabetes mellitus, etc. Recently, investigators focussed on exploring the link between chronic periodontitis (CP) and erectile dysfunction (ED) by contributing to the endothelial dysfunction. Both the diseases share common risk factors. Various studies conducted in different parts of the world in recent years reported the evidence linking this relationship as well as improvement in ED with periodontal treatment. Systemic exposure to the periodontal pathogen and periodontal infection-induced systemic inflammation was thought to associate with these conditions. The objective of this review was to highlight the evidence of the link between CP and ED and the importance of oral health in preventing the systemic conditions. PMID:29142443

New technologies in predicting, preventing and controlling emerging infectious diseases.

PubMed

Christaki, Eirini

2015-01-01

Surveillance of emerging infectious diseases is vital for the early identification of public health threats. Emergence of novel infections is linked to human factors such as population density, travel and trade and ecological factors like climate change and agricultural practices. A wealth of new technologies is becoming increasingly available for the rapid molecular identification of pathogens but also for the more accurate monitoring of infectious disease activity. Web-based surveillance tools and epidemic intelligence methods, used by all major public health institutions, are intended to facilitate risk assessment and timely outbreak detection. In this review, we present new methods for regional and global infectious disease surveillance and advances in epidemic modeling aimed to predict and prevent future infectious diseases threats.

New technologies in predicting, preventing and controlling emerging infectious diseases

PubMed Central

Christaki, Eirini

2015-01-01

Surveillance of emerging infectious diseases is vital for the early identification of public health threats. Emergence of novel infections is linked to human factors such as population density, travel and trade and ecological factors like climate change and agricultural practices. A wealth of new technologies is becoming increasingly available for the rapid molecular identification of pathogens but also for the more accurate monitoring of infectious disease activity. Web-based surveillance tools and epidemic intelligence methods, used by all major public health institutions, are intended to facilitate risk assessment and timely outbreak detection. In this review, we present new methods for regional and global infectious disease surveillance and advances in epidemic modeling aimed to predict and prevent future infectious diseases threats. PMID:26068569

Isolation and Differentiation of Murine Macrophages.

PubMed

Rios, Francisco J; Touyz, Rhian M; Montezano, Augusto C

2017-01-01

Macrophages play a major role in inflammation, wound healing, and tissue repair. Infiltrated monocytes differentiate into different macrophage subtypes with protective or pathogenic activities in vascular lesions. In the heart and vascular tissues, pathological activation promotes cardiovascular inflammation and remodeling and there is increasing evidence that macrophages play important mechanisms in this environment. Primary murine macrophages can be obtained from: bone marrow by different treatments (granulocyte-macrophage colony-stimulating factor-GM-CSF, macrophage colony-stimulating factor-M-CSF or supernatant of murine fibroblast L929), peritoneal cavity (resident or thioglycolate elicit macrophages), from the lung (alveolar macrophages) or from adipose tissue. In this chapter we describe some protocols to obtain primary murine macrophages and how to identify a pure macrophage population or activation phenotypes using different markers.

Pathogenic flora composition and overview of the trends used for bacterial pathogenicity identifications.

PubMed

Orji, Frank Anayo; Ugbogu, Ositadinma Chinyere; Ugbogu, Eziuche Amadike; Barbabosa-Pliego, Alberto; Monroy, Jose Cedillo; Elghandour, Mona M M Y; Salem, Abdelfattah Z M

2018-05-05

Over 250 species of resident flora in the class of bacteria are known to be associated with humans. These conventional flora compositions is often determined by factors which may not be limited to genetics, age, sex, stress and nutrition of humans. Man is constantly in contact with bacteria through media such as air, water, soil and food. This paper reviews the concept of bacterial pathogenesis from the sequential point of colonization to tissue injury. The paper in addition to examination of the factors which enhance virulence in bacterial pathogens also x-rayed the concept of pathogenicity islands and the next generation approaches or rather current trends/methods used in the bacterial pathogenicity investigations. In terms of pathogenicity which of course is the capacity to cause disease in animals, requires that the attacking bacterial strain is virulent, and has ability to bypass the host immune defensive mechanisms. In order to achieve or exhibit pathogenicity, the virulence factors required by microorganisms include capsule, pigments, enzymes, iron acquisition through siderophores. Bacterial Pathogenicity Islands as a distinct concept in bacterial pathogenesis are just loci on the chromosome or extra chromosomal units which are acquired by horizontal gene transfer within pathogens in a microbial community or biofilm. In the area of laboratory investigations, bacterial pathogenesis was initially carried out using culture dependent approaches, which can only detect about 1% of human and veterinary-important pathogens. However, in the recent paradigms shift, the use of proteomics, metagenomics, phylogenetic tree analyses, spooligotyping, and finger printing etc. have made it possible that 100% of the bacterial pathogens in nature can be extensively studied. Copyright © 2018 Elsevier Ltd. All rights reserved.

High-throughput microarray technology in diagnostics of enterobacteria based on genome-wide probe selection and regression analysis.

PubMed

Friedrich, Torben; Rahmann, Sven; Weigel, Wilfried; Rabsch, Wolfgang; Fruth, Angelika; Ron, Eliora; Gunzer, Florian; Dandekar, Thomas; Hacker, Jörg; Müller, Tobias; Dobrindt, Ulrich

2010-10-21

The Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens. We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes. Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.

Molecular identification of tick-borne pathogens infecting cattle in Mymensingh district of Bangladesh reveals emerging species of Anaplasma and Babesia.

PubMed

Roy, B C; Krücken, J; Ahmed, J S; Majumder, S; Baumann, M P; Clausen, P-H; Nijhof, A M

2018-04-01

Tick-borne diseases are considered a major hindrance to the health and productive performance of cattle in Bangladesh. To elucidate the epidemiology of tick-borne pathogens (TBPs) in local cattle, a cross-sectional study was performed in the 12 subdistricts (Upazilas) of Mymensingh district in Bangladesh. Blood samples and ticks were collected from 384 clinically healthy cattle kept by 135 farmers from 96 randomly selected villages. DNA extracted from the blood samples was subsequently screened by polymerase chain reaction (PCR) and a Reverse Line Blot (RLB) hybridization assay using an in-house prepared chemiluminescence solution for the presence of Anaplasma, Ehrlichia, Rickettsia, Babesia and Theileria spp. A total of 2,287 ticks were collected from 232 infested cattle (60.4%, 232/384) and identified morphologically as Rhipicephalus (Boophilus) microplus (n = 1,432, 62.6%) and Haemaphysalis bispinosa (n = 855; 37.4%). The RLB results demonstrated that the majority of the cattle (62.2%) were infected with at least one TBP. Theileria orientalis infections were most common (212/384, 55.2%) followed by infections with Anaplasma bovis (137/384, 35.67%), Anaplasma marginale (16/384, 4.17%), Babesia bigemina (4/384, 1.04%) and Babesia bovis (2/384, 0.52%). A previously uncharacterized Anaplasma sp. (Anaplasma sp. Mymensingh) and Babesia sp. (Babesia sp. Mymensingh), which are genetically closely related to Anaplasma platys and B. bigemina, were detected in 50 of 384 (13.0%) and 1 of 384 (0.3%) of the blood samples, respectively. Key risk factors for the occurrence of T. orientalis, A. marginale and Anaplasma sp. Mymensingh were identified. In conclusion, this study revealed that cattle in Mymensingh district are mainly infested with R. microplus and H. bispinosa ticks and may carry multiple TBPs. In addition, two previously uncharacterized pathogens were detected in the bovine blood samples. The pathogenicity of these species remains to be determined. © 2017 Blackwell Verlag GmbH.

Germline genetic variants in men with prostate cancer and one or more additional cancers.

PubMed

Pilié, Patrick G; Johnson, Anna M; Hanson, Kristen L; Dayno, Megan E; Kapron, Ashley L; Stoffel, Elena M; Cooney, Kathleen A

2017-10-15

Prostate cancer has a significant heritable component, and rare deleterious germline variants in certain genes can increase the risk of the disease. The aim of the current study was to describe the prevalence of pathogenic germline variants in cancer-predisposing genes in men with prostate cancer and at least 1 additional primary cancer. Using a multigene panel, the authors sequenced germline DNA from 102 men with prostate cancer and at least 1 additional primary cancer who also met ≥1 of the following criteria: 1) age ≤55 years at the time of diagnosis of the first malignancy; 2) rare tumor type or atypical presentation of a common tumor; and/or 3) ≥3 primary malignancies. Cancer family history and clinicopathologic data were independently reviewed by a clinical genetic counselor to determine whether the patient met established criteria for testing for a hereditary cancer syndrome. Sequencing identified approximately 3500 variants. Nine protein-truncating deleterious mutations were found across 6 genes, including BRCA2, ataxia telangiectasia mutated (ATM), mutL homolog 1 (MLH1), BRCA1 interacting protein C-terminal helicase 1 (BRIP1), partner and localizer of BRCA2 (PALB2), and fibroblast growth factor receptor 3 (FGFR3). Likely pathogenic missense variants were identified in checkpoint kinase 2 (CHEK2) and homeobox protein Hox-B13 (HOXB13). In total, 11 of 102 patients (10.8%) were found to have pathogenic or likely pathogenic mutations in cancer-predisposing genes. The majority of these men (64%) did not meet current clinical criteria for germline testing. Men with prostate cancer and at least 1 additional primary cancer are enriched for harboring a germline deleterious mutation in a cancer-predisposing gene that may impact cancer prognosis and treatment, but the majority do not meet current criteria for clinical genetic testing. Cancer 2017;123:3925-32. © 2017 American Cancer Society. © 2017 American Cancer Society.

Molecular Pathogenesis of Chlamydia Disease Complications: Epithelial-Mesenchymal Transition and Fibrosis.

PubMed

Igietseme, Joseph U; Omosun, Yusuf; Nagy, Tamas; Stuchlik, Olga; Reed, Matthew S; He, Qing; Partin, James; Joseph, Kahaliah; Ellerson, Debra; George, Zenas; Goldstein, Jason; Eko, Francis O; Bandea, Claudiu; Pohl, Jan; Black, Carolyn M

2018-01-01

The reproductive system complications of genital chlamydial infection include fallopian tube fibrosis and tubal factor infertility. However, the molecular pathogenesis of these complications remains poorly understood. The induction of pathogenic epithelial-mesenchymal transition (EMT) through microRNA (miRNA) dysregulation was recently proposed as the pathogenic basis of chlamydial complications. Focusing on fibrogenesis, we investigated the hypothesis that chlamydia-induced fibrosis is caused by EMT-driven generation of myofibroblasts, the effector cells of fibrosis that produce excessive extracellular matrix (ECM) proteins. The results revealed that the targets of a major category of altered miRNAs during chlamydial infection are key components of the pathophysiological process of fibrogenesis; these target molecules include collagen types I, III, and IV, transforming growth factor β (TGF-β), TGF-β receptor 1 (TGF-βR1), connective tissue growth factor (CTGF), E-cadherin, SRY-box 7 (SOX7), and NFAT (nuclear factor of activated T cells) kinase dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1a (Dyrk1a). Chlamydial induction of EMT resulted in the generation of α-smooth muscle actin (α-SMA)-positive myofibroblasts that produced ECM proteins, including collagen types I and III and fibronectin. Furthermore, the inhibition of EMT prevented the generation of myofibroblasts and production of ECM proteins during chlamydial infection. These findings may provide useful avenues for targeting EMT or specific components of the EMT pathways as a therapeutic intervention strategy to prevent chlamydia-related complications. Copyright © 2017 American Society for Microbiology.

Honey bee (Apis mellifera) colony health and pathogen composition in migratory beekeeping operations involved in California almond pollination

PubMed Central

Daughenbaugh, Katie F.; Radford, Rosemarie; Kegley, Susan E.

2017-01-01

Honey bees are important pollinators of agricultural crops. Pathogens and other factors have been implicated in high annual losses of honey bee colonies in North America and some European countries. To further investigate the relationship between multiple factors, including pathogen prevalence and abundance and colony health, we monitored commercially managed migratory honey bee colonies involved in California almond pollination in 2014. At each sampling event, honey bee colony health was assessed, using colony population size as a proxy for health, and the prevalence and abundance of seven honey bee pathogens was evaluated using PCR and quantitative PCR, respectively. In this sample cohort, pathogen prevalence and abundance did not correlate with colony health, but did correlate with the date of sampling. In general, pathogen prevalence (i.e., the number of specific pathogens harbored within a colony) was lower early in the year (January—March) and was greater in the summer, with peak prevalence occurring in June. Pathogen abundance in individual honey bee colonies varied throughout the year and was strongly associated with the sampling date, and was influenced by beekeeping operation, colony health, and mite infestation level. Together, data from this and other observational cohort studies that monitor individual honey bee colonies and precisely account for sampling date (i.e., day of year) will lead to a better understanding of the influence of pathogens on colony mortality and the effects of other factors on these associations. PMID:28817641

Honey bee (Apis mellifera) colony health and pathogen composition in migratory beekeeping operations involved in California almond pollination.

PubMed

Glenny, William; Cavigli, Ian; Daughenbaugh, Katie F; Radford, Rosemarie; Kegley, Susan E; Flenniken, Michelle L

2017-01-01

Honey bees are important pollinators of agricultural crops. Pathogens and other factors have been implicated in high annual losses of honey bee colonies in North America and some European countries. To further investigate the relationship between multiple factors, including pathogen prevalence and abundance and colony health, we monitored commercially managed migratory honey bee colonies involved in California almond pollination in 2014. At each sampling event, honey bee colony health was assessed, using colony population size as a proxy for health, and the prevalence and abundance of seven honey bee pathogens was evaluated using PCR and quantitative PCR, respectively. In this sample cohort, pathogen prevalence and abundance did not correlate with colony health, but did correlate with the date of sampling. In general, pathogen prevalence (i.e., the number of specific pathogens harbored within a colony) was lower early in the year (January-March) and was greater in the summer, with peak prevalence occurring in June. Pathogen abundance in individual honey bee colonies varied throughout the year and was strongly associated with the sampling date, and was influenced by beekeeping operation, colony health, and mite infestation level. Together, data from this and other observational cohort studies that monitor individual honey bee colonies and precisely account for sampling date (i.e., day of year) will lead to a better understanding of the influence of pathogens on colony mortality and the effects of other factors on these associations.

Prevalence of Bovine Viral Diarrhoea Virus (BVDV), Bovine Herpes Virus 1 (BHV 1), Leptospirosis and Neosporosis, and associated risk factors in 161 Irish beef herds.

PubMed

Barrett, Damien; Parr, Mervyn; Fagan, John; Johnson, Alan; Tratalos, Jamie; Lively, Francis; Diskin, Michael; Kenny, David

2018-01-06

There are limited data available, in Ireland or elsewhere, to determine the extent of exposure to various endemic diseases among beef cows and factors associated with exposure to causative pathogens. The objectives of this study were to determine the herd and within herd prevalence of Bovine Viral Diarrhoea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Leptospirosis and Neosporosis in a large scale study of commercial beef herds on the island of Ireland, and to examine herd level factors associated with exposure to these pathogens in these herds. The average number of cows tested per herd was 35.5 (median 30). Herd level seroprevalence to Bovine Herpesvirus-1(BHV-1), Bovine Viral-Diarrhoea Virus (BVDV), Leptospirosis and Neosporosis was 90%, 100%, 91% and 67%, respectively, while the mean within herd prevalence for the these pathogens was 40%, 77.7%, 65.7% and 5.7%, respectively. The study confirms that the level of seroconversion for the four pathogens of interest increases with herd size. There was also evidence that exposure to one pathogen may increase the risk of exposure to another pathogen. Herd level seroprevalences were in excess of 90% for BVDV, BHV-1 and Leptosporosis. Larger herds were subject to increased exposure to disease pathogens. This study suggests that exposure to several pathogens may be associated with the further exposure to other pathogens.

Anaplasma marginale superinfection attributable to pathogen strains with distinct genomic backgrounds.

USDA-ARS?s Scientific Manuscript database

Microbial strain structure is dynamic over space and time; shifts in pathogen strain structure result in changing patterns of disease. The scale of change in space and time differs markedly among pathogens depending on multiple factors including pathogen-specific mechanisms of genetic change and the...

Sequence variation in the M2 ion channel protein influences its intracellular localization during avian influenza replication

USDA-ARS?s Scientific Manuscript database

Avian influenza virus (AIV) is a constant threat to poultry worldwide due to its ability to mutate from a low pathogenic (LP) form into a highly pathogenic (HP) one. It is known that the incorporation of a polybasic cleavage site (PBCS) on the hemagglutinin (HA) gene is a major indicator of pathogen...

Differential Impact of LPG-and PG-Deficient Leishmania major Mutants on the Immune Response of Human Dendritic Cells

PubMed Central

Jayakumar, Asha; Hickerson, Suzanne; Mostrom, Janet; Turco, Salvatore J.; Beverley, Stephen M.; McDowell, Mary Ann

2015-01-01

Background Leishmania major infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction. Methodology/Principal Findings Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-), or generally deficient for all PGs, (FV1 lpg2-). Infection with metacyclic, infective stage, L. major or purified LPG induced high levels of IL12B subunit gene transcripts in hDCs, which was abrogated with FV1 lpg1- infections. In contrast, hDC infections with FV1 lpg2- displayed increased IL12B expression, suggesting other PG-related/LPG2 dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 lpg1-, FV1 lpg2- infections revealed that FV1 lpg1- mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB) and Interferon Regulatory Factor (IRF) mediated transcription. Conclusions/Significance These data suggest that L. major LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring Leishmania surface glycoconjugates that result in modulation of host cellular IL12. PMID:26630499

The non-canonical roles of clathrin and actin in pathogen internalization, egress and spread.

PubMed

Humphries, Ashley C; Way, Michael

2013-08-01

The role of clathrin in pathogen entry has received much attention and has highlighted the adaptability of clathrin during internalization. Recent studies have now uncovered additional roles for clathrin and have put the spotlight on its role in pathogen spread. Here, we discuss the manipulation of clathrin by pathogens, with specific attention to the processes that occur at the plasma membrane. In the majority of cases, both clathrin and the actin cytoskeleton are hijacked, so we also examine the interplay between these two systems and their role during pathogen internalization, egress and spread.

Antibody Levels to Persistent Pathogens and Incident Stroke in Mexican Americans

PubMed Central

Sealy-Jefferson, Shawnita; Gillespie, Brenda W.; Aiello, Allison E.; Haan, Mary N.; Morgenstern, Lewis B.; Lisabeth, Lynda D.

2013-01-01

Background Persistent pathogens have been proposed as risk factors for stroke; however, the evidence remains inconclusive. Mexican Americans have an increased risk of stroke especially at younger ages, as well as a higher prevalence of infections caused by several persistent pathogens. Methodology/Principal Findings Using data from the Sacramento Area Latino Study on Aging (n = 1621), the authors used discrete-time regression to examine associations between stroke risk and (1) immunoglobulin G antibody levels to Helicobacter pylori (H. pylori), Cytomegalovirus, Varicella Zoster Virus, Toxoplasma gondii and Herpes simplex virus 1, and (2) concurrent exposure to several pathogens (pathogen burden), defined as: (a) summed sero-positivity, (b) number of pathogens eliciting high antibody levels, and (c) average antibody level. Models were adjusted for socio-demographics and stroke risk factors. Antibody levels to H. pylori predicted incident stroke in fully adjusted models (Odds Ratio: 1.58; 95% Confidence Interval: 1.09, 2.28). No significant associations were found between stroke risk and antibody levels to the other four pathogens. No associations were found for pathogen burden and incident stroke in fully adjusted models. Conclusions/Significance Our results suggest that exposure to H. pylori may be a stroke risk factor in Mexican Americans and may contribute to ethnic differences in stroke risk given the increased prevalence of exposure to H. pylori in this population. Future studies are needed to confirm this association. PMID:23799066

Structural and Functional Analysis of VQ Motif-Containing Proteins in Arabidopsis as Interacting Proteins of WRKY Transcription Factors1[W][OA

PubMed Central

Cheng, Yuan; Zhou, Yuan; Yang, Yan; Chi, Ying-Jun; Zhou, Jie; Chen, Jian-Ye; Wang, Fei; Fan, Baofang; Shi, Kai; Zhou, Yan-Hong; Yu, Jing-Quan; Chen, Zhixiang

2012-01-01

WRKY transcription factors are encoded by a large gene superfamily with a broad range of roles in plants. Recently, several groups have reported that proteins containing a short VQ (FxxxVQxLTG) motif interact with WRKY proteins. We have recently discovered that two VQ proteins from Arabidopsis (Arabidopsis thaliana), SIGMA FACTOR-INTERACTING PROTEIN1 and SIGMA FACTOR-INTERACTING PROTEIN2, act as coactivators of WRKY33 in plant defense by specifically recognizing the C-terminal WRKY domain and stimulating the DNA-binding activity of WRKY33. In this study, we have analyzed the entire family of 34 structurally divergent VQ proteins from Arabidopsis. Yeast (Saccharomyces cerevisiae) two-hybrid assays showed that Arabidopsis VQ proteins interacted specifically with the C-terminal WRKY domains of group I and the sole WRKY domains of group IIc WRKY proteins. Using site-directed mutagenesis, we identified structural features of these two closely related groups of WRKY domains that are critical for interaction with VQ proteins. Quantitative reverse transcription polymerase chain reaction revealed that expression of a majority of Arabidopsis VQ genes was responsive to pathogen infection and salicylic acid treatment. Functional analysis using both knockout mutants and overexpression lines revealed strong phenotypes in growth, development, and susceptibility to pathogen infection. Altered phenotypes were substantially enhanced through cooverexpression of genes encoding interacting VQ and WRKY proteins. These findings indicate that VQ proteins play an important role in plant growth, development, and response to environmental conditions, most likely by acting as cofactors of group I and IIc WRKY transcription factors. PMID:22535423

Structural and functional analysis of VQ motif-containing proteins in Arabidopsis as interacting proteins of WRKY transcription factors.

PubMed

Cheng, Yuan; Zhou, Yuan; Yang, Yan; Chi, Ying-Jun; Zhou, Jie; Chen, Jian-Ye; Wang, Fei; Fan, Baofang; Shi, Kai; Zhou, Yan-Hong; Yu, Jing-Quan; Chen, Zhixiang

2012-06-01

WRKY transcription factors are encoded by a large gene superfamily with a broad range of roles in plants. Recently, several groups have reported that proteins containing a short VQ (FxxxVQxLTG) motif interact with WRKY proteins. We have recently discovered that two VQ proteins from Arabidopsis (Arabidopsis thaliana), SIGMA FACTOR-INTERACTING PROTEIN1 and SIGMA FACTOR-INTERACTING PROTEIN2, act as coactivators of WRKY33 in plant defense by specifically recognizing the C-terminal WRKY domain and stimulating the DNA-binding activity of WRKY33. In this study, we have analyzed the entire family of 34 structurally divergent VQ proteins from Arabidopsis. Yeast (Saccharomyces cerevisiae) two-hybrid assays showed that Arabidopsis VQ proteins interacted specifically with the C-terminal WRKY domains of group I and the sole WRKY domains of group IIc WRKY proteins. Using site-directed mutagenesis, we identified structural features of these two closely related groups of WRKY domains that are critical for interaction with VQ proteins. Quantitative reverse transcription polymerase chain reaction revealed that expression of a majority of Arabidopsis VQ genes was responsive to pathogen infection and salicylic acid treatment. Functional analysis using both knockout mutants and overexpression lines revealed strong phenotypes in growth, development, and susceptibility to pathogen infection. Altered phenotypes were substantially enhanced through cooverexpression of genes encoding interacting VQ and WRKY proteins. These findings indicate that VQ proteins play an important role in plant growth, development, and response to environmental conditions, most likely by acting as cofactors of group I and IIc WRKY transcription factors.

Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES).

PubMed

Pardo, Carlos A; Nabbout, Rima; Galanopoulou, Aristea S

2014-04-01

The mechanisms of epileptogenesis in pediatric epileptic syndromes are diverse, and may involve disturbances of neurodevelopmental trajectories, synaptic homeostasis, and cortical connectivity, which may occur during brain development, early infancy, or childhood. Although genetic or structural/metabolic factors are frequently associated with age-specific epileptic syndromes, such as infantile spasms and West syndrome, other syndromes may be determined by the effect of immunopathogenic mechanisms or energy-dependent processes in response to environmental challenges, such as infections or fever in normally-developed children during early or late childhood. Immune-mediated mechanisms have been suggested in selected pediatric epileptic syndromes in which acute and rapidly progressive encephalopathies preceded by fever and/or infections, such as febrile infection-related epilepsy syndrome, or in chronic progressive encephalopathies, such as Rasmussen encephalitis. A definite involvement of adaptive and innate immune mechanisms driven by cytotoxic CD8(+) T lymphocytes and neuroglial responses has been demonstrated in Rasmussen encephalitis, although the triggering factor of these responses remains unknown. Although the beneficial response to steroids and adrenocorticotropic hormone of infantile spasms, or preceding fever or infection in FIRES, may support a potential role of neuroinflammation as pathogenic factor, no definite demonstration of such involvement has been achieved, and genetic or metabolic factors are suspected. A major challenge for the future is discovering pathogenic mechanisms and etiological factors that facilitate the introduction of novel targets for drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments in these pediatric epileptic syndromes.

Prevalence of bovine subclinical mastitis and isolation of its major causes in Bishoftu Town, Ethiopia.

PubMed

Birhanu, Misrak; Leta, Samson; Mamo, Gezahegne; Tesfaye, Shimelis

2017-12-21

A cross-sectional study was conducted from November 2015 to March 2016 to estimate the prevalence, to assess the risk factors and to isolate the major etiological agent of subclinical mastitis in Bishoftu town. The study was conducted on 262 cross breed lactating cows selected from 12 intensively managed dairy farms. California mastitis test (CMT) and bacteriological culture methods were used as diagnostic tools. From 262 cows examined, 105 (40.1%) and from 1048 quarters examined, 170 (16.1%) were positive for sub-clinical mastitis using CMT. All CMT positive samples were cultured for etiological agent identification. From 170 samples cultured, 153 were positive for known subclinical mastitis pathogens. The dominant bacteria isolated were Staphylococcus species from these Staphylococcus aureus (44.9%) was the major one followed by Streptococcus spp. (25.3%) and other gram negative enteric bacteria, Escherichia coli (8.8%). Age, body condition score, milk yield, and number of parity were considered as potential risk factors; among these, age and number of parity have statistically significance association with the occurrence of subclinical mastitis (P < 0.05) both in the CMT and the bacteriological tests.

Transcriptional Control of Drug Resistance, Virulence and Immune System Evasion in Pathogenic Fungi: A Cross-Species Comparison.

PubMed

Pais, Pedro; Costa, Catarina; Cavalheiro, Mafalda; Romão, Daniela; Teixeira, Miguel C

2016-01-01

Transcription factors are key players in the control of the activation or repression of gene expression programs in response to environmental stimuli. The study of regulatory networks taking place in fungal pathogens is a promising research topic that can help in the fight against these pathogens by targeting specific fungal pathways as a whole, instead of targeting more specific effectors of virulence or drug resistance. This review is focused on the analysis of regulatory networks playing a central role in the referred mechanisms in the human fungal pathogens Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida parapsilosis , and Candida tropicalis . Current knowledge on the activity of the transcription factors characterized in each of these pathogenic fungal species will be addressed. Particular focus is given to their mechanisms of activation, regulatory targets and phenotypic outcome. The review further provides an evaluation on the conservation of transcriptional circuits among different fungal pathogens, highlighting the pathways that translate common or divergent traits among these species in what concerns their drug resistance, virulence and host immune evasion features. It becomes evident that the regulation of transcriptional networks is complex and presents significant variations among different fungal pathogens. Only the oxidative stress regulators Yap1 and Skn7 are conserved among all studied species; while some transcription factors, involved in nutrient homeostasis, pH adaptation, drug resistance and morphological switching are present in several, though not all species. Interestingly, in some cases not very homologous transcription factors display orthologous functions, whereas some homologous proteins have diverged in terms of their function in different species. A few cases of species specific transcription factors are also observed.

Evolution of disease response genes in loblolly pine: insights from candidate genes.

PubMed

Ersoz, Elhan S; Wright, Mark H; González-Martínez, Santiago C; Langley, Charles H; Neale, David B

2010-12-06

Host-pathogen interactions that may lead to a competitive co-evolution of virulence and resistance mechanisms present an attractive system to study molecular evolution because strong, recent (or even current) selective pressure is expected at many genomic loci. However, it is unclear whether these selective forces would act to preserve existing diversity, promote novel diversity, or reduce linked neutral diversity during rapid fixation of advantageous alleles. In plants, the lack of adaptive immunity places a larger burden on genetic diversity to ensure survival of plant populations. This burden is even greater if the generation time of the plant is much longer than the generation time of the pathogen. Here, we present nucleotide polymorphism and substitution data for 41 candidate genes from the long-lived forest tree loblolly pine, selected primarily for their prospective influences on host-pathogen interactions. This dataset is analyzed together with 15 drought-tolerance and 13 wood-quality genes from previous studies. A wide range of neutrality tests were performed and tested against expectations from realistic demographic models. Collectively, our analyses found that axr (auxin response factor), caf1 (chromatin assembly factor) and gatabp1 (gata binding protein 1) candidate genes carry patterns consistent with directional selection and erd3 (early response to drought 3) displays patterns suggestive of a selective sweep, both of which are consistent with the arm-race model of disease response evolution. Furthermore, we have identified patterns consistent with diversifying selection at erf1-like (ethylene responsive factor 1), ccoaoemt (caffeoyl-CoA-O-methyltransferase), cyp450-like (cytochrome p450-like) and pr4.3 (pathogen response 4.3), expected under the trench-warfare evolution model. Finally, a drought-tolerance candidate related to the plant cell wall, lp5, displayed patterns consistent with balancing selection. In conclusion, both arms-race and trench-warfare models seem compatible with patterns of polymorphism found in different disease-response candidate genes, indicating a mixed strategy of disease tolerance evolution for loblolly pine, a major tree crop in southeastern United States.

Lack of the COMPASS Component Ccl1 Reduces H3K4 Trimethylation Levels and Affects Transcription of Secondary Metabolite Genes in Two Plant-Pathogenic Fusarium Species.

PubMed

Studt, Lena; Janevska, Slavica; Arndt, Birgit; Boedi, Stefan; Sulyok, Michael; Humpf, Hans-Ulrich; Tudzynski, Bettina; Strauss, Joseph

2016-01-01

In the two fungal pathogens Fusarium fujikuroi and Fusarium graminearum , secondary metabolites (SMs) are fitness and virulence factors and there is compelling evidence that the coordination of SM gene expression is under epigenetic control. Here, we characterized Ccl1, a subunit of the COMPASS complex responsible for methylating lysine 4 of histone H3 (H3K4me). We show that Ccl1 is not essential for viability but a regulator of genome-wide trimethylation of H3K4 (H3K4me3). Although, recent work in Fusarium and Aspergillus spp. detected only sporadic H3K4 methylation at the majority of the SM gene clusters, we show here that SM profiles in CCL1 deletion mutants are strongly deviating from the wild type. Cross-complementation experiments indicate high functional conservation of Ccl1 as phenotypes of the respective △ ccl1 were rescued in both fungi. Strikingly, biosynthesis of the species-specific virulence factors gibberellic acid and deoxynivalenol produced by F. fujikuroi and F. graminearum , respectively, was reduced in axenic cultures but virulence was not attenuated in these mutants, a phenotype which goes in line with restored virulence factor production levels in planta. This suggests that yet unknown plant-derived signals are able to compensate for Ccl1 function during pathogenesis.

Cryptococcus neoformans Requires the ESCRT Protein Vps23 for Iron Acquisition from Heme, for Capsule Formation, and for Virulence

PubMed Central

Hu, Guanggan; Caza, Mélissa; Cadieux, Brigitte; Chan, Vivienne; Liu, Victor

2013-01-01

Iron availability is a key regulator of virulence factor elaboration in Cryptococcus neoformans, the causative agent of fungal meningoencephalitis in HIV/AIDS patients. In addition, iron is an essential nutrient for pathogen proliferation in mammalian hosts but little is known about the mechanisms of iron sensing and uptake in fungal pathogens that attack humans. In this study, we mutagenized C. neoformans by Agrobacterium-mediated T-DNA insertion and screened for mutants with reduced growth on heme as the sole iron source. Among 34 mutants, we identified a subset with insertions in the gene for the ESCRT-I (endosomal sorting complex required for transport) protein Vps23 that resulted in a growth defect on heme, presumably due to a defect in uptake via endocytosis or misregulation of iron acquisition from heme. Remarkably, vps23 mutants were also defective in the elaboration of the cell-associated capsular polysaccharide that is a major virulence factor, while overexpression of Vps23 resulted in cells with a slightly enlarged capsule. These phenotypes were mirrored by a virulence defect in the vps23 mutant in a mouse model of cryptococcosis and by hypervirulence of the overexpression strain. Overall, these results reveal an important role for trafficking via ESCRT functions in both heme uptake and capsule formation, and they further reinforce the connection between iron and virulence factor deployment in C. neoformans. PMID:23132495

Cryptococcus neoformans requires the ESCRT protein Vps23 for iron acquisition from heme, for capsule formation, and for virulence.

PubMed

Hu, Guanggan; Caza, Mélissa; Cadieux, Brigitte; Chan, Vivienne; Liu, Victor; Kronstad, James

2013-01-01

Iron availability is a key regulator of virulence factor elaboration in Cryptococcus neoformans, the causative agent of fungal meningoencephalitis in HIV/AIDS patients. In addition, iron is an essential nutrient for pathogen proliferation in mammalian hosts but little is known about the mechanisms of iron sensing and uptake in fungal pathogens that attack humans. In this study, we mutagenized C. neoformans by Agrobacterium-mediated T-DNA insertion and screened for mutants with reduced growth on heme as the sole iron source. Among 34 mutants, we identified a subset with insertions in the gene for the ESCRT-I (endosomal sorting complex required for transport) protein Vps23 that resulted in a growth defect on heme, presumably due to a defect in uptake via endocytosis or misregulation of iron acquisition from heme. Remarkably, vps23 mutants were also defective in the elaboration of the cell-associated capsular polysaccharide that is a major virulence factor, while overexpression of Vps23 resulted in cells with a slightly enlarged capsule. These phenotypes were mirrored by a virulence defect in the vps23 mutant in a mouse model of cryptococcosis and by hypervirulence of the overexpression strain. Overall, these results reveal an important role for trafficking via ESCRT functions in both heme uptake and capsule formation, and they further reinforce the connection between iron and virulence factor deployment in C. neoformans.

A secretome view of colonisation factors in Shiga toxin-encoding Escherichia coli (STEC): from enterohaemorrhagic E. coli (EHEC) to related enteropathotypes.

PubMed

Monteiro, Ricardo; Ageorges, Valentin; Rojas-Lopez, Maricarmen; Schmidt, Herbert; Weiss, Agnes; Bertin, Yolande; Forano, Evelyne; Jubelin, Grégory; Henderson, Ian R; Livrelli, Valérie; Gobert, Alain P; Rosini, Roberto; Soriani, Marco; Desvaux, Mickaël

2016-08-01

Shiga toxin-encoding Escherichia coli (STEC) regroup strains that carry genes encoding Shiga toxin (Stx). Among intestinal pathogenic E. coli, enterohaemorrhagic E. coli (EHEC) constitute the major subgroup of virulent STEC. EHEC cause serious human disease such as haemorrhagic colitis and haemolytic-uremic syndrome. While EHEC have evolved from enteropathogenic E. coli, hybrids with enteroaggregative E. coli have recently emerged. Of note, some enteroinvasive E. coli also belong to the STEC group. While the LEE (locus of enterocyte effacement) is a key and prominent molecular determinant in the pathogenicity, neither all EHEC nor STEC contain the LEE, suggesting that they possess additional virulence and colonisation factors. Currently, nine protein secretion systems have been described in diderm-lipopolysaccharide bacteria (archetypal Gram-negative) and can be involved in the secretion of extracellular effectors, cell-surface proteins or assembly of cell-surface organelles, such as flagella or pili. In this review, we focus on the secretome of STEC and related enteropathotypes, which are relevant to the colonisation of biotic and abiotic surfaces. Considering the wealth of potential protein trafficking mechanisms, the different combinations of colonisation factors and modulation of their expression is further emphasised with regard to the ecophysiology of STEC. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Bombyx mori Transcription Factors: Genome-Wide Identification, Expression Profiles and Response to Pathogens by Microarray Analysis

PubMed Central

Huang, Lulin; Cheng, Tingcai; Xu, Pingzhen; Fang, Ting; Xia, Qingyou

2012-01-01

Transcription factors are present in all living organisms, and play vital roles in a wide range of biological processes. Studies of transcription factors will help reveal the complex regulation mechanism of organisms. So far, hundreds of domains have been identified that show transcription factor activity. Here, 281 reported transcription factor domains were used as seeds to search the transcription factors in genomes of Bombyx mori L. (Lepidoptera: Bombycidae) and four other model insects. Overall, 666 transcription factors including 36 basal factors and 630 other factors were identified in B. mori genome, which accounted for 4.56% of its genome. The silkworm transcription factors' expression profiles were investigated in relation to multiple tissues, developmental stages, sexual dimorphism, and responses to oral infection by pathogens and direct bacterial injection. These all provided rich clues for revealing the transcriptional regulation mechanism of silkworm organ differentiation, growth and development, sexual dimorphism, and response to pathogen infection. PMID:22943524

Recent progress in melasma pathogenesis.

PubMed

Lee, Ai-Young

2015-11-01

Melasma is a common skin pigmentation condition. Given therapeutic difficulty as one of the biggest concerns, understanding of the etiology and pathogenesis of melasma becomes essential. UV irradiation, female sex hormones, and inflammatory processes are addressed as triggering factors with genetic predisposition. The mechanism of UV-induced melanogenesis has been extensively investigated as a model system to study melasma pathogenesis. Hitherto, treatment modalities for melasma are similar to other hyperpigmentation disorders. However, individual triggering factors induce a separate pigmentation disease, whose pathogenic mechanisms and clinical phenotypes are different from the ones encountered in melasma. Fortunately, there have been ongoing updates on melasma pathogenesis with regard to major triggering factors. Presence of certain factors working independently of UV exposure and role of dermal factors and microRNAs are being identified as novel discoveries about melasma pathogenesis. In this review, the melasma pathogenesis is reviewed in association with updated and new findings. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

PubMed

Dobón, Albor; Canet, Juan Vicente; García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

2015-04-01

Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

Identification of secreted bacterial proteins by noncanonical amino acid tagging

PubMed Central

Mahdavi, Alborz; Szychowski, Janek; Ngo, John T.; Sweredoski, Michael J.; Graham, Robert L. J.; Hess, Sonja; Schneewind, Olaf; Mazmanian, Sarkis K.; Tirrell, David A.

2014-01-01

Pathogenic microbes have evolved complex secretion systems to deliver virulence factors into host cells. Identification of these factors is critical for understanding the infection process. We report a powerful and versatile approach to the selective labeling and identification of secreted pathogen proteins. Selective labeling of microbial proteins is accomplished via translational incorporation of azidonorleucine (Anl), a methionine surrogate that requires a mutant form of the methionyl-tRNA synthetase for activation. Secreted pathogen proteins containing Anl can be tagged by azide-alkyne cycloaddition and enriched by affinity purification. Application of the method to analysis of the type III secretion system of the human pathogen Yersinia enterocolitica enabled efficient identification of secreted proteins, identification of distinct secretion profiles for intracellular and extracellular bacteria, and determination of the order of substrate injection into host cells. This approach should be widely useful for the identification of virulence factors in microbial pathogens and the development of potential new targets for antimicrobial therapy. PMID:24347637

Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella henselae

PubMed Central

2011-01-01

Bartonella henselae, the agent of cat scratch disease and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis, contains to date two groups of described pathogenicity factors: adhesins and type IV secretion systems. Bartonella adhesin A (BadA), the Trw system and possibly filamentous hemagglutinin act as promiscous or specific adhesins, whereas the virulence locus (Vir)B/VirD4 type IV secretion system modulates a variety of host cell functions. BadA mediates bacterial adherence to endothelial cells and extracellular matrix proteins and triggers the induction of angiogenic gene programming. The VirB/VirD4 type IV secretion system is responsible for, e.g., inhibition of host cell apoptosis, bacterial persistence in erythrocytes, and endothelial sprouting. The Trw-conjugation system of Bartonella spp. mediates host-specific adherence to erythrocytes. Filamentous hemagglutinins represent additional potential pathogenicity factors which are not yet characterized. The exact molecular functions of these pathogenicity factors and their contribution to an orchestral interplay need to be analyzed to understand B. henselae pathogenicity in detail. PMID:21489243

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

PubMed Central

Wang, Yimin; Du, Xiaonan; Bin, Rao; Yu, Shanshan; Xia, Zhezhi; Zheng, Guo; Zhong, Jianmin; Zhang, Yunjian; Jiang, Yong-hui; Wang, Yi

2017-01-01

Genetic factors play a major role in the etiology of epilepsy disorders. Recent genomics studies using next generation sequencing (NGS) technique have identified a large number of genetic variants including copy number (CNV) and single nucleotide variant (SNV) in a small set of genes from individuals with epilepsy. These discoveries have contributed significantly to evaluate the etiology of epilepsy in clinic and lay the foundation to develop molecular specific treatment. However, the molecular basis for a majority of epilepsy patients remains elusive, and furthermore, most of these studies have been conducted in Caucasian children. Here we conducted a targeted exome-sequencing of 63 trios of Chinese epilepsy families using a custom-designed NGS panel that covers 412 known and candidate genes for epilepsy. We identified pathogenic and likely pathogenic variants in 15 of 63 (23.8%) families in known epilepsy genes including SCN1A, CDKL5, STXBP1, CHD2, SCN3A, SCN9A, TSC2, MBD5, POLG and EFHC1. More importantly, we identified likely pathologic variants in several novel candidate genes such as GABRE, MYH1, and CLCN6. Our results provide the evidence supporting the application of custom-designed NGS panel in clinic and indicate a conserved genetic susceptibility for epilepsy between Chinese and Caucasian children. PMID:28074849

The secreted polyketide boydone A is responsible for the anti-Staphylococcus aureus activity of Scedosporium boydii.

PubMed

Staerck, Cindy; Landreau, Anne; Herbette, Gaëtan; Roullier, Catherine; Bertrand, Samuel; Siegler, Benjamin; Larcher, Gérald; Bouchara, Jean-Philippe; Fleury, Maxime J J

2017-12-01

Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii may also cause various infections in human. Particularly, it is one of the major causative agents of fungal colonization of the airways in patients with cystic fibrosis (CF). To compete with other microorganisms in the environment, fungi have evolved sophisticated strategies, including the production of secondary metabolites with antimicrobial activity that may also help them to establish successfully within the respiratory tract of receptive hosts. Here, the culture filtrate from a human pathogenic strain of S. boydii was investigated searching for an antibacterial activity, mainly against the major CF bacterial pathogens. A high antibacterial activity against Staphylococcus aureus, including methicillin-resistant strains of this species, was observed. Bio-guided fractionation and analysis of the active fractions by nuclear magnetic resonance or by high-performance liquid chromatography and high-resolution electrospray ionization-mass spectrometry allowed us to identify boydone A as responsible for this antibacterial activity. Together, these results suggest that this six-membered cyclic polyketide could be one of the virulence factors of the fungus. Genes involved in the synthesis of this secreted metabolite are currently being identified in order to confirm the role of this polyketide in pathogenesis. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A novel approach to probe host-pathogen interactions of bovine digital dermatitis, a model of a complex polymicrobial infection.

PubMed

Marcatili, Paolo; Nielsen, Martin W; Sicheritz-Pontén, Thomas; Jensen, Tim K; Schafer-Nielsen, Claus; Boye, Mette; Nielsen, Morten; Klitgaard, Kirstine

2016-12-01

Polymicrobial infections represent a great challenge for the clarification of disease etiology and the development of comprehensive diagnostic or therapeutic tools, particularly for fastidious and difficult-to-cultivate bacteria. Using bovine digital dermatitis (DD) as a disease model, we introduce a novel strategy to study the pathogenesis of complex infections. The strategy combines meta-transcriptomics with high-density peptide-microarray technology to screen for in vivo-expressed microbial genes and the host antibody response at the site of infection. Bacterial expression patterns supported the assumption that treponemes were the major DD pathogens but also indicated the active involvement of other phyla (primarily Bacteroidetes). Bacterial genes involved in chemotaxis, flagellar synthesis and protection against oxidative and acidic stress were among the major factors defining the disease. The extraordinary diversity observed in bacterial expression, antigens and host antibody responses between individual cows pointed toward microbial variability as a hallmark of DD. Persistence of infection and DD reinfection in the same individual is common; thus, high microbial diversity may undermine the host's capacity to mount an efficient immune response and maintain immunological memory towards DD. The common antigenic markers identified here using a high-density peptide microarray address this issue and may be useful for future preventive measures against DD.

Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia.

PubMed

Anderson, Ronald; Nel, Jan G; Feldman, Charles

2018-04-11

Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.

Identification and expression analysis of WRKY transcription factor genes in canola (Brassica napus L.) in response to fungal pathogens and hormone treatments.

PubMed

Yang, Bo; Jiang, Yuanqing; Rahman, Muhammad H; Deyholos, Michael K; Kav, Nat N V

2009-06-03

Members of plant WRKY transcription factor families are widely implicated in defense responses and various other physiological processes. For canola (Brassica napus L.), no WRKY genes have been described in detail. Because of the economic importance of this crop, and its evolutionary relationship to Arabidopsis thaliana, we sought to characterize a subset of canola WRKY genes in the context of pathogen and hormone responses. In this study, we identified 46 WRKY genes from canola by mining the expressed sequence tag (EST) database and cloned cDNA sequences of 38 BnWRKYs. A phylogenetic tree was constructed using the conserved WRKY domain amino acid sequences, which demonstrated that BnWRKYs can be divided into three major groups. We further compared BnWRKYs to the 72 WRKY genes from Arabidopsis and 91 WRKY from rice, and we identified 46 presumptive orthologs of AtWRKY genes. We examined the subcellular localization of four BnWRKY proteins using green fluorescent protein (GFP) and we observed the fluorescent green signals in the nucleus only.The responses of 16 selected BnWRKY genes to two fungal pathogens, Sclerotinia sclerotiorum and Alternaria brassicae, were analyzed by quantitative real time-PCR (qRT-PCR). Transcript abundance of 13 BnWRKY genes changed significantly following pathogen challenge: transcripts of 10 WRKYs increased in abundance, two WRKY transcripts decreased after infection, and one decreased at 12 h post-infection but increased later on (72 h). We also observed that transcript abundance of 13/16 BnWRKY genes was responsive to one or more hormones, including abscisic acid (ABA), and cytokinin (6-benzylaminopurine, BAP) and the defense signaling molecules jasmonic acid (JA), salicylic acid (SA), and ethylene (ET). We compared these transcript expression patterns to those previously described for presumptive orthologs of these genes in Arabidopsis and rice, and observed both similarities and differences in expression patterns. We identified a set of 13 BnWRKY genes from among 16 BnWRKY genes assayed, that are responsive to both fungal pathogens and hormone treatments, suggesting shared signaling mechanisms for these responses. This study suggests that a large number of BnWRKY proteins are involved in the transcriptional regulation of defense-related genes in response to fungal pathogens and hormone stimuli.

Transcription Factors Encoded on Core and Accessory Chromosomes of Fusarium oxysporum Induce Expression of Effector Genes

PubMed Central

van der Does, H. Charlotte; Schmidt, Sarah M.; Langereis, Léon; Hughes, Timothy R.

2016-01-01

Proteins secreted by pathogens during host colonization largely determine the outcome of pathogen-host interactions and are commonly called ‘effectors’. In fungal plant pathogens, coordinated transcriptional up-regulation of effector genes is a key feature of pathogenesis and effectors are often encoded in genomic regions with distinct repeat content, histone code and rate of evolution. In the tomato pathogen Fusarium oxysporum f. sp. lycopersici (Fol), effector genes reside on one of four accessory chromosomes, known as the ‘pathogenicity’ chromosome, which can be exchanged between strains through horizontal transfer. The three other accessory chromosomes in the Fol reference strain may also be important for virulence towards tomato. Expression of effector genes in Fol is highly up-regulated upon infection and requires Sge1, a transcription factor encoded on the core genome. Interestingly, the pathogenicity chromosome itself contains 13 predicted transcription factor genes and for all except one, there is a homolog on the core genome. We determined DNA binding specificity for nine transcription factors using oligonucleotide arrays. The binding sites for homologous transcription factors were highly similar, suggesting that extensive neofunctionalization of DNA binding specificity has not occurred. Several DNA binding sites are enriched on accessory chromosomes, and expression of FTF1, its core homolog FTF2 and SGE1 from a constitutive promoter can induce expression of effector genes. The DNA binding sites of only these three transcription factors are enriched among genes up-regulated during infection. We further show that Ftf1, Ftf2 and Sge1 can activate transcription from their binding sites in yeast. RNAseq analysis revealed that in strains with constitutive expression of FTF1, FTF2 or SGE1, expression of a similar set of plant-responsive genes on the pathogenicity chromosome is induced, including most effector genes. We conclude that the Fol pathogenicity chromosome may be partially transcriptionally autonomous, but there are also extensive transcriptional connections between core and accessory chromosomes. PMID:27855160

A pilot systematic genomic comparison of recurrence risks of hepatitis B virus-associated hepatocellular carcinoma with low- and high-degree liver fibrosis.

PubMed

Yoo, Seungyeul; Wang, Wenhui; Wang, Qin; Fiel, M Isabel; Lee, Eunjee; Hiotis, Spiros P; Zhu, Jun

2017-12-07

Chronic hepatitis B virus (HBV) infection leads to liver fibrosis, which is a major risk factor in hepatocellular carcinoma (HCC) and an independent risk factor of recurrence after HCC tumor resection. The HBV genome can be inserted into the human genome, and chronic inflammation may trigger somatic mutations. However, how HBV integration and other genomic changes contribute to the risk of tumor recurrence with regards to the different degree of liver fibrosis is not clearly understood. We sequenced mRNAs of 21 pairs of tumor and distant non-neoplastic liver tissues of HBV-HCC patients and performed comprehensive genomic analyses of our RNAseq data and public available HBV-HCC sequencing data. We developed a robust pipeline for sensitively identifying HBV integration sites based on sequencing data. Simulations showed that our method outperformed existing methods. Applying it to our data, 374 and 106 HBV host genes were identified in non-neoplastic liver and tumor tissues, respectively. When applying it to other RNA sequencing datasets, consistently more HBV integrations were identified in non-neoplastic liver than in tumor tissues. HBV host genes identified in non-neoplastic liver samples significantly overlapped with known tumor suppressor genes. More significant enrichment of tumor suppressor genes was observed among HBV host genes identified from patients with tumor recurrence, indicating the potential risk of tumor recurrence driven by HBV integration in non-neoplastic liver tissues. We also compared SNPs of each sample with SNPs in a cancer census database and inferred samples' pathogenic SNP loads. Pathogenic SNP loads in non-neoplastic liver tissues were consistently higher than those in normal liver tissues. Additionally, HBV host genes identified in non-neoplastic liver tissues significantly overlapped with pathogenic somatic mutations, suggesting that HBV integration and somatic mutations targeting the same set of genes are important to tumorigenesis. HBV integrations and pathogenic mutations showed distinct patterns between low and high liver fibrosis patients with regards to tumor recurrence. The results suggest that HBV integrations and pathogenic SNPs in non-neoplastic tissues are important for tumorigenesis and different recurrence risk models are needed for patients with low and high degrees of liver fibrosis.

Detection Methodologies for Pathogen and Toxins: A Review.

PubMed

Alahi, Md Eshrat E; Mukhopadhyay, Subhas Chandra

2017-08-16

Pathogen and toxin-contaminated foods and beverages are a major source of illnesses, even death, and have a significant economic impact worldwide. Human health is always under a potential threat, including from biological warfare, due to these dangerous pathogens. The agricultural and food production chain consists of many steps such as harvesting, handling, processing, packaging, storage, distribution, preparation, and consumption. Each step is susceptible to threats of environmental contamination or failure to safeguard the processes. The production process can be controlled in the food and agricultural sector, where smart sensors can play a major role, ensuring greater food quality and safety by low cost, fast, reliable, and profitable methods of detection. Techniques for the detection of pathogens and toxins may vary in cost, size, and specificity, speed of response, sensitivity, and precision. Smart sensors can detect, analyse and quantify at molecular levels contents of different biological origin and ensure quality of foods against spiking with pesticides, fertilizers, dioxin, modified organisms, anti-nutrients, allergens, drugs and so on. This paper reviews different methodologies to detect pathogens and toxins in foods and beverages.

The evolution of immunity in relation to colonization and migration.

PubMed

O'Connor, Emily A; Cornwallis, Charlie K; Hasselquist, Dennis; Nilsson, Jan-Åke; Westerdahl, Helena

2018-05-01

Colonization and migration have a crucial effect on patterns of biodiversity, with disease predicted to play an important role in these processes. However, evidence of the effect of pathogens on broad patterns of colonization and migration is limited. Here, using phylogenetic analyses of 1,311 species of Afro-Palaearctic songbirds, we show that colonization events from regions of high (sub-Saharan Africa) to low (the Palaearctic) pathogen diversity were up to 20 times more frequent than the reverse, and that migration has evolved 3 times more frequently from African- as opposed to Palaearctic-resident species. We also found that resident species that colonized the Palaearctic from Africa, as well as African species that evolved long-distance migration to breed in the Palaearctic, have reduced diversity of key immune genes associated with pathogen recognition (major histocompatibility complex class I). These results suggest that changes in the pathogen community that occur during colonization and migration shape the evolution of the immune system, potentially by adjusting the trade-off between the benefits of extensive pathogen recognition and the costs of immunopathology that result from high major histocompatibility complex class I diversity.

Microbiology of Fresh Produce: Route of Contamination, Detection Methods, and Remedy.

PubMed

Rajwar, Asmita; Srivastava, Pragati; Sahgal, Manvika

2016-10-25

Fresh fruits and vegetables are an important part of a healthful diet. They provide vitamins, minerals and fiber to help keep our body healthy. Occasionally, fresh fruits and vegetables can become contaminated with harmful bacteria or viruses, which are also known as pathogens. The major family of pathogen associated with food are members of Enterobacteriaceae which commonly form a part of microbiological criteria and their presence is traditionally related to hygiene and safety of foods. Organic fertilizers, irrigation water quality and soil are major source of contamination. For removal of pathogens, various decontamination procedures are also followed to reduce microbial load on the fruits. These are chemical preservatives and irradiation. Microbiological study of fresh produce can be done by various phenotypic, biochemical and molecular techniques so that pathogen can properly be identified. The World Health Organization (WHO) developed global risk communication message and training materials to assist countries in strengthening their food educating programs. There is a need for improved surveillance systems on food-borne pathogens, on food products and on outbreaks so that comparable data are available from a wider range of countries.

Genomes and Virulence Factors of Novel Bacterial Pathogens Causing Bleaching Disease in the Marine Red Alga Delisea pulchra

PubMed Central

Fernandes, Neil; Case, Rebecca J.; Longford, Sharon R.; Seyedsayamdost, Mohammad R.; Steinberg, Peter D.; Kjelleberg, Staffan; Thomas, Torsten

2011-01-01

Nautella sp. R11, a member of the marine Roseobacter clade, causes a bleaching disease in the temperate-marine red macroalga, Delisea pulchra. To begin to elucidate the molecular mechanisms underpinning the ability of Nautella sp. R11 to colonize, invade and induce bleaching of D. pulchra, we sequenced and analyzed its genome. The genome encodes several factors such as adhesion mechanisms, systems for the transport of algal metabolites, enzymes that confer resistance to oxidative stress, cytolysins, and global regulatory mechanisms that may allow for the switch of Nautella sp. R11 to a pathogenic lifestyle. Many virulence effectors common in phytopathogenic bacteria are also found in the R11 genome, such as the plant hormone indole acetic acid, cellulose fibrils, succinoglycan and nodulation protein L. Comparative genomics with non-pathogenic Roseobacter strains and a newly identified pathogen, Phaeobacter sp. LSS9, revealed a patchy distribution of putative virulence factors in all genomes, but also led to the identification of a quorum sensing (QS) dependent transcriptional regulator that was unique to pathogenic Roseobacter strains. This observation supports the model that a combination of virulence factors and QS-dependent regulatory mechanisms enables indigenous members of the host alga's epiphytic microbial community to switch to a pathogenic lifestyle, especially under environmental conditions when innate host defence mechanisms are compromised. PMID:22162749

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

PubMed Central

Wang, Lisa; Aasly, Jan O.; Annesi, Grazia; Bardien, Soraya; Bozi, Maria; Brice, Alexis; Carr, Jonathan; Chung, Sun J.; Clarke, Carl; Crosiers, David; Deutschländer, Angela; Eckstein, Gertrud; Farrer, Matthew J.; Goldwurm, Stefano; Garraux, Gaetan; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Klein, Christine; Jeon, Beom; Kim, Yun J.; Lesage, Suzanne; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pihlstrøm, Lasse; Pramstaller, Peter P.; Park, Sung S.; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Silburn, Peter A.; Theuns, Jessie; Tan, Eng K.; Tomiyama, Hiroyuki; Toft, Mathias; Van Broeckhoven, Christine; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius M.; Krüger, Rejko

2015-01-01

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD. PMID:26354989

Strain-associated virulence factors of Streptococcus iniae in hybrid-striped bass.

PubMed

Buchanan, John T; Colvin, Kelly M; Vicknair, Mike R; Patel, Silpa K; Timmer, Anjuli M; Nizet, Victor

2008-09-18

Streptococcus iniae is a major fish pathogen producing invasive infections that result in economic losses in aquaculture. Development of in vitro models of S. iniae virulence may provide insight to the pathogenesis of infection in vivo. Three S. iniae strains (K288, 94-426, and 29178) were tested for virulence in a hybrid-striped bass (HSB) model using intraperitoneal injection. S. iniae strains K288 and 94-426 caused high levels of mortality in HSB (lethal dose 2x10(5)CFU) while strain 29178 was avirulent even upon IP challenge with 1000-fold higher inocula. In vitro assays were developed to test for the presence of characteristics previously associated with virulence in other species of pathogenic Streptococcus in animals and humans. In vitro differences relevant to virulence were not detected for beta-hemolysin activity, sensitivity to antimicrobial peptides, or adherence and invasion of epithelial cell layers. However, in whole-blood killing assays, the pathogenic strains were resistant to blood clearance, while 29178 was cleared (P<0.001) and more sensitive to complement (P<0.001). The avirulent strain 29178 was most efficiently phagocytosed and was most susceptible to intracellular killing (P<0.01) by the carp leukocyte cell line (CLC). When exposed to reactive oxygen species, strain 29178 was most susceptible. When the oxidative burst of CLC cells was inhibited, intracellular survival of 29178 was rescued fivefold, while no significant enhancement in survival of K288 or 94-426 was detected. Our results indicate that resistance to phagocytosis, oxidative killing, and associated phagocytic clearance is a significant factor in S. iniae virulence.

Disturbed hypoxic responses as a pathogenic mechanism of diabetic foot ulcers.

PubMed

Catrina, Sergiu-Bogdan; Zheng, Xiaowei

2016-01-01

Diabetic foot ulceration (DFU) is a chronic complication of diabetes that is characterized by impaired wound healing in the lower extremities. DFU remains a major clinical challenge because of poor understanding of its pathogenic mechanisms. Impaired wound healing in diabetes is characterized by decreased angiogenesis, reduced bone marrow-derived endothelial progenitor cell (EPC) recruitment, and decreased fibroblast and keratinocyte proliferation and migration. Recently, increasing evidence has suggested that increased hypoxic conditions and impaired cellular responses to hypoxia are essential pathogenic factors of delayed wound healing in DFU. Hypoxia-inducible factor-1 (HIF-1, a heterodimer of HIF-1α and HIF-1β) is a master regulator of oxygen homeostasis that mediates the adaptive cellular responses to hypoxia by regulating the expression of genes involved in angiogenesis, metabolic changes, proliferation, migration, and cell survival. However, HIF-1 signalling is inhibited in diabetes as a result of hyperglycaemia-induced HIF-1α destabilization and functional repression. Increasing HIF-1α expression and activity using various approaches promotes angiogenesis, EPC recruitment, and granulation, thereby improving wound healing in experimental diabetes. The mechanisms underlying HIF-1α regulation in diabetes and the therapeutic strategies targeting HIF-1 signalling for the treatment of diabetic wounds are discussed in this review. Further investigations of the pathways involved in HIF-1α regulation in diabetes are required to advance our understanding of the mechanisms underlying impaired wound healing in diabetes and to provide a foundation for developing novel therapeutic approaches to treat DFU. Copyright © 2016 John Wiley & Sons, Ltd.

Quantitative Proteomics of an Amphibian Pathogen, Batrachochytrium dendrobatidis, following Exposure to Thyroid Hormone

PubMed Central

Thekkiniath, Jose; Zabet-Moghaddam, Masoud; Kottapalli, Kameswara Rao; Pasham, Mithun R.; San Francisco, Susan; San Francisco, Michael

2015-01-01

Batrachochytrium dendrobatidis (Bd), a chytrid fungus, has increasingly been implicated as a major factor in the worldwide decline of amphibian populations. The fungus causes chytridiomycosis in susceptible species leading to massive die-offs of adult amphibians. Although Bd infects the keratinized mouthparts of tadpoles and negatively affects foraging behavior, these infections are non-lethal. An important morphogen controlling amphibian metamorphosis is thyroid hormone (T3). Tadpoles may be infected with Bd and the fungus may be exposed to T3 during metamorphosis. We hypothesize that exposure of Bd to T3 may induce the expression of factors associated with host colonization and pathogenicity. We utilized a proteomics approach to better understand the dynamics of the Bd-T3 interaction. Using liquid chromatography-mass spectrometry (LC-MS), we generated a data set of a large number of cytoplasmic and membrane proteins following exposure of Bd to T3. From these data, we identified a total of 263 proteins whose expression was significantly changed following T3 exposure. We provide evidence for expression of an array of proteins that may play key roles in both genomic and non-genomic actions of T3 in Bd. Additionally, our proteomics study shows an increase in several proteins including proteases and a class of uncommon crinkler and crinkler-like effector proteins suggesting their importance in Bd pathogenicity as well as those involved in metabolism and energy transfer, protein fate, transport and stress responses. This approach provides insights into the mechanistic basis of the Bd-amphibian interaction following T3 exposure. PMID:26046527

Quantitative Proteomics of an Amphibian Pathogen, Batrachochytrium dendrobatidis, following Exposure to Thyroid Hormone.

PubMed

Thekkiniath, Jose; Zabet-Moghaddam, Masoud; Kottapalli, Kameswara Rao; Pasham, Mithun R; San Francisco, Susan; San Francisco, Michael

2015-01-01

Batrachochytrium dendrobatidis (Bd), a chytrid fungus, has increasingly been implicated as a major factor in the worldwide decline of amphibian populations. The fungus causes chytridiomycosis in susceptible species leading to massive die-offs of adult amphibians. Although Bd infects the keratinized mouthparts of tadpoles and negatively affects foraging behavior, these infections are non-lethal. An important morphogen controlling amphibian metamorphosis is thyroid hormone (T3). Tadpoles may be infected with Bd and the fungus may be exposed to T3 during metamorphosis. We hypothesize that exposure of Bd to T3 may induce the expression of factors associated with host colonization and pathogenicity. We utilized a proteomics approach to better understand the dynamics of the Bd-T3 interaction. Using liquid chromatography-mass spectrometry (LC-MS), we generated a data set of a large number of cytoplasmic and membrane proteins following exposure of Bd to T3. From these data, we identified a total of 263 proteins whose expression was significantly changed following T3 exposure. We provide evidence for expression of an array of proteins that may play key roles in both genomic and non-genomic actions of T3 in Bd. Additionally, our proteomics study shows an increase in several proteins including proteases and a class of uncommon crinkler and crinkler-like effector proteins suggesting their importance in Bd pathogenicity as well as those involved in metabolism and energy transfer, protein fate, transport and stress responses. This approach provides insights into the mechanistic basis of the Bd-amphibian interaction following T3 exposure.

Effects of dietary L-glutamine supplementation on specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine.

PubMed

Chen, Shuai; Liu, Shuping; Zhang, Fengmei; Ren, Wenkai; Li, Nengzhang; Yin, Jie; Duan, Jielin; Peng, Yuanyi; Liu, Gang; Yin, Yulong; Wu, Guoyao

2014-10-01

Little is known about effects of dietary glutamine supplementation on specific and general defense responses in a vaccine-immunized animal model. Thus, this study determined roles for dietary glutamine supplementation in specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine. The measured variables included: (1) the production of pathogen-specific antibodies; (2) mRNA levels for pro-inflammatory cytokines, toll-like receptors and anti-oxidative factors; and (3) the distribution of P. multocida in tissues and the expression of its major virulence factors in vivo. Dietary supplementation with 0.5 % glutamine had a better protective role than 1 or 2 % glutamine against P. multocida infection in vaccine-immunized mice, at least partly resulting from its effects in modulation of general defense responses. Dietary glutamine supplementation had little effects on the production of P. multocida-specific antibodies. Compared to the non-supplemented group, dietary supplementation with 0.5 % glutamine had no effect on bacterial burden in vivo but decreased the expression of major virulence factors in the spleen. Collectively, supplementing 0.5 % glutamine to a conventional diet provides benefits in vaccine-immunized mice by enhancing general defense responses and decreasing expression of specific virulence factors.

Necrotrophic pathogens use the salicylic acid signaling pathway to promote disease development in tomato.

PubMed

Rahman, Taha Abd El; Oirdi, Mohamed El; Gonzalez-Lamothe, Rocio; Bouarab, Kamal

2012-12-01

Plants use different immune pathways to combat pathogens. The activation of the jasmonic acid (JA)-signaling pathway is required for resistance against necrotrophic pathogens; however, to combat biotrophic pathogens, the plants activate mainly the salicylic acid (SA)-signaling pathway. SA can antagonize JA signaling and vice versa. NPR1 (noninducible pathogenesis-related 1) is considered a master regulator of SA signaling. NPR1 interacts with TGA transcription factors, ultimately leading to the activation of SA-dependent responses. SA has been shown to promote disease development caused by the necrotrophic pathogen Botrytis cinerea through NPR1, by suppressing the expression of two JA-dependent defense genes, proteinase inhibitors I and II. We show here that the transcription factor TGA1.a contributes to disease development caused by B. cinerea in tomato by suppressing the expression of proteinase inhibitors I and II. Finally, we present evidence that the SA-signaling pathway contributes to disease development caused by another necrotrophic pathogen, Alternaria solani, in tomato. Disease development promoted by SA through NPR1 requires the TGA1.a transcription factor. These data highlight how necrotrophs manipulate the SAsignaling pathway to promote their disease in tomato.

The cause of global amphibian declines: a developmental endocrinologist's perspective.

PubMed

Hayes, T B; Falso, P; Gallipeau, S; Stice, M

2010-03-15

Greater than 70% of the world's amphibian species are in decline. We propose that there is probably not a single cause for global amphibian declines and present a three-tiered hierarchical approach that addresses interactions among and between ultimate and proximate factors that contribute to amphibian declines. There are two immediate (proximate) causes of amphibian declines: death and decreased recruitment (reproductive failure). Although much attention has focused on death, few studies have addressed factors that contribute to declines as a result of failed recruitment. Further, a great deal of attention has focused on the role of pathogens in inducing diseases that cause death, but we suggest that pathogen success is profoundly affected by four other ultimate factors: atmospheric change, environmental pollutants, habitat modification and invasive species. Environmental pollutants arise as likely important factors in amphibian declines because they have realized potential to affect recruitment. Further, many studies have documented immunosuppressive effects of pesticides, suggesting a role for environmental contaminants in increased pathogen virulence and disease rates. Increased attention to recruitment and ultimate factors that interact with pathogens is important in addressing this global crisis.

The cause of global amphibian declines: a developmental endocrinologist's perspective

PubMed Central

Hayes, T. B.; Falso, P.; Gallipeau, S.; Stice, M.

2010-01-01

Greater than 70% of the world's amphibian species are in decline. We propose that there is probably not a single cause for global amphibian declines and present a three-tiered hierarchical approach that addresses interactions among and between ultimate and proximate factors that contribute to amphibian declines. There are two immediate (proximate) causes of amphibian declines: death and decreased recruitment (reproductive failure). Although much attention has focused on death, few studies have addressed factors that contribute to declines as a result of failed recruitment. Further, a great deal of attention has focused on the role of pathogens in inducing diseases that cause death, but we suggest that pathogen success is profoundly affected by four other ultimate factors: atmospheric change, environmental pollutants, habitat modification and invasive species. Environmental pollutants arise as likely important factors in amphibian declines because they have realized potential to affect recruitment. Further, many studies have documented immunosuppressive effects of pesticides, suggesting a role for environmental contaminants in increased pathogen virulence and disease rates. Increased attention to recruitment and ultimate factors that interact with pathogens is important in addressing this global crisis. PMID:20190117

Tuberculosis in Antelopes in a Zoo in Poland--Problem of Public Health.

PubMed

Krajewska, Monika; Załuski, Michał; Zabost, Anna; Orłowska, Blanka; Augustynowicz-Kopeć, Ewa; Anusz, Krzysztof; Lipiec, Marek; Weiner, Marcin; Szulowski, Krzysztof

2015-01-01

Bovine tuberculosis is an infectious disease that occurs in many species of both domestic and wild animals, as well as those held in captivity. The etiological factor is the acid resistant bacillus (Mycobacterium bovis or Mycobacterium caprae), which is characterized by the major pathogenicity among mycobacteria belonging to the Mycobacterium tuberculosis complex. The material from 8 antelopes from the zoo, suspected for tuberculosis were examined, and M. bovis strains were isolated from 6 of them. The spoligotyping method showing spoligo pattern 676763777777600. In Poland, this spoligotype has not been observed so far.

MANAGING WATERBORNE PATHOGENS ASSOCIATED WITH CONCENTRATED ANIMAL FEEDING OPERATIONS

EPA Science Inventory

Pathogenic microorganisms of fecal origin are the leading cause of river and stream impairments in the United States. Runoff from agricultural operations, particularly animal agricultural, can be a major contributor of fecal microbial pollution in a watershed. Several management...

The effects of demographic, social, and environmental characteristics on pathogen prevalence in wild felids across a gradient of urbanization

PubMed Central

Logan, Kenneth A.; Alldredge, Mat W.; Carver, Scott; Bevins, Sarah N.; Lappin, Michael; VandeWoude, Sue; Crooks, Kevin R.

2017-01-01

Transmission of pathogens among animals is influenced by demographic, social, and environmental factors. Anthropogenic alteration of landscapes can impact patterns of disease dynamics in wildlife populations, increasing the potential for spillover and spread of emerging infectious diseases in wildlife, human, and domestic animal populations. We evaluated the effects of multiple ecological mechanisms on patterns of pathogen exposure in animal populations. Specifically, we evaluated how ecological factors affected the prevalence of Toxoplasma gondii (Toxoplasma), Bartonella spp. (Bartonella), feline immunodeficiency virus (FIV), and feline calicivirus (FCV) in bobcat and puma populations across wildland-urban interface (WUI), low-density exurban development, and wildland habitat on the Western Slope (WS) and Front Range (FR) of Colorado during 2009–2011. Samples were collected from 37 bobcats and 29 pumas on the WS and FR. As predicted, age appeared to be positively related to the exposure to pathogens that are both environmentally transmitted (Toxoplasma) and directly transmitted between animals (FIV). In addition, WS bobcats appeared more likely to be exposed to Toxoplasma with increasing intraspecific space-use overlap. However, counter to our predictions, exposure to directly-transmitted pathogens (FCV and FIV) was more likely with decreasing space-use overlap (FCV: WS bobcats) and potential intraspecific contacts (FIV: FR pumas). Environmental factors, including urbanization and landscape covariates, were generally unsupported in our models. This study is an approximation of how pathogens can be evaluated in relation to demographic, social, and environmental factors to understand pathogen exposure in wild animal populations. PMID:29121060

Dynamics of E.coli virulence factors in dairy cow herds

USDA-ARS?s Scientific Manuscript database

Background. Dairy farms are known reservoirs of entero-pathogenic E. coli (EPEC). EPEC, or the virulence factors associated with pathogenicity, have been detected in manure, milk, and the farm environment. However, it is unclear which farm compartments are reservoirs contributing to EPEC persistence...

Human milk inactivates pathogens individually, additively, and synergistically.

PubMed

Isaacs, Charles E

2005-05-01

Breast-feeding can reduce the incidence and the severity of gastrointestinal and respiratory infections in the suckling neonate by providing additional protective factors to the infant's mucosal surfaces. Human milk provides protection against a broad array of infectious agents through redundancy. Protective factors in milk can target multiple early steps in pathogen replication and target each step with more than one antimicrobial compound. The antimicrobial activity in human milk results from protective factors working not only individually but also additively and synergistically. Lipid-dependent antimicrobial activity in milk results from the additive activity of all antimicrobial lipids and not necessarily the concentration of one particular lipid. Antimicrobial milk lipids and peptides can work synergistically to decrease both the concentrations of individual compounds required for protection and, as importantly, greatly reduce the time needed for pathogen inactivation. The more rapidly pathogens are inactivated the less likely they are to establish an infection. The total antimicrobial protection provided by human milk appears to be far more than can be elucidated by examining protective factors individually.

Social and behavioral barriers to pathogen transmission in wild animal populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loehle, C.S.

Disease and pathogens have been studied as regulators of animal populations but not really as selective forces. The authors propose that pathogens can be major selective forces influencing social behaviors when these are successful at reducing disease transmission. The behaviors whose evolution could have been influenced by pathogen effects include group size, group isolation, mixed species flocking, migration, seasonal sociality, social avoidance, and dominance behaviors. Mate choice, mating system, and sexual selection are put in a new light when examined in terms of disease transmission. It is concluded that pathogen avoidance is a more powerful selective force than has heretoforemore » been recognized.« less

Secretome Analysis Identifies Potential Pathogenicity/Virulence Factors of Tilletia indica, a Quarantined Fungal Pathogen Inciting Karnal Bunt Disease in Wheat.

PubMed

Pandey, Vishakha; Singh, Manoj; Pandey, Dinesh; Marla, Soma; Kumar, Anil

2018-04-01

Tilletia indica is a smut fungus that incites Karnal bunt in wheat. It has been considered as quarantine pest in more than 70 countries. Despite its quarantine significance, there is meager knowledge regarding the molecular mechanisms of disease pathogenesis. Moreover, various disease management strategies have proven futile. Development of effective disease management strategy requires identification of pathogenicity/virulence factors. With this aim, the present study was conducted to compare the secretomes of T. indica isolates, that is, highly (TiK) and low (TiP) virulent isolates. About 120 and 95 protein spots were detected reproducibly in TiK and TiP secretome gel images. Nineteen protein spots, which were consistently observed as upregulated/differential in the secretome of TiK isolate, were selected for their identification by MALDI-TOF/TOF. Identified proteins exhibited homology with fungal proteins playing important role in fungal adhesion, penetration, invasion, protection against host-derived reactive oxygen species, production of virulence factors, cellular signaling, and degradation of host cell wall proteins and antifungal proteins. These results were complemented with T. indica genome sequence leading to identification of candidate pathogenicity/virulence factors homologs that were further subjected to sequence- and structure-based functional annotation. Thus, present study reports the first comparative secretome analysis of T. indica for identification of pathogenicity/virulence factors. This would provide insights into pathogenic mechanisms of T. indica and aid in devising effective disease management strategies. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Climate extremes promote fatal co-infections during canine distemper epidemics in African lions.

PubMed

Munson, Linda; Terio, Karen A; Kock, Richard; Mlengeya, Titus; Roelke, Melody E; Dubovi, Edward; Summers, Brian; Sinclair, Anthony R E; Packer, Craig

2008-06-25

Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five "silent" CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become increasingly common if climate extremes disrupt historic stable relationships between co-existing pathogens and their susceptible hosts.

Climate Extremes Promote Fatal Co-Infections during Canine Distemper Epidemics in African Lions

PubMed Central

Munson, Linda; Terio, Karen A.; Kock, Richard; Mlengeya, Titus; Roelke, Melody E.; Dubovi, Edward; Summers, Brian; Sinclair, Anthony R. E.; Packer, Craig

2008-01-01

Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five “silent” CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become increasingly common if climate extremes disrupt historic stable relationships between co-existing pathogens and their susceptible hosts. PMID:18575601

Factors Affecting the Initial Adhesion and Retention of the Plant Pathogen Xylella fastidiosa in the Foregut of an Insect Vector

PubMed Central

Almeida, Rodrigo P. P.

2014-01-01

Vector transmission of bacterial plant pathogens involves three steps: pathogen acquisition from an infected host, retention within the vector, and inoculation of cells into susceptible tissue of an uninfected plant. In this study, a combination of plant and artificial diet systems were used to determine the importance of several genes on the initial adhesion and retention of the bacterium Xylella fastidiosa to an efficient insect vector. Mutant strains included fimbrial (fimA and pilB) and afimbrial (hxfA and hxfB) adhesins and three loci involved in regulatory systems (rpfF, rpfC, and cgsA). Transmission assays with variable retention time indicated that HxfA and HxfB were primarily important for early adhesion to vectors, while FimA was necessary for both adhesion and retention. The long pilus protein PilB was not deficient in initial adhesion but may be important for retention. Genes upregulated under the control of rpfF are important for both initial adhesion and retention, as transmission rates of this mutant strain were initially low and decreased over time, while disruption of rpfC and cgsA yielded trends similar to that shown by the wild-type control. Because induction of an X. fastidiosa transmissible state requires pectin, a series of experiments were used to test the roles of a polygalacturonase (pglA) and the pectin and galacturonic acid carbohydrates on the transmission of X. fastidiosa. Results show that galacturonic acid, or PglA activity breaking pectin into its major subunit (galacturonic acid), is required for X. fastidiosa vector transmission using an artificial diet system. This study shows that early adhesion and retention of X. fastidiosa are mediated by different factors. It also illustrates that the interpretation of results of vector transmission experiments, in the context of vector-pathogen interaction studies, is highly dependent on experimental design. PMID:24185853

Factors affecting the initial adhesion and retention of the plant pathogen Xylella fastidiosa in the foregut of an insect vector.

PubMed

Killiny, Nabil; Almeida, Rodrigo P P

2014-01-01

Vector transmission of bacterial plant pathogens involves three steps: pathogen acquisition from an infected host, retention within the vector, and inoculation of cells into susceptible tissue of an uninfected plant. In this study, a combination of plant and artificial diet systems were used to determine the importance of several genes on the initial adhesion and retention of the bacterium Xylella fastidiosa to an efficient insect vector. Mutant strains included fimbrial (fimA and pilB) and afimbrial (hxfA and hxfB) adhesins and three loci involved in regulatory systems (rpfF, rpfC, and cgsA). Transmission assays with variable retention time indicated that HxfA and HxfB were primarily important for early adhesion to vectors, while FimA was necessary for both adhesion and retention. The long pilus protein PilB was not deficient in initial adhesion but may be important for retention. Genes upregulated under the control of rpfF are important for both initial adhesion and retention, as transmission rates of this mutant strain were initially low and decreased over time, while disruption of rpfC and cgsA yielded trends similar to that shown by the wild-type control. Because induction of an X. fastidiosa transmissible state requires pectin, a series of experiments were used to test the roles of a polygalacturonase (pglA) and the pectin and galacturonic acid carbohydrates on the transmission of X. fastidiosa. Results show that galacturonic acid, or PglA activity breaking pectin into its major subunit (galacturonic acid), is required for X. fastidiosa vector transmission using an artificial diet system. This study shows that early adhesion and retention of X. fastidiosa are mediated by different factors. It also illustrates that the interpretation of results of vector transmission experiments, in the context of vector-pathogen interaction studies, is highly dependent on experimental design.

Assessment of Cpa, Scl1 and Scl2 in clinical group A streptococcus isolates and patients from north India: an evaluation of the host pathogen interaction.

PubMed

Chaudhary, Priyanka; Kumar, Rajesh; Sagar, Vivek; Sarkar, Subendu; Singh, Rupneet; Ghosh, Sujata; Singh, Surjit; Chakraborti, Anuradha

2018-01-01

Group A streptococcus (GAS) infection remains a major concern due to multiple diseases including pharyngitis, impetigo, acute rheumatic fever (ARF) and rheumatic heart disease (RHD). It uses different adhesins and virulence factors like Cpa (collagen binding protein) and Scl (collagen-like protein) in its pathogenicity. Scl having similarities with human collagen may contribute to inducing autoimmunity in the host. Here we assessed gene expression, antibody titer of Cpa, Scl1 and Scl2 in both clinical GAS isolates (n = 45) and blood (n = 45) obtained from pharyngitis, ARF (acute rheumatic fever) and RHD respectively. Skin isolates (n = 30) were obtained from impetigo patients. The study revealed a total of 27 GAS emm types. Frequency of cpa, scl1, scl2 was high in ARF isolates. The antibody titer of these proteins was high in all isolates, and also in patients with pharyngitis and ARF. All isolates showed high binding affinity toward collagen I and IV, which further indicates a potential host pathogen interaction. Our study reflects a strong association of Cpa and Scls in early and post-GAS pathogenicity. However, the increased antibody titer of Scl1 and Scl2 during ARF may be attributed to a cogent immune response in the host. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Manipulation of Neutrophils by Porphyromonas gingivalis in the Development of Periodontitis

PubMed Central

Sochalska, Maja; Potempa, Jan

2017-01-01

The pathogenesis of the chronic periodontal disease is associated with a skewed host inflammatory response to periodontal pathogens, such as Porphyromonas gingivalis, that accounts for the majority of periodontal tissue damage. Neutrophils are the most abundant leukocytes in periodontal pockets and depending on the stage of the disease, also plentiful PMNs are present in the inflamed gingival tissue and the gingival crevice. They are the most efficient phagocytes and eliminate pathogens by a variety of means, which are either oxygen-dependent or -independent. However, these secretory lethal weapons do not strictly discriminate between pathogens and host tissue. Current studies describe conflicting findings about neutrophil involvement in periodontal disease. On one hand literature indicate that hyper-reactive neutrophils are the main immune cell type responsible for this observed tissue damage and disease progression. Deregulation of neutrophil survival and functions, such as chemotaxis, migration, secretion of antimicrobial peptides or enzymes, and production of reactive oxygen species, contribute to observed tissue injury and the clinical signs of periodontal disease. On the other hand neutrophils deficiencies in patients and mice also result in periodontal phenotype. Therefore, P. gingivalis represents a periodontal pathogen that manipulates the immune responses of PMNs, employing several virulence factors, such as gingipains, serine proteases, lipid phosphatases, or fimbriae. This review will sum up studies devoted to understanding different strategies utilized by P. gingivalis to manipulate PMNs survival and functions in order to inhibit killing by a granular content, prolong inflammation, and gain access to nutrient resources. PMID:28589098

Contamination of water resources by pathogenic bacteria

PubMed Central

2014-01-01

Water-borne pathogen contamination in water resources and related diseases are a major water quality concern throughout the world. Increasing interest in controlling water-borne pathogens in water resources evidenced by a large number of recent publications clearly attests to the need for studies that synthesize knowledge from multiple fields covering comparative aspects of pathogen contamination, and unify them in a single place in order to present and address the problem as a whole. Providing a broader perceptive of pathogen contamination in freshwater (rivers, lakes, reservoirs, groundwater) and saline water (estuaries and coastal waters) resources, this review paper attempts to develop the first comprehensive single source of existing information on pathogen contamination in multiple types of water resources. In addition, a comprehensive discussion describes the challenges associated with using indicator organisms. Potential impacts of water resources development on pathogen contamination as well as challenges that lie ahead for addressing pathogen contamination are also discussed. PMID:25006540

Predictive compound accumulation rules yield a broad-spectrum antibiotic

NASA Astrophysics Data System (ADS)

Richter, Michelle F.; Drown, Bryon S.; Riley, Andrew P.; Garcia, Alfredo; Shirai, Tomohiro; Svec, Riley L.; Hergenrother, Paul J.

2017-05-01

Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs against these pathogens challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negative bacteria is largely based on retrospective analyses of antibacterial agents, which suggest that polarity and molecular weight are key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate that these findings will aid in the discovery and development of antibiotics against Gram-negative bacteria.

Immunopathogenesis of Staphylococcus aureus pulmonary infection

PubMed Central

Parker, Dane; Prince, Alice

2013-01-01

Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the α-hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia. PMID:22037948

Predictive rules for compound accumulation yield a broad-spectrum antibiotic

PubMed Central

Richter, Michelle F.; Drown, Bryon S.; Riley, Andrew P.; Garcia, Alfredo; Shirai, Tomohiro; Svec, Riley L.; Hergenrother, Paul J.

2017-01-01

Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs for these pathogens very challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negatives is largely based on retrospective analyses of antibacterials that suggest polarity and molecular weight as key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate these findings will aid in the discovery and development of antibiotics effective against Gram-negative bacteria. PMID:28489819

Accumulation of anthocyanins in tomato skin extends shelf life.

PubMed

Bassolino, Laura; Zhang, Yang; Schoonbeek, Henk-Jan; Kiferle, Claudia; Perata, Pierdomenico; Martin, Cathie

2013-11-01

Shelf life is one of the most important traits for the tomato (Solanum lycopersicum) industry. Two key factors, post-harvest over-ripening and susceptibility to post-harvest pathogen infection, determine tomato shelf life. Anthocyanins accumulate in the skin of Aft/Aft atv/atv tomatoes, the result of introgressing alleles affecting anthocyanin biosynthesis in fruit from two wild relatives of tomato, which results in extended fruit shelf life. Compared with ordinary, anthocyanin-less tomatoes, the fruits of Aft/Aft atv/atv keep longer during storage and are less susceptible to Botrytis cinerea, a major tomato pathogen, post-harvest. Using genetically modified tomatoes over-producing anthocyanins, we confirmed that skin-specific accumulation of anthocyanins in tomato is sufficient to reduce the susceptibility of fruit to Botrytis cinerea. Our data indicate that accumulation of anthocyanins in tomato fruit, achieved either by traditional breeding or genetic engineering can be an effective way to extend tomato shelf life. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

ATG16L1: A multifunctional susceptibility factor in Crohn disease

PubMed Central

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

2015-01-01

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease. PMID:25906181

ATG16L1: A multifunctional susceptibility factor in Crohn disease.

PubMed

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

2015-04-03

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease.

Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis

PubMed Central

Mercer, Frances; Ng, Shek Hang; Brown, Taylor M.; Boatman, Grace; Johnson, Patricia J.

2018-01-01

T. vaginalis, a human-infective parasite, causes the most common nonviral sexually transmitted infection (STI) worldwide and contributes to adverse inflammatory disorders. The immune response to T. vaginalis is poorly understood. Neutrophils (polymorphonuclear cells [PMNs]) are the major immune cell present at the T. vaginalis–host interface and are thought to clear T. vaginalis. However, the mechanism of PMN clearance of T. vaginalis has not been characterized. We demonstrate that human PMNs rapidly kill T. vaginalis in a dose-dependent, contact-dependent, and neutrophil extracellular trap (NET)-independent manner. In contrast to phagocytosis, we observed that PMN killing of T. vaginalis involves taking “bites” of T. vaginalis prior to parasite death, using trogocytosis to achieve pathogen killing. Both trogocytosis and parasite killing are dependent on the presence of PMN serine proteases and human serum factors. Our analyses provide the first demonstration, to our knowledge, of a mammalian phagocyte using trogocytosis for pathogen clearance and reveal a novel mechanism used by PMNs to kill a large, highly motile target. PMID:29408891

The Problem of Auto-Correlation in Parasitology

PubMed Central

Pollitt, Laura C.; Reece, Sarah E.; Mideo, Nicole; Nussey, Daniel H.; Colegrave, Nick

2012-01-01

Explaining the contribution of host and pathogen factors in driving infection dynamics is a major ambition in parasitology. There is increasing recognition that analyses based on single summary measures of an infection (e.g., peak parasitaemia) do not adequately capture infection dynamics and so, the appropriate use of statistical techniques to analyse dynamics is necessary to understand infections and, ultimately, control parasites. However, the complexities of within-host environments mean that tracking and analysing pathogen dynamics within infections and among hosts poses considerable statistical challenges. Simple statistical models make assumptions that will rarely be satisfied in data collected on host and parasite parameters. In particular, model residuals (unexplained variance in the data) should not be correlated in time or space. Here we demonstrate how failure to account for such correlations can result in incorrect biological inference from statistical analysis. We then show how mixed effects models can be used as a powerful tool to analyse such repeated measures data in the hope that this will encourage better statistical practices in parasitology. PMID:22511865

Computational Analysis Reveals a Key Regulator of Cryptococcal Virulence and Determinant of Host Response

PubMed Central

Gish, Stacey R.; Maier, Ezekiel J.; Haynes, Brian C.; Santiago-Tirado, Felipe H.; Srikanta, Deepa L.; Ma, Cynthia Z.; Li, Lucy X.; Williams, Matthew; Crouch, Erika C.; Khader, Shabaana A.

2016-01-01

ABSTRACT Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen that kills over 600,000 people annually. Here, we report integrated computational and experimental investigations of the role and mechanisms of transcriptional regulation in cryptococcal infection. Major cryptococcal virulence traits include melanin production and the development of a large polysaccharide capsule upon host entry; shed capsule polysaccharides also impair host defenses. We found that both transcription and translation are required for capsule growth and that Usv101 is a master regulator of pathogenesis, regulating melanin production, capsule growth, and capsule shedding. It does this by directly regulating genes encoding glycoactive enzymes and genes encoding three other transcription factors that are essential for capsule growth: GAT201, RIM101, and SP1. Murine infection with cryptococci lacking Usv101 significantly alters the kinetics and pathogenesis of disease, with extended survival and, unexpectedly, death by pneumonia rather than meningitis. Our approaches and findings will inform studies of other pathogenic microbes. PMID:27094327

Wildlife health in a rapidly changing North: focus on avian disease

USGS Publications Warehouse

Van Hemert, Caroline R.; Pearce, John M.; Handel, Colleen M.

2014-01-01

Climate-related environmental changes have increasingly been linked to emerging infectious diseases in wildlife. The Arctic is facing a major ecological transition that is expected to substantially affect animal and human health. Changes in phenology or environmental conditions that result from climate warming may promote novel species assemblages as host and pathogen ranges expand to previously unoccupied areas. Recent evidence from the Arctic and subarctic suggests an increase in the spread and prevalence of some wildlife diseases, but baseline data necessary to detect and verify such changes are still lacking. Wild birds are undergoing rapid shifts in distribution and have been implicated in the spread of wildlife and zoonotic diseases. Here, we review evidence of current and projected changes in the abundance and distribution of avian diseases and outline strategies for future research. We discuss relevant climatic and environmental factors, emerging host–pathogen contact zones, the relationship between host condition and immune function, and potential wildlife and human health outcomes in northern regions.

PATHOGEN MONITORING - OLD BAGGAGE FROM THE LAST MILLENIUM

EPA Science Inventory

Pathogen monitoring has concerned microbiologists for nearly a century. Over several years, numerous factors have inflated the value of pathogen monitoring for public health protection and led to such developments as the promulgation of the Information Collection Rule (ICR). Eigh...

First report of an Armillaria root disease pathogen, Armillaria gallica, associated with several new hosts in Hawaii

Treesearch

M.-S. Kim; J. W. Hanna; N. B. Klopfenstein

2010-01-01

The loss and decline of native tree species caused by invasive plant pathogens is a major threat to the endangered endemic forests of the Hawaiian Islands (3). Thus, it is critical to characterize existing pathogens to evaluate potential invasiveness. In August 2005, rhizomorphs and mycelial bark fans of genet HI-4 were collected from dead/declining, mature trees of...

Vectors as Epidemiological Sentinels: Patterns of Within-Tick Borrelia burgdorferi Diversity

PubMed Central

Walter, Katharine S.; Carpi, Giovanna; Evans, Benjamin R.; Caccone, Adalgisa; Diuk-Wasser, Maria A.

2016-01-01

Hosts including humans, other vertebrates, and arthropods, are frequently infected with heterogeneous populations of pathogens. Within-host pathogen diversity has major implications for human health, epidemiology, and pathogen evolution. However, pathogen diversity within-hosts is difficult to characterize and little is known about the levels and sources of within-host diversity maintained in natural populations of disease vectors. Here, we examine genomic variation of the Lyme disease bacteria, Borrelia burgdorferi (Bb), in 98 individual field-collected tick vectors as a model for study of within-host processes. Deep population sequencing reveals extensive and previously undocumented levels of Bb variation: the majority (~70%) of ticks harbor mixed strain infections, which we define as levels Bb diversity pre-existing in a diverse inoculum. Within-tick diversity is thus a sample of the variation present within vertebrate hosts. Within individual ticks, we detect signatures of positive selection. Genes most commonly under positive selection across ticks include those involved in dissemination in vertebrate hosts and evasion of the vertebrate immune complement. By focusing on tick-borne Bb, we show that vectors can serve as epidemiological and evolutionary sentinels: within-vector pathogen diversity can be a useful and unbiased way to survey circulating pathogen diversity and identify evolutionary processes occurring in natural transmission cycles. PMID:27414806