Biogeography of Human Infectious Diseases: A Global Historical Analysis
Cashdan, Elizabeth
2014-01-01
Objectives Human pathogen richness and prevalence vary widely across the globe, yet we know little about whether global patterns found in other taxa also predict diversity in this important group of organisms. This study (a) assesses the relative importance of temperature, precipitation, habitat diversity, and population density on the global distributions of human pathogens and (b) evaluates the species-area predictions of island biogeography for human pathogen distributions on oceanic islands. Methods Historical data were used in order to minimize the influence of differential access to modern health care on pathogen prevalence. The database includes coded data (pathogen, environmental and cultural) for a worldwide sample of 186 non-industrial cultures, including 37 on islands. Prevalence levels for 10 pathogens were combined into a pathogen prevalence index, and OLS regression was used to model the environmental determinants of the prevalence index and number of pathogens. Results Pathogens (number and prevalence index) showed the expected latitudinal gradient, but predictors varied by latitude. Pathogens increased with temperature in high-latitude zones, while mean annual precipitation was a more important predictor in low-latitude zones. Other environmental factors associated with more pathogens included seasonal dry extremes, frost-free climates, and human population density outside the tropics. Islands showed the expected species-area relationship for all but the smallest islands, and the relationship was not mediated by habitat diversity. Although geographic distributions of free-living and parasitic taxa typically have different determinants, these data show that variables that influence the distribution of free-living organisms also shape the global distribution of human pathogens. Understanding the cause of these distributions is potentially important, since geographical variation in human pathogens has an important influence on global disparities in human welfare. PMID:25271730
Biogeography of human infectious diseases: a global historical analysis.
Cashdan, Elizabeth
2014-01-01
Human pathogen richness and prevalence vary widely across the globe, yet we know little about whether global patterns found in other taxa also predict diversity in this important group of organisms. This study (a) assesses the relative importance of temperature, precipitation, habitat diversity, and population density on the global distributions of human pathogens and (b) evaluates the species-area predictions of island biogeography for human pathogen distributions on oceanic islands. Historical data were used in order to minimize the influence of differential access to modern health care on pathogen prevalence. The database includes coded data (pathogen, environmental and cultural) for a worldwide sample of 186 non-industrial cultures, including 37 on islands. Prevalence levels for 10 pathogens were combined into a pathogen prevalence index, and OLS regression was used to model the environmental determinants of the prevalence index and number of pathogens. Pathogens (number and prevalence index) showed the expected latitudinal gradient, but predictors varied by latitude. Pathogens increased with temperature in high-latitude zones, while mean annual precipitation was a more important predictor in low-latitude zones. Other environmental factors associated with more pathogens included seasonal dry extremes, frost-free climates, and human population density outside the tropics. Islands showed the expected species-area relationship for all but the smallest islands, and the relationship was not mediated by habitat diversity. Although geographic distributions of free-living and parasitic taxa typically have different determinants, these data show that variables that influence the distribution of free-living organisms also shape the global distribution of human pathogens. Understanding the cause of these distributions is potentially important, since geographical variation in human pathogens has an important influence on global disparities in human welfare.
Lekshmi, Manjusha; Ammini, Parvathi; Kumar, Sanath; Varela, Manuel F
2017-03-14
Food-borne pathogens are a serious human health concern worldwide, and the emergence of antibiotic-resistant food pathogens has further confounded this problem. Once-highly-efficacious antibiotics are gradually becoming ineffective against many important pathogens, resulting in severe treatment crises. Among several reasons for the development and spread of antimicrobial resistance, their overuse in animal food production systems for purposes other than treatment of infections is prominent. Many pathogens of animals are zoonotic, and therefore any development of resistance in pathogens associated with food animals can spread to humans through the food chain. Human infections by antibiotic-resistant pathogens such as Campylobacter spp., Salmonella spp., Escherichia coli and Staphylococcus aureus are increasing. Considering the human health risk due to emerging antibiotic resistance in food animal-associated bacteria, many countries have banned the use of antibiotic growth promoters and the application in animals of antibiotics critically important in human medicine. Concerted global efforts are necessary to minimize the use of antimicrobials in food animals in order to control the development of antibiotic resistance in these systems and their spread to humans via food and water.
Biofilms in Water, Its role and impact in human disease transmission
2008-01-01
increasing realization of the importance of the world’s oceans as a source of potentially pathogenic microorganisms. Human bacterial pathogens...colorimetric microtitre model for the detection of Staphylococcus aureus biofilms. Lett Appl Microbiol 2008, 46:249-254. A new microplate model for...Polz M: Diversity, sources, and detection of human bacterial pathogens in the marine environment. In Oceans and Health: Pathogens in the Marine
Gauthier, Gregory M; Keller, Nancy P
2013-12-01
The outbreak of fungal meningitis associated with contaminated methylprednisolone acetate has thrust the importance of fungal infections into the public consciousness. The predominant pathogen isolated from clinical specimens, Exserohilum rostratum (teleomorph: Setosphaeria rostrata), is a dematiaceous fungus that infects grasses and rarely humans. This outbreak highlights the potential for fungal pathogens to infect both plants and humans. Most crossover or trans-kingdom pathogens are soil saprophytes and include fungi in Ascomycota and Mucormycotina phyla. To establish infection, crossover fungi must overcome disparate, host-specific barriers, including protective surfaces (e.g. cuticle, skin), elevated temperature, and immune defenses. This review illuminates the underlying mechanisms used by crossover fungi to cause infection in plants and mammals, and highlights critical events that lead to human infection by these pathogens. Several genes including veA, laeA, and hapX are important in regulating biological processes in fungi important for both invasive plant and animal infections. Copyright © 2013 Elsevier Inc. All rights reserved.
Interrelationships of food safety and plant pathology: the life cycle of human pathogens on plants.
Barak, Jeri D; Schroeder, Brenda K
2012-01-01
Bacterial food-borne pathogens use plants as vectors between animal hosts, all the while following the life cycle script of plant-associated bacteria. Similar to phytobacteria, Salmonella, pathogenic Escherichia coli, and cross-domain pathogens have a foothold in agricultural production areas. The commonality of environmental contamination translates to contact with plants. Because of the chronic absence of kill steps against human pathogens for fresh produce, arrival on plants leads to persistence and the risk of human illness. Significant research progress is revealing mechanisms used by human pathogens to colonize plants and important biological interactions between and among bacteria in planta. These findings articulate the difficulty of eliminating or reducing the pathogen from plants. The plant itself may be an untapped key to clean produce. This review highlights the life of human pathogens outside an animal host, focusing on the role of plants, and illustrates areas that are ripe for future investigation.
van Baarlen, Peter; van Belkum, Alex; Thomma, Bart P H J
2007-02-01
Relatively simple eukaryotic model organisms such as the genetic model weed plant Arabidopsis thaliana possess an innate immune system that shares important similarities with its mammalian counterpart. In fact, some human pathogens infect Arabidopsis and cause overt disease with human symptomology. In such cases, decisive elements of the plant's immune system are likely to be targeted by the same microbial factors that are necessary for causing disease in humans. These similarities can be exploited to identify elementary microbial pathogenicity factors and their corresponding targets in a green host. This circumvents important cost aspects that often frustrate studies in humans or animal models and, in addition, results in facile ethical clearance.
Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R
2017-06-01
Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides ; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients- Candida , Pneumocystis , and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.
Xing, Junji; Ly, Hinh
2014-01-01
ABSTRACT Arenavirus pathogens cause a wide spectrum of diseases in humans ranging from central nervous system disease to lethal hemorrhagic fevers with few treatment options. The reason why some arenaviruses can cause severe human diseases while others cannot is unknown. We find that the Z proteins of all known pathogenic arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Lassa, Junin, Machupo, Sabia, Guanarito, Chapare, Dandenong, and Lujo viruses, can inhibit retinoic acid-inducible gene 1 (RIG-i) and Melanoma Differentiation-Associated protein 5 (MDA5), in sharp contrast to those of 14 other nonpathogenic arenaviruses. Inhibition of the RIG-i-like receptors (RLRs) by pathogenic Z proteins is mediated by the protein-protein interactions of Z and RLRs, which lead to the disruption of the interactions between RLRs and mitochondrial antiviral signaling (MAVS). The Z-RLR interactive interfaces are located within the N-terminal domain (NTD) of the Z protein and the N-terminal CARD domains of RLRs. Swapping of the LCMV Z NTD into the nonpathogenic Pichinde virus (PICV) genome does not affect virus growth in Vero cells but significantly inhibits the type I interferon (IFN) responses and increases viral replication in human primary macrophages. In summary, our results show for the first time an innate immune-system-suppressive mechanism shared by the diverse pathogenic arenaviruses and thus shed important light on the pathogenic mechanism of human arenavirus pathogens. IMPORTANCE We show that all known human-pathogenic arenaviruses share an innate immune suppression mechanism that is based on viral Z protein-mediated RLR inhibition. Our report offers important insights into the potential mechanism of arenavirus pathogenesis, provides a convenient way to evaluate the pathogenic potential of known and/or emerging arenaviruses, and reveals a novel target for the development of broad-spectrum therapies to treat this group of diverse pathogens. More broadly, our report provides a better understanding of the mechanisms of viral immune suppression and host-pathogen interactions. PMID:25552708
Hemocytes from Pediculus humanus humanus are hosts for human bacterial pathogens
Coulaud, Pierre-Julien; Lepolard, Catherine; Bechah, Yassina; Berenger, Jean-Michel; Raoult, Didier; Ghigo, Eric
2015-01-01
Pediculus humanus humanus is an human ectoparasite which represents a serious public health threat because it is vector for pathogenic bacteria. It is important to understand and identify where bacteria reside in human body lice to define new strategies to counterstroke the capacity of vectorization of the bacterial pathogens by body lice. It is known that phagocytes from vertebrates can be hosts or reservoirs for several microbes. Therefore, we wondered if Pediculus humanus humanus phagocytes could hide pathogens. In this study, we characterized the phagocytes from Pediculus humanus humanus and evaluated their contribution as hosts for human pathogens such as Rickettsia prowazekii, Bartonella Quintana, and Acinetobacter baumannii. PMID:25688336
Paillot, Romain; Steward, Karen F.; Webb, Katy; Ainslie, Fern; Jourdan, Thibaud; Bason, Nathalie C.; Holroyd, Nancy E.; Mungall, Karen; Quail, Michael A.; Sanders, Mandy; Simmonds, Mark; Willey, David; Brooks, Karen; Aanensen, David M.; Spratt, Brian G.; Jolley, Keith A.; Maiden, Martin C. J.; Kehoe, Michael; Chanter, Neil; Bentley, Stephen D.; Robinson, Carl; Maskell, Duncan J.; Parkhill, Julian; Waller, Andrew S.
2009-01-01
The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A2 toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci. PMID:19325880
Gerstein, Aleeza C; Nielsen, Kirsten
2017-04-01
Cryptococcus is predominantly an AIDS-related pathogen that causes significant morbidity and mortality in immunocompromised patients. Research studies have historically focused on understanding how the organism causes human disease through the use of in vivo and in vitro model systems to identify virulence factors. Cryptococcus is not an obligate pathogen, however, as human-human transmission is either absent or rare. Selection in the environment must thus be invoked to shape the evolution of this taxa, and directly influences genotypic and trait diversity. Importantly, the evolution and maintenance of pathogenicity must also stem directly from environmental selection. To that end, here we examine abiotic and biotic stresses in the environment, and discuss how they could shape the factors that are commonly identified as important virulence traits. We identify a number of important unanswered questions about Cryptococcus diversity and evolution that are critical for understanding this deadly pathogen, and discuss how implementation of modern sampling and genomic tools could be utilized to answer these questions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Three microsporidial species from the genus Encephalitozoon, E. hellem, E. cuniculi and E. intestinalis, have emerged as important opportunistic pathogens of humans affecting organ transplant recipients, AIDS patients, and other immunocompromised patients. Even though these thre...
Risks Posed by Reston, the Forgotten Ebolavirus
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
Human soil-borne pathogens and risks associated with land use change
NASA Astrophysics Data System (ADS)
Pereg, Lily
2017-04-01
Soil is a source of pathogenic, neutral and beneficial microorganisms. Natural events and anthropogenic activity can affect soil biodiversity and influence the balance and distribution of soil-borne human pathogens. Important bacterial and fungal pathogens, such as Bacillus anthracis, Coxiella bernetii, Clostridium tetani, Escherichia coli 0157:H7, Listeria monocytogenes, Aspergillus fumigatus and Sporothrix schenckii will be discussed. This presentation will concentrate on soil pathogenic microorganisms and the effects of land use change on their prevalence and distribution. In particular, the potential of agricultural soil cultivation to enhance pathogen transmission to human through the release of soil microbes into the air attached to dust particles, contamination of waterways and infection of food plants and animal. Emerging solutions, such as biocontrol and probiotics, will be discussed.
The bacterial microbiome of dermacentor andersoni ticks influences pathogen susceptibility
USDA-ARS?s Scientific Manuscript database
Ticks are of medical and veterinary importance due to their ability to transmit pathogens to humans and animals. The Rocky Mountain wood tick, Dermacentor andersoni, is a vector of a number of pathogens, including Anaplasma marginale, which is the most widespread tick-borne pathogen of livestock. Al...
Evaluating the importance of faecal sources in human-impacted waters.
Schoen, Mary E; Soller, Jeffrey A; Ashbolt, Nicholas J
2011-04-01
Quantitative microbial risk assessment (QMRA) was used to evaluate the relative contribution of faecal indicators and pathogens when a mixture of human sources impacts a recreational waterbody. The waterbody was assumed to be impacted with a mixture of secondary-treated disinfected municipal wastewater and untreated (or poorly treated) sewage, using Norovirus as the reference pathogen and enterococci as the reference faecal indicator. The contribution made by each source to the total waterbody volume, indicator density, pathogen density, and illness risk was estimated for a number of scenarios that accounted for pathogen and indicator inactivation based on the age of the effluent (source-to-receptor), possible sedimentation of microorganisms, and the addition of a non-pathogenic source of faecal indicators (such as old sediments or an animal population with low occurrence of human-infectious pathogens). The waterbody indicator density was held constant at 35 CFU 100 mL(-1) enterococci to compare results across scenarios. For the combinations evaluated, either the untreated sewage or the non-pathogenic source of faecal indicators dominated the recreational waterbody enterococci density assuming a culture method. In contrast, indicator density assayed by qPCR, pathogen density, and bather gastrointestinal illness risks were largely dominated by secondary disinfected municipal wastewater, with untreated sewage being increasingly less important as the faecal indicator load increased from a non-pathogenic source. The results support the use of a calibrated qPCR total enterococci indicator, compared to a culture-based assay, to index infectious human enteric viruses released in treated human wastewater, and illustrate that the source contributing the majority of risk in a mixture may be overlooked when only assessing faecal indicators by a culture-based method. Published by Elsevier Ltd.
The behavioural immune system and the psychology of human sociality.
Schaller, Mark
2011-12-12
Because immunological defence against pathogens is costly and merely reactive, human anti-pathogen defence is also characterized by proactive behavioural mechanisms that inhibit contact with pathogens in the first place. This behavioural immune system comprises psychological processes that infer infection risk from perceptual cues, and that respond to these perceptual cues through the activation of aversive emotions, cognitions and behavioural impulses. These processes are engaged flexibly, producing context-contingent variation in the nature and magnitude of aversive responses. These processes have important implications for human social cognition and social behaviour-including implications for social gregariousness, person perception, intergroup prejudice, mate preferences, sexual behaviour and conformity. Empirical evidence bearing on these many implications is reviewed and discussed. This review also identifies important directions for future research on the human behavioural immune system--including the need for enquiry into underlying mechanisms, additional behavioural consequences and implications for human health and well-being.
The behavioural immune system and the psychology of human sociality
Schaller, Mark
2011-01-01
Because immunological defence against pathogens is costly and merely reactive, human anti-pathogen defence is also characterized by proactive behavioural mechanisms that inhibit contact with pathogens in the first place. This behavioural immune system comprises psychological processes that infer infection risk from perceptual cues, and that respond to these perceptual cues through the activation of aversive emotions, cognitions and behavioural impulses. These processes are engaged flexibly, producing context–contingent variation in the nature and magnitude of aversive responses. These processes have important implications for human social cognition and social behaviour—including implications for social gregariousness, person perception, intergroup prejudice, mate preferences, sexual behaviour and conformity. Empirical evidence bearing on these many implications is reviewed and discussed. This review also identifies important directions for future research on the human behavioural immune system—including the need for enquiry into underlying mechanisms, additional behavioural consequences and implications for human health and well-being. PMID:22042918
Hostile takeover: Manipulation of HIF-1 signaling in pathogen-associated cancers (Review).
Zhu, Caixia; Zhu, Qing; Wang, Chong; Zhang, Liming; Wei, Fang; Cai, Qiliang
2016-10-01
Hypoxia-inducible factor (HIF)-1 is a central regulator in the adaptation process of cell response to hypoxia (low oxygen). Emerging evidence has demonstrated that HIF-1 plays an important role in the development and progression of many types of human diseases, including pathogen-associated cancers. In the present review, we summarize the recent understandings of how human pathogenic agents including viruses, bacteria and parasites deregulate cellular HIF-1 signaling pathway in their associated cancer cells, and highlight the common molecular mechanisms of HIF-1 signaling activated by these pathogenic infection, which could act as potential diagnostic markers and new therapeutic strategies against human infectious cancers.
Assessment of sources of human pathogens and fecal contamination in a Florida freshwater lake.
Staley, Christopher; Reckhow, Kenneth H; Lukasik, Jerzy; Harwood, Valerie J
2012-11-01
We investigated the potential for a variety of environmental reservoirs to harbor or contribute fecal indicator bacteria (FIB), DNA markers of human fecal contamination, and human pathogens to a freshwater lake. We hypothesized that submerged aquatic vegetation (SAV), sediments, and stormwater act as reservoirs and/or provide inputs of FIB and human pathogens to this inland water. Analysis included microbial source tracking (MST) markers of sewage contamination (Enterococcus faecium esp gene, human-associated Bacteroides HF183, and human polyomaviruses), pathogens (Salmonella, Cryptosporidium, Giardia, and enteric viruses), and FIB (fecal coliforms, Escherichia coli, and enterococci). Bayesian analysis was used to assess relationships among microbial and physicochemical variables. FIB in the water were correlated with concentrations in SAV and sediment. Furthermore, the correlation of antecedent rainfall and major rain events with FIB concentrations and detection of human markers and pathogens points toward multiple reservoirs for microbial contaminants in this system. Although pathogens and human-source markers were detected in 55% and 21% of samples, respectively, markers rarely coincided with pathogen detection. Bayesian analysis revealed that low concentrations (<45 CFU × 100 ml(-1)) of fecal coliforms were associated with 93% probability that pathogens would not be detected; furthermore the Bayes net model showed associations between elevated temperature and rainfall with fecal coliform and enterococci concentrations, but not E. coli. These data indicate that many under-studied matrices (e.g. SAV, sediment, stormwater) are important reservoirs for FIB and potentially human pathogens and demonstrate the usefulness of Bayes net analysis for water quality assessment. Copyright © 2012 Elsevier Ltd. All rights reserved.
The most important parasites in Serbia involving the foodborne route of transmission
NASA Astrophysics Data System (ADS)
Petrović, J. M.; Prodanov-Radulović, J. Z.; Vasilev, S. D.
2017-09-01
Food can be an important route for transmission of parasites to humans. Compared to other foodborne pathogens in Serbia, foodborne (or potentially foodborne) parasites do not get the attention they undoubtedly deserve. The aim of this article is to give an overview of the most important parasitic pathogens that can be transmitted by food, and that cause disease in humans: Echinococcus, Trichinella, Taenia solium and Toxoplasma gondii. For each of these pathogens, the severity of human diseases they cause, incidence, mortality and case fatality rate among humans in Serbia as well as their prevalence in animal species in Serbia are described. Some of the described foodborne parasites can induce severe disease symptoms in humans associated with high case fatality rates, while others can cause massive outbreaks. All of the aforementioned parasites occur throughout Serbia and cause both severe public health problems and substantial economic losses in livestock production. In conclusion, the control measures of foodborne parasites certainly need to include education of farmers and improvement of veterinary sanitary measures in animal farming and animal waste control.
Comparison of the h-Index Scores Among Pathogens Identified as Emerging Hazards in North America.
Cox, R; McIntyre, K M; Sanchez, J; Setzkorn, C; Baylis, M; Revie, C W
2016-02-01
Disease surveillance must assess the relative importance of pathogen hazards. Here, we use the Hirsch index (h-index) as a novel method to identify and rank infectious pathogens that are likely to be a hazard to human health in the North American region. This bibliometric index was developed to quantify an individual's scientific research output and was recently used as a proxy measure for pathogen impact. Analysis of more than 3000 infectious organisms indicated that 651 were human pathogen species that had been recorded in the North American region. The h-index of these pathogens ranged from 0 to 584. The h-index of emerging pathogens was greater than non-emerging pathogens as was the h-index of frequently pathogenic pathogens when compared to non-pathogenic pathogens. As expected, the h-index of pathogens varied over time between 1960 and 2011. We discuss how the h-index can contribute to pathogen prioritization and as an indicator of pathogen emergence. © 2014 Blackwell Verlag GmbH.
Neumann, Wilma; Hadley, Rose C.; Nolan, Elizabeth M.
2017-01-01
Transition metals are essential nutrients for all organisms and important players in the host-microbe interaction. During bacterial infection, a tug-of-war between the host and microbe for nutrient metals occurs: the host innate immune system responds to the pathogen by reducing metal availability and the pathogen tries to outmaneuver this response. The outcome of this competition, which involves metal-sequestering host-defense proteins and microbial metal acquisition machinery, is an important variable for whether infection occurs. One strategy bacterial pathogens employ to overcome metal restriction involves hijacking abundant host metalloproteins. The obligate human pathogens Neisseria spp. express TonB-dependent transport systems that capture human metalloproteins, extract the bound metal ions, and deliver these nutrients into the bacterial cell. This Essay highlights structural and mechanistic investigations that provide insights into how Neisseria acquire iron from the Fe(III)-transport protein transferrin, the Fe(III)-chelating host-defense protein lactoferrin, and the oxygen-transport protein hemoglobin, and obtain zinc from the metal-sequestering antimicrobial protein calprotectin. PMID:28487398
Nonribosomal peptide synthetase biosynthetic clusters of ESKAPE pathogens.
Gulick, Andrew M
2017-08-02
Covering: up to 2017.Natural products are important secondary metabolites produced by bacterial and fungal species that play important roles in cellular growth and signaling, nutrient acquisition, intra- and interspecies communication, and virulence. A subset of natural products is produced by nonribosomal peptide synthetases (NRPSs), a family of large, modular enzymes that function in an assembly line fashion. Because of the pharmaceutical activity of many NRPS products, much effort has gone into the exploration of their biosynthetic pathways and the diverse products they make. Many interesting NRPS pathways have been identified and characterized from both terrestrial and marine bacterial sources. Recently, several NRPS pathways in human commensal bacterial species have been identified that produce molecules with antibiotic activity, suggesting another source of interesting NRPS pathways may be the commensal and pathogenic bacteria that live on the human body. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) have been identified as a significant cause of human bacterial infections that are frequently multidrug resistant. The emerging resistance profile of these organisms has prompted calls from multiple international agencies to identify novel antibacterial targets and develop new approaches to treat infections from ESKAPE pathogens. Each of these species contains several NRPS biosynthetic gene clusters. While some have been well characterized and produce known natural products with important biological roles in microbial physiology, others have yet to be investigated. This review catalogs the NRPS pathways of ESKAPE pathogens. The exploration of novel NRPS products may lead to a better understanding of the chemical communication used by human pathogens and potentially to the discovery of novel therapeutic approaches.
Natural selection and infectious disease in human populations
Karlsson, Elinor K.; Kwiatkowski, Dominic P.; Sabeti, Pardis C.
2015-01-01
The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology. PMID:24776769
Walter, Katharine S.; Pepin, Kim M.; Webb, Colleen T.; Gaff, Holly D.; Krause, Peter J.; Pitzer, Virginia E.; Diuk-Wasser, Maria A.
2016-01-01
Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach—occupancy modelling—to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease. PMID:27252022
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-30
... enhance the lab capabilities to handle human pathogenic bacteria in animal feed. DATES: Important dates... supplemental grant funds will enable analyses of human pathogenic bacteria found in animal feed, for samples... bacteria in animal feed. This additional program will be compatible with other FERN Cooperative Agreement...
Human pathogens in plant biofilms: Formation, physiology, and detection
USDA-ARS?s Scientific Manuscript database
Fresh produce, viewed as an essential part of a healthy life style is usually consumed in the form of raw or minimally processed fruits and vegetables, and is a potentially important source of food-borne human pathogenic bacteria and viruses. These are passed on to the consumer since the bacteria ca...
Genomic Islands in Pathogenic Filamentous Fungus Aspergillus fumigatus
USDA-ARS?s Scientific Manuscript database
We present the genome sequences of a new clinical isolate, CEA10, of an important human pathogen, Aspergillus fumigatus, and two closely related, but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of CEA10 with the recently sequen...
USDA-ARS?s Scientific Manuscript database
Arthropods transmit a variety of important infectious diseases of humans and animals. Importantly, replication and development of pathogen infectivity is tightly linked to vector feeding on the mammalian host; thus analysis of the transcriptomes of both vector and pathogen during feeding is fundamen...
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.
Human Milk Blocks DC-SIGN–Pathogen Interaction via MUC1
Koning, Nathalie; Kessen, Sabine F. M.; Van Der Voorn, J. Patrick; Appelmelk, Ben J.; Jeurink, Prescilla V.; Knippels, Leon M. J.; Garssen, Johan; Van Kooyk, Yvette
2015-01-01
Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens and long-term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA or lactoferrin, the mechanisms of immune modulation are not fully understood. Recent studies identified important beneficial effects of glycans in human milk, such as those expressed in oligosaccharides or on glycoproteins. Glycans are recognized by the carbohydrate receptors C-type lectins on dendritic cell (DC) and specific tissue macrophages, which exert important functions in immune modulation and immune homeostasis. A well-characterized C-type lectin is dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), which binds terminal fucose. The present study shows that in human milk, MUC1 is the major milk glycoprotein that binds to the lectin domain of DC-SIGN and prevents pathogen interaction through the presence of Lewis x-type oligosaccharides. Surprisingly, this was specific for human milk, as formula, bovine or camel milk did not show any presence of proteins that interacted with DC-SIGN. The expression of DC-SIGN is found in young infants along the entire gastrointestinal tract. Our data thus suggest the importance of human milk glycoproteins for blocking pathogen interaction to DC in young children. Moreover, a potential benefit of human milk later in life in shaping the infants immune system through DC-SIGN cannot be ruled out. PMID:25821450
[New insight into bacterial zoonotic pathogens posing health hazards to humans].
Ciszewski, Marcin; Czekaj, Tomasz; Szewczyk, Eligia Maria
2014-01-01
This article presents the problem of evolutionary changes of zoonotic pathogens responsible for human diseases. Everyone is exposed to the risk of zoonotic infection, particularly employees having direct contact with animals, i.e. veterinarians, breeders, butchers and workers of animal products' processing industry. The article focuses on pathogens monitored by the European Centre for Disease Prevention and Control (ECDC), which has been collecting statistical data on zoonoses from all European Union countries for 19 years and publishing collected data in annual epidemiological reports. Currently, the most important 11 pathogens responsible for causing human zoonotic diseases are being monitored, of which seven are bacteria: Salmonella spp., Campylobacter spp., Listeria monocytogenes, Mycobacterium bovis, Brucella spp., Coxiella burnetti and Verotoxin-producing E. coli (VTEC)/Shiga-like toxin producing E. coli (STEC). As particularly important are considered foodborne pathogens. The article also includes new emerging zoonotic bacteria, which are not currently monitored by ECDC but might pose a serious epidemiological problem in a foreseeable future: Streptococcus iniae, S. suis, S. dysgalactiae and staphylococci: Staphylococcus intermedius, S. pseudintermedius. Those species have just crossed the animal-human interspecies barrier. The exact mechanism of this phenomenon remains unknown, it is connected, however, with genetic variability, capability to survive in changing environment. These abilities derive from DNA rearrangement and horizontal gene transfer between bacterial cells. Substantial increase in the number of scientific publications on this subject, observed over the last few years, illustrates the importance of the problem.
Tick-borne pathogens in tick species infesting humans in Sibiu County, central Romania.
Andersson, Martin O; Marga, Georgeta; Banu, Teofilia; Dobler, Gerhard; Chitimia-Dobler, Lidia
2018-05-01
Romania has a highly diverse tick fauna. Consequently, a high diversity of tick-transmitted pathogens might be a potential threat to humans. However, only a limited number of tick species regularly infest humans, and pathogens present in such species are therefore of particular interest from a medical perspective. In this study, 297 ticks were collected from humans during 2013 and 2014. Ixodes ricinus was the predominant tick species, accounting for 272 specimens or 91.6% of the ticks in the study. Nevertheless, other tick species were also found to infest humans: Dermacentor marginatus constituted 7% of the ticks found on humans (21/297), Haemaphysalis punctata 1% (3/297), and Haemaphysalis concinna 0.3% (1/297). Ticks were tested by PCR for a wide range of tick-borne pathogens. In total, 11.8% of the ticks carried human pathogenic bacteria, while no viral or protozoan pathogens were detected. The most frequently detected pathogen was Rickettsia spp., occurring in 5.4% of the ticks (16/297) and comprising three species: Rickettsia (R.) raoultii, R. monacensis, and R. helvetica. Borrelia s.l. occurred in 3% (9/297) of the ticks. "Candidatus Neoehrlichia mikurensis" occurred in 1.7% (5/297) and Anaplasma phagocytophilum in 1.3% (4/297). Anaplasma bovis was detected in an H. punctata and Borrelia miyamotoi in an I. ricinus. These results point to the need for further studies on the medical importance of tick-borne pathogens in Romania.
Field-applied manure is an important source of pathogenic exposure in surface water bodies for humans and ecological receptors. We analyzed the persistence and decay of fecal indicator bacteria and bacterial pathogens from three sources (cattle, poultry, swine) for agricultural f...
Schaumburg, Frieder; Mugisha, Lawrence; Peck, Bruce; Becker, Karsten; Gillespie, Thomas R; Peters, Georg; Leendertz, Fabian H
2012-12-01
Reintroduction of sanctuary apes to natural habitat is considered an important tool for conservation; however, reintroduction has the potential to endanger resident wild apes through the introduction of human pathogens. We found a high prevalence of drug-resistant, human-associated lineages of Staphylococcus aureus in sanctuary chimpanzees (Pan troglodytes) from Zambia and Uganda. This pathogen is associated with skin and soft tissue diseases and severe invasive infections (i.e. pneumonia and septicemia). Colonization by this bacterium is difficult to clear due to frequent recolonization. In addition to its pathogenic potential, human-related S. aureus can serve as an indicator organism for the transmission of other potential pathogens like pneumococci or mycobacteria. Plans to reintroduce sanctuary apes should be reevaluated in light of the high risk of introducing human-adapted S. aureus into wild ape populations where treatment is impossible. © 2012 Wiley Periodicals, Inc.
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
Reduced Set of Virulence Genes Allows High Accuracy Prediction of Bacterial Pathogenicity in Humans
Iraola, Gregorio; Vazquez, Gustavo; Spangenberg, Lucía; Naya, Hugo
2012-01-01
Although there have been great advances in understanding bacterial pathogenesis, there is still a lack of integrative information about what makes a bacterium a human pathogen. The advent of high-throughput sequencing technologies has dramatically increased the amount of completed bacterial genomes, for both known human pathogenic and non-pathogenic strains; this information is now available to investigate genetic features that determine pathogenic phenotypes in bacteria. In this work we determined presence/absence patterns of different virulence-related genes among more than finished bacterial genomes from both human pathogenic and non-pathogenic strains, belonging to different taxonomic groups (i.e: Actinobacteria, Gammaproteobacteria, Firmicutes, etc.). An accuracy of 95% using a cross-fold validation scheme with in-fold feature selection is obtained when classifying human pathogens and non-pathogens. A reduced subset of highly informative genes () is presented and applied to an external validation set. The statistical model was implemented in the BacFier v1.0 software (freely available at ), that displays not only the prediction (pathogen/non-pathogen) and an associated probability for pathogenicity, but also the presence/absence vector for the analyzed genes, so it is possible to decipher the subset of virulence genes responsible for the classification on the analyzed genome. Furthermore, we discuss the biological relevance for bacterial pathogenesis of the core set of genes, corresponding to eight functional categories, all with evident and documented association with the phenotypes of interest. Also, we analyze which functional categories of virulence genes were more distinctive for pathogenicity in each taxonomic group, which seems to be a completely new kind of information and could lead to important evolutionary conclusions. PMID:22916122
Corsi, Steven R.; Borchardt, Mark A.; Carvin, Rebecca B.; Burch, Tucker R; Spencer, Susan K.; Lutz, Michelle A.; McDermott, Colleen M.; Busse, Kimberly M.; Kleinheinz, Gregory; Feng, Xiaoping; Zhu, Jun
2016-01-01
Waterborne pathogens were measured at three beaches in Lake Michigan, environmental factors for predicting pathogen concentrations were identified, and the risk of swimmer infection and illness was estimated. Waterborne pathogens were detected in 96% of samples collected at three Lake Michigan beaches in summer, 2010. Samples were quantified for 22 pathogens in four microbial categories (human viruses, bovine viruses, protozoa, and pathogenic bacteria). All beaches had detections of human and bovine viruses and pathogenic bacteria indicating influence of multiple contamination sources at these beaches. Occurrence ranged from 40 to 87% for human viruses, 65–87% for pathogenic bacteria, and 13–35% for bovine viruses. Enterovirus, adenovirus A, Salmonella spp., Campylobacter jejuni, bovine polyomavirus, and bovine rotavirus A were present most frequently. Variables selected in multiple regression models used to explore environmental factors that influence pathogens included wave direction, cloud cover, currents, and water temperature. Quantitative Microbial Risk Assessment was done for C. jejuni, Salmonella spp., and enteroviruses to estimate risk of infection and illness. Median infection risks for one-time swimming events were approximately 3 × 10–5, 7 × 10–9, and 3 × 10–7 for C. jejuni, Salmonella spp., and enteroviruses, respectively. Results highlight the importance of investigating multiple pathogens within multiple categories to avoid underestimating the prevalence and risk of waterborne pathogens.
Conservation of Erwinia amylovora pathogenicity-relevant genes among Erwinia genomes.
Borruso, Luigimaria; Salomone-Stagni, Marco; Polsinelli, Ivan; Schmitt, Armin Otto; Benini, Stefano
2017-12-01
The Erwinia genus comprises species that are plant pathogens, non-pathogen, epiphytes, and opportunistic human pathogens. Within the genus, Erwinia amylovora ranks among the top 10 plant pathogenic bacteria. It causes the fire blight disease and is a global threat to commercial apple and pear production. We analyzed the presence/absence of the E. amylovora genes reported to be important for pathogenicity towards Rosaceae within various Erwinia strains genomes. This simple bottom-up approach, allowed us to correlate the analyzed genes to pathogenicity, host specificity, and make useful considerations to drive targeted studies.
USDA-ARS?s Scientific Manuscript database
Pseudomonas aeruginosa pathogenicity island 1 (PAPI-1) is one of the largest genomic islands of this important opportunistic human pathogen. Previous studies have shown that PAPI-1 encodes several putative virulence factors, a major regulator of biofilm formation, and antibiotic-resistance traits, a...
Yarham, John W.; Blakely, Emma L.; Alston, Charlotte L.; Roberts, Mark E.; Ealing, John; Pal, Piyali; Turnbull, Douglass M.; McFarland, Robert; Taylor, Robert W.
2013-01-01
Mitochondrial tRNA point mutations are important causes of human disease, and have been associated with a diverse range of clinical phenotypes. Definitively proving the pathogenicity of any given mt-tRNA mutation requires combined molecular, genetic and functional studies. Subsequent evaluation of the mutation using a pathogenicity scoring system is often very helpful in concluding whether or not the mutation is causing disease. Despite several independent reports linking the m.3291T>C mutation to disease in humans, albeit in association with several different phenotypes, its pathogenicity remains controversial. A lack of conclusive functional evidence and an over-emphasis on the poor evolutionary conservation of the affected nucleotide have contributed to this controversy. Here we describe an adult patient who presented with deafness and lipomas and evidence of mitochondrial abnormalities in his muscle biopsy, who harbours the m.3291T > C mutation, providing conclusive evidence of pathogenicity through analysis of mutation segregation with cytochrome c oxidase (COX) deficiency in single muscle fibres, underlining the importance of performing functional studies when assessing pathogenicity. PMID:23273904
Laboratory containment practices for arthropod vectors of human and animal pathogens.
Tabachnick, Walter J
2006-03-01
Arthropod-borne pathogens have an impact on the health and well-being of humans and animals throughout the world. Research involving arthropod vectors of disease is often dependent on the ability to maintain the specific arthropod species in laboratory colonies. The author reviews current arthropod containment practices and discusses their importance from public health and ecological perspectives.
USDA-ARS?s Scientific Manuscript database
Escherichia coli strains are important commensals of the intestinal tract of humans and animals; however, pathogenic strains, including diarrhea-inducing E. coli and extraintestinal pathogenic E. coli. Intestinal E. coli pathotypes may cause a dehydrating watery diarrhea, or more severe diseases su...
Recent human-to-poultry host jump, adaptation, and pandemic spread of Staphylococcus aureus.
Lowder, Bethan V; Guinane, Caitriona M; Ben Zakour, Nouri L; Weinert, Lucy A; Conway-Morris, Andrew; Cartwright, Robyn A; Simpson, A John; Rambaut, Andrew; Nübel, Ulrich; Fitzgerald, J Ross
2009-11-17
The impact of globalization on the emergence and spread of pathogens is an important veterinary and public health issue. Staphylococcus aureus is a notorious human pathogen associated with serious nosocomial and community-acquired infections. In addition, S. aureus is a major cause of animal diseases including skeletal infections of poultry, which are a large economic burden on the global broiler chicken industry. Here, we provide evidence that the majority of S. aureus isolates from broiler chickens are the descendants of a single human-to-poultry host jump that occurred approximately 38 years ago (range, 30 to 63 years ago) by a subtype of the worldwide human ST5 clonal lineage unique to Poland. In contrast to human subtypes of the ST5 radiation, which demonstrate strong geographic clustering, the poultry ST5 clade was distributed in different continents, consistent with wide dissemination via the global poultry industry distribution network. The poultry ST5 clade has undergone genetic diversification from its human progenitor strain by acquisition of novel mobile genetic elements from an avian-specific accessory gene pool, and by the inactivation of several proteins important for human disease pathogenesis. These genetic events have resulted in enhanced resistance to killing by chicken heterophils, reflecting avian host-adaptive evolution. Taken together, we have determined the evolutionary history of a major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. These data provide a new paradigm for the impact of human activities on the emergence of animal pathogens.
Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus.
Collado, M C; Meriluoto, J; Salminen, S
2007-10-01
The aims of this study present were to assess and to evaluate in vitro the abilities of commercial probiotic strains derived from fermented milk products and related sources currently marketed in European countries, to inhibit, compete and displace the adhesion of selected potential pathogens to immobilized human mucus. The adhesion was assessed by measuring the radioactivity of bacteria adhered to the human mucus. We tested 12 probiotic strains against eight selected pathogens. All strains tested were able to adhere to mucus. All probiotic strains tested were able to inhibit and displace (P<0.05) the adhesion of Bacteroides, Clostridium, Staphylococcus and Enterobacter. In addition, the abilities to inhibit and to displace adhered pathogens depended on both the probiotic and the pathogen strains tested suggesting that several complementary mechanisms are implied in the processes. Our results indicate the need for a case-by-case assessment in order to select strains with the ability to inhibit or displace a specific pathogen. Probiotics could be useful to correct deviations observed in intestinal microbiota associated with specific diseases and also, to prevent pathogen infections. The competitive exclusion properties of probiotics as well as their ability to displace and inhibit pathogens are the most importance for therapeutic manipulation of the enteric microbiota. The application of such strategies could contribute to expand the beneficial properties on human health against pathogen infection.
A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts.
Gerwien, Franziska; Safyan, Abu; Wisgott, Stephanie; Hille, Fabrice; Kaemmer, Philipp; Linde, Jörg; Brunke, Sascha; Kasper, Lydia; Hube, Bernhard
2016-10-18
Iron is an essential micronutrient for both pathogens and their hosts, which restrict iron availability during infections in an effort to prevent microbial growth. Successful human pathogens like the yeast Candida glabrata have thus developed effective iron acquisition strategies. Their regulation has been investigated well for some pathogenic fungi and in the model organism Saccharomyces cerevisiae, which employs an evolutionarily derived system. Here, we show that C. glabrata uses a regulation network largely consisting of components of the S. cerevisiae regulon but also of elements of other pathogenic fungi. Specifically, similarly to baker's yeast, Aft1 is the main positive regulator under iron starvation conditions, while Cth2 degrades mRNAs encoding iron-requiring enzymes. However, unlike the case with S. cerevisiae, a Sef1 ortholog is required for full growth under iron limitation conditions, making C. glabrata an evolutionary intermediate to SEF1-dependent fungal pathogens. Therefore, C. glabrata has evolved an iron homeostasis system which seems to be unique within the pathogenic fungi. The fungus Candida glabrata represents an evolutionarily close relative of the well-studied and benign baker's yeast and model organism Saccharomyces cerevisiae On the other hand, C. glabrata is an important opportunistic human pathogen causing both superficial and systemic infections. The ability to acquire trace metals, in particular, iron, and to tightly regulate this process during infection is considered an important virulence attribute of a variety of pathogens. Importantly, S. cerevisiae uses a highly derivative regulatory system distinct from those of other fungi. Until now, the regulatory mechanism of iron homeostasis in C. glabrata has been mostly unknown. Our study revealed a hybrid iron regulation network that is unique to C. glabrata and is placed at an evolutionary midpoint between those of S. cerevisiae and related fungal pathogens. We thereby show that, in the host, even a successful human pathogen can rely largely on a strategy normally found in nonpathogenic fungi from a terrestrial environment. Copyright © 2016 Gerwien et al.
Best Practices for Preventing Vector-Borne Diseases in Dogs and Humans.
Dantas-Torres, Filipe; Otranto, Domenico
2016-01-01
Vector-borne diseases constitute a diversified group of illnesses, which are caused by a multitude of pathogens transmitted by arthropod vectors, such as mosquitoes, fleas, ticks, and sand flies. Proper management of these diseases is important from both human and veterinary medicine standpoints, given that many of these pathogens are transmissible to humans and dogs, which often live in close contact. In this review, we summarize the most important vector-borne diseases of dogs and humans and the best practices for their prevention. The control of these diseases would ultimately improve animal and human health and wellbeing, particularly in developing countries in the tropics, where the risk of these diseases is high and access to health care is poor. Copyright © 2015 Elsevier Ltd. All rights reserved.
Huang, Chengchen; Hu, Yue; Wang, Lin; Wang, Yuanfei; Li, Na; Guo, Yaqiong; Xiao, Lihua
2017-01-01
ABSTRACT The environmental transport of Cryptosporidium spp. through combined sewer overflow (CSO) and the occurrence of several emerging human-pathogenic Cryptosporidium species in developing countries remain unclear. In this study, we collected 40 CSO samples and 40 raw wastewater samples from Shanghai, China, and examined them by PCR and DNA sequencing for Cryptosporidium species (targeting the small subunit rRNA gene) and Giardia duodenalis (targeting the triosephosphate isomerase, β-giardin, and glutamate dehydrogenase genes) and Enterocytozoon bieneusi (targeting the ribosomal internal transcribed spacer) genotypes. Human-pathogenic Cryptosporidium species were further subtyped by sequence analysis of the 60-kDa glycoprotein gene, with additional multilocus sequence typing on the emerging zoonotic pathogen Cryptosporidium ubiquitum. Cryptosporidium spp., G. duodenalis, and E. bieneusi were detected in 12 and 15, 33 and 32, and 37 and 40 CSO and wastewater samples, respectively, including 10 Cryptosporidium species, 3 G. duodenalis assemblages, and 8 E. bieneusi genotypes. In addition to Cryptosporidium hominis and Cryptosporidium parvum, two new pathogens identified in industrialized nations, C. ubiquitum and Cryptosporidium viatorum, were frequently detected. The two novel C. ubiquitum subtype families identified appeared to be genetic recombinants of known subtype families. Similarly, the dominant group 1 E. bieneusi genotypes and G. duodenalis subassemblage AII are known human pathogens. The similar distribution of human-pathogenic Cryptosporidium species and E. bieneusi and G. duodenalis genotypes between wastewater and CSO samples reaffirms that storm overflow is potentially a significant contamination source of pathogens in surface water. The frequent identification of C. ubiquitum and C. viatorum in urban wastewater suggests that these newly identified human pathogens may be endemic in China. IMPORTANCE Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are major waterborne pathogens. Their transport into surface water through combined sewer overflow, which remains largely untreated in developing countries, has not been examined. In addition, the identification of these pathogens to genotypes and subtypes in urban storm overflow and wastewater is necessary for rapid and accurate assessment of pathogen transmission in humans and transport in the environment. Data from this study suggest that, like untreated urban wastewater, combined sewer overflow is commonly contaminated with human-pathogenic Cryptosporidium, G. duodenalis, and E. bieneusi genotypes and subtypes, and urban storm overflow potentially plays a significant role in the contamination of drinking source water and recreational water with human pathogens. They also indicate that Cryptosporidium ubiquitum and Cryptosporidium viatorum, two newly identified human pathogens, may be common in China, and genetic recombination can lead to the emergence of novel C. ubiquitum subtype families. PMID:28600310
Alternatives to antibiotics: why and how
USDA-ARS?s Scientific Manuscript database
The antibiotic resistance problem is the mobilization of genes that confer resistance to medically important antibiotics into human pathogens. The acquisition of such resistance genes by pathogens prevents disease treatment, increases health care costs, and increases morbidity and mortality. As ant...
Qi, Wenbao; Jia, Weixin; Liu, Di; Li, Jing; Bi, Yuhai; Xie, Shumin; Li, Bo; Hu, Tao; Du, Yingying; Xing, Li; Zhang, Jiahao; Zhang, Fuchun; Wei, Xiaoman; Eden, John-Sebastian; Li, Huanan; Tian, Huaiyu; Li, Wei; Su, Guanming; Lao, Guangjie; Xu, Chenggang; Xu, Bing; Liu, Wenjun; Zhang, Guihong; Ren, Tao; Holmes, Edward C; Cui, Jie; Shi, Weifeng; Gao, George F; Liao, Ming
2018-01-15
Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant. IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed the molecular features and compared the relative characteristics of one H7N9 LPAIV and two H7N9 HPAIVs isolated from chickens and two human-origin H7N9 HPAIVs in chicken and mouse models. We found that all HPAIVs both are highly pathogenic and have valid transmissibility in chickens. Strikingly, the human-origin viruses were more highly pathogenic than the avian-origin viruses in mice, and dynamic mutations were confirmed by NGS and Sanger sequencing. Our findings offer important insight into the origin, adaptation, pathogenicity, and transmissibility of these viruses to both poultry and mammals. Copyright © 2018 American Society for Microbiology.
Kang, Min; Lau, Eric H Y; Guan, Wenda; Yang, Yuwei; Song, Tie; Cowling, Benjamin J; Wu, Jie; Peiris, Malik; He, Jianfeng; Mok, Chris Ka Pun
2017-07-06
We describe the epidemiology of highly pathogenic avian influenza (HPAI) A(H7N9) based on poultry market environmental surveillance and laboratory-confirmed human cases (n = 9) in Guangdong, China. We also compare the epidemiology between human cases of high- and low-pathogenic avian influenza A(H7N9) (n = 51) in Guangdong. Case fatality and severity were similar. Touching sick or dead poultry was the most important risk factor for HPAI A(H7N9) infections and should be highlighted for the control of future influenza A(H7N9) epidemics. This article is copyright of The Authors, 2017.
Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano
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.
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.
van den Bosch, Frank; Gottwald, Timothy R.; Alonso Chavez, Vasthi
2017-01-01
The spread of pathogens into new environments poses a considerable threat to human, animal, and plant health, and by extension, human and animal wellbeing, ecosystem function, and agricultural productivity, worldwide. Early detection through effective surveillance is a key strategy to reduce the risk of their establishment. Whilst it is well established that statistical and economic considerations are of vital importance when planning surveillance efforts, it is also important to consider epidemiological characteristics of the pathogen in question—including heterogeneities within the epidemiological system itself. One of the most pronounced realisations of this heterogeneity is seen in the case of vector-borne pathogens, which spread between ‘hosts’ and ‘vectors’—with each group possessing distinct epidemiological characteristics. As a result, an important question when planning surveillance for emerging vector-borne pathogens is where to place sampling resources in order to detect the pathogen as early as possible. We answer this question by developing a statistical function which describes the probability distributions of the prevalences of infection at first detection in both hosts and vectors. We also show how this method can be adapted in order to maximise the probability of early detection of an emerging pathogen within imposed sample size and/or cost constraints, and demonstrate its application using two simple models of vector-borne citrus pathogens. Under the assumption of a linear cost function, we find that sampling costs are generally minimised when either hosts or vectors, but not both, are sampled. PMID:28846676
Recent human-to-poultry host jump, adaptation, and pandemic spread of Staphylococcus aureus
Lowder, Bethan V.; Guinane, Caitriona M.; Ben Zakour, Nouri L.; Weinert, Lucy A.; Conway-Morris, Andrew; Cartwright, Robyn A.; Simpson, A. John; Rambaut, Andrew; Nübel, Ulrich; Fitzgerald, J. Ross
2009-01-01
The impact of globalization on the emergence and spread of pathogens is an important veterinary and public health issue. Staphylococcus aureus is a notorious human pathogen associated with serious nosocomial and community-acquired infections. In addition, S. aureus is a major cause of animal diseases including skeletal infections of poultry, which are a large economic burden on the global broiler chicken industry. Here, we provide evidence that the majority of S. aureus isolates from broiler chickens are the descendants of a single human-to-poultry host jump that occurred approximately 38 years ago (range, 30 to 63 years ago) by a subtype of the worldwide human ST5 clonal lineage unique to Poland. In contrast to human subtypes of the ST5 radiation, which demonstrate strong geographic clustering, the poultry ST5 clade was distributed in different continents, consistent with wide dissemination via the global poultry industry distribution network. The poultry ST5 clade has undergone genetic diversification from its human progenitor strain by acquisition of novel mobile genetic elements from an avian-specific accessory gene pool, and by the inactivation of several proteins important for human disease pathogenesis. These genetic events have resulted in enhanced resistance to killing by chicken heterophils, reflecting avian host-adaptive evolution. Taken together, we have determined the evolutionary history of a major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. These data provide a new paradigm for the impact of human activities on the emergence of animal pathogens. PMID:19884497
Gondard, Mathilde; Cabezas-Cruz, Alejandro; Charles, Roxanne A; Vayssier-Taussat, Muriel; Albina, Emmanuel; Moutailler, Sara
2017-01-01
Ticks are obligate hematophagous arthropods of significant importance to human and veterinary medicine. They transmit a vast array of pathogens, including bacteria, viruses, protozoa, and helminths. Most epidemiological data on ticks and tick-borne pathogens (TBPs) in the West Indies are limited to common livestock pathogens such as Ehrlichia ruminantium, Babesia spp. (i.e., B. bovis and B. bigemina ), and Anaplasma marginale , and less information is available on companion animal pathogens. Of note, human tick-borne diseases (TBDs) remain almost completely uncharacterized in the West Indies. Information on TBP presence in wildlife is also missing. Herein, we provide a comprehensive review of the ticks and TBPs affecting human and animal health in the Caribbean, and introduce the challenges associated with understanding TBD epidemiology and implementing successful TBD management in this region. In particular, we stress the need for innovative and versatile surveillance tools using high-throughput pathogen detection (e.g., high-throughput real-time microfluidic PCR). The use of such tools in large epidemiological surveys will likely improve TBD prevention and control programs in the Caribbean.
Andoh, Masako; Sakata, Akiko; Takano, Ai; Kawabata, Hiroki; Fujita, Hiromi; Une, Yumi; Goka, Koichi; Kishimoto, Toshio; Ando, Shuji
2015-01-01
One of the major routes of transmission of rickettsial and ehrlichial diseases is via ticks that infest numerous host species, including humans. Besides mammals, reptiles and amphibians also carry ticks that may harbor Rickettsia and Ehrlichia strains that are pathogenic to humans. Furthermore, reptiles and amphibians are exempt from quarantine in Japan, thus facilitating the entry of parasites and pathogens to the country through import. Accordingly, in the current study, we examined the presence of Rickettsia and Ehrlichia spp. genes in ticks associated with reptiles and amphibians originating from outside Japan. Ninety-three ticks representing nine tick species (genera Amblyomma and Hyalomma) were isolated from at least 28 animals spanning 10 species and originating from 12 countries (Ghana, Jordan, Madagascar, Panama, Russia, Sri Lanka, Sudan, Suriname, Tanzania, Togo, Uzbekistan, and Zambia). None of the nine tick species are indigenous in Japan. The genes encoding the common rickettsial 17-kDa antigen, citrate synthase (gltA), and outer membrane protein A (ompA) were positively detected in 45.2% (42/93), 40.9% (38/93), and 23.7% (22/93) of the ticks, respectively, by polymerase chain reaction (PCR). The genes encoding ehrlichial heat shock protein (groEL) and major outer membrane protein (omp-1) were PCR-positive in 7.5% (7/93) and 2.2% (2/93) of the ticks, respectively. The p44 gene, which encodes the Anaplasma outer membrane protein, was not detected. Phylogenetic analysis showed that several of the rickettsial and ehrlichial sequences isolated in this study were highly similar to human pathogen genes, including agents not previously detected in Japan. These data demonstrate the global transportation of pathogenic Rickettsia and Ehrlichia through reptile- and amphibian-associated ticks. These imported animals have potential to transfer pathogens into human life. These results highlight the need to control the international transportation of known and potential pathogens carried by ticks in reptiles, amphibians, and other animals, in order to improve national and international public health.
Bacterial and protozoal pathogens found in ticks collected from humans in Corum province of Turkey
Karasartova, Djursun; Gureser, Ayse Semra; Gokce, Tuncay; Celebi, Bekir; Yapar, Derya; Keskin, Adem; Celik, Selim; Ece, Yasemin; Erenler, Ali Kemal; Usluca, Selma; Mumcuoglu, Kosta Y.
2018-01-01
Background Tick-borne diseases are increasing all over the word, including Turkey. The aim of this study was to determine the bacterial and protozoan vector-borne pathogens in ticks infesting humans in the Corum province of Turkey. Methodology/Principal findings From March to November 2014 a total of 322 ticks were collected from patients who attended the local hospitals with tick bites. Ticks were screened by real time-PCR and PCR, and obtained amplicons were sequenced. The dedected tick was belonging to the genus Hyalomma, Haemaphysalis, Rhipicephalus, Dermacentor and Ixodes. A total of 17 microorganism species were identified in ticks. The most prevalent Rickettsia spp. were: R. aeschlimannii (19.5%), R. slovaca (4.5%), R. raoultii (2.2%), R. hoogstraalii (1.9%), R. sibirica subsp. mongolitimonae (1.2%), R. monacensis (0.31%), and Rickettsia spp. (1.2%). In addition, the following pathogens were identified: Borrelia afzelii (0.31%), Anaplasma spp. (0.31%), Ehrlichia spp. (0.93%), Babesia microti (0.93%), Babesia ovis (0.31%), Babesia occultans (3.4%), Theileria spp. (1.6%), Hepatozoon felis (0.31%), Hepatozoon canis (0.31%), and Hemolivia mauritanica (2.1%). All samples were negative for Francisella tularensis, Coxiella burnetii, Bartonella spp., Toxoplasma gondii and Leishmania spp. Conclusions/Significance Ticks in Corum carry a large variety of human and zoonotic pathogens that were detected not only in known vectors, but showed a wider vector diversity. There is an increase in the prevalence of ticks infected with the spotted fever group and lymphangitis-associated rickettsiosis, while Ehrlichia spp. and Anaplasma spp. were reported for the first time from this region. B. microti was detected for the first time in Hyalomma marginatum infesting humans. The detection of B. occultans, B. ovis, Hepatozoon spp., Theileria spp. and Hemolivia mauritanica indicate the importance of these ticks as vectors of pathogens of veterinary importance, therefore patients with a tick infestation should be followed for a variety of pathogens with medical importance. PMID:29649265
Bacterial and protozoal pathogens found in ticks collected from humans in Corum province of Turkey.
Karasartova, Djursun; Gureser, Ayse Semra; Gokce, Tuncay; Celebi, Bekir; Yapar, Derya; Keskin, Adem; Celik, Selim; Ece, Yasemin; Erenler, Ali Kemal; Usluca, Selma; Mumcuoglu, Kosta Y; Taylan-Ozkan, Aysegul
2018-04-01
Tick-borne diseases are increasing all over the word, including Turkey. The aim of this study was to determine the bacterial and protozoan vector-borne pathogens in ticks infesting humans in the Corum province of Turkey. From March to November 2014 a total of 322 ticks were collected from patients who attended the local hospitals with tick bites. Ticks were screened by real time-PCR and PCR, and obtained amplicons were sequenced. The dedected tick was belonging to the genus Hyalomma, Haemaphysalis, Rhipicephalus, Dermacentor and Ixodes. A total of 17 microorganism species were identified in ticks. The most prevalent Rickettsia spp. were: R. aeschlimannii (19.5%), R. slovaca (4.5%), R. raoultii (2.2%), R. hoogstraalii (1.9%), R. sibirica subsp. mongolitimonae (1.2%), R. monacensis (0.31%), and Rickettsia spp. (1.2%). In addition, the following pathogens were identified: Borrelia afzelii (0.31%), Anaplasma spp. (0.31%), Ehrlichia spp. (0.93%), Babesia microti (0.93%), Babesia ovis (0.31%), Babesia occultans (3.4%), Theileria spp. (1.6%), Hepatozoon felis (0.31%), Hepatozoon canis (0.31%), and Hemolivia mauritanica (2.1%). All samples were negative for Francisella tularensis, Coxiella burnetii, Bartonella spp., Toxoplasma gondii and Leishmania spp. Ticks in Corum carry a large variety of human and zoonotic pathogens that were detected not only in known vectors, but showed a wider vector diversity. There is an increase in the prevalence of ticks infected with the spotted fever group and lymphangitis-associated rickettsiosis, while Ehrlichia spp. and Anaplasma spp. were reported for the first time from this region. B. microti was detected for the first time in Hyalomma marginatum infesting humans. The detection of B. occultans, B. ovis, Hepatozoon spp., Theileria spp. and Hemolivia mauritanica indicate the importance of these ticks as vectors of pathogens of veterinary importance, therefore patients with a tick infestation should be followed for a variety of pathogens with medical importance.
Callaway, T R; Edrington, T S; Nisbet, D J
2014-04-01
Pathogenic bacteria can live asymptomatically within and on cattle and can enter the food chain but also can be transmitted to humans by fecal or direct animal contact. Reducing pathogenic bacterial incidence and populations within live cattle represents an important step in improving food safety. A broad range of preslaughter intervention strategies are being developed, which can be loosely classified as 1) directly antipathogen strategies, 2) competitive enhancement strategies (that use the microbiome's competitive nature against pathogens), and 3) animal management strategies. Included within these broad categories are such diverse methods as vaccination against foodborne pathogens, probiotics and prebiotics, bacterial viruses (i.e., bacteriophages), sodium chlorate feeding, and dietary and management changes that specifically alter the microbiome. The simultaneous application of 1 or more preharvest strategies has the potential to reduce human foodborne illnesses by erecting multiple hurdles preventing entry into humans. However, economic factors that govern producer profitability must be kept in mind while improving food safety.
Adhesins in Human Fungal Pathogens: Glue with Plenty of Stick
de Groot, Piet W. J.; Bader, Oliver; de Boer, Albert D.; Weig, Michael
2013-01-01
Understanding the pathogenesis of an infectious disease is critical for developing new methods to prevent infection and diagnose or cure disease. Adherence of microorganisms to host tissue is a prerequisite for tissue invasion and infection. Fungal cell wall adhesins involved in adherence to host tissue or abiotic medical devices are critical for colonization leading to invasion and damage of host tissue. Here, with a main focus on pathogenic Candida species, we summarize recent progress made in the field of adhesins in human fungal pathogens and underscore the importance of these proteins in establishment of fungal diseases. PMID:23397570
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.
Plant immunity: towards an integrated view of plant-pathogen interactions.
Dodds, Peter N; Rathjen, John P
2010-08-01
Plants are engaged in a continuous co-evolutionary struggle for dominance with their pathogens. The outcomes of these interactions are of particular importance to human activities, as they can have dramatic effects on agricultural systems. The recent convergence of molecular studies of plant immunity and pathogen infection strategies is revealing an integrated picture of the plant-pathogen interaction from the perspective of both organisms. Plants have an amazing capacity to recognize pathogens through strategies involving both conserved and variable pathogen elicitors, and pathogens manipulate the defence response through secretion of virulence effector molecules. These insights suggest novel biotechnological approaches to crop protection.
Human milk inactivates pathogens individually, additively, and synergistically.
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.
Phylogenetically marking the limits of the genus Fusarium for post-Article 59 usage
USDA-ARS?s Scientific Manuscript database
Fusarium (Hypocreales, Nectriaceae) is one of the most important and systematically challenging groups of mycotoxigenic, plant pathogenic, and human pathogenic fungi. We conducted maximum likelihood (ML), maximum parsimony (MP) and Bayesian (B) analyses on partial nucleotide sequences of genes encod...
Hwang, Jusun; Lee, Kyunglee; Walsh, Daniel P.; Kim, SangWha; Sleeman, Jonathan M.; Lee, Hang
2018-01-01
Wildlife-associated diseases and pathogens have increased in importance; however, management of a large number of diseases and diversity of hosts is prohibitively expensive. Thus, the determination of priority wildlife pathogens and risk factors for disease emergence is warranted. We used an online questionnaire survey to assess release and exposure risks, and consequences of wildlife-associated diseases and pathogens in the Republic of Korea (ROK). We also surveyed opinions on pathways for disease exposure, and risk factors for disease emergence and spread. For the assessment of risk, we employed a two-tiered, statistical K-means clustering algorithm to group diseases into three levels (high, medium and low) of perceived risk based on release and exposure risks, societal consequences and the level of uncertainty of the experts’ opinions. To examine the experts’ perceived risk of routes of introduction of pathogens and disease amplification and spread, we used a Bayesian, multivariate normal order-statistics model. Six diseases or pathogens, including four livestock and two wildlife diseases, were identified as having high risk with low uncertainty. Similarly, 13 diseases were characterized as having high risk with medium uncertainty with three of these attributed to livestock, six associated with human disease, and the remainder having the potential to affect human, livestock and wildlife (i.e., One Health). Lastly, four diseases were described as high risk with high certainty, and were associated solely with fish diseases. Experts identified migration of wildlife, international human movement and illegal importation of wildlife as the three routes posing the greatest risk of pathogen introduction into ROK. Proximity of humans, livestock and wildlife was the most significant risk factor for promoting the spread of wildlife-associated diseases and pathogens, followed by high density of livestock populations, habitat loss and environmental degradation, and climate change. This study provides useful information to decision makers responsible for allocating resources to address disease risks. This approach provided a rapid, cost-effective method of risk assessment of wildlife-associated diseases and pathogens for which the published literature is sparse.
Harper, Kristin N; Armelagos, George J
2013-12-01
Though agriculture is often viewed as one of humanity's crowning achievements, skeletal evidence indicates that dependence on domesticated plants and animals was accompanied by an increase in infectious disease. Scientists have proposed that many important infections emerged in the period following the advent of agriculture, as a result of newly dense populations and novel proximity to domestic animals that served as reservoirs for novel pathogens. Here, we review genomic evidence regarding pathogen origins, analyzing these data using the epidemiological transition framework. Genetic information has forced us to reconsider how and when many important pathogens emerged; it appears that a number of infections thought to result from contact with domesticated animals arose much earlier than agriculture was adopted. We also consider the broader effect of agriculture upon the microbiome, exploring potential consequences for human health. We end by discussing the changes in the human microbe-scape we are likely to see in the future. Copyright © 2013 Wiley Periodicals, Inc.
Chemical ecology of animal and human pathogen vectors in a changing global climate.
Pickett, John A; Birkett, Michael A; Dewhirst, Sarah Y; Logan, James G; Omolo, Maurice O; Torto, Baldwyn; Pelletier, Julien; Syed, Zainulabeuddin; Leal, Walter S
2010-01-01
Infectious diseases affecting livestock and human health that involve vector-borne pathogens are a global problem, unrestricted by borders or boundaries, which may be exacerbated by changing global climate. Thus, the availability of effective tools for control of pathogen vectors is of the utmost importance. The aim of this article is to review, selectively, current knowledge of the chemical ecology of pathogen vectors that affect livestock and human health in the developed and developing world, based on key note lectures presented in a symposium on "The Chemical Ecology of Disease Vectors" at the 25th Annual ISCE meeting in Neuchatel, Switzerland. The focus is on the deployment of semiochemicals for monitoring and control strategies, and discusses briefly future directions that such research should proceed along, bearing in mind the environmental challenges associated with climate change that we will face during the 21st century.
Natural soil reservoirs for human pathogenic and fecal indicator bacteria
Boschiroli, Maria L; Falkinham, Joseph; Favre-Bonte, Sabine; Nazaret, Sylvie; Piveteau, Pascal; Sadowsky, Michael J.; Byappanahalli, Muruleedhara; Delaquis, Pascal; Hartmann, Alain
2016-01-01
Soils receive inputs of human pathogenic and indicator bacteria through land application of animal manures or sewage sludge, and inputs by wildlife. Soil is an extremely heterogeneous substrate and contains meso- and macrofauna that may be reservoirs for bacteria of human health concern. The ability to detect and quantify bacteria of human health concern is important in risk assessments and in evaluating the efficacy of agricultural soil management practices that are protective of crop quality and protective of adjacent water resources. The present chapter describes the distribution of selected Gram-positive and Gram-negative bacteria in soils. Methods for detecting and quantifying soilborne bacteria including extraction, enrichment using immunomagnetic capture, culturing, molecular detection and deep sequencing of metagenomic DNA to detect pathogens are overviewed. Methods for strain phenotypic and genotypic characterization are presented, as well as how comparison with clinical isolates can inform the potential for human health risk.
Legionella and Mycobacterium Occurrence/Persistence in Homes and Office Buildings
Legionella and non-tuberculous Mycobacterium species are two of the more important environmental pathogens that cause human health effects. They contribute to the highest economic burden and one of the heaviest disease burdens of all of the waterborne pathogens that pose a risk t...
Ma, Ying; Feng, Youjun; Liu, Di; Gao, George F
2009-09-27
The outbreak and spread of severe acute respiratory syndrome-associated coronavirus and the subsequent identification of its animal origin study have heightened the world's awareness of animal-borne or zoonotic pathogens. In addition to SARS, the highly pathogenic avian influenza virus (AIV), H5N1, and the lower pathogenicity H9N2 AIV have expanded their host ranges to infect human beings and other mammalian species as well as birds. Even the 'well-known' reservoir animals for influenza virus, migratory birds, became victims of the highly pathogenic H5N1 virus. Not only the viruses, but bacteria can also expand their host range: a new disease, streptococcal toxic shock syndrome, caused by human Streptococcus suis serotype 2 infection, has been observed in China with 52 human fatalities in two separate outbreaks (1998 and 2005, respectively). Additionally, enterohaemorrhagic Escherichia coli O157:H7 infection has increased worldwide with severe disease. Several outbreaks and sporadic isolations of this pathogen in China have made it an important target for disease control. A new highly pathogenic variant of porcine reproductive and respiratory syndrome virus (PRRSV) has been isolated in both China and Vietnam recently; although PRRSV is not a zoonotic human pathogen, its severe outbreaks have implications for food safety. All of these pathogens occur in Southeast Asia, including China, with severe consequences; therefore, we discuss the issues in this article by addressing the situation of the zoonotic threat in China.
Krüger, Thomas; Luo, Ting; Schmidt, Hella; Shopova, Iordana; Kniemeyer, Olaf
2015-12-14
Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.
Singh, B B; Gajadhar, A A
2014-10-01
Evolving land use practices have led to an increase in interactions at the human/wildlife interface. The presence and poor knowledge of zoonotic pathogens in India's wildlife and the occurrence of enormous human populations interfacing with, and critically linked to, forest ecosystems warrant attention. Factors such as diverse migratory bird populations, climate change, expanding human population and shrinking wildlife habitats play a significant role in the emergence and re-emergence of zoonotic pathogens from India's wildlife. The introduction of a novel Kyasanur forest disease virus (family flaviviridae) into human populations in 1957 and subsequent occurrence of seasonal outbreaks illustrate the key role that India's wild animals play in the emergence and reemergence of zoonotic pathogens. Other high priority zoonotic diseases of wildlife origin which could affect both livestock and humans include influenza, Nipah, Japanese encephalitis, rabies, plague, leptospirosis, anthrax and leishmaniasis. Continuous monitoring of India's extensively diverse and dispersed wildlife is challenging, but their use as indicators should facilitate efficient and rapid disease-outbreak response across the region and occasionally the globe. Defining and prioritizing research on zoonotic pathogens in wildlife are essential, particularly in a multidisciplinary one-world one-health approach which includes human and veterinary medical studies at the wildlife-livestock-human interfaces. This review indicates that wild animals play an important role in the emergence and re-emergence of zoonotic pathogens and provides brief summaries of the zoonotic diseases that have occurred in wild animals in India. Copyright © 2014 Elsevier B.V. All rights reserved.
Taylor-Mulneix, Dawn L; Hamidou Soumana, Illiassou; Linz, Bodo; Harvill, Eric T
2017-01-01
The genus Bordetella comprises several bacterial species that colonize the respiratory tract of mammals. It includes B. pertussis , a human-restricted pathogen that is the causative agent of Whooping Cough. In contrast, the closely related species B. bronchiseptica colonizes a broad range of animals as well as immunocompromised humans. Recent metagenomic studies have identified known and novel bordetellae isolated from different environmental sources, providing a new perspective on their natural history. Using phylogenetic analysis, we have shown that human and animal pathogenic bordetellae have most likely evolved from ancestors that originated from soil and water. Our recent study found that B. bronchiseptica can evade amoebic predation and utilize Dictyostelium discoideum as an expansion and transmission vector, which suggests that the evolutionary pressure to evade the amoebic predator enabled the rise of bordetellae as respiratory pathogens. Interactions with amoeba may represent the starting point for bacterial adaptation to eukaryotic cells. However, as bacteria evolve and adapt to a novel host, they can become specialized and restricted to a specific host. B. pertussis is known to colonize and cause infection only in humans, and this specialization to a closed human-to-human lifecycle has involved genome reduction and the loss of ability to utilize amoeba as an environmental reservoir. The discoveries from studying the interaction of Bordetella species with amoeba will elicit a better understanding of the evolutionary history of these and other important human pathogens.
Comparative Review of Antimicrobial Resistance in Humans and Nonhuman Primates.
Kim, Jeffrey; Coble, Dondrae J; Salyards, Gregory W; Habing, Gregory G
2018-04-02
Antimicrobial resistance (AMR) presents serious threats to human and animal health. Although AMR of pathogens is often evaluated independently between humans and animals, comparative analysis of AMR between humans and animals is necessary for zoonotic pathogens. Major surveillance systems monitor AMR of zoonotic pathogens in humans and food animals, but comprehensive AMR data in veterinary medicine is not diligently monitored for most animal species with which humans commonly contact, including NHP. The objective of this review is to provide a complete report of the prevalences of AMR among zoonotic bacteria that present the greatest threats to NHP, occupational, and public health. High prevalences of AMR exist among Shigella, Campylobacter, and Yersinia, including resistance to antimicrobials important to public health, such as macrolides. Despite improvements in regulations, standards, policies, practices, and zoonotic awareness, occupational exposures to and illnesses due to zoonotic pathogens continue to be reported and, given the documented prevalences of AMR, constitute an occupational and public health risk. However, published literature is sparse, thus indicating the need for veterinarians to proactively monitor AMR in dangerous zoonotic bacteria, to enable veterinarians to make more informed decisions to maximize antimicrobial therapy and minimize occupational risk.
Comparative Review of Antimicrobial Resistance in Humans and Nonhuman Primates.
Kim, Jeffrey; Coble, Dondrae J; Salyards, Gregory W; Habing, Gregory G
2019-03-01
Antimicrobial resistance (AMR) presents serious threats to human and animal health. Although AMR of pathogens is often evaluated independently between humans and animals, comparative analysis of AMR between humans and animals is necessary for zoonotic pathogens. Major surveillance systems monitor AMR of zoonotic pathogens in humans and food animals, but comprehensive AMR data in veterinary medicine is not diligently monitored for most animal species with which humans commonly contact, including NHP. The objective of this review is to provide a complete report of the prevalences of AMR among zoonotic bacteria that present the greatest threats to NHP, occupational, and public health. High prevalences of AMR exist among Shigella, Campylobacter, and Yersinia, including resistance to antimicrobials important to public health, such as macrolides. Despite improvements in regulations, standards, policies, practices, and zoonotic awareness, occupational exposures to and illnesses due to zoonotic pathogens continue to be reported and, given the documented prevalences of AMR, constitute an occupational and public health risk. However, published literature is sparse, thus indicating the need for veterinarians to proactively monitor AMR in dangerous zoonotic bacteria, to enable veterinarians to make more informed decisions to maximize antimicrobial therapy and minimize occupational risk.
Pfliegler, Walter P; Boros, Enikő; Pázmándi, Kitti; Jakab, Ágnes; Zsuga, Imre; Kovács, Renátó; Urbán, Edit; Antunovics, Zsuzsa; Bácsi, Attila; Sipiczki, Matthias; Majoros, László; Pócsi, István
2017-11-01
Saccharomyces cerevisiae is one of the most important microbes in food industry, but there is growing evidence on its potential pathogenicity as well. Its status as a member of human mycobiome is still not fully understood. In this study, we characterize clinical S. cerevisiae isolates from Hungarian hospitals along with commercial baking and probiotic strains, and determine their phenotypic parameters, virulence factors, interactions with human macrophages, and pathogenicity. Four of the clinical isolates could be traced back to commercial strains based on genetic fingerprinting. Our observations indicate that the commercial-derived clinical isolates have evolved new phenotypes and show similar, or in two cases, significantly decreased pathogenicity. Furthermore, immunological experiments revealed that the variability in human primary macrophage activation after coincubation with yeasts is largely donor and not isolate dependent. Isolates in this study offer an interesting insight into the potential microevolution of probiotic and food strains in human hosts. These commensal yeasts display various changes in their phenotypes, indicating that the colonization of the host does not necessarily impose a selective pressure toward higher virulence/pathogenicity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
As the incidence of human fungal infection increases, the ability to detect and identify pathogenic fungi in potential environmental reservoirs becomes increasingly important for disease control. PCR based assays are widely used for diagnostic purposes, but may be inadequate for...
Label-free SERS detection of Salmonella Typhimurium on DNA aptamer modified AgNR substrates
USDA-ARS?s Scientific Manuscript database
Salmonella Typhimurium is an important foodborne pathogen which causes gastroenteritis in both humans and animals. Currently available rapid methods have relied on antibodies to offer specific recognition of the pathogen from the background. As a substitute of antibodies, nucleic acid aptamers offer...
USDA-ARS?s Scientific Manuscript database
Campylobacter jejuni is an important foodborne pathogen that causes severe diarrhea in humans. Chickens act as the reservoir host for Campylobacter, wherein the pathogen colonizes the ceca leading to contaminated poultry products during slaughter. The potential of natural intervention strategies, in...
Context-dependent conservation responses to emerging wildlife diseases
Kate E Langwig; Jamie Voyles; Mark Q Wilber; Winifred F Frick; Kris A Murray; Benjamin M Bolker; James P Collins; Tina L Cheng; Matthew C Fisher; Joseph R Hoyt; Daniel L Lindner; Hamish I McCallum; Robert Puschendorf; Erica Bree Rosenblum; Mary Toothman; Craig KR Willis; Cheryl J Briggs; A Marm Kilpatrick
2015-01-01
Emerging infectious diseases pose an important threat to wildlife. While established protocols exist for combating outbreaks of human and agricultural pathogens, appropriate management actions before, during, and after the invasion of wildlife pathogens have not been developed. We describe stage-specific goals and management actions that minimize disease impacts on...
Proteomics As a Tool for Studying Bacterial Virulence and Antimicrobial Resistance
Pérez-Llarena, Francisco J.; Bou, Germán
2016-01-01
Proteomic studies have improved our understanding of the microbial world. The most recent advances in this field have helped us to explore aspects beyond genomics. For example, by studying proteins and their regulation, researchers now understand how some pathogenic bacteria have adapted to the lethal actions of antibiotics. Proteomics has also advanced our knowledge of mechanisms of bacterial virulence and some important aspects of how bacteria interact with human cells and, thus, of the pathogenesis of infectious diseases. This review article addresses these issues in some of the most important human pathogens. It also reports some applications of Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) mass spectrometry that may be important for the diagnosis of bacterial resistance in clinical laboratories in the future. The reported advances will enable new diagnostic and therapeutic strategies to be developed in the fight against some of the most lethal bacteria affecting humans. PMID:27065974
TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.
Marchesan, Julie; Jiao, Yizu; Schaff, Riley A; Hao, Jie; Morelli, Thiago; Kinney, Janet S; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J; Inohara, Naohiro; Giannobile, William V
2016-06-01
Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
TLR4, NOD1 and NOD2 Mediate Immune Recognition of Putative Newly-Identified Periodontal Pathogens
Schaff, Riley A.; Hao, Jie; Morelli, Thiago; Kinney, Janet S.; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J.; Inohara, Naohiro; Giannobile, William V.
2015-01-01
SUMMARY Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. While the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, 6 being classical pathogens and 4 putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone marrow–derived macrophages (BMDM) from wild-type (WT) and toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. C. concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney (HEK) cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2-stimulatory activity. These studies allowed us to provide important evidence on newly-identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). PMID:26177212
Summer, Elizabeth J.; Gill, Jason J.; Upton, Chris; Gonzalez, Carlos F.; Young, Ry
2007-01-01
Summary Most bacteria of the genus Burkholderia are soil- and rhizosphere- associated, noted for their metabolic plasticity in the utilization of a wide range of organic compounds as carbon sources. Many Burkholderia species are also opportunistic human and plant pathogens and the distinction between environmental, plant, and human pathogens is not always clear. Burkholderia phages are not uncommon and multiple cryptic prophages are identifiable in the sequenced Burkholderia genomes. Phages have played a crucial role in the transmission of virulence factors among many important pathogens, however, the data does not yet support a significant correlation between phages and pathogenicity in the Burkholderia. This may be due to the role of Burkholderia as a “versaphile” such that selection is occurring in several niches, including roles as a pathogen and in the context of environmental survival. PMID:17719265
Schwind, Jessica S; Goldstein, Tracey; Thomas, Kate; Mazet, Jonna A K; Smith, Woutrina A
2014-07-04
The capacity to conduct zoonotic pathogen surveillance in wildlife is critical for the recognition and identification of emerging health threats. The PREDICT project, a component of United States Agency for International Development's Emerging Pandemic Threats program, has introduced capacity building efforts to increase zoonotic pathogen surveillance in wildlife in global 'hot spot' regions where zoonotic disease emergence is likely to occur. Understanding priorities, challenges, and opportunities from the perspectives of the stakeholders is a key component of any successful capacity building program. A survey was administered to wildlife officials and to PREDICT-implementing in-country project scientists in 16 participating countries in order to identify similarities and differences in perspectives between the groups regarding capacity needs for zoonotic pathogen surveillance in wildlife. Both stakeholder groups identified some human-animal interfaces (i.e. areas of high contact between wildlife and humans with the potential risk for disease transmission), such as hunting and markets, as important for ongoing targeting of wildlife surveillance. Similarly, findings regarding challenges across stakeholder groups showed some agreement in that a lack of sustainable funding across regions was the greatest challenge for conducting wildlife surveillance for zoonotic pathogens (wildlife officials: 96% and project scientists: 81%). However, the opportunity for improving zoonotic pathogen surveillance capacity identified most frequently by wildlife officials as important was increasing communication or coordination among agencies, sectors, or regions (100% of wildlife officials), whereas the most frequent opportunities identified as important by project scientists were increasing human capacity, increasing laboratory capacity, and the growing interest or awareness regarding wildlife disease or surveillance programs (all identified by 69% of project scientists). A One Health approach to capacity building applied at local and global scales will have the greatest impact on improving zoonotic pathogen surveillance in wildlife. This approach will involve increasing communication and cooperation across ministries and sectors so that experts and stakeholders work together to identify and mitigate surveillance gaps. Over time, this transdisciplinary approach to capacity building will help overcome existing challenges and promote efficient targeting of high risk interfaces for zoonotic pathogen transmission.
Productivity, biodiversity, and pathogens influence the global hunter-gatherer population density.
Tallavaara, Miikka; Eronen, Jussi T; Luoto, Miska
2018-02-06
The environmental drivers of species distributions and abundances are at the core of ecological research. However, the effects of these drivers on human abundance are not well-known. Here, we report how net primary productivity, biodiversity, and pathogen stress affect human population density using global ethnographic hunter-gatherer data. Our results show that productivity has significant effects on population density globally. The most important direct drivers, however, depend on environmental conditions: biodiversity influences population density exclusively in low-productivity regions, whereas pathogen stress does so in high-productivity regions. Our results also indicate that subtropical and temperate forest biomes provide the highest carrying capacity for hunter-gatherer populations. These findings document that environmental factors play a key role in shaping global population density patterns of preagricultural humans.
Pathogens transmitted in animal feces in low- and middle-income countries.
Delahoy, Miranda J; Wodnik, Breanna; McAliley, Lydia; Penakalapati, Gauthami; Swarthout, Jenna; Freeman, Matthew C; Levy, Karen
2018-05-01
Animals found in close proximity to humans in low-and middle-income countries (LMICs) harbor many pathogens capable of infecting humans, transmissible via their feces. Contact with animal feces poses a currently unquantified-though likely substantial-risk to human health. In LMIC settings, human exposure to animal feces may explain some of the limited success of recent water, sanitation, and hygiene interventions that have focused on limiting exposure to human excreta, with less attention to containing animal feces. We conducted a review to identify pathogens that may substantially contribute to the global burden of disease in humans through their spread in animal feces in the domestic environment in LMICs. Of the 65 potentially pathogenic organisms considered, 15 were deemed relevant, based on burden of disease and potential for zoonotic transmission. Of these, five were considered of highest concern based on a substantial burden of disease for which transmission in animal feces is potentially important: Campylobacter, non-typhoidal Salmonella (NTS), Lassa virus, Cryptosporidium, and Toxoplasma gondii. Most of these have a wide range of animal hosts, except Lassa virus, which is spread through the feces of rats indigenous to sub-Saharan Africa. Combined, these five pathogens cause close to one million deaths annually. More than half of these deaths are attributed to invasive NTS. We do not estimate an overall burden of disease from improperly managed animal feces in LMICs, because it is unknown what proportion of illnesses caused by these pathogens can be attributed to contact with animal feces. Typical water quantity, water quality, and handwashing interventions promoted in public health and development address transmission routes for both human and animal feces; however, sanitation interventions typically focus on containing human waste, often neglecting the residual burden of disease from pathogens transmitted via animal feces. This review compiles evidence on which pathogens may contribute to the burden of disease through transmission in animal feces; these data will help prioritize intervention types and regions that could most benefit from interventions aimed at reducing human contact with animal feces. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.
Lu, Dan; Liu, Shen; Shang, Shengzhe; Wu, Fangfang; Wen, Xiao; Li, Zhiyuan; Li, Yan; Hu, Xiaoxiang; Zhao, Yaofeng; Li, Qiuyan; Li, Ning
2015-01-01
Human lysozyme is a natural non-specific immune factor in human milk that plays an important role in the defense of breastfed infants against pathogen infection. Although lysozyme is abundant in human milk, there is only trace quantities in pig milk. Here, we successfully generated transgenic cloned pigs with the expression vector pBAC-hLF-hLZ-Neo and their first generation hybrids (F1). The highest concentration of recombinant human lysozyme (rhLZ) with in vitro bioactivity was 2759.6 ± 265.0 mg/L in the milk of F0 sows. Compared with wild-type milk, rhLZ milk inhibited growth of Escherichia coli K88 during the exponential growth phase. Moreover, rhLZ in milk from transgenic sows was directly absorbed by the intestine of piglets with no observable anaphylactic reaction. Our strategy may provide a powerful tool for large-scale production of this important human protein in pigs to improve resistance to pathogen infection.
Ijaz, M Khalid; Zargar, Bahram; Wright, Kathryn E; Rubino, Joseph R; Sattar, Syed A
2016-09-02
Indoor air can be an important vehicle for a variety of human pathogens. This review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. The following groups of human pathogens are covered because of their known or potential airborne spread: vegetative bacteria (staphylococci and legionellae), fungi (Aspergillus, Penicillium, and Cladosporium spp and Stachybotrys chartarum), enteric viruses (noro- and rotaviruses), respiratory viruses (influenza and coronaviruses), mycobacteria (tuberculous and nontuberculous), and bacterial spore formers (Clostridium difficile and Bacillus anthracis). An overview of methods for experimentally generating and recovering airborne human pathogens is included, along with a discussion of factors that influence microbial survival in indoor air. Available guidelines from the U.S. Environmental Protection Agency and other global regulatory bodies for the study of airborne pathogens are critically reviewed with particular reference to microbial surrogates that are recommended. Recent developments in experimental facilities to contaminate indoor air with microbial aerosols are presented, along with emerging technologies to decontaminate indoor air under field-relevant conditions. Furthermore, the role that air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings is discussed. Copyright © 2016. Published by Elsevier Inc.
Drivers, dynamics, and control of emerging vector-borne zoonotic diseases
Kilpatrick, A. Marm; Randolph, Sarah E.
2013-01-01
Emerging vector-borne diseases represent an important issue for global health. Many vector-borne pathogens have appeared in new regions in the past two decades, and many endemic diseases have increased in incidence. Although introductions and local emergence are frequently considered distinct processes, many emerging endemic pathogens are in fact invading at a local scale coincident with habitat change. We highlight key differences in the dynamics and disease burden that result from increased pathogen transmission following habitat change compared with the introduction of pathogens to new regions. Truly in situ emergence is commonly driven by changes in human factors as much as by enhanced enzootic cycles whereas pathogen invasion results from anthropogenic trade and travel and suitable conditions for a pathogen, including hosts, vectors, and climate. Once established, ecological factors related to vector characteristics shape the evolutionary selective pressure on pathogens that may result in increased use of humans as transmission hosts. We describe challenges inherent in the control of vector-borne zoonotic diseases and some emerging non-traditional strategies that may be more effective in the long term. PMID:23200503
Cabello, Felipe C; Godfrey, Henry P; Tomova, Alexandra; Ivanova, Larisa; Dölz, Humberto; Millanao, Ana; Buschmann, Alejandro H
2013-07-01
The worldwide growth of aquaculture has been accompanied by a rapid increase in therapeutic and prophylactic usage of antimicrobials including those important in human therapeutics. Approximately 80% of antimicrobials used in aquaculture enter the environment with their activity intact where they select for bacteria whose resistance arises from mutations or more importantly, from mobile genetic elements containing multiple resistance determinants transmissible to other bacteria. Such selection alters biodiversity in aquatic environments and the normal flora of fish and shellfish. The commonality of the mobilome (the total of all mobile genetic elements in a genome) between aquatic and terrestrial bacteria together with the presence of residual antimicrobials, biofilms, and high concentrations of bacteriophages where the aquatic environment may also be contaminated with pathogens of human and animal origin can stimulate exchange of genetic information between aquatic and terrestrial bacteria. Several recently found genetic elements and resistance determinants for quinolones, tetracyclines, and β-lactamases are shared between aquatic bacteria, fish pathogens, and human pathogens, and appear to have originated in aquatic bacteria. Excessive use of antimicrobials in aquaculture can thus potentially negatively impact animal and human health as well as the aquatic environment and should be better assessed and regulated. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.
Detection of hepatitis E virus and other livestock-related pathogens in Iowa streams
Givens, Carrie E.; Kolpin, Dana W.; Borchardt, Mark A.; Duris, Joseph W.; Moorman, Thomas B.; Spencer, Susan K.
2016-01-01
Manure application is a source of pathogens to the environment. Through overland runoff and tile drainage, zoonotic pathogens can contaminate surface water and streambed sediment and could affect both wildlife and human health. This study examined the environmental occurrence of gene markers for livestock-related bacterial, protozoan, and viral pathogens and antibiotic resistance in surface waters within the South Fork Iowa River basin before and after periods of swine manure application on agricultural land. Increased concentrations of indicator bacteria after manure application exceeding Iowa's state bacteria water quality standards suggest that swine manure contributes to diminished water quality and may pose a risk to human health. Additionally, the occurrence of HEV and numerous bacterial pathogen genes for Escherichia coli, Enterococcus spp., Salmonella sp., and Staphylococcus aureus in both manure samples and in corresponding surface water following periods of manure application suggests a potential role for swine in the spreading of zoonotic pathogens to the surrounding environment. During this study, several zoonotic pathogens were detected including Shiga-toxin producing E. coli, Campylobacter jejuni, pathogenic enterococci, and S. aureus; all of which can pose mild to serious health risks to swine, humans, and other wildlife. This research provides the foundational understanding required for future assessment of the risk to environmental health from livestock-related zoonotic pathogen exposures in this region. This information could also be important for maintaining swine herd biosecurity and protecting the health of wildlife near swine facilities.
USDA-ARS?s Scientific Manuscript database
Campylobacter spp. are major food-borne pathogens responsible for a significant portion of the human cases of bacterial mediated gastrointestinal disease, and poultry products are an important source of infections. Reducing the numbers of this pathogen on poultry products should lower the incidence...
Profiling a killer, the development of Cryptococcus neoformans
Kozubowski, Lukasz; Heitman, Joseph
2012-01-01
The ability of fungi to transition between unicellular and multicellular growth has a profound impact on our health and the economy. Many important fungal pathogens of humans, animals, and plants are dimorphic, and the ability to switch between morphological states has been associated with their virulence. Cryptococcus neoformans is a human fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised and, in some cases, immunocompetent hosts. Cryptococcus neoformans grows vegetatively as a budding yeast and switches to hyphal growth during the sexual cycle, which is important in the study of cryptococcal pathogenicity because spores resulting from sexual development are infectious propagules and can colonize the lungs of a host. In addition, sexual reproduction contributes to the genotypic variability of Cryptococcus species, which may lead to increased fitness and virulence. Despite significant advances in our understanding of the mechanisms behind the development of C. neoformans, our knowledge is still incomplete. Recent studies have led to the emergence of many intriguing questions and hypotheses. In this review, we describe and discuss the most interesting aspects of C. neoformans development and address their impact on pathogenicity. PMID:21658085
Linking environmental nutrient enrichment and disease emergence in humans and wildlife
Johnson, Pieter T. J.; Townsend, Alan R.; Cleveland, Cory C.; Glibert, Patricia M.; Howarth, Robert W.; McKenzie, Valerie J.; Rejmankova, Eliska; Ward, Mary H.
2009-01-01
Worldwide increases in the numbers of human and wildlife diseases present ecologists with the challenge of understanding how large-scale environmental changes affect host-parasite interactions. One of the most profound changes to Earth’s ecosystems is the alteration of global nutrient cycles, including those of phosphorus (P) and especially nitrogen (N). Alongside the obvious direct benefits of nutrient application for food production, growing evidence suggests that anthropogenic inputs of N and P can indirectly affect the abundance of infectious and noninfectious pathogens, sometimes leading to epidemic conditions. However, the mechanisms underpinning observed correlations, and how such patterns vary with disease type, have long remained conjectural. Here, we discuss recent experimental advances in this area to critically evaluate the relationship between environmental nutrient enrichment and disease. Given the inter-related nature of human and wildlife disease emergence, we include a broad range of human and wildlife examples from terrestrial, marine and freshwater ecosystems. We examine the consequences of nutrient pollution on directly transmitted, vector-borne, complex life cycle, and noninfectious pathogens, including West Nile virus, malaria, harmful algal blooms, coral reef diseases and amphibian malformations. Our synthetic examination suggests that the effects of environmental nutrient enrichment on disease are complex and multifaceted, varying with the type of pathogen, host species and condition, attributes of the ecosystem and the degree of enrichment; some pathogens increase in abundance whereas others decline or disappear. Nevertheless, available evidence indicates that ecological changes associated with nutrient enrichment often exacerbate infection and disease caused by generalist parasites with direct or simple life cycles. Observed mechanisms include changes in host/vector density, host distribution, infection resistance, pathogen virulence or toxicity, or the direct supplementation of pathogens. Collectively, these pathogens may be particularly dangerous because they can continue to cause mortality even as their hosts decline, potentially leading to sustained epidemics or chronic pathology. We suggest that interactions between nutrient enrichment and disease will become increasingly important in tropical and subtropical regions, where forecasted increases in nutrient application will occur in an environment rich with infectious pathogens. We emphasize the importance of careful disease management in conjunction with continued intensification of global nutrient cycles. PMID:20349828
Effect of Intermediate Hosts on Emerging Zoonoses.
Cui, Jing-An; Chen, Fangyuan; Fan, Shengjie
2017-08-01
Most emerging zoonotic pathogens originate from animals. They can directly infect humans through natural reservoirs or indirectly through intermediate hosts. As a bridge, an intermediate host plays different roles in the transmission of zoonotic pathogens. In this study, we present three types of pathogen transmission to evaluate the effect of intermediate hosts on emerging zoonotic diseases in human epidemics. These types are identified as follows: TYPE 1, pathogen transmission without an intermediate host for comparison; TYPE 2, pathogen transmission with an intermediate host as an amplifier; and TYPE 3, pathogen transmission with an intermediate host as a vessel for genetic variation. In addition, we established three mathematical models to elucidate the mechanisms underlying zoonotic disease transmission according to these three types. Stability analysis indicated that the existence of intermediate hosts increased the difficulty of controlling zoonotic diseases because of more difficult conditions to satisfy for the disease to die out. The human epidemic would die out under the following conditions: TYPE 1: [Formula: see text] and [Formula: see text]; TYPE 2: [Formula: see text], [Formula: see text], and [Formula: see text]; and TYPE 3: [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] Simulation with similar parameters demonstrated that intermediate hosts could change the peak time and number of infected humans during a human epidemic; intermediate hosts also exerted different effects on controlling the prevalence of a human epidemic with natural reservoirs in different periods, which is important in addressing problems in public health. Monitoring and controlling the number of natural reservoirs and intermediate hosts at the right time would successfully manage and prevent the prevalence of emerging zoonoses in humans.
Opportunistic pathogens enriched in showerhead biofilms
Feazel, Leah M.; Baumgartner, Laura K.; Peterson, Kristen L.; Frank, Daniel N.; Harris, J. Kirk; Pace, Norman R.
2009-01-01
The environments we humans encounter daily are sources of exposure to diverse microbial communities, some of potential concern to human health. In this study, we used culture-independent technology to investigate the microbial composition of biofilms inside showerheads as ecological assemblages in the human indoor environment. Showers are an important interface for human interaction with microbes through inhalation of aerosols, and showerhead waters have been implicated in disease. Although opportunistic pathogens commonly are cultured from shower facilities, there is little knowledge of either their prevalence or the nature of other microorganisms that may be delivered during shower usage. To determine the composition of showerhead biofilms and waters, we analyzed rRNA gene sequences from 45 showerhead sites around the United States. We find that variable and complex, but specific, microbial assemblages occur inside showerheads. Particularly striking was the finding that sequences representative of non-tuberculous mycobacteria (NTM) and other opportunistic human pathogens are enriched to high levels in many showerhead biofilms, >100-fold above background water contents. We conclude that showerheads may present a significant potential exposure to aerosolized microbes, including documented opportunistic pathogens. The health risk associated with showerhead microbiota needs investigation in persons with compromised immune or pulmonary systems. PMID:19805310
Andoh, Masako; Sakata, Akiko; Takano, Ai; Kawabata, Hiroki; Fujita, Hiromi; Une, Yumi; Goka, Koichi; Kishimoto, Toshio; Ando, Shuji
2015-01-01
One of the major routes of transmission of rickettsial and ehrlichial diseases is via ticks that infest numerous host species, including humans. Besides mammals, reptiles and amphibians also carry ticks that may harbor Rickettsia and Ehrlichia strains that are pathogenic to humans. Furthermore, reptiles and amphibians are exempt from quarantine in Japan, thus facilitating the entry of parasites and pathogens to the country through import. Accordingly, in the current study, we examined the presence of Rickettsia and Ehrlichia spp. genes in ticks associated with reptiles and amphibians originating from outside Japan. Ninety-three ticks representing nine tick species (genera Amblyomma and Hyalomma) were isolated from at least 28 animals spanning 10 species and originating from 12 countries (Ghana, Jordan, Madagascar, Panama, Russia, Sri Lanka, Sudan, Suriname, Tanzania, Togo, Uzbekistan, and Zambia). None of the nine tick species are indigenous in Japan. The genes encoding the common rickettsial 17-kDa antigen, citrate synthase (gltA), and outer membrane protein A (ompA) were positively detected in 45.2% (42/93), 40.9% (38/93), and 23.7% (22/93) of the ticks, respectively, by polymerase chain reaction (PCR). The genes encoding ehrlichial heat shock protein (groEL) and major outer membrane protein (omp-1) were PCR-positive in 7.5% (7/93) and 2.2% (2/93) of the ticks, respectively. The p44 gene, which encodes the Anaplasma outer membrane protein, was not detected. Phylogenetic analysis showed that several of the rickettsial and ehrlichial sequences isolated in this study were highly similar to human pathogen genes, including agents not previously detected in Japan. These data demonstrate the global transportation of pathogenic Rickettsia and Ehrlichia through reptile- and amphibian-associated ticks. These imported animals have potential to transfer pathogens into human life. These results highlight the need to control the international transportation of known and potential pathogens carried by ticks in reptiles, amphibians, and other animals, in order to improve national and international public health. PMID:26207382
Biochemistry and Molecular Biology of Flaviviruses.
Barrows, Nicholas J; Campos, Rafael K; Liao, Kuo-Chieh; Prasanth, K Reddisiva; Soto-Acosta, Ruben; Yeh, Shih-Chia; Schott-Lerner, Geraldine; Pompon, Julien; Sessions, October M; Bradrick, Shelton S; Garcia-Blanco, Mariano A
2018-04-25
Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA-protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.
Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans
da Silva Dantas, Alessandra; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet
2015-01-01
Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552
Hwang, J; Lee, K; Walsh, D; Kim, S W; Sleeman, J M; Lee, H
2018-02-01
Wildlife-associated diseases and pathogens have increased in importance; however, management of a large number of diseases and diversity of hosts is prohibitively expensive. Thus, the determination of priority wildlife pathogens and risk factors for disease emergence is warranted. We used an online questionnaire survey to assess release and exposure risks, and consequences of wildlife-associated diseases and pathogens in the Republic of Korea (ROK). We also surveyed opinions on pathways for disease exposure, and risk factors for disease emergence and spread. For the assessment of risk, we employed a two-tiered, statistical K-means clustering algorithm to group diseases into three levels (high, medium and low) of perceived risk based on release and exposure risks, societal consequences and the level of uncertainty of the experts' opinions. To examine the experts' perceived risk of routes of introduction of pathogens and disease amplification and spread, we used a Bayesian, multivariate normal order-statistics model. Six diseases or pathogens, including four livestock and two wildlife diseases, were identified as having high risk with low uncertainty. Similarly, 13 diseases were characterized as having high risk with medium uncertainty with three of these attributed to livestock, six associated with human disease, and the remainder having the potential to affect human, livestock and wildlife (i.e., One Health). Lastly, four diseases were described as high risk with high certainty, and were associated solely with fish diseases. Experts identified migration of wildlife, international human movement and illegal importation of wildlife as the three routes posing the greatest risk of pathogen introduction into ROK. Proximity of humans, livestock and wildlife was the most significant risk factor for promoting the spread of wildlife-associated diseases and pathogens, followed by high density of livestock populations, habitat loss and environmental degradation, and climate change. This study provides useful information to decision makers responsible for allocating resources to address disease risks. This approach provided a rapid, cost-effective method of risk assessment of wildlife-associated diseases and pathogens for which the published literature is sparse. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Identification of Tick-Borne Pathogens in Ticks Feeding on Humans in Turkey
Orkun, Ömer; Karaer, Zafer; Çakmak, Ayşe; Nalbantoğlu, Serpil
2014-01-01
Background The importance of tick-borne diseases is increasing all over the world, including Turkey. The tick-borne disease outbreaks reported in recent years and the abundance of tick species and the existence of suitable habitats increase the importance of studies related to the epidemiology of ticks and tick-borne pathogens in Turkey. The aim of this study was to investigate the presence of and to determine the infection rates of some tick-borne pathogens, including Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in the ticks removed from humans in different parts of Ankara. Methodology/Principal Findings A total of 169 ticks belonging to the genus Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus were collected by removing from humans in different parts of Ankara. Ticks were molecularly screened for Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae by PCR and sequencing analysis. We detected 4 Babesia spp.; B. crassa, B. major, B. occultans and B. rossi, one Borrelia spp.; B. burgdorferi sensu stricto and 3 spotted fever group rickettsiae; R. aeschlimannii, R. slovaca and R. hoogstraalii in the tick specimens analyzed. This is the report showing the presence of B. rossi in a region that is out of Africa and in the host species Ha. parva. In addition, B. crassa, for which limited information is available on its distribution and vector species, and B. occultans, for which no conclusive information is available on its presence in Turkey, were identified in Ha. parva and H. marginatum, respectively. Two human pathogenic rickettsia species (R. aeschlimannii and R. slovaca) were detected with a high prevalence in ticks. Additionally, B. burgdorferi sensu stricto was detected in unusual tick species (H. marginatum, H. excavatum, Hyalomma spp. (nymph) and Ha. parva). Conclusions/Significance This study investigates both the distribution of several tick-borne pathogens affecting humans and animals, and the presence of new tick-borne pathogens in Turkey. More epidemiological studies are warranted for B. rossi, which is very pathogenic for dogs, because the presented results suggest that B. rossi might have a wide distribution in Turkey. Furthermore, we recommend that tick-borne pathogens, especially R. aeschlimannii, R. slovaca, and B. burgdorferi sensu stricto, should be taken into consideration in patients who had a tick bite in Turkey. PMID:25101999
Identification of tick-borne pathogens in ticks feeding on humans in Turkey.
Orkun, Ömer; Karaer, Zafer; Çakmak, Ayşe; Nalbantoğlu, Serpil
2014-08-01
The importance of tick-borne diseases is increasing all over the world, including Turkey. The tick-borne disease outbreaks reported in recent years and the abundance of tick species and the existence of suitable habitats increase the importance of studies related to the epidemiology of ticks and tick-borne pathogens in Turkey. The aim of this study was to investigate the presence of and to determine the infection rates of some tick-borne pathogens, including Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in the ticks removed from humans in different parts of Ankara. A total of 169 ticks belonging to the genus Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus were collected by removing from humans in different parts of Ankara. Ticks were molecularly screened for Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae by PCR and sequencing analysis. We detected 4 Babesia spp.; B. crassa, B. major, B. occultans and B. rossi, one Borrelia spp.; B. burgdorferi sensu stricto and 3 spotted fever group rickettsiae; R. aeschlimannii, R. slovaca and R. hoogstraalii in the tick specimens analyzed. This is the report showing the presence of B. rossi in a region that is out of Africa and in the host species Ha. parva. In addition, B. crassa, for which limited information is available on its distribution and vector species, and B. occultans, for which no conclusive information is available on its presence in Turkey, were identified in Ha. parva and H. marginatum, respectively. Two human pathogenic rickettsia species (R. aeschlimannii and R. slovaca) were detected with a high prevalence in ticks. Additionally, B. burgdorferi sensu stricto was detected in unusual tick species (H. marginatum, H. excavatum, Hyalomma spp. (nymph) and Ha. parva). This study investigates both the distribution of several tick-borne pathogens affecting humans and animals, and the presence of new tick-borne pathogens in Turkey. More epidemiological studies are warranted for B. rossi, which is very pathogenic for dogs, because the presented results suggest that B. rossi might have a wide distribution in Turkey. Furthermore, we recommend that tick-borne pathogens, especially R. aeschlimannii, R. slovaca, and B. burgdorferi sensu stricto, should be taken into consideration in patients who had a tick bite in Turkey.
Epidemiological role of birds in the transmission and maintenance of zoonoses.
Contreras, A; Gómez-Martín, A; Paterna, A; Tatay-Dualde, J; Prats-Van Der Ham, M; Corrales, J C; De La Fe, C; Sánchez, A
2016-12-01
The risk of zoonoses spreading from birds to humans is lower, quantitatively speaking, than the risk of transmission between other host groups, because the two taxonomic groups share fewer pathogens. Nevertheless, birds have a number of epidemiological characteristics that make them extremely important hosts in the transmission and maintenance of zoonoses, including their susceptibility to pathogens that are extremely hazardous to humans (such as highly pathogenic avian influenza virus, West Nile virus and Chlamydia psittaci) and their ability to travel long distances, especially in the case of migratory birds. The fact that the human diet includes poultry products (meat, eggs and their by-products) also means that most human cases of foodborne zoonoses are infections of avian origin. Lastly, close contact between humans and pet birds or urban birds leads to interactions of public health concern. This article sets out to describe the main factors that determine the role of birds in the epidemiology of zoonotic infections. © OIE (World Organisation for Animal Health), 2016.
Avian influenza viruses in humans.
Malik Peiris, J S
2009-04-01
Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.
[Animals as a potential source of human fungal infections].
Dworecka-Kaszak, Bozena
2008-01-01
Changing environment is a reason, that many saprotrophic fungi became opportunists and in the end also maybe a pathogenic. Host specific adaptation is not so strong among fungi, so there are many common fungal pathogens for people and for animals. Animals suffering from dermatomycosis are well recognize as source of human superficial mycoses. Breeding of different exotic animals such as parrots, various Reptiles and Amphibians, miniature Rodents and keeping them as a pets in the peoples houses, have become more and more popular in the recent years. This article is shortly presenting which animals maybe a potential source of fungal infections for humans. Looking for the other mycoses as systemic mycoses, especially candidiasis or aspergilosis there are no data, which allow excluding sick animals as a source of infection for human, even if those deep mycoses have endogenic reactivation mechanism. Immunocompromised people are in high-risk group when they take care of animals. Another important source of potentially pathogenic, mostly air-born fungi may be animal use in experimental laboratory work. During the experiments is possible that laboratory workers maybe hurt and these animals and their environment, food and house boxes could be the possible source of microorganisms, pathogenic for humans or other animals. Unusual way to inoculate these potentially pathogens into the skin of laboratory personnel may cause granulomatous, local lesions on their hands.
Sun, Honglei; Pu, Juan; Wei, Yandi; Sun, Yipeng; Hu, Jiao; Liu, Litao; Xu, Guanlong; Gao, Weihua; Li, Chong; Zhang, Xuxiao; Huang, Yinhua; Chang, Kin-Chow; Liu, Xiufan
2016-01-01
ABSTRACT Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans. IMPORTANCE Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored. PMID:27122581
Thammahong, Arsa; Puttikamonkul, Srisombat; Perfect, John R.; Brennan, Richard G.
2017-01-01
SUMMARY Invasive fungal infections cause significant morbidity and mortality in part due to a limited antifungal drug arsenal. One therapeutic challenge faced by clinicians is the significant host toxicity associated with antifungal drugs. Another challenge is the fungistatic mechanism of action of some drugs. Consequently, the identification of fungus-specific drug targets essential for fitness in vivo remains a significant goal of medical mycology research. The trehalose biosynthetic pathway is found in a wide variety of organisms, including human-pathogenic fungi, but not in humans. Genes encoding proteins involved in trehalose biosynthesis are mechanistically linked to the metabolism, cell wall homeostasis, stress responses, and virulence of Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. While there are a number of pathways for trehalose production across the tree of life, the TPS/TPP (trehalose-6-phosphate synthase/trehalose-6-phosphate phosphatase) pathway is the canonical pathway found in human-pathogenic fungi. Importantly, data suggest that proteins involved in trehalose biosynthesis play other critical roles in fungal metabolism and in vivo fitness that remain to be fully elucidated. By further defining the biology and functions of trehalose and its biosynthetic pathway components in pathogenic fungi, an opportunity exists to leverage this pathway as a potent antifungal drug target. The goal of this review is to cover the known roles of this important molecule and its associated biosynthesis-encoding genes in the human-pathogenic fungi studied to date and to employ these data to critically assess the opportunities and challenges facing development of this pathway as a therapeutic target. PMID:28298477
Vibrio vulnificus: new insights into a deadly opportunistic pathogen.
Baker-Austin, Craig; Oliver, James D
2018-02-01
Vibrio vulnificus is a Gram-negative aquatic bacterium first isolated by the United States (US) Centers for Disease Control and Prevention (CDC) in 1964. This bacterium is part of the normal microbiota of estuarine waters and occurs in high numbers in molluscan shellfish around the world, particularly in warmer months. Infections in humans are derived from consumption of seafood produce and from water exposure. Vibrio vulnificus is a striking and enigmatic human pathogen, yet many aspects related to its biology, genomics, virulence capabilities and epidemiology remain elusive and poorly understood. This pathogen is responsible for over 95% of seafood-related deaths in the United States, and carries the highest fatality rate of any food-borne pathogen. Indeed, infections associated with this pathogen that progress to primary septicaemia have a similar case fatality rate to category BSL 3 and 4 pathogens, such as anthrax, bubonic plague, Ebola and Marburg fever. Interestingly, V. vulnificus infections disproportionately affect males (∼85% of cases) and older patients (> 40 years), especially those with underlying conditions such as liver diseases, diabetes and immune disorders. New insights from molecular studies and comparative genomic approaches have offered tantalising insights into this pathogen. A recent increase and geographical spread in reported infections, in particular wound cases, underlines the growing international importance of V. vulnificus, particularly in the context of coastal warming. We outline and explore here a range of current data gaps regarding this important pathogen, and provide some current thoughts on approaches to elucidate key aspects associated with this bacterium. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.
Ticks collected from humans, domestic animals, and wildlife in Yucatan, Mexico
USDA-ARS?s Scientific Manuscript database
Domestic animals and wildlife play important roles as reservoirs of zoonotic pathogens that are transmitted to humans by ticks. Besides their role as vectors of several classes of microorganisms of veterinary and public health relevance, ticks also burden human and animal populations through their o...
Water quality indicators: bacteria, coliphages, enteric viruses.
Lin, Johnson; Ganesh, Atheesha
2013-12-01
Water quality through the presence of pathogenic enteric microorganisms may affect human health. Coliform bacteria, Escherichia coli and coliphages are normally used as indicators of water quality. However, the presence of above-mentioned indicators do not always suggest the presence of human enteric viruses. It is important to study human enteric viruses in water. Human enteric viruses can tolerate fluctuating environmental conditions and survive in the environment for long periods of time becoming causal agents of diarrhoeal diseases. Therefore, the potential of human pathogenic viruses as significant indicators of water quality is emerging. Human Adenoviruses and other viruses have been proposed as suitable indices for the effective identification of such organisms of human origin contaminating water systems. This article reports on the recent developments in the management of water quality specifically focusing on human enteric viruses as indicators.
Balabanova, Yanina; Gilsdorf, Andreas; Buda, Silke; Burger, Reinhard; Eckmanns, Tim; Gärtner, Barbara; Groß, Uwe; Haas, Walter; Hamouda, Osamah; Hübner, Johannes; Jänisch, Thomas; Kist, Manfred; Kramer, Michael H.; Ledig, Thomas; Mielke, Martin; Pulz, Matthias; Stark, Klaus; Suttorp, Norbert; Ulbrich, Uta; Wichmann, Ole; Krause, Gérard
2011-01-01
Introduction To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research. Methods We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups. Results 127 pathogens were scored. Eighty-six experts participated in the weighting; “Case fatality rate” was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus. Discussion While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings. PMID:21991334
Kokashvili, Tamar; Whitehouse, Chris A.; Tskhvediani, Ana; Grim, Christopher J.; Elbakidze, Tinatin; Mitaishvili, Nino; Janelidze, Nino; Jaiani, Ekaterine; Haley, Bradd J.; Lashkhi, Nino; Huq, Anwar; Colwell, Rita R.; Tediashvili, Marina
2015-01-01
Among the more than 70 different Vibrio species inhabiting marine, estuarine, and freshwater ecosystems, 12 are recognized as human pathogens. The warm subtropical climate of the Black Sea coastal area and inland regions of Georgia likely provides a favorable environment for various Vibrio species. From 2006 to 2009, the abundance, ecology, and diversity of clinically important Vibrio species were studied in different locations in Georgia and across seasons. Over a 33-month period, 1,595 presumptive Vibrio isolates were collected from the Black Sea (n = 657) and freshwater lakes around Tbilisi (n = 938). Screening of a subset of 440 concentrated and enriched water samples by PCR-electrospray ionization/mass spectrometry (PCR-ESI/MS) detected the presence of DNA from eight clinically important Vibrio species: V. cholerae, V. parahaemolyticus, V. vulnificus, V. mimicus, V. alginolyticus, V. harveyi, V. metschnikovii, and V. cincinnatiensis. Almost 90% of PCR/ESI-MS samples positive for Vibrio species were collected from June through November. Three important human-pathogenic Vibrio species (V. cholerae, V. parahaemolyticus, and V. vulnificus) were detected in 62.8, 37.8, and 21.4% of samples testing positive for Vibrios, respectively. The results of these activities suggest that natural reservoirs for human-pathogenic Vibrios exist in Georgian aquatic environments. Water temperature at all sampling sites was positively correlated with the abundance of clinically important Vibrio spp. (except V. metschnikovii), and salinity was correlated with species composition at particular Black Sea sites as well as inland reservoirs. PMID:26528464
Gold Nanoparticles: An Efficient Antimicrobial Agent against Enteric Bacterial Human Pathogen
Shamaila, Shahzadi; Zafar, Noshin; Riaz, Saira; Sharif, Rehana; Nazir, Jawad; Naseem, Shahzad
2016-01-01
Enteric bacterial human pathogens, i.e., Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Klebsiella pneumoniae, are the major cause of diarrheal infections in children and adults. Their structure badly affects the human immune system. It is important to explore new antibacterial agents instead of antibiotics for treatment. This project is an attempt to explain how gold nanoparticles affect these bacteria. We investigated the important role of the mean particle size, and the inhibition of a bacterium is dose-dependent. Ultra Violet (UV)-visible spectroscopy revealed the size of chemically synthesized gold nanoparticle as 6–40 nm. Atomic force microscopy (AFM) analysis confirmed the size and X-ray diffractometry (XRD) analysis determined the polycrystalline nature of gold nanoparticles. The present findings explained how gold nanoparticles lyse Gram-negative and Gram-positive bacteria. PMID:28335198
Borchert, D; Sheridan, L; Papatsoris, A; Faruquz, Z; Barua, J M; Junaid, I; Pati, Y; Chinegwundoh, F; Buchholz, N
2008-04-01
The spiralling costs of antibiotic therapy, the appearance of multiresistant bacteria and more importantly for patients and clinicians, unsatisfactory therapeutic options in recurrent urinary tract infection (RUTI) calls for alternative and advanced medical solutions. So far no sufficient means to successfully prevent painful and disabling RUTI has been found. Even though long-term oral antibiotic treatment has been used with some success as a therapeutic option, this is no longer secure due to the development of bacterial resistance. One promising alternative is the use of live microorganisms (probiotics) to prevent and treat recurrent complicated and uncomplicated urinary tract infection (UTI).The human normal bacterial flora is increasingly recognised as an important defence to infection. Since the advent of antibiotic treatment five decades ago, a linear relation between antibiotic use and reduction in pathogenic bacteria has become established as medical conventional wisdom. But with the use of antibiotics the beneficial bacterial flora hosted by the human body is destroyed and pathogenic bacteria are selectively enabled to overgrow internal and external surfaces. The benign bacterial flora is crucial for body function and oervgrowth with pathogenic microorganisms leads to illness. Thus the concept of supporting the human body's normal flora with live microorganisms conferring a beneficial health effect is an important medical strategy.
Mycobacterium bovis and Other Uncommon Members of the Mycobacterium tuberculosis Complex.
Esteban, Jaime; Muñoz-Egea, Maria-Carmen
2016-12-01
Since its discovery by Theobald Smith, Mycobacterium bovis has been a human pathogen closely related to animal disease. At present, M. bovis tuberculosis is still a problem of importance in many countries and is considered the main cause of zoonotic tuberculosis throughout the world. Recent development of molecular epidemiological tools has helped us to improve our knowledge about transmission patterns of this organism, which causes a disease indistinguishable from that caused by Mycobacterium tuberculosis. Diagnosis and treatment of this mycobacterium are similar to those for conventional tuberculosis, with the important exceptions of constitutive resistance to pyrazinamide and the fact that multidrug-resistant and extremely drug-resistant M. bovis strains have been described. Among other members of this complex, Mycobacterium africanum is the cause of many cases of tuberculosis in West Africa and can be found in other areas mainly in association with immigration. M. bovis BCG is the currently available vaccine for tuberculosis, but it can cause disease in some patients. Other members of the M. tuberculosis complex are mainly animal pathogens with only exceptional cases of human disease, and there are even some strains, like "Mycobacterium canettii," which is a rare human pathogen that could have an important role in the knowledge of the evolution of tuberculosis in the history.
Makthal, Nishanth; Nguyen, Kimberly; Do, Hackwon; Gavagan, Maire; Chandrangsu, Pete; Helmann, John D; Olsen, Randall J; Kumaraswami, Muthiah
2017-07-01
Bacterial pathogens must overcome host immune mechanisms to acquire micronutrients for successful replication and infection. Streptococcus pyogenes, also known as group A streptococcus (GAS), is a human pathogen that causes a variety of clinical manifestations, and disease prevention is hampered by lack of a human GAS vaccine. Herein, we report that the mammalian host recruits calprotectin (CP) to GAS infection sites and retards bacterial growth by zinc limitation. However, a GAS-encoded zinc importer and a nuanced zinc sensor aid bacterial defense against CP-mediated growth inhibition and contribute to GAS virulence. Immunization of mice with the extracellular component of the zinc importer confers protection against systemic GAS challenge. Together, we identified a key early stage host-GAS interaction and translated that knowledge into a novel vaccine strategy against GAS infection. Furthermore, we provided evidence that a similar struggle for zinc may occur during other streptococcal infections, which raises the possibility of a broad-spectrum prophylactic strategy against multiple streptococcal pathogens. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
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.
Wyrsch, Ethan R; Roy Chowdhury, Piklu; Chapman, Toni A; Charles, Ian G; Hammond, Jeffrey M; Djordjevic, Steven P
2016-01-01
Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance.
Samir, M; Hamed, M; Abdallah, F; Kinh Nguyen, V; Hernandez-Vargas, E A; Seehusen, F; Baumgärtner, W; Hussein, A; Ali, A A H; Pessler, F
2018-06-01
The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause major problems in poultry and can, although rarely, cause human infection. Being enzootic in domestic poultry, Egyptian isolates are continuously evolving, and novel clades vary in their pathogenicity in avian hosts. Considering the importance of domestic ducks as natural hosts of HPAI H5N1 viruses and their likelihood of physical contact with other avian hosts and humans, it is of utmost importance to characterize the pathogenicity of newly emerged HPAI strains in the domestic duck. The most recently identified Egyptian clade 2.2.1.2 HPAI H5N1 viruses have been isolated from naturally infected pigeons, turkeys and humans. However, essentially nothing is known about their pathogenicity in domestic ducks. We therefore characterized the pathogenicity of an Egyptian HPAI H5N1 isolate A/chicken/Faquos/amn12/2011 (clade 2.2.1.2) in Sudani duck, a domestic duck breed commonly reared in Egypt. While viral transcription (HA mRNA) was highest in lung, heart and kidney peaking between 40 and 48 hpi, lower levels were detected in brain. Weight loss of infected ducks started at 16 hpi and persisted until 120 hpi. The first severe clinical signs were noted by 32 hpi and peaked in severity at 72 and 96 hpi. Haematological analyses showed a decline in total leucocytes, granulocytes, platelets and granulocyte/lymphocyte ratio, but lymphocytosis. Upon necropsy, lesions were obvious in heart, liver, spleen and pancreas and consisted mainly of necrosis and petechial haemorrhage. Histologically, lungs were the most severely affected organs, whereas brain only showed mild neuronal degeneration and gliosis at 48 hpi despite obvious neurological clinical signs. Taken together, our results provide first evidence that this HPAI H5N1 isolate (clade 2.2.1.2) is highly pathogenic to Sudani ducks and highlight the importance of this breed as potential reservoir and disseminator of HPAI strains from this clade. © 2018 Blackwell Verlag GmbH.
HOOSHYAR, Hossein; ROSTAMKHANI, Parvin; REZAEIAN, Mostafa
2015-01-01
Background: The number of valid of pathogen and non-pathogen species of Entamoeba has continuously increased in human and animals. This review is performed to provide an update list and some summarized information on Entamoeba species, which were identified up to the 2014. Methods: We evaluated the Entamoeba genus with a broad systematic review of the literature, books and electronic databases until February 2014. The synonyms, hosts, pathogenicity and geographical distribution of valid species were considered and recorded. Repeated and unrelated cases were excluded. Results: Totally 51 defined species of Entamoeba were found and arranged by the number of nuclei in mature cyst according to Levin’s grouping. Seven of these species within the 4 nucleate mature cysts group and 1 species with one nucleate mature cyst are pathogen. E. histolytica, E. invadence, E. rananrum and E. anatis causes lethal infection in human, reptiles, amphibians and brides respectively, four species causes non-lethal mild dysentery. The other species were non-pathogen and are important to differential diagnosis of amoebiasis. Conclusion: There are some unknown true species of Entamoeba that available information on the morphology, hosts, pathogenicity and distribution of them are still very limited and more considerable investigation will be needed in order to clarify the status of them. PMID:26246811
Sterk, Ankie; Schijven, Jack; de Nijs, Ton; de Roda Husman, Ana Maria
2013-11-19
Climate change is likely to affect the infectious disease burden from exposure to pathogens in water used for drinking and recreation. Effective intervention measures require quantification of impacts of climate change on the distribution of pathogens in the environment and their potential effects on human health. Objectives of this systematic review were to summarize current knowledge available to estimate how climate change may directly and indirectly affect infection risks due to Campylobacter, Cryptosporidium, norovirus, and Vibrio. Secondary objectives were to prioritize natural processes and interactions that are susceptible to climate change and to identify knowledge gaps. Search strategies were determined based on a conceptual model and scenarios with the main emphasis on The Netherlands. The literature search resulted in a large quantity of publications on climate variables affecting pathogen input and behavior in aquatic environments. However, not all processes and pathogens are evenly covered by the literature, and in many cases, the direction of change is still unclear. To make useful predictions of climate change, it is necessary to combine both negative and positive effects. This review provides an overview of the most important effects of climate change on human health and shows the importance of QMRA to quantify the net effects.
DOE Office of Scientific and Technical Information (OSTI.GOV)
McDermott, Jason E.; Braun, Pascal; Bonneau, Richard A.
Pathogenic infections are a major cause of both human disease and loss of crop yields and animal stocks and thus cause immense damage to the worldwide economy. The significance of infectious diseases is expected to increase in an ever more connected warming world, in which new viral, bacterial and fungal pathogens can find novel hosts and ecologic niches. At the same time, the complex and sophisticated mechanisms by which diverse pathogenic agents evade defense mechanisms and subvert their hosts networks to suit their lifestyle needs is still very incompletely understood especially from a systems perspective [1]. Thus, understanding host-pathogen interactionsmore » is both an important and a scientifically fascinating topic. Recently, technology has offered the opportunity to investigate host-pathogen interactions on a level of detail and scope that offers immense computational and analytical possibilities. Genome sequencing was pioneered on some of these pathogens, and the number of strains and variants of pathogens sequenced to date vastly outnumbers the number of host genomes available. At the same time, for both plant and human hosts more and more data on population level genomic variation becomes available and offers a rich field for analysis into the genetic interactions between host and pathogen.« less
Martínez, Isidoro; Oliveros, Juan C.; Cuesta, Isabel; de la Barrera, Jorge; Ausina, Vicente; Casals, Cristina; de Lorenzo, Alba; García, Ernesto; García-Fojeda, Belén; Garmendia, Junkal; González-Nicolau, Mar; Lacoma, Alicia; Menéndez, Margarita; Moranta, David; Nieto, Amelia; Ortín, Juan; Pérez-González, Alicia; Prat, Cristina; Ramos-Sevillano, Elisa; Regueiro, Verónica; Rodriguez-Frandsen, Ariel; Solís, Dolores; Yuste, José; Bengoechea, José A.; Melero, José A.
2017-01-01
Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here. PMID:28298903
Mahmoud, D.A.; Hassanein, N.M.; Youssef, K.A.; Abou Zeid, M.A.
2011-01-01
This study was conducted to evaluate the effect of aqueous, ethanolic and ethyl acetate extracts from neem leaves on growth of some human pathogens (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Candida albicans and Microsporum gypseum) in vitro. Different concentrations (5, 10, 15 and 20%) prepared from these extracts inhibited the growth of the test pathogens and the effect gradually increased with concentration. The 20% ethyl acetate extract gave the strongest inhibition compared with the activity obtained by the same concentration of the other extracts. High Performance Liquid Chromatography (HPLC) analysis of ethyl acetate extract showed the presence of a main component (nimonol) which was purified and chemically confirmed by Nuclear Magnetic Resonance (NMR) spectroscopic analysis. The 20% ethyl acetate extract lost a part of its antifungal effect after pooling out the nimonol and this loss in activity was variable on test pathogens. The purified nimonol as a separate compound did not show any antifungal activity when assayed against all the six fungal pathogens. PMID:24031718
Identification of DNA Methyltransferase Genes in Human Pathogenic Bacteria by Comparative Genomics.
Brambila-Tapia, Aniel Jessica Leticia; Poot-Hernández, Augusto Cesar; Perez-Rueda, Ernesto; Rodríguez-Vázquez, Katya
2016-06-01
DNA methylation plays an important role in gene expression and virulence in some pathogenic bacteria. In this report, we describe DNA methyltransferases (MTases) present in human pathogenic bacteria and compared them with related species, which are not pathogenic or less pathogenic, based in comparative genomics. We performed a search in the KEGG database of the KEGG database orthology groups associated with adenine and cytosine DNA MTase activities (EC: 2.1.1.37, EC: 2.1.1.113 and EC: 2.1.1.72) in 37 human pathogenic species and 18 non/less pathogenic relatives and performed comparisons of the number of these MTases sequences according to their genome size, the DNA MTase type and with their non-less pathogenic relatives. We observed that Helicobacter pylori and Neisseria spp. presented the highest number of MTases while ten different species did not present a predicted DNA MTase. We also detected a significant increase of adenine MTases over cytosine MTases (2.19 vs. 1.06, respectively, p < 0.001). Adenine MTases were the only MTases associated with restriction modification systems and DNA MTases associated with type I restriction modification systems were more numerous than those associated with type III restriction modification systems (0.84 vs. 0.17, p < 0.001); additionally, there was no correlation with the genome size and the total number of DNA MTases, indicating that the number of DNA MTases is related to the particular evolution and lifestyle of specific species, regulating the expression of virulence genes in some pathogenic bacteria.
Tropical environments, human activities, and the transmission of infectious diseases.
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.
Ye, Luona; Guo, Mengpei; Ren, Pengfei; Wang, Gangzheng; Bian, Yinbing; Xiao, Yang; Zhou, Yan
2018-03-01
Coprinus comatus is an edible mushroom widely cultivated in China as a delicious food. Various diseases have occurred on C. comatus with the cultivated area increasing. In this study, the pathogenic bacterium JTG-B1, identified as Achromobacter xylosoxidans by 16S rDNA and nrdA gene sequencing, was isolated from edible mushroom Coprinus comatus with serious rot disease on its stipe. A. xylosoxidans has been confirmed as an important opportunistic human pathogenic bacterium and has been isolated from respiratory samples from cystic fibrosis. It is widely distributed in the environment. Here, we first report that fungi can also serve as a host for A. xylosoxidans. We confirmed that it can cross-kingdom infect between animals (mice) and fungi (C. comatus). The results of pathogenicity tests, physiological, biochemical and genotyping analysis of A. xylosoxidans from different hosts suggested that different strain of A. xylosoxidans may have pathogenicity differentiation. A. xylosoxidans not only is pathogenic to C. comatus but also may threaten human health. Copyright © 2017 Elsevier GmbH. All rights reserved.
Jakobsen, Tim Holm; Hansen, Martin Asser; Jensen, Peter Østrup; Hansen, Lars; Riber, Leise; Cockburn, April; Kolpen, Mette; Rønne Hansen, Christine; Ridderberg, Winnie; Eickhardt, Steffen; Hansen, Marlene; Kerpedjiev, Peter; Alhede, Morten; Qvortrup, Klaus; Burmølle, Mette; Moser, Claus; Kühl, Michael; Ciofu, Oana; Givskov, Michael; Sørensen, Søren J.; Høiby, Niels; Bjarnsholt, Thomas
2013-01-01
Achromobacter xylosoxidans is an environmental opportunistic pathogen, which infects an increasing number of immunocompromised patients. In this study we combined genomic analysis of a clinical isolated A. xylosoxidans strain with phenotypic investigations of its important pathogenic features. We present a complete assembly of the genome of A. xylosoxidans NH44784-1996, an isolate from a cystic fibrosis patient obtained in 1996. The genome of A. xylosoxidans NH44784-1996 contains approximately 7 million base pairs with 6390 potential protein-coding sequences. We identified several features that render it an opportunistic human pathogen, We found genes involved in anaerobic growth and the pgaABCD operon encoding the biofilm adhesin poly-β-1,6-N-acetyl-D-glucosamin. Furthermore, the genome contains a range of antibiotic resistance genes coding efflux pump systems and antibiotic modifying enzymes. In vitro studies of A. xylosoxidans NH44784-1996 confirmed the genomic evidence for its ability to form biofilms, anaerobic growth via denitrification, and resistance to a broad range of antibiotics. Our investigation enables further studies of the functionality of important identified genes contributing to the pathogenicity of A. xylosoxidans and thereby improves our understanding and ability to treat this emerging pathogen. PMID:23894309
Human susceptibility to legionnaires' disease.
Berrington, William R; Hawn, Thomas R
2013-01-01
Legionella pneumophila is a facultative intracellular pathogen that is an important cause of pneumonia. Although host factors that may predispose to acquisition of Legionnaire's Disease (LD) include comorbid illnesses (e.g., diabetes, chronic lung disease), age, male sex, and smoking, many individuals have no identifiable risk factors. Some studies suggest that genetic factors may enhance susceptibility to LD. In this chapter we discuss current techniques and scientific methods to identify genetic susceptibility factors. These genetic studies provide insight into the human immune response to intracellular pathogens and may improve strategies for treatment and vaccine development.
Praveen, Praveen Kumar; Debnath, Chanchal; Shekhar, Shashank; Dalai, Nirupama; Ganguly, Subha
2016-01-01
Aeromonas is recognized to cause a variety of diseases in man. In humans, they are associated with intestinal and extra-intestinal infections. With the growing importance of Aeromonas as an emerging pathogen, it is important to combat this organism. It is indisputable that Aeromonas strains may produce many different putative virulence factors such as enterotoxins, hemolysins or cytotoxins, and antibiotic resistance against different antibiotics. The ability of these bacteria to grow competitively at 5°C may be indicative of their potential as a public health hazard. Comprehensive enteric disease surveillance strategies, prevention and education are essential for meeting the challenges in the years ahead. It is important for us to promote the value of enteric cultures when patients have a gastrointestinal illness or bloody diarrhea or when multiple cases of enteric disease occur after a common exposure. With the growing importance of Aeromonas as an emerging pathogen, it is important to combat this organism. It is indisputable that Aeromonas strains may produce many different putative virulence factors, such as enterotoxins, hemolysins or cytotoxins. It has been established that aerolysin is a virulence factor contributing to the pathogenesis of Aeromonas hydrophila infection. Fish and chicken play an important role in the transmission of this pathogen to humans. In the present study, the high prevalence of toxin-producing strains was found among the Aeromonas isolates. The ability of these bacteria to grow competitively at 5°C may be indicative of their potential as a public health hazard. The present review was constructed with a view to highlight the zoonotic importance of Aeromonas pathogen in fish and chicken meat.
Praveen, Praveen Kumar; Debnath, Chanchal; Shekhar, Shashank; Dalai, Nirupama; Ganguly, Subha
2016-01-01
Aeromonas is recognized to cause a variety of diseases in man. In humans, they are associated with intestinal and extra-intestinal infections. With the growing importance of Aeromonas as an emerging pathogen, it is important to combat this organism. It is indisputable that Aeromonas strains may produce many different putative virulence factors such as enterotoxins, hemolysins or cytotoxins, and antibiotic resistance against different antibiotics. The ability of these bacteria to grow competitively at 5°C may be indicative of their potential as a public health hazard. Comprehensive enteric disease surveillance strategies, prevention and education are essential for meeting the challenges in the years ahead. It is important for us to promote the value of enteric cultures when patients have a gastrointestinal illness or bloody diarrhea or when multiple cases of enteric disease occur after a common exposure. With the growing importance of Aeromonas as an emerging pathogen, it is important to combat this organism. It is indisputable that Aeromonas strains may produce many different putative virulence factors, such as enterotoxins, hemolysins or cytotoxins. It has been established that aerolysin is a virulence factor contributing to the pathogenesis of Aeromonas hydrophila infection. Fish and chicken play an important role in the transmission of this pathogen to humans. In the present study, the high prevalence of toxin-producing strains was found among the Aeromonas isolates. The ability of these bacteria to grow competitively at 5°C may be indicative of their potential as a public health hazard. The present review was constructed with a view to highlight the zoonotic importance of Aeromonas pathogen in fish and chicken meat. PMID:27051177
Goyette-Desjardins, Guillaume; Auger, Jean-Philippe; Xu, Jianguo; Segura, Mariela; Gottschalk, Marcelo
2014-01-01
Streptococcus suis is an important pathogen causing economic problems in the pig industry. Moreover, it is a zoonotic agent causing severe infections to people in close contact with infected pigs or pork-derived products. Although considered sporadic in the past, human S. suis infections have been reported during the last 45 years, with two large outbreaks recorded in China. In fact, the number of reported human cases has significantly increased in recent years. In this review, we present the worldwide distribution of serotypes and sequence types (STs), as determined by multilocus sequence typing, for pigs (between 2002 and 2013) and humans (between 1968 and 2013). The methods employed for S. suis identification and typing, the current epidemiological knowledge regarding serotypes and STs and the zoonotic potential of S. suis are discussed. Increased awareness of S. suis in both human and veterinary diagnostic laboratories and further establishment of typing methods will contribute to our knowledge of this pathogen, especially in regions where complete and/or recent data is lacking. More research is required to understand differences in virulence that occur among S. suis strains and if these differences can be associated with specific serotypes or STs. PMID:26038745
Metallothionein: a Potential Link in the Regulation of Zinc in Nutritional Immunity.
Rahman, Mohammad Tariqur; Karim, Muhammad Manjurul
2018-03-01
Nutritional immunity describes mechanisms for withholding essential transition metals as well as directing the toxicity of these metals against infectious agents. Zinc is one of these transition elements that are essential for both humans and microbial pathogens. At the same time, Zn can be toxic both for man and microbes if its concentration is higher than the tolerance limit. Therefore a "delicate" balance of Zn must be maintained to keep the immune cells surveilling while making the level of Zn either to starve or to intoxicate the pathogens. On the other hand, the invading pathogens will exploit the host Zn pool for its survival and replication. Apparently, different sets of protein in human and bacteria are involved to maintain their Zn need. Metallothionein (MT)-a group of low molecular weight proteins, is well known for its Zn-binding ability and is expected to play an important role in that Zn balance at the time of active infection. However, the differences in structural, functional, and molecular control of biosynthesis between human and bacterial MT might play an important role to determine the proper use of Zn and the winning side. The current review explains the possible involvement of human and bacterial MT at the time of infection to control and exploit Zn for their need.
Sserwadda, Ivan; Amujal, Marion; Namatovu, Norah
2018-01-01
HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers. PMID:29755620
Tick-borne pathogens and the vector potential of ticks in China.
Yu, Zhijun; Wang, Hui; Wang, Tianhong; Sun, Wenying; Yang, Xiaolong; Liu, Jingze
2015-01-14
Ticks, as obligate blood-sucking ectoparasites, attack a broad range of vertebrates and transmit a great diversity of pathogenic microorganisms. They are considered second only to mosquitoes as vectors of human disease, and the most important vector of pathogens of domestic and wild animals. Of the 117 described species in the Chinese tick fauna, 60 are known to transmit one or more diseases: 36 species isolated within China and 24 species isolated outside China. Moreover, 38 of these species carry multiple pathogens, indicating the potentially vast role of these vectors in transmitting pathogens. Spotted fever is the most common tick-borne disease, and is carried by at least 27 tick species, with Lyme disease and human granulocytic anaplasmosis ranked as the second and third most widespread tick-borne diseases, carried by 13 and 10 species, respectively. Such knowledge provides us with clues for the identification of tick-associated pathogens and suggests ideas for the control of tick-borne diseases in China. However, the numbers of tick-associated pathogens and tick-borne diseases in China are probably underestimated because of the complex distribution and great diversity of tick species in this country.
Ferguson, Christobel M; Croke, Barry F W; Beatson, Peter J; Ashbolt, Nicholas J; Deere, Daniel A
2007-06-01
In drinking water catchments, reduction of pathogen loads delivered to reservoirs is an important priority for the management of raw source water quality. To assist with the evaluation of management options, a process-based mathematical model (pathogen catchment budgets - PCB) is developed to predict Cryptosporidium, Giardia and E. coli loads generated within and exported from drinking water catchments. The model quantifies the key processes affecting the generation and transport of microorganisms from humans and animals using land use and flow data, and catchment specific information including point sources such as sewage treatment plants and on-site systems. The resultant pathogen catchment budgets (PCB) can be used to prioritize the implementation of control measures for the reduction of pathogen risks to drinking water. The model is applied in the Wingecarribee catchment and used to rank those sub-catchments that would contribute the highest pathogen loads in dry weather, and in intermediate and large wet weather events. A sensitivity analysis of the model identifies that pathogen excretion rates from animals and humans, and manure mobilization rates are significant factors determining the output of the model and thus warrant further investigation.
Epidemics to eradication: the modern history of poliomyelitis
De Jesus, Nidia H
2007-01-01
Poliomyelitis has afflicted humankind since antiquity, and for nearly a century now, we have known the causative agent, poliovirus. This pathogen is an enterovirus that in recent history has been the source of a great deal of human suffering. Although comparatively small, its genome is packed with sufficient information to make it a formidable pathogen. In the last 20 years the Global Polio Eradication Initiative has proven successful in greatly diminishing the number of cases worldwide but has encountered obstacles in its path which have made halting the transmission of wild polioviruses a practical impossibility. As we begin to realize that a change in strategy may be crucial in achieving success in this venture, it is imperative that we critically evaluate what is known about the molecular biology of this pathogen and the intricacies of its interaction with its host so that in future attempts we may better equipped to more effectively combat this important human pathogen. PMID:17623069
Epidemics to eradication: the modern history of poliomyelitis.
De Jesus, Nidia H
2007-07-10
Poliomyelitis has afflicted humankind since antiquity, and for nearly a century now, we have known the causative agent, poliovirus. This pathogen is an enterovirus that in recent history has been the source of a great deal of human suffering. Although comparatively small, its genome is packed with sufficient information to make it a formidable pathogen. In the last 20 years the Global Polio Eradication Initiative has proven successful in greatly diminishing the number of cases worldwide but has encountered obstacles in its path which have made halting the transmission of wild polioviruses a practical impossibility. As we begin to realize that a change in strategy may be crucial in achieving success in this venture, it is imperative that we critically evaluate what is known about the molecular biology of this pathogen and the intricacies of its interaction with its host so that in future attempts we may better equipped to more effectively combat this important human pathogen.
Urban Breeding Corvids as Disseminators of Ticks and Emerging Tick-Borne Pathogens.
Sándor, Attila D; Kalmár, Zsuzsa; Matei, Ioana; Ionică, Angela Monica; Mărcuţan, Ioan-Daniel
2017-02-01
Crows (Corvidae) are common city dwellers worldwide and are increasingly important subjects of epidemiology studies. Although their importance as hosts and transmitters of a number of zoonotic parasites and pathogens is well known, there are no studies on their importance as tick hosts. After mosquitoes, ticks are the most important vectors of zoonotic pathogens, especially for those causing emerging zoonotic diseases. Pathogenic bacteria, especially Borrelia spp., Rickettsia spp., and Anaplasma spp., vectored by ticks, are the cause for most vector-borne diseases in Europe. Here we report on ticks and tick-borne pathogens harbored by urban breeding crows. A total of 36 birds (33.33%, n = 108) hosted ticks, with 91 individual ticks belonging to 6 species (Haemaphysalis concinna, Haemaphysalis parva, Haemaphysalis punctata, Hyalomma marginatum, Ixodes arboricola, and Ixodes ricinus). Rickettsia spp. DNA was found in 6.6% of ticks and 1.9% of bird tissues, whereas Anaplasma phagocytophilum was found in 5.9% of ticks and 0.9% of birds. Two rickettsial genospecies were located, Rickettsia helvetica and Rickettsia monacensis. This is the first study to determine such a diverse tick spectrum feeding on urban corvids, while highlighting their importance as tick hosts and raising concerns about their potential risk to human health.
Bueno, I; Smith, K M; Sampedro, F; Machalaba, C C; Karesh, W B; Travis, D A
2016-06-01
Wildlife trade (both formal and informal) is a potential driver of disease introduction and emergence. Legislative proposals aim to prevent these risks by banning wildlife imports, and creating 'white lists' of species that are cleared for importation. These approaches pose economic harm to the pet industry, and place substantial burden on importers and/or federal agencies to provide proof of low risk for importation of individual species. As a feasibility study, a risk prioritization tool was developed to rank the pathogens found in rodent species imported from Latin America into the United States with the highest risk of zoonotic consequence in the United States. Four formally traded species and 16 zoonotic pathogens were identified. Risk scores were based on the likelihood of pathogen release and human exposure, and the severity of the disease (consequences). Based on the methodology applied, three pathogens (Mycobacterium microti, Giardia spp. and Francisella tularensis) in one species (Cavia porcellus) were ranked as highest concern. The goal of this study was to present a methodological approach by which preliminary management resources can be allocated to the identified high-concern pathogen-species combinations when warranted. This tool can be expanded to other taxa and geographic locations to inform policy surrounding the wildlife trade. © 2015 Blackwell Verlag GmbH.
Interactions between the microbiota and pathogenic bacteria in the gut
Bäumler, Andreas J.; Sperandio, Vanessa
2016-01-01
The microbiome has an important role in human health. Changes in the microbiota can confer resistance to or promote infection by pathogenic bacteria. Antibiotics have a profound impact on the microbiota that alters the nutritional landscape of the gut and can lead to the expansion of pathogenic populations. Pathogenic bacteria exploit microbiota-derived sources of carbon and nitrogen as nutrients and regulatory signals to promote their own growth and virulence. By eliciting inflammation, these bacteria alter the intestinal environment and use unique systems for respiration and metal acquisition to drive their expansion. Unravelling the interactions between the microbiota, the host and pathogenic bacteria will produce strategies for manipulating the microbiota against infectious diseases. PMID:27383983
Interactions between the microbiota and pathogenic bacteria in the gut.
Bäumler, Andreas J; Sperandio, Vanessa
2016-07-07
The microbiome has an important role in human health. Changes in the microbiota can confer resistance to or promote infection by pathogenic bacteria. Antibiotics have a profound impact on the microbiota that alters the nutritional landscape of the gut and can lead to the expansion of pathogenic populations. Pathogenic bacteria exploit microbiota-derived sources of carbon and nitrogen as nutrients and regulatory signals to promote their own growth and virulence. By eliciting inflammation, these bacteria alter the intestinal environment and use unique systems for respiration and metal acquisition to drive their expansion. Unravelling the interactions between the microbiota, the host and pathogenic bacteria will produce strategies for manipulating the microbiota against infectious diseases.
[Human coronavirus infections: importance and diagnosis].
Vabret, A; Brouard, J; Petitjean, J; Eugene-Ruellan, G; Freymuth, F
1998-11-14
POORLY-KNOWN VIRUS: Coronaviruses, so named because of their sun-ray-like aspect, were discovered in the sixties. The biology of these RNA viruses is complex and poorly understood. KNOWN PATHOGENS: Coronaviruses are known pathogens in veterinary medicine, causing disease states in several domestic species. In human medicine, they can cause benign respiratory infections, but few laboratories include coronaviruses in their routine diagnostic tests. SUSPECTED PATHOGENS: There is some data in the literature suggesting coronaviruses might be implicated in more severe diseases including multiple sclerosis, necrotizing enterocolitis, and lower respiratory tract infections, particularly in infants. IMPROVING DIAGNOSTIC METHODS: Due to the lack of reliable and sensitive diagnostic techniques, it is impossible to date to correctly assess the medical impact of these ubiquitous and endemic viruses. Molecular biology techniques enabling detection of human coronavirus infections should be applied to verifying the suspected implication of these viruses in diverse disease states.
Virus-Bacteria Interactions: Implications and Potential for the Applied and Agricultural Sciences.
Moore, Matthew D; Jaykus, Lee-Ann
2018-02-02
Eukaryotic virus-bacteria interactions have recently become an emerging topic of study due to multiple significant examples related to human pathogens of clinical interest. However, such omnipresent and likely important interactions for viruses and bacteria relevant to the applied and agricultural sciences have not been reviewed or compiled. The fundamental basis of this review is that these interactions have importance and deserve more investigation, as numerous potential consequences and applications arising from their discovery are relevant to the applied sciences. The purpose of this review is to highlight and summarize eukaryotic virus-bacteria findings in the food/water, horticultural, and animal sciences. In many cases in the agricultural sciences, mechanistic understandings of the effects of virus-bacteria interactions remain unstudied, and many studies solely focus on co-infections of bacterial and viral pathogens. Given recent findings relative to human viral pathogens, further research related to virus-bacteria interactions would likely result in numerous discoveries and beneficial applications.
Integrated inference and evaluation of host–fungi interaction networks
Remmele, Christian W.; Luther, Christian H.; Balkenhol, Johannes; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus T.
2015-01-01
Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host–pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse. To establish large-scale host–fungi interaction networks on a systems biology scale, we develop an extended inference approach based on protein orthology and data on gene functions. Using human and yeast intraspecies networks as template, we derive a large network of pathogen–host interactions (PHI). Rigorous filtering and refinement steps based on cellular localization and pathogenicity information of predicted interactors yield a primary scaffold of fungi–human and fungi–mouse interaction networks. Specific enrichment of known pathogenicity-relevant genes indicates the biological relevance of the predicted PHI. A detailed inspection of functionally relevant subnetworks reveals novel host–fungal interaction candidates such as the Candida virulence factor PLB1 and the anti-fungal host protein APP. Our results demonstrate the applicability of interolog-based prediction methods for host–fungi interactions and underline the importance of filtering and refinement steps to attain biologically more relevant interactions. This integrated network framework can serve as a basis for future analyses of high-throughput host–fungi transcriptome and proteome data. PMID:26300851
Cis-encoded non-coding antisense RNAs in streptococci and other low GC Gram (+) bacterial pathogens
Cho, Kyu Hong; Kim, Jeong-Ho
2015-01-01
Due to recent advances of bioinformatics and high throughput sequencing technology, discovery of regulatory non-coding RNAs in bacteria has been increased to a great extent. Based on this bandwagon, many studies searching for trans-acting small non-coding RNAs in streptococci have been performed intensively, especially in the important human pathogen, group A and B streptococci. However, studies for cis-encoded non-coding antisense RNAs in streptococci have been scarce. A recent study shows antisense RNAs are involved in virulence gene regulation in group B streptococcus, S. agalactiae. This suggests antisense RNAs could have important roles in the pathogenesis of streptococcal pathogens. In this review, we describe recent discoveries of chromosomal cis-encoded antisense RNAs in streptococcal pathogens and other low GC Gram (+) bacteria to provide a guide for future studies. PMID:25859258
House-to-house human movement drives dengue virus transmission
Stoddard, Steven T.; Forshey, Brett M.; Morrison, Amy C.; Paz-Soldan, Valerie A.; Vazquez-Prokopec, Gonzalo M.; Astete, Helvio; Reiner, Robert C.; Vilcarromero, Stalin; Elder, John P.; Halsey, Eric S.; Kochel, Tadeusz J.; Kitron, Uriel; Scott, Thomas W.
2013-01-01
Dengue is a mosquito-borne disease of growing global health importance. Prevention efforts focus on mosquito control, with limited success. New insights into the spatiotemporal drivers of dengue dynamics are needed to design improved disease-prevention strategies. Given the restricted range of movement of the primary mosquito vector, Aedes aegypti, local human movements may be an important driver of dengue virus (DENV) amplification and spread. Using contact-site cluster investigations in a case-control design, we demonstrate that, at an individual level, risk for human infection is defined by visits to places where contact with infected mosquitoes is likely, independent of distance from the home. Our data indicate that house-to-house human movements underlie spatial patterns of DENV incidence, causing marked heterogeneity in transmission rates. At a collective level, transmission appears to be shaped by social connections because routine movements among the same places, such as the homes of family and friends, are often similar for the infected individual and their contacts. Thus, routine, house-to-house human movements do play a key role in spread of this vector-borne pathogen at fine spatial scales. This finding has important implications for dengue prevention, challenging the appropriateness of current approaches to vector control. We argue that reexamination of existing paradigms regarding the spatiotemporal dynamics of DENV and other vector-borne pathogens, especially the importance of human movement, will lead to improvements in disease prevention. PMID:23277539
Bhat, Meera; Firth, Matthew A.; Williams, Simon H.; Frye, Matthew J.; Simmonds, Peter; Conte, Juliette M.; Ng, James; Garcia, Joel; Bhuva, Nishit P.; Lee, Bohyun; Che, Xiaoyu; Quan, Phenix-Lan; Lipkin, W. Ian
2014-01-01
ABSTRACT Norway rats (Rattus norvegicus) are globally distributed and concentrate in urban environments, where they live and feed in closer proximity to human populations than most other mammals. Despite the potential role of rats as reservoirs of zoonotic diseases, the microbial diversity present in urban rat populations remains unexplored. In this study, we used targeted molecular assays to detect known bacterial, viral, and protozoan human pathogens and unbiased high-throughput sequencing to identify novel viruses related to agents of human disease in commensal Norway rats in New York City. We found that these rats are infected with bacterial pathogens known to cause acute or mild gastroenteritis in people, including atypical enteropathogenic Escherichia coli, Clostridium difficile, and Salmonella enterica, as well as infectious agents that have been associated with undifferentiated febrile illnesses, including Bartonella spp., Streptobacillus moniliformis, Leptospira interrogans, and Seoul hantavirus. We also identified a wide range of known and novel viruses from groups that contain important human pathogens, including sapoviruses, cardioviruses, kobuviruses, parechoviruses, rotaviruses, and hepaciviruses. The two novel hepaciviruses discovered in this study replicate in the liver of Norway rats and may have utility in establishing a small animal model of human hepatitis C virus infection. The results of this study demonstrate the diversity of microbes carried by commensal rodent species and highlight the need for improved pathogen surveillance and disease monitoring in urban environments. PMID:25316698
Jordan, D; McEwen, S A; Lammerding, A M; McNab, W B; Wilson, J B
1999-06-29
A Monte Carlo simulation model was constructed for assessing the quantity of microbial hazards deposited on cattle carcasses under different pre-slaughter management regimens. The model permits comparison of industry-wide and abattoir-based mitigation strategies and is suitable for studying pathogens such as Escherichia coli O157:H7 and Salmonella spp. Simulations are based on a hierarchical model structure that mimics important aspects of the cattle population prior to slaughter. Stochastic inputs were included so that uncertainty about important input assumptions (such as prevalence of a human pathogen in the live cattle-population) would be reflected in model output. Control options were built into the model to assess the benefit of having prior knowledge of animal or herd-of-origin pathogen status (obtained from the use of a diagnostic test). Similarly, a facility was included for assessing the benefit of re-ordering the slaughter sequence based on the extent of external faecal contamination. Model outputs were designed to evaluate the performance of an abattoir in a 1-day period and included outcomes such as the proportion of carcasses contaminated with a pathogen, the daily mean and selected percentiles of pathogen counts per carcass, and the position of the first infected animal in the slaughter run. A measure of the time rate of introduction of pathogen into the abattoir was provided by assessing the median, 5th percentile, and 95th percentile cumulative pathogen counts at 10 equidistant points within the slaughter run. Outputs can be graphically displayed as frequency distributions, probability densities, cumulative distributions or x-y plots. The model shows promise as an inexpensive method for evaluating pathogen control strategies such as those forming part of a Hazard Analysis and Critical Control Point (HACCP) system.
Merkx-Jacques, Alexandra; Coors, Anja; Brousseau, Roland; Masson, Luke; Mazza, Alberto; Tien, Yuan-Ching; Topp, Edward
2013-04-01
The detection and abundance of Escherichia coli in water is used to monitor and mandate the quality of drinking and recreational water. Distinguishing commensal waterborne E. coli isolates from those that cause diarrhea or extraintestinal disease in humans is important for quantifying human health risk. A DNA microarray was used to evaluate the distribution of virulence genes in 148 E. coli environmental isolates from a watershed in eastern Ontario, Canada, and in eight clinical isolates. Their pathogenic potential was evaluated with Caenorhabditis elegans, and the concordance between the bioassay result and the pathotype deduced by genotyping was explored. Isolates identified as potentially pathogenic on the basis of their complement of virulence genes were significantly more likely to be pathogenic to C. elegans than those determined to be potentially nonpathogenic. A number of isolates that were identified as nonpathogenic on the basis of genotyping were pathogenic in the infection assay, suggesting that genotyping did not capture all potentially pathogenic types. The detection of the adhesin-encoding genes sfaD, focA, and focG, which encode adhesins; of iroN2, which encodes a siderophore receptor; of pic, which encodes an autotransporter protein; and of b1432, which encodes a putative transposase, was significantly associated with pathogenicity in the infection assay. Overall, E. coli isolates predicted to be pathogenic on the basis of genotyping were indeed so in the C. elegans infection assay. Furthermore, the detection of C. elegans-infective environmental isolates predicted to be nonpathogenic on the basis of genotyping suggests that there are hitherto-unrecognized virulence factors or combinations thereof that are important in the establishment of infection.
Disease Risk in a Dynamic Environment: The Spread of Tick-Borne Pathogens in Minnesota, USA
Robinson, Stacie J.; Neitzel, David F.; Moen, Ronald A.; Craft, Meggan E.; Hamilton, Karin E.; Johnson, Lucinda B.; Mulla, David J.; Munderloh, Ulrike G.; Redig, Patrick T.; Smith, Kirk E.; Turner, Clarence L.; Umber, Jamie K.; Pelican, Katharine M.
2015-01-01
As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease. PMID:25281302
[Important vector-borne infectious diseases among humans in Germany. Epidemiological aspects].
Frank, C; Faber, M; Hellenbrand, W; Wilking, H; Stark, K
2014-05-01
Vector-borne infections pathogenic to humans play an important role in Germany. The relevant zoonotic pathogens are either endemic throughout Germany (e.g. Borrelia burgdorferi sensu latu) or only in specific regions, e.g. tick-borne encephalitis (TBE) virus and hantavirus. They cause a substantial burden of disease. Prevention and control largely rely on public advice and the application of personal protective measures (e.g. TBE virus vaccination and protection against vectors). High quality surveillance and targeted epidemiological studies are fundamental for the evaluation of temporal and spatial risks of infection and the effectiveness of preventive measures. Aside from endemic pathogens, vector-borne infections acquired abroad, mostly transmitted by mosquitoes, have to be systematically and intensively monitored as well, to assess the risk of infection for German residents traveling abroad and to adequately evaluate the risk of autochthonous transmission. Related issues, such as invasive species of mosquitoes in Germany and climate change, have to be taken into consideration. Such pathogens include West Nile, dengue and chikungunya viruses, as well as malaria parasites (Plasmodium species). The article presents an overview of the epidemiological situation of selected relevant vector-borne infections in Germany.
Non-Cholera Vibrios: The Microbial Barometer of Climate Change.
Baker-Austin, Craig; Trinanes, Joaquin; Gonzalez-Escalona, Narjol; Martinez-Urtaza, Jaime
2017-01-01
There is a growing interest in the role of climate change in driving the spread of waterborne infectious diseases, such as those caused by bacterial pathogens. One particular group of pathogenic bacteria - vibrios - are a globally important cause of diseases in humans and aquatic animals. These Gram-negative bacteria, including the species Vibrio vulnificus, Vibrio parahaemolyticus and Vibrio cholerae, grow in warm, low-salinity waters, and their abundance in the natural environment mirrors ambient environmental temperatures. In a rapidly warming marine environment, there are greater numbers of human infections, and most notably outbreaks linked to extreme weather events such as heatwaves in temperate regions such as Northern Europe. Because the growth of pathogenic vibrios in the natural environment is largely dictated by temperature, we argue that this group of pathogens represents an important and tangible barometer of climate change in marine systems. We provide a number of specific examples of the impacts of climate change on this group of bacteria and their associated diseases, and discuss advanced strategies to improve our understanding of these emerging waterborne diseases through the integration of microbiological, genomic, epidemiological, climatic, and ocean sciences. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.
Disease risk in a dynamic environment: the spread of tick-borne pathogens in Minnesota, USA.
Robinson, Stacie J; Neitzel, David F; Moen, Ronald A; Craft, Meggan E; Hamilton, Karin E; Johnson, Lucinda B; Mulla, David J; Munderloh, Ulrike G; Redig, Patrick T; Smith, Kirk E; Turner, Clarence L; Umber, Jamie K; Pelican, Katharine M
2015-03-01
As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease.
Thammahong, Arsa; Puttikamonkul, Srisombat; Perfect, John R; Brennan, Richard G; Cramer, Robert A
2017-06-01
Invasive fungal infections cause significant morbidity and mortality in part due to a limited antifungal drug arsenal. One therapeutic challenge faced by clinicians is the significant host toxicity associated with antifungal drugs. Another challenge is the fungistatic mechanism of action of some drugs. Consequently, the identification of fungus-specific drug targets essential for fitness in vivo remains a significant goal of medical mycology research. The trehalose biosynthetic pathway is found in a wide variety of organisms, including human-pathogenic fungi, but not in humans. Genes encoding proteins involved in trehalose biosynthesis are mechanistically linked to the metabolism, cell wall homeostasis, stress responses, and virulence of Candida albicans , Cryptococcus neoformans , and Aspergillus fumigatus . While there are a number of pathways for trehalose production across the tree of life, the TPS/TPP (trehalose-6-phosphate synthase/trehalose-6-phosphate phosphatase) pathway is the canonical pathway found in human-pathogenic fungi. Importantly, data suggest that proteins involved in trehalose biosynthesis play other critical roles in fungal metabolism and in vivo fitness that remain to be fully elucidated. By further defining the biology and functions of trehalose and its biosynthetic pathway components in pathogenic fungi, an opportunity exists to leverage this pathway as a potent antifungal drug target. The goal of this review is to cover the known roles of this important molecule and its associated biosynthesis-encoding genes in the human-pathogenic fungi studied to date and to employ these data to critically assess the opportunities and challenges facing development of this pathway as a therapeutic target. Copyright © 2017 American Society for Microbiology.
Diapause in ticks of the medically important Ixodes ricinus species complex
Gray, Jeremy S.; Kahl, Olaf; Lane, Robert S.; Levin, Michael L.; Tsao, Jean I.
2017-01-01
Four members of the Ixodes ricinus species complex, Ixodes pacificus, Ixodes persulcatus, Ixodes ricinus and Ixodes scapularis, have, between them, a worldwide distribution within the northern hemisphere. They are responsible for the transmission of several animal and human pathogens, including the causal agents of Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis and human babesiosis. Despite the importance of these ticks as vectors, the knowledge and understanding of the role that diapause plays in their complex life cycles are confused and incomplete. In view of the continuing geographic spread of these tick species, as well as the effects of climate change on vector-borne diseases, it is timely encourage research on diapause phenomena to improve understanding of their biology and of pathogen transmission dynamics. In our review we seek to clarify thinking on the topic and to address gaps in our knowledge that require the attention of researchers. PMID:27263092
[Helminths of carnivores relevant to veterinary practice].
Hasslinger, M A
1986-01-01
Especially in an urban environment man and carnivores live closely together, whereby one has to pay attention not only to animal parasites, but also to human pathogenic connections regarding these parasites. Because of the infection risk the animal owner has to be competently informed by his veterinarian. While some cestodes make great demands on hygiene, with others the cycle can be interrupted by consequent diet restrictions. Of all nematodes the stomach worm of the cat is of greater importance as it is easily overlooked because of its small size, is difficult to diagnose and is occurring in our regions with an infestation rate of about 40%. "Larva migrans visceralis" and "Larva migrans cutanea" caused by ascaride and hookworm larvae are important in human medicine and demand therapeutic measures. The contamination of parks, playgrounds and beaches with these parasites caused by carnivores requires a critical evaluation of the human pathogen interests.
Tissue Distribution of the Ehrlichia muris-Like Agent in a Tick Vector
Lynn, Geoffrey E.; Oliver, Jonathan D.; Nelson, Curtis M.; Felsheim, Roderick F.; Kurtti, Timothy J.; Munderloh, Ulrike G.
2015-01-01
Human pathogens transmitted by ticks undergo complex life cycles alternating between the arthropod vector and a mammalian host. While the latter has been investigated to a greater extent, examination of the biological interactions between microbes and the ticks that carry them presents an equally important opportunity for disruption of the disease cycle. In this study, we used in situ hybridization to demonstrate infection by the Ehrlichia muris-like organism, a newly recognized human pathogen, of Ixodes scapularis ticks, a primary vector for several important human disease agents. This allowed us to assess whole sectioned ticks for the patterns of tissue invasion, and demonstrate generalized dissemination of ehrlichiae in a variety of cell types and organs within ticks infected naturally via blood feeding. Electron microscopy was used to confirm these results. Here we describe a strong ehrlichial affinity for epithelial cells, neuronal cells of the synganglion, salivary glands, and male accessory glands. PMID:25781930
Díaz, Adrián; Flores, Fernando S; Quaglia, Agustín I; Contigiani, Marta S
2018-05-14
St.Louis encephalitis virus (SLEV) is an emerging human pathogen flavivirus in Argentina. Recently, it has reemerged in the United States. We evaluated the role as amplifying host of six resident bird species and analyzed their capacity as host during the 2005 encephalitis outbreak of SLEV in Córdoba. Eared dove, picui ground dove, and house sparrow were the three species with highest host competence index. At a city level, eared doves and picui ground doves were the most important amplifying hosts during the 2005 SLEV human outbreak in Córdoba city. This finding highlighted important differences in the SLEV ecology between Argentina and the United States. Characterizing and evaluating the SLEV hosts contribute to our knowledge about its ecology and could help us to understand the causes that promote its emergence as a human pathogen in South America.
The scourge of antibiotic resistance: the important role of the environment.
Finley, Rita L; Collignon, Peter; Larsson, D G Joakim; McEwen, Scott A; Li, Xian-Zhi; Gaze, William H; Reid-Smith, Richard; Timinouni, Mohammed; Graham, David W; Topp, Edward
2013-09-01
Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, β-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.
A comprehensive review of non-enterica subspecies of Salmonella enterica.
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.
Spoor, Laura E.; McAdam, Paul R.; Weinert, Lucy A.; Rambaut, Andrew; Hasman, Henrik; Aarestrup, Frank M.; Kearns, Angela M.; Larsen, Anders R.; Skov, Robert L.; Fitzgerald, J. Ross
2013-01-01
ABSTRACT The importance of livestock as a source of bacterial pathogens with the potential for epidemic spread in human populations is unclear. In recent years, there has been a global increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections of healthy humans, but an understanding of the different evolutionary origins of CA-MRSA clones and the basis for their recent expansion is lacking. Here, using a high-resolution phylogenetic approach, we report the discovery of two emergent clones of human epidemic CA-MRSA which resulted from independent livestock-to-human host jumps by the major bovine S. aureus complex, CC97. Of note, one of the new clones was isolated from human infections on four continents, demonstrating its global dissemination since the host jump occurred over 40 years ago. The emergence of both human S. aureus clones coincided with the independent acquisition of mobile genetic elements encoding antimicrobial resistance and human-specific mediators of immune evasion, consistent with an important role for these genetic events in the capacity to survive and transmit among human populations. In conclusion, we provide evidence that livestock represent a reservoir for the emergence of new human-pathogenic S. aureus clones with the capacity for pandemic spread. These findings have major public health implications highlighting the importance of surveillance for early identification of emergent clones and improved transmission control measures at the human-livestock interface. PMID:23943757
Xu, Jun; Saunders, Charles W; Hu, Ping; Grant, Raymond A; Boekhout, Teun; Kuramae, Eiko E; Kronstad, James W; Deangelis, Yvonne M; Reeder, Nancy L; Johnstone, Kevin R; Leland, Meredith; Fieno, Angela M; Begley, William M; Sun, Yiping; Lacey, Martin P; Chaudhary, Tanuja; Keough, Thomas; Chu, Lien; Sears, Russell; Yuan, Bo; Dawson, Thomas L
2007-11-20
Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases, aspartyl proteases, and acid sphingomyelinases) was found in the M. globosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex.
Xu, Jun; Saunders, Charles W.; Hu, Ping; Grant, Raymond A.; Boekhout, Teun; Kuramae, Eiko E.; Kronstad, James W.; DeAngelis, Yvonne M.; Reeder, Nancy L.; Johnstone, Kevin R.; Leland, Meredith; Fieno, Angela M.; Begley, William M.; Sun, Yiping; Lacey, Martin P.; Chaudhary, Tanuja; Keough, Thomas; Chu, Lien; Sears, Russell; Yuan, Bo; Dawson, Thomas L.
2007-01-01
Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases, aspartyl proteases, and acid sphingomyelinases) was found in the M. globosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex. PMID:18000048
Unprecedented Abundance of Protein Tyrosine Phosphorylation Modulates Shigella flexneri Virulence.
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.
Kienesberger, Sabine; Sprenger, Hanna; Wolfgruber, Stella; Halwachs, Bettina; Thallinger, Gerhard G.; Perez-Perez, Guillermo I.; Blaser, Martin J.; Zechner, Ellen L.; Gorkiewicz, Gregor
2014-01-01
Campylobacter fetus are important animal and human pathogens and the two major subspecies differ strikingly in pathogenicity. C. fetus subsp. venerealis is highly niche-adapted, mainly infecting the genital tract of cattle. C. fetus subsp. fetus has a wider host-range, colonizing the genital- and intestinal-tract of animals and humans. We report the complete genomic sequence of C. fetus subsp. venerealis 84-112 and comparisons to the genome of C. fetus subsp. fetus 82-40. Functional analysis of genes predicted to be involved in C. fetus virulence was performed. The two subspecies are highly syntenic with 92% sequence identity but C. fetus subsp. venerealis has a larger genome and an extra-chromosomal element. Aside from apparent gene transfer agents and hypothetical proteins, the unique genes in both subspecies comprise two known functional groups: lipopolysaccharide production, and type IV secretion machineries. Analyses of lipopolysaccharide-biosynthesis genes in C. fetus isolates showed linkage to particular pathotypes, and mutational inactivation demonstrated their roles in regulating virulence and host range. The comparative analysis presented here broadens knowledge of the genomic basis of C. fetus pathogenesis and host specificity. It further highlights the importance of surface-exposed structures to C. fetus pathogenicity and demonstrates how evolutionary forces optimize the fitness and host-adaptation of these pathogens. PMID:24416416
Wyrsch, Ethan R.; Roy Chowdhury, Piklu; Chapman, Toni A.; Charles, Ian G.; Hammond, Jeffrey M.; Djordjevic, Steven P.
2016-01-01
Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance. PMID:27379026
Computational prediction of host-pathogen protein-protein interactions.
Dyer, Matthew D; Murali, T M; Sobral, Bruno W
2007-07-01
Infectious diseases such as malaria result in millions of deaths each year. An important aspect of any host-pathogen system is the mechanism by which a pathogen can infect its host. One method of infection is via protein-protein interactions (PPIs) where pathogen proteins target host proteins. Developing computational methods that identify which PPIs enable a pathogen to infect a host has great implications in identifying potential targets for therapeutics. We present a method that integrates known intra-species PPIs with protein-domain profiles to predict PPIs between host and pathogen proteins. Given a set of intra-species PPIs, we identify the functional domains in each of the interacting proteins. For every pair of functional domains, we use Bayesian statistics to assess the probability that two proteins with that pair of domains will interact. We apply our method to the Homo sapiens-Plasmodium falciparum host-pathogen system. Our system predicts 516 PPIs between proteins from these two organisms. We show that pairs of human proteins we predict to interact with the same Plasmodium protein are close to each other in the human PPI network and that Plasmodium pairs predicted to interact with same human protein are co-expressed in DNA microarray datasets measured during various stages of the Plasmodium life cycle. Finally, we identify functionally enriched sub-networks spanned by the predicted interactions and discuss the plausibility of our predictions. Supplementary data are available at http://staff.vbi.vt.edu/dyermd/publications/dyer2007a.html. Supplementary data are available at Bioinformatics online.
USDA-ARS?s Scientific Manuscript database
Human health is a broad category that encompasses the entirety of the food production system. Livestock production practices have important impacts on human health because livestock are not only a primary food source, but also can be the source of pathogenic bacteria that may enter the food chain i...
New trends in emerging pathogens.
Skovgaard, Niels
2007-12-15
The emergence of pathogens is the result of a number of impact in all parts of the food chain. The emerging technologies in food production explain how new pathogens can establish themselves in the food chain and compromise food safety. The impact of the food technology is analysed for several bacteria, such as Yersinia, Campylobacter, Arcobacter, Helicobacter pullorum, Enterobacter sakazakii, Mycobacterium avium spp. paratuberculosis, prions related to vCJD and others. The importance of the ability of many microbes to form VBNC forms is elaborated on. Research on culture independent methods may address this outstanding issue to the better understanding of emerging pathogens. The "demerging" of pathogens also occur, and examples of this are explained. The reaction of bacteria to stresses and sublethal treatments, and how exposure to one stress factor can confer resistance to other stresses, literally speaking causing contagious resistance, are explained. The implication of this e.g. in modern approaches of food preservation, such as Minimally processed Foods, is considerable. Intestinal colonization of EHEC may be regulated by Quorum sensing, and this ability of microbes plays an important role in the colonization of microbes in food and on food processing equipment, an important factor in the emergence of pathogens. The emergence of Saccharomyces cerevisiae, as an opportunistic human pathogen, used for centuries for food and production of alcoholic beverages, calls for research in molecular tools to distinguish between probiotic and clinical strains. Cyclospora cayetanensis and Norovirus outbreaks can no longer be designated as emerging pathogens, they share however one characteristic in the epidemiology of emerging nature, the importance of the hygiene in the primary production stage, including supply of potable water, and the application of GMP and the HACCP principles in the beginning of the food chain. Hepatitis E virus is a potential emerging food borne pathogen and swine may serve as a source of infection in human, a most challenging issue in greater part of the world raising pigs. Tick-borne encephalitis virus infection, either thick borne or caused by consumption of raw milk, is an increasing trend in the industrialized part of the world. Consumer awareness, ethics of food, sustainability in food production, and trust in foods, are of growing importance to the consumer. The reaction of the consumer to new technology, such as nanotechnology, is unpredictable. Many efforts should be devoted to communication of non-biased information to both the food producers as well as the consumer.
Molecular assessment of bacterial pathogens - a contribution to drinking water safety.
Brettar, Ingrid; Höfle, Manfred G
2008-06-01
Human bacterial pathogens are considered as an increasing threat to drinking water supplies worldwide because of the growing demand of high-quality drinking water and the decreasing quality and quantity of available raw water. Moreover, a negative impact of climate change on freshwater resources is expected. Recent advances in molecular detection technologies for bacterial pathogens in drinking water bear the promise in improving the safety of drinking water supplies by precise detection and identification of the pathogens. More importantly, the array of molecular approaches allows understanding details of infection routes of waterborne diseases, the effects of changes in drinking water treatment, and management of freshwater resources.
A Novel aadA Aminoglycoside Resistance Gene in Bovine and Porcine Pathogens.
Cameron, Andrew; Klima, Cassidy L; Ha, Reuben; Gruninger, Robert J; Zaheer, Rahat; McAllister, Tim A
2018-01-01
A novel variant of the AAD(3″) class of aminoglycoside-modifying enzymes was discovered in fatal bovine respiratory disease-associated pathogens Pasteurella multocida and Histophilus somni . The aadA31 gene encodes a spectinomycin/streptomycin adenylyltransferase and was located in a variant of the integrative and conjugative element ICE Mh1 , a mobile genetic element transmissible among members of the family Pasteurellaceae . The gene was also detected in Mannheimia haemolytica from a case of porcine pneumonia and in Moraxella bovoculi from a case of keratoconjunctivitis. IMPORTANCE Aminoglycosides are important antimicrobials used worldwide for prophylaxis and/or therapy in multiple production animal species. The emergence of new resistance genes jeopardizes current pathogen detection and treatment methods. The risk of resistance gene transfer to other animal and human pathogens is elevated when resistance genes are carried by mobile genetic elements. This study identified a new variant of a spectinomycin/streptomycin resistance gene harbored in a self-transmissible mobile element. The gene was also present in four different bovine pathogen species.
A Novel aadA Aminoglycoside Resistance Gene in Bovine and Porcine Pathogens
Cameron, Andrew; Klima, Cassidy L.; Ha, Reuben; Gruninger, Robert J.; Zaheer, Rahat
2018-01-01
ABSTRACT A novel variant of the AAD(3″) class of aminoglycoside-modifying enzymes was discovered in fatal bovine respiratory disease-associated pathogens Pasteurella multocida and Histophilus somni. The aadA31 gene encodes a spectinomycin/streptomycin adenylyltransferase and was located in a variant of the integrative and conjugative element ICEMh1, a mobile genetic element transmissible among members of the family Pasteurellaceae. The gene was also detected in Mannheimia haemolytica from a case of porcine pneumonia and in Moraxella bovoculi from a case of keratoconjunctivitis. IMPORTANCE Aminoglycosides are important antimicrobials used worldwide for prophylaxis and/or therapy in multiple production animal species. The emergence of new resistance genes jeopardizes current pathogen detection and treatment methods. The risk of resistance gene transfer to other animal and human pathogens is elevated when resistance genes are carried by mobile genetic elements. This study identified a new variant of a spectinomycin/streptomycin resistance gene harbored in a self-transmissible mobile element. The gene was also present in four different bovine pathogen species. PMID:29507894
Water, Water Everywhere, But is it Safe to Drink?
Drinking water disinfection by-products (DBPs) have been associated with adverse human health effects, including bladder cancer, early term miscarriage, and birth defects. While it is vitally important to kill harmful pathogens in water, it is also important to minimize harmful ...
Lauzi, Stefania; Maia, João P; Epis, Sara; Marcos, Ricardo; Pereira, Cristina; Luzzago, Camilla; Santos, Marta; Puente-Payo, Pablo; Giordano, Alessia; Pajoro, Massimo; Sironi, Giuseppe; Faustino, Augusto
2016-07-01
Tick-borne diseases are emerging worldwide and have an important zoonotic relevance. Dogs play an important role in the epidemiology of several zoonotic tick-borne pathogens acting as sentinels and/or reservoirs. This study focused on the molecular identification of tick-borne pathogens in blood samples of 153 autochthonous asymptomatic dogs in Maio Island, Cape Verde archipelago. Eighty-four (54.9%) dogs were positive for one or more pathogens. Fifty-five (35.9%) dogs were infected with Hepatozoon canis, 53 (34.6%) with Anaplasma platys, five (3.3%) with Ehrlichia canis and Rickettsia monacensis, an emerging human pathogen, was also identified in a single dog (0.7%). The former three pathogens cause important canine tick-borne diseases that are transmitted or potentially transmitted by Rhipicephalus sanguineus s.l., the only hard tick identified in Cape Verde. Furthermore, Wolbachia spp. was amplified from the blood of one dog. None of the dogs were positive for Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, Midichloria mitochondrii, Bartonella spp., Babesia spp. or Theileria spp. Fifty-four (35.3%) animals showed single infections and 30 (19.6%) co-infections, with A. platys and H. canis co-infection being the most frequent (28 dogs, 18.3%). The frequency of E. canis infection was statistically different among age groups (P=0.017), being higher among dogs older than 4 years compared to younger dogs. Infection by A. platys was also statistically different among age groups (P=0.031), being higher in dogs younger than 2 years compared to older dogs. The statistical analyses showed no significant association of PCR positivity with gender or location. The frequency of tick-borne pathogens detected in dogs in Maio Island, including R. monacensis, highlights the need to improve diagnosis and control in order to prevent the risk of transmission of these pathogens among dogs and humans living in or travelling to this touristic island. Copyright © 2016 Elsevier GmbH. All rights reserved.
Host-feeding patterns of mosquito species in Germany.
Börstler, Jessica; Jöst, Hanna; Garms, Rolf; Krüger, Andreas; Tannich, Egbert; Becker, Norbert; Schmidt-Chanasit, Jonas; Lühken, Renke
2016-06-03
Mosquito-borne pathogens are of growing importance in many countries of Europe including Germany. At the same time, the transmission cycles of most mosquito-borne pathogens (e.g. viruses or filarial parasites) are not completely understood. There is especially a lack of knowledge about the vector capacity of the different mosquito species, which is strongly influenced by their host-feeding patterns. While this kind of information is important to identify the relevant vector species, e.g. to direct efficient control measures, studies about the host-feeding patterns of mosquito species in Germany are scarce and outdated. Between 2012 and 2015, 775 blood-fed mosquito specimens were collected. Sampling was conducted with Heavy Duty Encephalitis Vector Survey traps, Biogents Sentinel traps, gravid traps, hand-held aspirators, sweep nets, and human-bait collection. The host species for each mosquito specimen was identified with polymerase chain reactions and subsequent Sanger sequencing of the cytochrome b gene. A total of 32 host species were identified for 23 mosquito species, covering 21 mammalian species (including humans) and eleven bird species. Three mosquito species accounted for nearly three quarters of all collected blood-fed mosquitoes: Aedes vexans (363 specimens, 46.8 % of all mosquito specimens), Culex pipiens pipiens form pipiens (100, 12.9 %) and Ochlerotatus cantans (99, 12.8 %). Non-human mammals dominated the host species (572 specimens, 73.8 % of all mosquito specimens), followed by humans (152, 19.6 %) and birds (51, 6.6 %). The most common host species were roe deer (Capreolus capreolus; 258 mosquito specimens, 33.3 % of all mosquito specimens, 65 % of all mosquito species), humans (Homo sapiens; 152, 19.6 %, 90 %), cattle (Bos taurus; 101, 13.0 %, 60 %), and wild boar (Sus scrofa; 116, 15.0 %, 50 %). There were no statistically significant differences in the spatial-temporal host-feeding patterns of the three most common mosquito species. Although the collected blood-fed mosquito species had a strong overlap of host species, two different host-feeding groups were identified with mosquito species feeding on (i) non-human mammals and humans or (ii) birds, non-human mammals, and humans, which make them potential vectors of pathogens only between mammals or between mammals and birds, respectively. Due to the combination of their host-feeding patterns and wide distribution in Germany, Cx. pipiens pipiens form pipiens and Cx. torrentium are potentially most important vectors for pathogens transmitted from birds to humans and the species Ae. vexans for pathogens transmitted from non-human mammals to humans. Finally, the presented study indicated a much broader host range compared to the classifications found in the literature for some of the species, which highlights the need for studies on the host-feeding patterns of mosquitoes to further assess their vector capacity and the disease ecology in Europe.
Antimicrobial resistance of mastitis pathogens.
Oliver, Stephen P; Murinda, Shelton E
2012-07-01
Antibiotics are used extensively in the dairy industry to combat disease and to improve animal performance. Antibiotics such as penicillin, cephalosporin, streptomycin, and tetracycline are used for the treatment and prevention of diseases affecting dairy cows caused by a variety of gram-positive and gram-negative bacteria. Antibiotics are often administrated routinely to entire herds to prevent mastitis during the dry period. An increase in the incidence of disease in a herd generally results in increased use of antimicrobials, which in turn increases the potential for antibiotic residues in milk and the potential for increased bacterial resistance to antimicrobials. Continued use of antibiotics in the treatment and prevention of diseases of dairy cows will continue to be scrutinized. It is clear that strategies employing the prudent use of antimicrobials are needed. This clearly illustrates the importance of effective herd disease prevention and control programs. Based on studies published to date, scientific evidence does not support widespread, emerging resistance among mastitis pathogens to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in dairy cows can contribute to increased antimicrobial resistance. While antimicrobial resistance does occur, we are of the opinion that the advantages of using antibiotics for the treatment of mastitis far outweigh the disadvantages. The clinical consequences of antimicrobial resistance of dairy pathogens affecting humans appear small. Antimicrobial resistance among dairy pathogens, particularly those found in milk, is likely not a human health concern as long as the milk is pasteurized. However, there are an increasing number of people who choose to consume raw milk. Transmission of an antimicrobial-resistant mastitis pathogen and/or foodborne pathogen to humans could occur if contaminated unpasteurized milk is consumed, which is another important reason why people should not consume raw milk. Likewise, resistant bacteria contaminating meat from dairy cows should not be a significant human health concern if the meat is cooked properly. Prudent use of antibiotics in the dairy industry is important, worthwhile, and necessary. Use of antibiotics at times when animals are susceptible to new infection such as the dry period is a sound management decision and a prudent use of antibiotics on the farm. Strategies involving prudent use of antibiotics for treatment encompass identification of the pathogen causing the infection, determining the susceptibility/resistance of the pathogen to assess the most appropriate antibiotic to use for treatment, and a sufficient treatment duration to ensure effective concentrations of the antibiotic to eliminate the pathogen. As the debate on the use of antibiotics in animal agriculture continues, we need to consider the consequences of, “What would happen if antibiotics are banned for use in the dairy industry and in other food-producing animals?” The implications of this question are far reaching and include such aspects as animal welfare, health, and well-being and impacts on food quantity, quality, and food costs. This question should be an important aspect in this ongoing and controversial debate!
Staphylococcus aureus Responds to the Central Metabolite Pyruvate To Regulate Virulence.
Harper, Lamia; Balasubramanian, Divya; Ohneck, Elizabeth A; Sause, William E; Chapman, Jessica; Mejia-Sosa, Bryan; Lhakhang, Tenzin; Heguy, Adriana; Tsirigos, Aristotelis; Ueberheide, Beatrix; Boyd, Jeffrey M; Lun, Desmond S; Torres, Victor J
2018-01-23
Staphylococcus aureus is a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens, S. aureus must adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environmental signals for S. aureus pathogenicity, only a limited number of these signals have been investigated in detail for their ability to modulate virulence. Here we show that pyruvate, a central metabolite, causes alterations in the overall metabolic flux of S. aureus and enhances its pathogenicity. We demonstrate that pyruvate induces the production of virulence factors such as the pore-forming leucocidins and that this induction results in increased virulence of community-acquired methicillin-resistant S. aureus (CA-MRSA) clone USA300. Specifically, we show that an efficient "pyruvate response" requires the activation of S. aureus master regulators AgrAC and SaeRS as well as the ArlRS two-component system. Altogether, our report further establishes a strong relationship between metabolism and virulence and identifies pyruvate as a novel regulatory signal for the coordination of the S. aureus virulon through intricate regulatory networks. IMPORTANCE Delineation of the influence of host-derived small molecules on the makeup of human pathogens is a growing field in understanding host-pathogen interactions. S. aureus is a prominent pathogen that colonizes up to one-third of the human population and can cause serious infections that result in mortality in ~15% of cases. Here, we show that pyruvate, a key nutrient and central metabolite, causes global changes to the metabolic flux of S. aureus and activates regulatory networks that allow significant increases in the production of leucocidins. These and other virulence factors are critical for S. aureus to infect diverse host niches, initiate infections, and effectively subvert host immune responses. Understanding how environmental signals, particularly ones that are essential to and prominent in the human host, affect virulence will allow us to better understand pathogenicity and consider more-targeted approaches to tackling the current S. aureus epidemic. Copyright © 2018 Harper et al.
J. Hall Cushman; Ross Meentemeyer
2006-01-01
Determining how Phytophthora ramorum is dispersed across the landscape is critical for understanding the ecology and epidemiology of this influential pathogen. To date, researchers have shown that abiotic factors â such as rain-splash, wind-blown rain and down-stream transport of inoculum â are critical mechanisms for the dispersal of this pathogen....
Schmidt-Posthaus, Heike; Nufer, Lisbeth; Wilson, Anthony; Svercel, Miroslav; Richter, Denis; Segner, Helmut; Pospischil, Andreas; Vaughan, Lloyd
2013-01-01
Chlamydia are obligate intracellular bacteria and important pathogens of humans and animals. Chlamydia-related bacteria are also major fish pathogens, infecting epithelial cells of the gills and skin to cause the disease epitheliocystis. Given the wide distribution, ancient origins and spectacular diversity of bony fishes, this group offers a rich resource for the identification and isolation of novel Chlamydia. The broad-nosed pipefish (Syngnathus typhle) is a widely distributed and genetically diverse temperate fish species, susceptible to epitheliocystis across much of its range. We describe here a new bacterial species, Candidatus Syngnamydia venezia; epitheliocystis agent of S. typhle and close relative to other chlamydial pathogens which are known to infect diverse hosts ranging from invertebrates to humans. PMID:23951025
Tick-Borne Zoonoses in the United States: Persistent and Emerging Threats to Human Health
Eisen, Rebecca J.; Kugeler, Kiersten J.; Eisen, Lars; Beard, Charles B.; Paddock, Christopher D.
2017-01-01
In the United States, ticks transmit the greatest diversity of arthropod-borne pathogens and are responsible for the most cases of all vector-borne diseases. In recent decades, the number of reported cases of notifiable tick-borne diseases has steadily increased, geographic distributions of many ticks and tick-borne diseases have expanded, and new tick-borne disease agents have been recognized. In this review, we (1) describe the known disease agents associated with the most commonly human-biting ixodid ticks, (2) review the natural histories of these ticks and their associated pathogens, (3) highlight spatial and temporal changes in vector tick distributions and tick-borne disease occurrence in recent decades, and (4) identify knowledge gaps and barriers to more effective prevention of tick-borne diseases. We describe 12 major tick-borne diseases caused by 15 distinct disease agents that are transmitted by the 8 most commonly human-biting ixodid ticks in the United States. Notably, 40% of these pathogens were described within the last two decades. Our assessment highlights the importance of animal studies to elucidate how tick-borne pathogens are maintained in nature, as well as advances in molecular detection of pathogens which has led to the discovery of several new tick-borne disease agents. PMID:28369515
Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J
2018-01-01
Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.
Prole, David L.; Taylor, Colin W.
2013-01-01
Mechanosensitive channels play important roles in the physiology of many organisms, and their dysfunction can affect cell survival. This suggests that they might be therapeutic targets in pathogenic organisms. Pathogenic protozoa lead to diseases such as malaria, dysentery, leishmaniasis and trypanosomiasis that are responsible for millions of deaths each year worldwide. We analyzed the genomes of pathogenic protozoa and show the existence within them of genes encoding putative homologues of mechanosensitive channels. Entamoeba histolytica, Leishmania spp., Trypanosoma cruzi and Trichomonas vaginalis have genes encoding homologues of Piezo channels, while most pathogenic protozoa have genes encoding homologues of mechanosensitive small-conductance (MscS) and K+-dependent (MscK) channels. In contrast, all parasites examined lack genes encoding mechanosensitive large-conductance (MscL), mini-conductance (MscM) and degenerin/epithelial Na+ (DEG/ENaC) channels. Multiple sequence alignments of evolutionarily distant protozoan, amoeban, plant, insect and vertebrate Piezo channel subunits define an absolutely conserved motif that may be involved in channel conductance or gating. MscS channels are not present in humans, and the sequences of protozoan and human homologues of Piezo channels differ substantially. This suggests the possibility for specific targeting of mechanosensitive channels of pathogens by therapeutic drugs. PMID:23785469
Norwegian Sheep Are an Important Reservoir for Human-Pathogenic Escherichia coli O26:H11
Sekse, Camilla; Lindstedt, Bjørn-Arne; Sunde, Marianne; Løbersli, Inger; Urdahl, Anne Margrete; Kapperud, Georg
2012-01-01
A previous national survey of Escherichia coli in Norwegian sheep detected eae-positive (eae+) E. coli O26:H11 isolates in 16.3% (80/491) of the flocks. The purpose of the present study was to evaluate the human-pathogenic potential of these ovine isolates by comparing them with E. coli O26 isolates from humans infected in Norway. All human E. coli O26 isolates studied carried the eae gene and shared flagellar type H11. Two-thirds of the sheep flocks and 95.1% of the patients harbored isolates containing arcA allele type 2 and espK and were classified as enterohemorrhagic E. coli (EHEC) (stx positive) or EHEC-like (stx negative). These isolates were further divided into group A (EspK2 positive), associated with stx2-EDL933 and stcEO103, and group B (EspK1 positive), associated with stx1a. Although the stx genes were more frequently present in isolates from patients (46.3%) than in those from sheep flocks (5%), more than half of the ovine isolates in the EHEC/EHEC-like group had multiple-locus variable number of tandem repeat analysis (MLVA) profiles that were identical to those seen in stx-positive human O26:H11 isolates. This indicates that EHEC-like ovine isolates may be able to acquire stx-carrying bacteriophages and thereby have the possibility to cause serious illness in humans. The remaining one-third of the sheep flocks and two of the patients had isolates fulfilling the criteria for atypical enteropathogenic E. coli (aEPEC): arcA allele type 1 and espK negative (group C). The majority of these ovine isolates showed MLVA profiles not previously seen in E. coli O26:H11 isolates from humans. However, according to their virulence gene profile, the aEPEC ovine isolates should be considered potentially pathogenic for humans. In conclusion, sheep are an important reservoir of human-pathogenic E. coli O26:H11 isolates in Norway. PMID:22492457
Carrier status of leptospirosis among cattle in Sri Lanka: a zoonotic threat to public health.
Gamage, C D; Koizumi, N; Perera, A K C; Muto, M; Nwafor-Okoli, C; Ranasinghe, S; Kularatne, S A M; Rajapakse, R P V J; Kanda, K; Lee, R B; Obayashi, Y; Ohnishi, M; Tamashiro, H
2014-02-01
Leptospirosis is a zoonotic disease of global importance and one of the notifiable diseases in Sri Lanka. Recent studies on human leptospirosis have suggested that the cattle could be one of the important reservoirs for human infection in the country. However, there is a dearth of local information on bovine leptospirosis, including its implications for human transmission. Thus, this study attempted to determine the carrier status of pathogenic Leptospira spp in cattle in Sri Lanka. A total of 164 cattle kidney samples were collected from the meat inspection hall in Colombo city during routine inspection procedures conducted by the municipal veterinary surgeons. The DNA was extracted and subjected to nested PCR for the detection of leptospiral flaB gene. Amplicons were sequenced, and phylogenic distances were calculated. Of 164 samples, 20 (12.2%) were positive for flaB-PCR. Sequenced amplicons revealed that Leptospira species were deduced to L. borgpetersenii (10/20, 50%), L. kirschneri (7/20, 35%) and L. interrogans (3/20, 15%). The results indicate that a high proportion of the sampled cattle harbour a variety of pathogenic Leptospira spp, which can serve as important reservoirs for human disease. © 2012 Blackwell Verlag GmbH.
USDA-ARS?s Scientific Manuscript database
Salmonella enterica is one of the most important pathogens responsible for gastrointestinal infections in humans. The increase of S. enterica strains showing resistance against antibiotics has resulted in limiting the effective treatment of human infections. The present study characterized the resi...
USDA-ARS?s Scientific Manuscript database
Companion animals are a source of zoonotic infections and especially important considering the potential of companion animals to harbor antibiotic resistant pathogens. In this study, blaNDM positive Escherichia coli from companion animals, humans, and the environment from Mansoura, Egypt were charac...
Emerging Disinfection By-Products and Other Emerging Environmental Contaminants: What's New
Drinking water disinfection by-products (DBPs) have been associated with adverse human health effects, including bladder cancer, early term miscarriage, and birth defects. While it is vitally important to kill harmful pathogens in water, it is also important to minimize harmful ...
Parallel independent evolution of pathogenicity within the genus Yersinia
Reuter, Sandra; Connor, Thomas R.; Barquist, Lars; Walker, Danielle; Feltwell, Theresa; Harris, Simon R.; Fookes, Maria; Hall, Miquette E.; Petty, Nicola K.; Fuchs, Thilo M.; Corander, Jukka; Dufour, Muriel; Ringwood, Tamara; Savin, Cyril; Bouchier, Christiane; Martin, Liliane; Miettinen, Minna; Shubin, Mikhail; Riehm, Julia M.; Laukkanen-Ninios, Riikka; Sihvonen, Leila M.; Siitonen, Anja; Skurnik, Mikael; Falcão, Juliana Pfrimer; Fukushima, Hiroshi; Scholz, Holger C.; Prentice, Michael B.; Wren, Brendan W.; Parkhill, Julian; Carniel, Elisabeth; Achtman, Mark; McNally, Alan; Thomson, Nicholas R.
2014-01-01
The genus Yersinia has been used as a model system to study pathogen evolution. Using whole-genome sequencing of all Yersinia species, we delineate the gene complement of the whole genus and define patterns of virulence evolution. Multiple distinct ecological specializations appear to have split pathogenic strains from environmental, nonpathogenic lineages. This split demonstrates that contrary to hypotheses that all pathogenic Yersinia species share a recent common pathogenic ancestor, they have evolved independently but followed parallel evolutionary paths in acquiring the same virulence determinants as well as becoming progressively more limited metabolically. Shared virulence determinants are limited to the virulence plasmid pYV and the attachment invasion locus ail. These acquisitions, together with genomic variations in metabolic pathways, have resulted in the parallel emergence of related pathogens displaying an increasingly specialized lifestyle with a spectrum of virulence potential, an emerging theme in the evolution of other important human pathogens. PMID:24753568
Iron Acquisition Mechanisms and Their Role in the Virulence of Burkholderia Species.
Butt, Aaron T; Thomas, Mark S
2017-01-01
Burkholderia is a genus within the β -Proteobacteriaceae that contains at least 90 validly named species which can be found in a diverse range of environments. A number of pathogenic species occur within the genus. These include Burkholderia cenocepacia and Burkholderia multivorans , opportunistic pathogens that can infect the lungs of patients with cystic fibrosis, and are members of the Burkholderia cepacia complex (Bcc). Burkholderia pseudomallei is also an opportunistic pathogen, but in contrast to Bcc species it causes the tropical human disease melioidosis, while its close relative Burkholderia mallei is the causative agent of glanders in horses. For these pathogens to survive within a host and cause disease they must be able to acquire iron. This chemical element is essential for nearly all living organisms due to its important role in many enzymes and metabolic processes. In the mammalian host, the amount of accessible free iron is negligible due to the low solubility of the metal ion in its higher oxidation state and the tight binding of this element by host proteins such as ferritin and lactoferrin. As with other pathogenic bacteria, Burkholderia species have evolved an array of iron acquisition mechanisms with which to capture iron from the host environment. These mechanisms include the production and utilization of siderophores and the possession of a haem uptake system. Here, we summarize the known mechanisms of iron acquisition in pathogenic Burkholderia species and discuss the evidence for their importance in the context of virulence and the establishment of infection in the host. We have also carried out an extensive bioinformatic analysis to identify which siderophores are produced by each Burkholderia species that is pathogenic to humans.
Iron Acquisition Mechanisms and Their Role in the Virulence of Burkholderia Species
Butt, Aaron T.; Thomas, Mark S.
2017-01-01
Burkholderia is a genus within the β-Proteobacteriaceae that contains at least 90 validly named species which can be found in a diverse range of environments. A number of pathogenic species occur within the genus. These include Burkholderia cenocepacia and Burkholderia multivorans, opportunistic pathogens that can infect the lungs of patients with cystic fibrosis, and are members of the Burkholderia cepacia complex (Bcc). Burkholderia pseudomallei is also an opportunistic pathogen, but in contrast to Bcc species it causes the tropical human disease melioidosis, while its close relative Burkholderia mallei is the causative agent of glanders in horses. For these pathogens to survive within a host and cause disease they must be able to acquire iron. This chemical element is essential for nearly all living organisms due to its important role in many enzymes and metabolic processes. In the mammalian host, the amount of accessible free iron is negligible due to the low solubility of the metal ion in its higher oxidation state and the tight binding of this element by host proteins such as ferritin and lactoferrin. As with other pathogenic bacteria, Burkholderia species have evolved an array of iron acquisition mechanisms with which to capture iron from the host environment. These mechanisms include the production and utilization of siderophores and the possession of a haem uptake system. Here, we summarize the known mechanisms of iron acquisition in pathogenic Burkholderia species and discuss the evidence for their importance in the context of virulence and the establishment of infection in the host. We have also carried out an extensive bioinformatic analysis to identify which siderophores are produced by each Burkholderia species that is pathogenic to humans. PMID:29164069
Impact of a Food Safety Campaign on Streptococcus suis Infection in Humans in Thailand.
Takeuchi, Dan; Kerdsin, Anusak; Akeda, Yukihiro; Chiranairadul, Piphat; Loetthong, Phacharaphan; Tanburawong, Nutchada; Areeratana, Prasanee; Puangmali, Panarat; Khamisara, Kasean; Pinyo, Wirasinee; Anukul, Rapeepun; Samerchea, Sutit; Lekhalula, Punpong; Nakayama, Tatsuya; Yamamoto, Kouji; Hirose, Masayo; Hamada, Shigeyuki; Dejsirilert, Surang; Oishi, Kazunori
2017-06-01
Abstract Streptococcus suis is an important zoonotic pathogen in swine and humans that causes sepsis and meningitis. Our previous study in Thailand showed that the prevalence of S. suis infection in humans, especially in northern areas of Thailand, and the transmission of the pathogen occurred mainly through the consumption of traditional raw pork products. Considering the high incidence proportion and mortality rate of the disease as an important public health problem, we implemented a food safety campaign in the Phayao Province in northern Thailand in 2011. We evaluated the effects of a food safety campaign by comparing the sociodemographic, clinical, and bacteriological characteristics of cases before and after the campaign. The follow-up study showed a marked decrease of the incidence proportion in the first 2 years, indicating the effectiveness of the campaign. In the third year, however, the incidence proportion slightly increased again, indicating the existence of deep-rooted cultural behaviors and the necessity of continuous public health intervention. Furthermore, epidemiological analysis of the cases made it possible to estimate the infectivity of the pathogen via the oral route of infection. In the present study, we showed the effectiveness of the food safety campaign for controlling the S. suis infection, and we present a role model public health intervention for prevalent areas affected by S. suis infection in humans.
Impact of a Food Safety Campaign on Streptococcus suis Infection in Humans in Thailand
Takeuchi, Dan; Kerdsin, Anusak; Akeda, Yukihiro; Chiranairadul, Piphat; Loetthong, Phacharaphan; Tanburawong, Nutchada; Areeratana, Prasanee; Puangmali, Panarat; Khamisara, Kasean; Pinyo, Wirasinee; Anukul, Rapeepun; Samerchea, Sutit; Lekhalula, Punpong; Nakayama, Tatsuya; Yamamoto, Kouji; Hirose, Masayo; Hamada, Shigeyuki; Dejsirilert, Surang; Oishi, Kazunori
2017-01-01
Streptococcus suis is an important zoonotic pathogen in swine and humans that causes sepsis and meningitis. Our previous study in Thailand showed that the prevalence of S. suis infection in humans, especially in northern areas of Thailand, and the transmission of the pathogen occurred mainly through the consumption of traditional raw pork products. Considering the high incidence proportion and mortality rate of the disease as an important public health problem, we implemented a food safety campaign in the Phayao Province in northern Thailand in 2011. We evaluated the effects of a food safety campaign by comparing the sociodemographic, clinical, and bacteriological characteristics of cases before and after the campaign. The follow-up study showed a marked decrease of the incidence proportion in the first 2 years, indicating the effectiveness of the campaign. In the third year, however, the incidence proportion slightly increased again, indicating the existence of deep-rooted cultural behaviors and the necessity of continuous public health intervention. Furthermore, epidemiological analysis of the cases made it possible to estimate the infectivity of the pathogen via the oral route of infection. In the present study, we showed the effectiveness of the food safety campaign for controlling the S. suis infection, and we present a role model public health intervention for prevalent areas affected by S. suis infection in humans. PMID:28719258
Liu, Da; Cui, Yue; Walcott, Ronald; Chen, Jinru
2018-01-01
Vegetable seeds contaminated with bacterial pathogens have been linked to fresh-produce-associated outbreaks of gastrointestinal infections. This study was undertaken to observe the physiological behavior of Salmonella enterica and enterohemorrhagic Escherichia coli (EHEC) cells artificially internalized into vegetable seeds during the germination process. Surface-decontaminated seeds of alfalfa, fenugreek, lettuce, and tomato were vacuum-infiltrated with four individual strains of Salmonella or EHEC. Contaminated seeds were germinated at 25°C for 9 days, and different sprout/seedling tissues were microbiologically analyzed every other day. The internalization of Salmonella and EHEC cells into vegetable seeds was confirmed by the absence of pathogens in seed-rinsing water and the presence of pathogens in seed homogenates after postinternalization seed surface decontamination. Results show that 317 (62%) and 343 (67%) of the 512 collected sprout/seedling tissue samples were positive for Salmonella and EHEC, respectively. The average Salmonella populations were significantly larger ( P < 0.05) than the EHEC populations. Significantly larger Salmonella populations were recovered from the cotyledon and seed coat tissues, followed by the root tissues, but the mean EHEC populations from all sampled tissue sections were statistically similar, except in pregerminated seeds. Three Salmonella and two EHEC strains had significantly larger cell populations on sprout/seedling tissues than other strains used in the study. Salmonella and EHEC populations from fenugreek and alfalfa tissues were significantly larger than those from tomato and lettuce tissues. The study showed the fate of internalized human pathogens on germinating vegetable seeds and sprout/seedling tissues and emphasized the importance of using pathogen-free seeds for sprout production. IMPORTANCE The internalization of microorganisms into vegetable seeds could occur naturally and represents a possible pathway of vegetable seed contamination by human pathogens. The present study investigated the ability of two important bacterial pathogens, Salmonella and enterohemorrhagic Escherichia coli (EHEC), when artificially internalized into vegetable seeds, to grow and disseminate along vegetable sprouts/seedlings during germination. The data from the study revealed that the pathogen cells artificially internalized into vegetable seeds caused the contamination of different tissues of sprouts/seedlings and that pathogen growth on germinating seeds is bacterial species and vegetable seed-type dependent. These results further stress the necessity of using pathogen-free vegetable seeds for edible sprout production. Copyright © 2017 American Society for Microbiology.
Shattuck, Wendy M C; Dyer, Megan C; Desrosiers, Joe; Fast, Loren D; Terry, Frances E; Martin, William D; Moise, Leonard; De Groot, Anne S; Mather, Thomas N
2014-01-01
Ticks are notorious vectors of disease for humans, and many species of ticks transmit multiple pathogens, sometimes in the same tick bite. Accordingly, a broad-spectrum vaccine that targets vector ticks and pathogen transmission at the tick/host interface, rather than multiple vaccines against every possible tickborne pathogen, could become an important tool for resolving an emerging public health crisis. The concept for such a tick protective vaccine comes from observations of an acquired tick resistance (ATR) that can develop in non-natural hosts of ticks following sensitization to tick salivary components. Mice are commonly used as models to study immune responses to human pathogens but normal mice are natural hosts for many species of ticks and fail to develop ATR. We evaluated HLA DR3 transgenic (tg) "humanized" mice as a potential model of ATR and assessed the possibility of using this animal model for tick protective vaccine discovery studies. Serial tick infestations with pathogen-free Ixodes scapularis ticks were used to tick-bite sensitize HLA DR3 tg mice. Sensitization resulted in a cytokine skew favoring a Th2 bias as well as partial (57%) protection to infection with Lyme disease spirochetes (Borrelia burgdorferi) following infected tick challenge when compared to tick naïve counterparts. I. scapularis salivary gland homogenate (SGH) and a group of immunoinformatic-predicted T cell epitopes identified from the I. scapularis salivary transcriptome were used separately to vaccinate HLA DR3 tg mice, and these mice also were assessed for both pathogen protection and epitope recognition. Reduced pathogen transmission along with a Th2 skew resulted from SGH vaccination, while no significant protection and a possible T regulatory bias was seen in epitope-vaccinated mice. This study provides the first proof-of-concept for using HLA DR tg "humanized" mice for studying the potential tick protective effects of immunoinformatic- or otherwise-derived tick salivary components as tickborne disease vaccines.
Climate Change in the North American Arctic: A One Health Perspective.
Dudley, Joseph P; Hoberg, Eric P; Jenkins, Emily J; Parkinson, Alan J
2015-12-01
Climate change is expected to increase the prevalence of acute and chronic diseases among human and animal populations within the Arctic and subarctic latitudes of North America. Warmer temperatures are expected to increase disease risks from food-borne pathogens, water-borne diseases, and vector-borne zoonoses in human and animal populations of Arctic landscapes. Existing high levels of mercury and persistent organic pollutant chemicals circulating within terrestrial and aquatic ecosystems in Arctic latitudes are a major concern for the reproductive health of humans and other mammals, and climate warming will accelerate the mobilization and biological amplification of toxic environmental contaminants. The adverse health impacts of Arctic warming will be especially important for wildlife populations and indigenous peoples dependent upon subsistence food resources from wild plants and animals. Additional research is needed to identify and monitor changes in the prevalence of zoonotic pathogens in humans, domestic dogs, and wildlife species of critical subsistence, cultural, and economic importance to Arctic peoples. The long-term effects of climate warming in the Arctic cannot be adequately predicted or mitigated without a comprehensive understanding of the interactive and synergistic effects between environmental contaminants and pathogens in the health of wildlife and human communities in Arctic ecosystems. The complexity and magnitude of the documented impacts of climate change on Arctic ecosystems, and the intimacy of connections between their human and wildlife communities, makes this region an appropriate area for development of One Health approaches to identify and mitigate the effects of climate warming at the community, ecosystem, and landscape scales.
Mier-y-Teran-Romero, Luis; Tatem, Andrew J.
2017-01-01
Mosquito-borne diseases are increasingly being recognized as global threats, with increased air travel accelerating their occurrence in travelers and their spread to new locations. Since the early days of aviation, concern over the possible transportation of infected mosquitoes has led to recommendations to disinsect aircraft. Despite rare reports of mosquitoes, most likely transported on aircraft, infecting people far from endemics areas, it is unclear how important the role of incidentally transported mosquitoes is compared to the role of traveling humans. We used data for Plasmodium falciparum and dengue viruses to estimate the probability of introduction of these pathogens by mosquitoes and by humans via aircraft under ideal conditions. The probability of introduction of either pathogen by mosquitoes is low due to few mosquitoes being found on aircraft, low infection prevalence among mosquitoes, and high mortality. Even without disinsection, introduction via infected human travelers was far more likely than introduction by infected mosquitoes; more than 1000 times more likely for P. falciparum and more than 200 times more likely for dengue viruses. Even in the absence of disinsection and under the most favorable conditions, introduction of mosquito-borne pathogens via air travel is far more likely to occur as a result of an infected human travelling rather than the incidental transportation of infected mosquitoes. Thus, while disinsection may serve a role in preventing the spread of vector species and other invasive insects, it is unlikely to impact the spread of mosquito-borne pathogens. PMID:28672006
Bonnet, Sarah I.; Binetruy, Florian; Hernández-Jarguín, Angelica M.; Duron, Olivier
2017-01-01
Ticks are among the most important vectors of pathogens affecting humans and other animals worldwide. They do not only carry pathogens however, as a diverse group of commensal and symbiotic microorganisms are also present in ticks. Unlike pathogens, their biology and their effect on ticks remain largely unexplored, and are in fact often neglected. Nonetheless, they can confer multiple detrimental, neutral, or beneficial effects to their tick hosts, and can play various roles in fitness, nutritional adaptation, development, reproduction, defense against environmental stress, and immunity. Non-pathogenic microorganisms may also play a role in driving transmission of tick-borne pathogens (TBP), with many potential implications for both human and animal health. In addition, the genetic proximity of some pathogens to mutualistic symbionts hosted by ticks is evident when studying phylogenies of several bacterial genera. The best examples are found within members of the Rickettsia, Francisella, and Coxiella genera: while in medical and veterinary research these bacteria are traditionally recognized as highly virulent vertebrate pathogens, it is now clear to evolutionary ecologists that many (if not most) Coxiella, Francisella, and Rickettsia bacteria are actually non-pathogenic microorganisms exhibiting alternative lifestyles as mutualistic ticks symbionts. Consequently, ticks represent a compelling yet challenging system in which to study microbiomes and microbial interactions, and to investigate the composition, functional, and ecological implications of bacterial communities. Ultimately, deciphering the relationships between tick microorganisms as well as tick symbiont interactions will garner invaluable information, which may aid in the future development of arthropod pest and vector-borne pathogen transmission control strategies. PMID:28642842
Bonnet, Sarah I; Binetruy, Florian; Hernández-Jarguín, Angelica M; Duron, Olivier
2017-01-01
Ticks are among the most important vectors of pathogens affecting humans and other animals worldwide. They do not only carry pathogens however, as a diverse group of commensal and symbiotic microorganisms are also present in ticks. Unlike pathogens, their biology and their effect on ticks remain largely unexplored, and are in fact often neglected. Nonetheless, they can confer multiple detrimental, neutral, or beneficial effects to their tick hosts, and can play various roles in fitness, nutritional adaptation, development, reproduction, defense against environmental stress, and immunity. Non-pathogenic microorganisms may also play a role in driving transmission of tick-borne pathogens (TBP), with many potential implications for both human and animal health. In addition, the genetic proximity of some pathogens to mutualistic symbionts hosted by ticks is evident when studying phylogenies of several bacterial genera. The best examples are found within members of the Rickettsia, Francisella , and Coxiella genera: while in medical and veterinary research these bacteria are traditionally recognized as highly virulent vertebrate pathogens, it is now clear to evolutionary ecologists that many (if not most) Coxiella, Francisella , and Rickettsia bacteria are actually non-pathogenic microorganisms exhibiting alternative lifestyles as mutualistic ticks symbionts. Consequently, ticks represent a compelling yet challenging system in which to study microbiomes and microbial interactions, and to investigate the composition, functional, and ecological implications of bacterial communities. Ultimately, deciphering the relationships between tick microorganisms as well as tick symbiont interactions will garner invaluable information, which may aid in the future development of arthropod pest and vector-borne pathogen transmission control strategies.
A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe
McIntyre, K. Marie; Setzkorn, Christian; Hepworth, Philip J.; Morand, Serge; Morse, Andrew P.; Baylis, Matthew
2014-01-01
Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps. PMID:25136810
Genome-wide phylogenetic analysis of the pathogenic potential of Vibrio furnissii
Lux, Thomas M.; Lee, Rob; Love, John
2014-01-01
We recently reported the genome sequence of a free-living strain of Vibrio furnissii (NCTC 11218) harvested from an estuarine environment. V. furnissii is a widespread, free-living proteobacterium and emerging pathogen that can cause acute gastroenteritis in humans and lethal zoonoses in aquatic invertebrates, including farmed crustaceans and molluscs. Here we present the analyses to assess the potential pathogenic impact of V. furnissii. We compared the complete genome of V. furnissii with 8 other emerging and pathogenic Vibrio species. We selected and analyzed more deeply 10 genomic regions based upon unique or common features, and used 3 of these regions to construct a phylogenetic tree. Thus, we positioned V. furnissii more accurately than before and revealed a closer relationship between V. furnissii and V. cholerae than previously thought. However, V. furnissii lacks several important features normally associated with virulence in the human pathogens V. cholera and V. vulnificus. A striking feature of the V. furnissii genome is the hugely increased Super Integron, compared to the other Vibrio. Analyses of predicted genomic islands resulted in the discovery of a protein sequence that is present only in Vibrio associated with diseases in aquatic animals. We also discovered evidence of high levels horizontal gene transfer in V. furnissii. V. furnissii seems therefore to have a dynamic and fluid genome that could quickly adapt to environmental perturbation or increase its pathogenicity. Taken together, these analyses confirm the potential of V. furnissii as an emerging marine and possible human pathogen, especially in the developing, tropical, coastal regions that are most at risk from climate change. PMID:25191313
Genome-wide phylogenetic analysis of the pathogenic potential of Vibrio furnissii.
Lux, Thomas M; Lee, Rob; Love, John
2014-01-01
We recently reported the genome sequence of a free-living strain of Vibrio furnissii (NCTC 11218) harvested from an estuarine environment. V. furnissii is a widespread, free-living proteobacterium and emerging pathogen that can cause acute gastroenteritis in humans and lethal zoonoses in aquatic invertebrates, including farmed crustaceans and molluscs. Here we present the analyses to assess the potential pathogenic impact of V. furnissii. We compared the complete genome of V. furnissii with 8 other emerging and pathogenic Vibrio species. We selected and analyzed more deeply 10 genomic regions based upon unique or common features, and used 3 of these regions to construct a phylogenetic tree. Thus, we positioned V. furnissii more accurately than before and revealed a closer relationship between V. furnissii and V. cholerae than previously thought. However, V. furnissii lacks several important features normally associated with virulence in the human pathogens V. cholera and V. vulnificus. A striking feature of the V. furnissii genome is the hugely increased Super Integron, compared to the other Vibrio. Analyses of predicted genomic islands resulted in the discovery of a protein sequence that is present only in Vibrio associated with diseases in aquatic animals. We also discovered evidence of high levels horizontal gene transfer in V. furnissii. V. furnissii seems therefore to have a dynamic and fluid genome that could quickly adapt to environmental perturbation or increase its pathogenicity. Taken together, these analyses confirm the potential of V. furnissii as an emerging marine and possible human pathogen, especially in the developing, tropical, coastal regions that are most at risk from climate change.
MacKenzie, Keith D.; Palmer, Melissa B.; Köster, Wolfgang L.; White, Aaron P.
2017-01-01
Salmonella are important pathogens worldwide and a predominant number of human infections are zoonotic in nature. The ability of strains to form biofilms, which is a multicellular behavior characterized by the aggregation of cells, is predicted to be a conserved strategy for increased persistence and survival. It may also contribute to the increasing number of infections caused by ingestion of contaminated fruits and vegetables. There is a correlation between biofilm formation and the ability of strains to colonize and replicate within the intestines of multiple host species. These strains predominantly cause localized gastroenteritis infections in humans. In contrast, there are salmonellae that cause systemic, disseminated infections in a select few host species; these “invasive” strains have a narrowed host range, and most are unable to form biofilms. This includes host-restricted Salmonella serovar Typhi, which are only able to infect humans, and atypical gastroenteritis strains associated with the opportunistic infection of immunocompromised patients. From the perspective of transmission, biofilm formation is advantageous for ensuring pathogen survival in the environment. However, from an infection point of view, biofilm formation may be an anti-virulence trait. We do not know if the capacity to form biofilms prevents a strain from accessing the systemic compartments within the host or if loss of the biofilm phenotype reflects a change in a strain’s interaction with the host. In this review, we examine the connections between biofilm formation, Salmonella disease states, degrees of host adaptation, and how this might relate to different transmission patterns. A better understanding of the dynamic lifecycle of Salmonella will allow us to reduce the burden of livestock and human infections caused by these important pathogens. PMID:29159172
Genetics: A New Landscape for Medical Geography
Carrel, Margaret; Emch, Michael
2014-01-01
The emergence and re-emergence of human pathogens resistant to medical treatment will present a challenge to the international public health community in the coming decades. Geography is uniquely positioned to examine the progressive evolution of pathogens across space and through time, and to link molecular change to interactions between population and environmental drivers. Landscape as an organizing principle for the integration of natural and cultural forces has a long history in geography, and, more specifically, in medical geography. Here, we explore the role of landscape in medical geography, the emergent field of landscape genetics, and the great potential that exists in the combination of these two disciplines. We argue that landscape genetics can enhance medical geographic studies of local-level disease environments with quantitative tests of how human-environment interactions influence pathogenic characteristics. In turn, such analyses can expand theories of disease diffusion to the molecular scale and distinguish the important factors in ecologies of disease that drive genetic change of pathogens. PMID:24558292
Reptiles as Reservoirs of Bacterial Infections: Real Threat or Methodological Bias?
Zancolli, Giulia; Mahsberg, Dieter; Sickel, Wiebke; Keller, Alexander
2015-10-01
Bacterial infections secondary to snakebites and human pathogens (e.g., Salmonella) have been linked to the oral microbiota of snakes and pet reptiles. Based on culture-dependent studies, it is speculated that snakes' oral microbiota reflects the fecal flora of their ingested preys. However, cultured-based techniques have been shown to be limited as they fail to identify unculturable microorganisms which represent the vast majority of the microbial diversity. Here, we used culture-independent high-throughput sequencing to identify reptile-associated pathogens and to characterize the oral microbial community of five snakes, one gecko, and two terrapins. Few potential human pathogens were detected at extremely low frequencies. Moreover, bacterial taxa represented in the snake's oral cavity bore little resemblance to their preys' fecal microbiota. Overall, we found distinct, highly diverse microbial communities with consistent, species-specific patterns contrary to previous culture-based studies. Our study does not support the widely held assumption that reptiles' oral cavity acts as pathogen reservoir and provides important insights for future research.
Listeria: A foodborne pathogen that knows how to survive.
Gandhi, Megha; Chikindas, Michael L
2007-01-01
The foodborne pathogen Listeria is the causative agent of listeriosis, a severe disease with high hospitalization and case fatality rates. Listeria monocytogenes can survive and grow over a wide range of environmental conditions such as refrigeration temperatures, low pH and high salt concentration. This allows the pathogen to overcome food preservation and safety barriers, and pose a potential risk to human health. This review focuses on the key issues such as survival of the pathogen in adverse environments, and the important adaptation and survival mechanisms such as biofilm formation, quorum sensing and antimicrobial resistance. Studies on the development of technologies to prevent and control L. monocytogenes contamination in foods and food processing facilities are also discussed.
de Souza, Tatiana de Arruda Campos Brasil; Graça-de Souza, Viviane Krominski; Lancheros, César Armando Contreras; Monteiro-Góes, Viviane; Krieger, Marco Aurélio; Goldenberg, Samuel; Yamauchi, Lucy Megumi; Yamada-Ogatta, Sueli Fumie
2011-03-01
In trypanosomatids, Ca²+-binding proteins can affect parasite growth, differentiation and invasion. Due to their importance for parasite maintenance, they become an attractive target for drug discovery and design. Phytomonas serpens 15T is a non-human pathogenic trypanosomatid that expresses important protein homologs of human pathogenic trypanosomatids. In this study, the coding sequence of calmodulin, a Ca²+-binding protein, of P. serpens 15T was cloned and characterized. The encoded polypeptide (CaMP) displayed high amino acid identity to homolog protein of Trypanosoma cruzi and four helix-loop-helix motifs were found. CaMP sequence analysis showed 20 amino acid substitutions compared to its mammalian counterparts. This gene is located on a chromosomal band with estimated size of 1,300 kb and two transcripts were detected by Northern blot analysis. A polyclonal antiserum raised against the recombinant protein recognized a polypeptide with an estimated size of 17 kDa in log-phase promastigote extracts. The recombinant CaMP retains its Ca²+-binding capacity.
Human infection with highly pathogenic H5N1 influenza virus.
Gambotto, Andrea; Barratt-Boyes, Simon M; de Jong, Menno D; Neumann, Gabriele; Kawaoka, Yoshihiro
2008-04-26
Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this Seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarise the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.
Fleas as parasites of the family Canidae
2011-01-01
Historically, flea-borne diseases are among the most important medical diseases of humans. Plague and murine typhus are known for centuries while the last years brought some new flea-transmitted pathogens, like R. felis and Bartonella henselae. Dogs may play an essential or an accidental role in the natural transmission cycle of flea-borne pathogens. They support the growth of some of the pathogens or they serve as transport vehicles for infected fleas between their natural reservoirs and humans. More than 15 different flea species have been described in domestic dogs thus far. Several other species have been found to be associated with wild canids. Fleas found on dogs originate from rodents, birds, insectivores and from other Carnivora. Dogs therefore may serve as ideal bridging hosts for the introduction of flea-borne diseases from nature to home. In addition to their role as ectoparasites they cause nuisance for humans and animals and may be the cause for severe allergic reactions. PMID:21767354
Search strategy has influenced the discovery rate of human viruses.
Rosenberg, Ronald; Johansson, Michael A; Powers, Ann M; Miller, Barry R
2013-08-20
A widely held concern is that the pace of infectious disease emergence has been increasing. We have analyzed the rate of discovery of pathogenic viruses, the preeminent source of newly discovered causes of human disease, from 1897 through 2010. The rate was highest during 1950-1969, after which it moderated. This general picture masks two distinct trends: for arthropod-borne viruses, which comprised 39% of pathogenic viruses, the discovery rate peaked at three per year during 1960-1969, but subsequently fell nearly to zero by 1980; however, the rate of discovery of nonarboviruses remained stable at about two per year from 1950 through 2010. The period of highest arbovirus discovery coincided with a comprehensive program supported by The Rockefeller Foundation of isolating viruses from humans, animals, and arthropod vectors at field stations in Latin America, Africa, and India. The productivity of this strategy illustrates the importance of location, approach, long-term commitment, and sponsorship in the discovery of emerging pathogens.
Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk.
den Hartog, Gerco; Jacobino, Shamir; Bont, Louis; Cox, Linda; Ulfman, Laurien H; Leusen, Jeanette H W; van Neerven, R J Joost
2014-01-01
Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV. ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.
Arenas, Ailan F; Salcedo, Gladys E; Gomez-Marin, Jorge E
2017-01-01
Pathogen-host protein-protein interaction systems examine the interactions between the protein repertoires of 2 distinct organisms. Some of these pathogen proteins interact with the host protein system and may manipulate it for their own advantages. In this work, we designed an R script by concatenating 2 functions called rowDM and rowCVmed to infer pathogen-host interaction using previously reported microarray data, including host gene enrichment analysis and the crossing of interspecific domain-domain interactions. We applied this script to the Toxoplasma-host system to describe pathogen survival mechanisms from human, mouse, and Toxoplasma Gene Expression Omnibus series. Our outcomes exhibited similar results with previously reported microarray analyses, but we found other important proteins that could contribute to toxoplasma pathogenesis. We observed that Toxoplasma ROP38 is the most differentially expressed protein among toxoplasma strains. Enrichment analysis and KEGG mapping indicated that the human retinal genes most affected by Toxoplasma infections are those related to antiapoptotic mechanisms. We suggest that proteins PIK3R1, PRKCA, PRKCG, PRKCB, HRAS, and c-JUN could be the possible substrates for differentially expressed Toxoplasma kinase ROP38. Likewise, we propose that Toxoplasma causes overexpression of apoptotic suppression human genes. PMID:29317802
Screening for Viral Pathogens in African Simian Bushmeat Seized at A French Airport.
Temmam, Sarah; Davoust, Bernard; Chaber, Anne-Lise; Lignereux, Yves; Michelle, Caroline; Monteil-Bouchard, Sonia; Raoult, Didier; Desnues, Christelle
2017-08-01
Illegal bushmeat traffic is an important threat to biodiversity conservation of several endangered species and may contribute to the emergence and spread of infectious diseases in humans. The hunting, manipulation and consumption of wildlife-based products, especially those of primate origin, may be a threat to human health; however, few studies have investigated the role of bushmeat trade and consumption as a potential source of human infections to date. In this study, we report the screening of viral pathogens in African simian game seized by French customs at Toulouse Blagnac Airport. Epifluorescence microscopy revealed the presence of virus-like particles in the samples, and further metagenomic sequencing of the DNA and RNA viromes confirmed the presence of sequences related to the Siphoviridae, Myoviridae and Podoviridae bacteriophage families; some of them infecting bacterial hosts that could be potentially pathogenic for humans. To increase the sensitivity of detection, twelve pan-generic PCRs targeting several viral zoonoses were performed, but no positive signal was detected. A large-scale inventory of bacteria, viruses and parasites is urgently needed to globally assess the risk for human health of the trade, manipulation and consumption of wildlife-related bushmeat. © 2016 Blackwell Verlag GmbH.
Main Concerns of Pathogenic Microorganisms in Meat
NASA Astrophysics Data System (ADS)
Nørrung, Birgit; Andersen, Jens Kirk; Buncic, Sava
Although various foods can serve as sources of foodborne illness, meat and meat products are important sources of human infections with a variety of foodborne pathogens, i.e. Salmonella spp., Campylobacter jejuni/coli, Yersinia enterocolitica, Verotoxigenic E. coli and, to some extent, Listeria monocytogenes. All these may be harboured in the gastrointestinal tract of food-producing animals. The most frequent chain of events leading to meat-borne illness involves food animals, which are healthy carriers of the pathogens that are subsequently transferred to humans through production, handling and consumption of meat and meat products. Occurrences of Salmonella spp., C. jejuni/coli, Y. enterocolitica and Verotoxigenic E. coli in fresh red meat vary relatively widely, although most often are between 1 and 10%, depending on a range of factors including the organism, geographical factors, farming and/or meat production practices.
Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F.; Dandekar, Thomas; Schuster, Stefan
2015-01-01
The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. PMID:26175718
Fusarium Species and Their Associated Mycotoxins.
Munkvold, Gary P
2017-01-01
The genus Fusarium includes numerous toxigenic species that are pathogenic to plants or humans, and are able to colonize a wide range of environments on earth. The genus comprises around 70 well-known species, identified by using a polyphasic approach, and as many as 300 putative species, according to phylogenetic species concepts; many putative species do not yet have formal names. Fusarium is one of the most economically important fungal genera because of yield loss due to plant pathogenic activity; mycotoxin contamination of food and feed products which often render them unaccep for marketing; and health impacts to humans and livestock, due to consumption of mycotoxins. Among the most important mycotoxins produced by species of Fusarium are the trichothecenes and the fumonisins. Fumonisins cause fatal livestock diseases and are considered potentially carcinogenic mycotoxins for humans, while trichothecenes are potent inhibitors of protein synthesis. This chapter summarizes the main aspects of morphology, pathology, and toxigenicity of the main Fusarium species that colonize different agricultural crops and environments worldwide, and cause mycotoxin contamination of food and feed.
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.
A New Family of Secreted Toxins in Pathogenic Neisseria Species
Jamet, Anne; Jousset, Agnès B.; Euphrasie, Daniel; Mukorako, Paulette; Boucharlat, Alix; Ducousso, Alexia; Charbit, Alain; Nassif, Xavier
2015-01-01
The genus Neisseria includes both commensal and pathogenic species which are genetically closely related. However, only meningococcus and gonococcus are important human pathogens. Very few toxins are known to be secreted by pathogenic Neisseria species. Recently, toxins secreted via type V secretion system and belonging to the widespread family of contact-dependent inhibition (CDI) toxins have been described in numerous species including meningococcus. In this study, we analyzed loci containing the maf genes in N. meningitidis and N. gonorrhoeae and proposed a novel uniform nomenclature for maf genomic islands (MGIs). We demonstrated that mafB genes encode secreted polymorphic toxins and that genes immediately downstream of mafB encode a specific immunity protein (MafI). We focused on a MafB toxin found in meningococcal strain NEM8013 and characterized its EndoU ribonuclease activity. maf genes represent 2% of the genome of pathogenic Neisseria, and are virtually absent from non-pathogenic species, thus arguing for an important biological role. Indeed, we showed that overexpression of one of the four MafB toxins of strain NEM8013 provides an advantage in competition assays, suggesting a role of maf loci in niche adaptation. PMID:25569427
Molecular identification of tick-borne pathogens in Nigerian ticks.
Ogo, Ndudim Isaac; de Mera, Isabel G Fernández; Galindo, Ruth C; Okubanjo, Oluyinka O; Inuwa, Hauwa Mairo; Agbede, Rowland I S; Torina, Alessandra; Alongi, Angelina; Vicente, Joaquín; Gortázar, Christian; de la Fuente, José
2012-07-06
A molecular epidemiology investigation was undertaken in two Nigerian states (Plateau and Nassarawa) to determine the prevalence of pathogens of veterinary and public health importance associated with ticks collected from cattle and dogs using PCR, cloning and sequencing or reverse line blot techniques. A total of 218 tick samples, Amblyomma variegatum (N=153), Rhipicephalus (Boophilus) decoloratus (N=45), and Rhipicephalus sanguineus (N=20) were sampled. Pathogens identified in ticks included piroplasmids (Babesia spp., Babesia bigemina and Babesia divergens), Anaplasma marginale and Rickettsia africae. Piroplasmids were identified in A. variegatum, A. marginale was found in R. decoloratus, while R. africae was detected in all tick species examined. Ehrlichia spp. and Theileria spp. were not identified in any of the ticks examined. Of the 218 ticks examined, 33 (15.1%) contained pathogen DNA, with the presence of B. divergens and R. africae that are zoonotic pathogens of public health and veterinary importance. The variety of tick-borne pathogens identified in this study suggests a risk for the emergence of tick-borne diseases in domestic animals and humans, especially amongst the Fulani pastoralists in Plateau and Nassarawa states of Nigeria. Copyright © 2012 Elsevier B.V. All rights reserved.
Extrolites of Aspergillus fumigatus and Other Pathogenic Species in Aspergillus Section Fumigati
Frisvad, Jens C.; Larsen, Thomas O.
2016-01-01
Aspergillus fumigatus is an important opportunistic human pathogen known for its production of a large array of extrolites. Up to 63 species have been described in Aspergillus section Fumigati, some of which have also been reliably reported to be pathogenic, including A. felis, A. fischeri, A. fumigatiaffinis, A. fumisynnematus, A. hiratsukae, A. laciniosus, A. lentulus, A. novofumigatus, A. parafelis, A. pseudofelis, A. pseudoviridinutans, A. spinosus, A. thermomutatus, and A. udagawae. These species share the production of hydrophobins, melanins, and siderophores and ability to grow well at 37°C, but they only share some small molecule extrolites, that could be important factors in pathogenicity. According to the literature gliotoxin and other exometabolites can be contributing factors to pathogenicity, but these exometabolites are apparently not produced by all pathogenic species. It is our hypothesis that species unable to produce some of these metabolites can produce proxy-exometabolites that may serve the same function. We tabulate all exometabolites reported from species in Aspergillus section Fumigati and by comparing the profile of those extrolites, suggest that those producing many different kinds of exometabolites are potential opportunistic pathogens. The exometabolite data also suggest that the profile of exometabolites are highly specific and can be used for identification of these closely related species. PMID:26779142
Global Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions
2012-10-26
viruses and vectors isolated over different geographic regions promote understanding of virus-vector co-evolution and the impact on dengue virus...AFRIMS Virology field site in KPP to be a participant in a regional phase 3 dengue vaccine efficacy trial. The trial is scheduled to begin in 2Q...important human pathogen producing severe illness known as dengue hemorrhagic fever (DHF). Dengue is considered an emerged global public health
Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M
2016-05-10
Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in infection that was reduced at later time points. A similar expression pattern was observed in the parasites. Our analyses provide specific insights into the interplay between human macrophages and Leishmania parasites and constitute an important general resource for the study of how pathogens evade host defenses and modulate the functions of the cell to survive intracellularly. Copyright © 2016 Fernandes et al.
β-lactam resistance in gram-negative pathogens isolated from animals.
Trott, Darren
2013-01-01
Although β-lactams remain a cornerstone of veterinary therapeutics, only a restricted number are actually approved for use in food-producing livestock in comparison to companion animals and wildlife. Nevertheless, both registered and off-label use of third and fourth-generation cephalosporins in livestock may have influenced the emergence of plasmid-encoded AmpC β-lactamases (pAmpC) (mainly CMY-2) and CTX-M extended-spectrum β-lactamases (ESBLs) in both Gram-negative pathogens and commensals isolated from animals. This presents a public health concern due to the potential risk of transfer of β-lactam-resistant pathogens from livestock to humans through food. The recent detection of pAmpC and ESBLs in multidrug-resistant Enterobacteriaceae isolated from dogs has also confirmed the public health importance of β-lactam resistance in companion animals, though in this case, human-to-animal transmission may be equally as relevant as animal-to-human transmission. Identification of pAmpC and ESBLs in Enterobacteriaceae isolated from wildlife and aquaculture species may be evidence of environmental selection pressure arising from both human and veterinary use of β- lactams. Such selection pressure in animals could be reduced by the availability of reliable alternative control measures such as vaccines, bacteriophage treatments and/or competitive exclusion models for endemic production animal diseases such as colibacillosis. The global emergence and pandemic spread of extraintestinal pathogenic E. coli O25-ST131 strains expressing CTX-M-15 ESBL in humans and its recent detection in livestock, companion animals and wildlife is a major cause for concern and goes against the paradigm that Gramnegative pathogens do not necessarily have to lose virulence in compensation for acquiring resistance.
Oliver, S P; Jayarao, B M; Almeida, R A
2005-01-01
Milk and products derived from milk of dairy cows can harbor a variety of microorganisms and can be important sources of foodborne pathogens. The presence of foodborne pathogens in milk is due to direct contact with contaminated sources in the dairy farm environment and to excretion from the udder of an infected animal. Most milk is pasteurized, so why should the dairy industry be concerned about the microbial quality of bulk tank milk? There are several valid reasons, including (1) outbreaks of disease in humans have been traced to the consumption of unpasteurized milk and have also been traced back to pasteurized milk, (2) unpasteurized milk is consumed directly by dairy producers, farm employees, and their families, neighbors, and raw milk advocates, (3) unpasteurized milk is consumed directly by a large segment of the population via consumption of several types of cheeses manufactured from unpasteurized milk, (4) entry of foodborne pathogens via contaminated raw milk into dairy food processing plants can lead to persistence of these pathogens in biofilms, and subsequent contamination of processed milk products and exposure of consumers to pathogenic bacteria, (5) pasteurization may not destroy all foodborne pathogens in milk, and (6) inadequate or faulty pasteurization will not destroy all foodborne pathogens. Furthermore, pathogens such as Listeria monocytogenes can survive and thrive in post-pasteurization processing environments, thus leading to recontamination of dairy products. These pathways pose a risk to the consumer from direct exposure to foodborne pathogens present in unpasteurized dairy products as well as dairy products that become re-contaminated after pasteurization. The purpose of this communication is to review literature published on the prevalence of bacterial foodborne pathogens in milk and in the dairy environment, and to discuss public health and food safety issues associated with foodborne pathogens found in the dairy environment. Information presented supports the model in which the presence of pathogens depends on ingestion of contaminated feed followed by amplification in bovine hosts and fecal dissemination in the farm environment. The final outcome of this cycle is a constantly maintained reservoir of foodborne pathogens that can reach humans by direct contact, ingestion of raw contaminated milk or cheese, or contamination during the processing of milk products. Isolation of bacterial pathogens with similar biotypes from dairy farms and from outbreaks of human disease substantiates this hypothesis.
sourceR: Classification and source attribution of infectious agents among heterogeneous populations
French, Nigel
2017-01-01
Zoonotic diseases are a major cause of morbidity, and productivity losses in both human and animal populations. Identifying the source of food-borne zoonoses (e.g. an animal reservoir or food product) is crucial for the identification and prioritisation of food safety interventions. For many zoonotic diseases it is difficult to attribute human cases to sources of infection because there is little epidemiological information on the cases. However, microbial strain typing allows zoonotic pathogens to be categorised, and the relative frequencies of the strain types among the sources and in human cases allows inference on the likely source of each infection. We introduce sourceR, an R package for quantitative source attribution, aimed at food-borne diseases. It implements a Bayesian model using strain-typed surveillance data from both human cases and source samples, capable of identifying important sources of infection. The model measures the force of infection from each source, allowing for varying survivability, pathogenicity and virulence of pathogen strains, and varying abilities of the sources to act as vehicles of infection. A Bayesian non-parametric (Dirichlet process) approach is used to cluster pathogen strain types by epidemiological behaviour, avoiding model overfitting and allowing detection of strain types associated with potentially high “virulence”. sourceR is demonstrated using Campylobacter jejuni isolate data collected in New Zealand between 2005 and 2008. Chicken from a particular poultry supplier was identified as the major source of campylobacteriosis, which is qualitatively similar to results of previous studies using the same dataset. Additionally, the software identifies a cluster of 9 multilocus sequence types with abnormally high ‘virulence’ in humans. sourceR enables straightforward attribution of cases of zoonotic infection to putative sources of infection. As sourceR develops, we intend it to become an important and flexible resource for food-borne disease attribution studies. PMID:28558033
Vasco, Karla; Graham, Jay P.
2016-01-01
ABSTRACT Animals are important reservoirs of zoonotic enteropathogens, and transmission to humans occurs more frequently in low- and middle-income countries (LMICs), where small-scale livestock production is common. In this study, we investigated the presence of zoonotic enteropathogens in stool samples from 64 asymptomatic children and 203 domestic animals of 62 households in a semirural community in Ecuador between June and August 2014. Multilocus sequence typing (MLST) was used to assess zoonotic transmission of Campylobacter jejuni and atypical enteropathogenic Escherichia coli (aEPEC), which were the most prevalent bacterial pathogens in children and domestic animals (30.7% and 10.5%, respectively). Four sequence types (STs) of C. jejuni and four STs of aEPEC were identical between children and domestic animals. The apparent sources of human infection were chickens, dogs, guinea pigs, and rabbits for C. jejuni and pigs, dogs, and chickens for aEPEC. Other pathogens detected in children and domestic animals were Giardia lamblia (13.1%), Cryptosporidium parvum (1.1%), and Shiga toxin-producing E. coli (STEC) (2.6%). Salmonella enterica was detected in 5 dogs and Yersinia enterocolitica was identified in 1 pig. Even though we identified 7 enteric pathogens in children, we encountered evidence of active transmission between domestic animals and humans only for C. jejuni and aEPEC. We also found evidence that C. jejuni strains from chickens were more likely to be transmitted to humans than those coming from other domestic animals. Our findings demonstrate the complex nature of enteropathogen transmission between domestic animals and humans and stress the need for further studies. IMPORTANCE We found evidence that Campylobacter jejuni, Giardia, and aEPEC organisms were the most common zoonotic enteropathogens in children and domestic animals in a region close to Quito, the capital of Ecuador. Genetic analysis of the isolates suggests transmission of some genotypes of C. jejuni and aEPEC from domestic animals to humans in this region. We also found that the genotypes associated with C. jejuni from chickens were present more often in children than were those from other domestic animals. The potential environmental factors associated with transmission of these pathogens to humans then are discussed. PMID:27208122
Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins
Brazier, Andrew J.; Avril, Marion; Bernabeu, Maria; Benjamin, Maxwell
2017-01-01
ABSTRACT Plasmodium falciparum, the most deadly of the human malaria parasites, is a member of the Laverania subgenus that also infects African Great Apes. The virulence of P. falciparum is related to cytoadhesion of infected erythrocytes in microvasculature, but the origin of dangerous parasite adhesion traits is poorly understood. To investigate the evolutionary history of the P. falciparum cytoadhesion pathogenicity determinant, we studied adhesion domains from the chimpanzee malaria parasite P. reichenowi. We demonstrate that the P. reichenowi var gene repertoire encodes cysteine-rich interdomain region (CIDR) domains which bind human CD36 and endothelial protein C receptor (EPCR) with the same levels of affinity and at binding sites similar to those bound by P. falciparum. Moreover, P. reichenowi domains interfere with the protective function of the activated protein C-EPCR pathway on endothelial cells, a presumptive virulence trait in humans. These findings provide evidence for ancient evolutionary origins of two key cytoadhesion properties of P. falciparum that contribute to human infection and pathogenicity. IMPORTANCE Cytoadhesion of P. falciparum-infected erythrocytes in the microcirculation is a major virulence determinant. P. falciparum is descended from a subgenus of parasites that also infect chimpanzees and gorillas and exhibits strict host species specificity. Despite their high genetic similarity to P. falciparum, it is unknown whether ape parasites encode adhesion properties similar to those of P. falciparum or are as virulent in their natural hosts. Consequently, it has been unclear when virulent adhesion traits arose in P. falciparum and how long they have been present in the parasite population. It is also unknown whether cytoadhesive interactions pose a barrier to cross-species transmission. We show that parasite domains from the chimpanzee malaria parasite P. reichenowi bind human receptors with specificity similar to that of P. falciparum. Our findings suggest that parasite adhesion traits associated with both mild and severe malaria have much earlier origins than previously appreciated and have important implications for virulence evolution in a major human pathogen. PMID:28101534
Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins.
Brazier, Andrew J; Avril, Marion; Bernabeu, Maria; Benjamin, Maxwell; Smith, Joseph D
2017-01-01
Plasmodium falciparum , the most deadly of the human malaria parasites, is a member of the Laverania subgenus that also infects African Great Apes. The virulence of P. falciparum is related to cytoadhesion of infected erythrocytes in microvasculature, but the origin of dangerous parasite adhesion traits is poorly understood. To investigate the evolutionary history of the P. falciparum cytoadhesion pathogenicity determinant, we studied adhesion domains from the chimpanzee malaria parasite P. reichenowi . We demonstrate that the P. reichenowi var gene repertoire encodes cysteine-rich interdomain region (CIDR) domains which bind human CD36 and endothelial protein C receptor (EPCR) with the same levels of affinity and at binding sites similar to those bound by P. falciparum . Moreover, P. reichenowi domains interfere with the protective function of the activated protein C-EPCR pathway on endothelial cells, a presumptive virulence trait in humans. These findings provide evidence for ancient evolutionary origins of two key cytoadhesion properties of P. falciparum that contribute to human infection and pathogenicity. IMPORTANCE Cytoadhesion of P. falciparum -infected erythrocytes in the microcirculation is a major virulence determinant. P. falciparum is descended from a subgenus of parasites that also infect chimpanzees and gorillas and exhibits strict host species specificity. Despite their high genetic similarity to P. falciparum , it is unknown whether ape parasites encode adhesion properties similar to those of P. falciparum or are as virulent in their natural hosts. Consequently, it has been unclear when virulent adhesion traits arose in P. falciparum and how long they have been present in the parasite population. It is also unknown whether cytoadhesive interactions pose a barrier to cross-species transmission. We show that parasite domains from the chimpanzee malaria parasite P. reichenowi bind human receptors with specificity similar to that of P. falciparum . Our findings suggest that parasite adhesion traits associated with both mild and severe malaria have much earlier origins than previously appreciated and have important implications for virulence evolution in a major human pathogen.
[Pathogenic factors of vibrios with special emphasis on Vibrio vulnificus].
Shinoda, Sumio
2005-07-01
Bacteria of the genus Vibrio are normal habitants of the aquatic environment and play roles for biocontrole of aquatic ecosystem, but some species are believed to be human pathogens. These species can be classified into two groups according to the types of diseases they cause: the gastrointestinal infections and the extraintestinal infections. The pathogenic species produce various pathogenic factors including enterotoxin, hemolysin, cytotoxin, protease, siderophore, adhesive factor, and hemagglutinin. We studied various pathogenic factors of vibrios with special emphasis on protease and hemolysin of V. vulnificus. V. vulnificus is now recognized as being among the most rapidly fatal of human pathogens, although the infection is appeared in patients having underlying disease(s) such as liver dysfunction, alcoholic cirrhosis or haemochromatosis. V. vulnificus protease (VVP) is thought to be a major toxic factor causing skin damage in the patients having septicemia. VVP is a metalloprotease and degrades a number of biologically important proteins including elastin, fibrinogen, and plasma proteinase inhibitors of complement components. VVP causes skin damages through activation of the Factor XII-plasma kallikrein-kinin cascade and/or exocytotic histamine release from mast cells, and a haemorrhagic lesion through digestion of the vascular basement membrane. Thus, the protease is the most probable candidate for tissue damage and bacterial invasion during an infection. Pathogenic roles and functional mechanism of other factors including hemolysins of V. vulnificus and V. mimicus are also shown in this review article.
[Food poisoning--importance of international perspective].
Nishibuchi, Mitsuaki
2012-08-01
It is important to obtain the information on food security in the countries other than Japan since more than 60 % of the food consumed come from these countries. Food security is now considered as a global issue. A global trend persuading us to provide safe food to humans is based on the concept of human security development associated with a sense of human mission to sustain one's life. Another global tendency pushing us to secure safety and hygiene of food is driven by the economic pressure coming from the rules in international trade established by Codex Committee under FAO/WHO. In contrast to these trends under globalization requesting safe and hygienic food, food habits based on tradition or religion are maintained locally in various parts of the world. These local habits include eating raw or improperly cooked foods, which may become a risk of being exposed to food poisoning pathogens. This issue may be adequately solved by a risk assessment approach based on the concept of appropriate level of protection (ALOP). Like or not, people in some local areas live in the unhygienic environment where they are unintentionally and frequently exposed to enteric pathogens or immunologically cross-reacting microorganisms through which they may acquire specific immunity to the pathogens and escape from infection by the pathogens. There are therefore many areas in the world where people understand the necessity to provide safe food at the international level (globalization) but actually consume food in varying hygienic conditions from area to area due in part to traditional food habits or living environments (localization); we call this situation as glocalization (global+local).
Kebbi-Beghdadi, Carole; Greub, Gilbert
2014-08-01
Free-living amoebae are distributed worldwide and are frequently in contact with humans and animals. As cysts, they can survive in very harsh conditions and resist biocides and most disinfection procedures. Several microorganisms, called amoeba-resisting microorganisms (ARMs), have evolved to survive and multiply within these protozoa. Among them are many important pathogens, such as Legionella and Mycobacteria, and also several newly discovered Chlamydia-related bacteria, such as Parachlamydia acanthamoebae, Estrella lausannensis, Simkania negevensis or Waddlia chondrophila whose pathogenic role towards human or animal is strongly suspected. Amoebae represent an evolutionary crib for their resistant microorganisms since they can exchange genetic material with other ARMs and develop virulence traits that will be further used to infect other professional phagocytes. Moreover, amoebae constitute an ideal tool to isolate strict intracellular microorganisms from complex microbiota, since they will feed on other fast-growing bacteria, such as coliforms potentially present in the investigated samples. The paradigm that ARMs are likely resistant to macrophages, another phagocytic cell, and that they are likely virulent towards humans and animals is only partially true. Indeed, we provide examples of the Chlamydiales order that challenge this assumption and suggest that the ability to multiply in protozoa does not strictly correlate with pathogenicity and that we should rather use the ability to replicate in multiple and diverse eukaryotic cells as an indirect marker of virulence towards mammals. Thus, cell-culture-based microbial culturomics should be used in the future to try to discover new pathogenic bacterial species. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.
Stephenson, Rachel E; Gutierrez, Daniel; Peters, Cindy; Nichols, Mark; Boles, Blaise R
2014-01-01
The human microbiome is influenced by a number of factors, including environmental exposure to microbes. Because many humans spend a large amount of time in built environments, it can be expected that the microbial ecology of these environments will influence the human microbiome. In an attempt to further understand the microbial ecology of built environments, the microbiota of car interiors was analyzed using culture dependent and culture independent methods. While it was found that the number and type of bacteria varied widely among the cars and sites tested, Staphylococcus and Propionibacterium were nearly always the dominant genera found at the locations sampled. Because Staphylococcus is of particular concern to human health, the characteristics of this genus found in car interiors were investigated. Staphylococcus epidermidis, S. aureus, and S. warnerii were the most prevalent staphylococcal species found, and 22.6% of S. aureus strains isolated from shared community vehicles were resistant to methicillin. The reduction in the prevalence of pathogenic bacteria in cars by using silver-based antimicrobial surface coatings was also evaluated. Coatings containing 5% silver ion additives were applied to steering wheels, placed in cars for five months and were found to eliminate the presence of culturable pathogenic bacteria recovered from these sites relative to controls. Together, these results provide new insight into the microbiota found in an important built environment, the automobile, and potential strategies for controlling the presence of human pathogens.
Stephenson, Rachel E.; Gutierrez, Daniel; Peters, Cindy; Nichols, Mark; Boles, Blaise R.
2014-01-01
The human microbiome is influenced by a number of factors, including environmental exposure to microbes. Because many humans spend a large amount of time in built environments, it can be expected that the microbial ecology of these environments will influence the human microbiome. In an attempt to further understand the microbial ecology of built environments, the microbiota of car interiors was analyzed using culture dependent and culture independent methods. While it was found that the number and type of bacteria varied widely among the cars and sites tested, Staphylococcus and Propionibacterium were nearly always the dominant genera found at the locations sampled. Because Staphylococcus is of particular concern to human health, the characteristics of this genus found in car interiors were investigated. Staphylococcus epidermidis, S. aureus, and S. warnerii were the most prevalent staphylococcal species found, and 22.6% of S. aureus strains isolated from shared community vehicles were resistant to methicillin. The reduction in the prevalence of pathogenic bacteria in cars by using silver-based antimicrobial surface coatings was also evaluated. Coatings containing 5% silver ion additives were applied to steering wheels, placed in cars for five months and were found to eliminate the presence of culturable pathogenic bacteria recovered from these sites relative to controls. Together, these results provide new insight into the microbiota found in an important built environment, the automobile, and potential strategies for controlling the presence of human pathogens. PMID:24564823
Lahodny, G E; Gautam, R; Ivanek, R
2015-01-01
Indirect transmission through the environment, pathogen shedding by infectious hosts, replication of free-living pathogens within the environment, and environmental decontamination are suspected to play important roles in the spread and control of environmentally transmitted infectious diseases. To account for these factors, the classic Susceptible-Infectious-Recovered-Susceptible epidemic model is modified to include a compartment representing the amount of free-living pathogen within the environment. The model accounts for host demography, direct and indirect transmission, replication of free-living pathogens in the environment, and removal of free-living pathogens by natural death or environmental decontamination. Based on the assumptions of the deterministic model, a continuous-time Markov chain model is developed. An estimate for the probability of disease extinction or a major outbreak is obtained by approximating the Markov chain with a multitype branching process. Numerical simulations illustrate important differences between the deterministic and stochastic counterparts, relevant for outbreak prevention, that depend on indirect transmission, pathogen shedding by infectious hosts, replication of free-living pathogens, and environmental decontamination. The probability of a major outbreak is computed for salmonellosis in a herd of dairy cattle as well as cholera in a human population. An explicit expression for the probability of disease extinction or a major outbreak in terms of the model parameters is obtained for systems with no direct transmission or replication of free-living pathogens.
How clean is the toothbrush that cleans your tooth?
Ankola, A V; Hebbal, M; Eshwar, S
2009-11-01
Until recently, little attention has been directed towards the role the toothbrush may play in human health, even though a report of toothbrush as a significant factor in the infection appeared in 1920. It is common knowledge that the human mouth harbours a wide variety of microorganisms, some of which, at any given time, can be assumed to be potential pathogens. This was not known when toothbrushes were originally designed, yet the common toothbrush has been used in basically the same form for about 200 years. In today's world of organ transplantation and alteration of the immune system, it is important to consider the toothbrush as a source of potential pathogens. Given the fact that very often people will traumatize themselves with their toothbrush, this trauma may become a potential portal of entry for organisms. In this article, we have attempted to demonstrate the importance of toothbrush disinfection, given tips on home toothbrush care and hope to motivate the dentists to educate the patients on the importance of toothbrush disinfection.
Mencke, Norbert
2013-08-01
The medical as well as the veterinary importance of parasitic arthropods or ectoparasites in general terms, is characterized by the primary or secondary impact on the health of humans and companion animals alike. The parasitic arthropods addressed here are those ectoparasites belong to the class of insects, such as fleas and sand flies, or the subclass of acarids, such as ticks. These parasitic arthropods interact intensively with their hosts by blood feeding. Fleas, sand flies and ticks hold the vector capacity to transmit pathogens such as virus, bacteria or protozoa to cats, dogs and humans. The diseases caused by these pathogens are summarized under the terms canine vector-borne diseases (CVBD), feline vector-borne diseases (FVBD) or metazoonoses. In small animal practice, it is important to understand that the transmitted pathogen may either lead to a disease with clinical signs, or more often to asymptomatic, clinically healthy, or silent infections. Blocking of the vector-host interactions, the blood feeding and subsequently the transmission of pathogens during blood feeding is a key element of CVBD control. The focus of this review is on the current knowledge of the epidemiology of parasitic vectors and three important CVBDs they transmit; rickettsiosis, tick borreliosis and canine leishmaniosis from a European perspective, and how veterinary medicine may contribute to the challenges of CVBDs and their control. Prevention of CVBDs is fundamentally based on ectoparasite control. Ectoparasite management in cats and dogs is important not only for the health and well-being of the individual companion animal but for public health in general and is therefore a perfect example of the 'One health' approach. Copyright © 2013. Published by Elsevier B.V.
Enterococci in the environment
Byappanahalli, Muruleedhara N.; Nevers, Meredith B.; Korajkic, Asja; Staley, Zachery R.; Harwood, Valerie J.
2012-01-01
Enterococci are common, commensal members of gut communities in mammals and birds, yet they are also opportunistic pathogens that cause millions of human and animal infections annually. Because they are shed in human and animal feces, are readily culturable, and predict human health risks from exposure to polluted recreational waters, they are used as surrogates for waterborne pathogens and as fecal indicator bacteria (FIB) in research and in water quality testing throughout the world. Evidence from several decades of research demonstrates, however, that enterococci may be present in high densities in the absence of obvious fecal sources and that environmental reservoirs of these FIB are important sources and sinks, with the potential to impact water quality. This review focuses on the distribution and microbial ecology of enterococci in environmental (secondary) habitats, including the effect of environmental stressors; an outline of their known and apparent sources, sinks, and fluxes; and an overview of the use of enterococci as FIB. Finally, the significance of emerging methodologies, such as microbial source tracking (MST) and empirical predictive models, as tools in water quality monitoring is addressed. The mounting evidence for widespread extraenteric sources and reservoirs of enterococci demonstrates the versatility of the genus Enterococcus and argues for the necessity of a better understanding of their ecology in natural environments, as well as their roles as opportunistic pathogens and indicators of human pathogens.
Enterococci in the Environment
Byappanahalli, Muruleedhara N.; Nevers, Meredith B.; Korajkic, Asja; Staley, Zachery R.
2012-01-01
Summary: Enterococci are common, commensal members of gut communities in mammals and birds, yet they are also opportunistic pathogens that cause millions of human and animal infections annually. Because they are shed in human and animal feces, are readily culturable, and predict human health risks from exposure to polluted recreational waters, they are used as surrogates for waterborne pathogens and as fecal indicator bacteria (FIB) in research and in water quality testing throughout the world. Evidence from several decades of research demonstrates, however, that enterococci may be present in high densities in the absence of obvious fecal sources and that environmental reservoirs of these FIB are important sources and sinks, with the potential to impact water quality. This review focuses on the distribution and microbial ecology of enterococci in environmental (secondary) habitats, including the effect of environmental stressors; an outline of their known and apparent sources, sinks, and fluxes; and an overview of the use of enterococci as FIB. Finally, the significance of emerging methodologies, such as microbial source tracking (MST) and empirical predictive models, as tools in water quality monitoring is addressed. The mounting evidence for widespread extraenteric sources and reservoirs of enterococci demonstrates the versatility of the genus Enterococcus and argues for the necessity of a better understanding of their ecology in natural environments, as well as their roles as opportunistic pathogens and indicators of human pathogens. PMID:23204362
Jones, Natalia R; Millman, Caroline; van der Es, Mike; Hukelova, Miroslava; Forbes, Ken J; Glover, Catherine; Haldenby, Sam; Hunter, Paul R; Jackson, Kathryn; O'Brien, Sarah J; Rigby, Dan; Strachan, Norval J C; Williams, Nicola; Lake, Iain R
2017-07-15
This paper introduces a novel method for sampling pathogens in natural environments. It uses fabric boot socks worn over walkers' shoes to allow the collection of composite samples over large areas. Wide-area sampling is better suited to studies focusing on human exposure to pathogens (e.g., recreational walking). This sampling method is implemented using a citizen science approach: groups of three walkers wearing boot socks undertook one of six routes, 40 times over 16 months in the North West (NW) and East Anglian (EA) regions of England. To validate this methodology, we report the successful implementation of this citizen science approach, the observation that Campylobacter bacteria were detected on 47% of boot socks, and the observation that multiple boot socks from individual walks produced consistent results. The findings indicate higher Campylobacter levels in the livestock-dominated NW than in EA (55.8% versus 38.6%). Seasonal differences in the presence of Campylobacter bacteria were found between the regions, with indications of winter peaks in both regions but a spring peak in the NW. The presence of Campylobacter bacteria on boot socks was negatively associated with ambient temperature ( P = 0.011) and positively associated with precipitation ( P < 0.001), results consistent with our understanding of Campylobacter survival and the probability of material adhering to boot socks. Campylobacter jejuni was the predominant species found; Campylobacter coli was largely restricted to the livestock-dominated NW. Source attribution analysis indicated that the potential source of C. jejuni was predominantly sheep in the NW and wild birds in EA but did not differ between peak and nonpeak periods of human incidence. IMPORTANCE There is debate in the literature on the pathways through which pathogens are transferred from the environment to humans. We report on the success of a novel method for sampling human-pathogen interactions using boot socks and citizen science techniques, which enable us to sample human-pathogen interactions that may occur through visits to natural environments. This contrasts with traditional environmental sampling, which is based on spot sampling techniques and does not sample human-pathogen interactions. Our methods are of practical value to scientists trying to understand the transmission of pathogens from the environment to people. Our findings provide insight into the risk of Campylobacter exposure from recreational visits and an understanding of seasonal differences in risk and the factors behind these patterns. We highlight the Campylobacter species predominantly encountered and the potential sources of C. jejuni . Copyright © 2017 Jones et al.
Millman, Caroline; van der Es, Mike; Hukelova, Miroslava; Forbes, Ken J.; Glover, Catherine; Haldenby, Sam; Hunter, Paul R.; Jackson, Kathryn; O'Brien, Sarah J.; Rigby, Dan; Strachan, Norval J. C.; Williams, Nicola; Lake, Iain R.
2017-01-01
ABSTRACT This paper introduces a novel method for sampling pathogens in natural environments. It uses fabric boot socks worn over walkers' shoes to allow the collection of composite samples over large areas. Wide-area sampling is better suited to studies focusing on human exposure to pathogens (e.g., recreational walking). This sampling method is implemented using a citizen science approach: groups of three walkers wearing boot socks undertook one of six routes, 40 times over 16 months in the North West (NW) and East Anglian (EA) regions of England. To validate this methodology, we report the successful implementation of this citizen science approach, the observation that Campylobacter bacteria were detected on 47% of boot socks, and the observation that multiple boot socks from individual walks produced consistent results. The findings indicate higher Campylobacter levels in the livestock-dominated NW than in EA (55.8% versus 38.6%). Seasonal differences in the presence of Campylobacter bacteria were found between the regions, with indications of winter peaks in both regions but a spring peak in the NW. The presence of Campylobacter bacteria on boot socks was negatively associated with ambient temperature (P = 0.011) and positively associated with precipitation (P < 0.001), results consistent with our understanding of Campylobacter survival and the probability of material adhering to boot socks. Campylobacter jejuni was the predominant species found; Campylobacter coli was largely restricted to the livestock-dominated NW. Source attribution analysis indicated that the potential source of C. jejuni was predominantly sheep in the NW and wild birds in EA but did not differ between peak and nonpeak periods of human incidence. IMPORTANCE There is debate in the literature on the pathways through which pathogens are transferred from the environment to humans. We report on the success of a novel method for sampling human-pathogen interactions using boot socks and citizen science techniques, which enable us to sample human-pathogen interactions that may occur through visits to natural environments. This contrasts with traditional environmental sampling, which is based on spot sampling techniques and does not sample human-pathogen interactions. Our methods are of practical value to scientists trying to understand the transmission of pathogens from the environment to people. Our findings provide insight into the risk of Campylobacter exposure from recreational visits and an understanding of seasonal differences in risk and the factors behind these patterns. We highlight the Campylobacter species predominantly encountered and the potential sources of C. jejuni. PMID:28500040
Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway.
Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter
2017-01-01
The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination.
Molecular detection of emerging tick-borne pathogens in Vojvodina, Serbia.
Potkonjak, Aleksandar; Gutiérrez, Ricardo; Savić, Sara; Vračar, Vuk; Nachum-Biala, Yaarit; Jurišić, Aleksandar; Kleinerman, Gabriela; Rojas, Alicia; Petrović, Aleksandra; Baneth, Gad; Harrus, Shimon
2016-02-01
Ticks play an important role in disease transmission globally due to their capability to serve as vectors for human and animal pathogens. The Republic of Serbia is an endemic area for a large number of tick-borne diseases. However, current knowledge on these diseases in Serbia is limited. The aim of this study was to investigate the presence of new emerging tick-borne pathogens in ticks collected from dogs and the vegetation from different parts of Vojvodina, Serbia. A total of 187 ticks, including 124 Rhipicephalus sanguineus, 45 Ixodes ricinus and 18 Dermacentor reticulatus were collected from dogs. In addition, 26 questing I. ricinus ticks were collected from the vegetation, using the flagging method, from 4 different localities in Vojvodina, Serbia. DNA was extracted from each tick individually and samples were tested by either conventional or real-time PCR assays for the presence of Rickettsia spp.-DNA (gltA and ompA gene fragments), Ehrlichia/Anaplasma spp.-DNA (16S rRNA gene fragment) and Hepatozoon spp./Babesia spp.-DNA (18S rRNA gene fragment). In addition, all I. ricinus DNA samples were tested for Bartonella spp.-DNA (ITS locus) by real-time PCR. In this study, the presence of novel emerging tick-borne pathogens including Rickettsia raoultii, Rickettsia massiliae, Babesia venatorum, Babesia microti, Hepatozoon canis and Candidatus Neoehrlichia mikurensis was identified for the first time in Serbia. Our findings also confirmed the presence of Rickettsia monacensis, Babesia canis and Anaplasma phagocytophilum in ticks from Serbia. The findings of the current study highlight the great diversity of tick-borne pathogens of human and animal importance in Serbia. Physicians, public health workers and veterinarians should increase alertness to the presence of these tick-borne pathogens in this country. Copyright © 2015 Elsevier GmbH. All rights reserved.
Pathogen Transmission from Humans to Great Apes is a Growing Threat to Primate Conservation.
Dunay, Emily; Apakupakul, Kathleen; Leard, Stephen; Palmer, Jamie L; Deem, Sharon L
2018-01-23
All six great ape species are listed as endangered or critically endangered by the IUCN and experiencing decreasing population trends. One of the threats to these non-human primates is the transmission of pathogens from humans. We conducted a literature review on occurrences of pathogen transmission from humans to great apes to highlight this often underappreciated issue. In total, we found 33 individual occurrences of probable or confirmed pathogen transmission from humans to great apes: 23 involved both pathogen and disease transmission, 7 pathogen transmission only, 2 positive antibody titers to zoonotic pathogens, and 1 pathogen transmission with probable disease. Great ape populations were categorized into captive, semi-free-living, and free-living conditions. The majority of occurrences involved chimpanzees (Pan troglodytes) (n = 23) or mountain gorillas (Gorilla beringei beringei) (n = 8). These findings have implications for conservation efforts and management of endangered great ape populations. Future efforts should focus on monitoring and addressing zoonotic pathogen and disease transmission between humans, great ape species, and other taxa to ensure the health of humans, wild and domestic animals, and the ecosystems we share.
The role of hyperparasitism in microbial pathogen ecology and evolution.
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.
Harnessing Whole Genome Sequencing in Medical Mycology.
Cuomo, Christina A
2017-01-01
Comparative genome sequencing studies of human fungal pathogens enable identification of genes and variants associated with virulence and drug resistance. This review describes current approaches, resources, and advances in applying whole genome sequencing to study clinically important fungal pathogens. Genomes for some important fungal pathogens were only recently assembled, revealing gene family expansions in many species and extreme gene loss in one obligate species. The scale and scope of species sequenced is rapidly expanding, leveraging technological advances to assemble and annotate genomes with higher precision. By using iteratively improved reference assemblies or those generated de novo for new species, recent studies have compared the sequence of isolates representing populations or clinical cohorts. Whole genome approaches provide the resolution necessary for comparison of closely related isolates, for example, in the analysis of outbreaks or sampled across time within a single host. Genomic analysis of fungal pathogens has enabled both basic research and diagnostic studies. The increased scale of sequencing can be applied across populations, and new metagenomic methods allow direct analysis of complex samples.
USDA-ARS?s Scientific Manuscript database
Invasion of intestinal epithelial cells by Campylobacter jejuni is a critical step during infection of the human intestine by this important human pathogen. In this study we investigated the role played by DNA supercoiling in the regulation of invasion of epithelial cells and the mechanism by which ...
Obame-Nkoghe, Judicaël; Leroy, Eric-Maurice; Paupy, Christophe
2017-04-12
The progressive anthropization of caves for food resources or economic purposes increases human exposure to pathogens that naturally infect cave-dwelling animals. The presence of wild or domestic animals in the immediate surroundings of caves also may contribute to increasing the risk of emergence of such pathogens. Some zoonotic pathogens are transmitted through direct contact, but many others require arthropod vectors, such as blood-feeding insects. In Africa, hematophagous insects often play a key role in the epidemiology of many pathogens; however, their ecology in cave habitats remains poorly known. During the last decades, several investigations carried out in Afrotropical caves suggested the medical and veterinary importance particularly of insect taxa of the Diptera order. Therefore, the role of some of these insects as vectors of pathogens that infect cave-dwelling vertebrates has been studied. The present review summarizes these findings, brings insights into the diversity of cave-dwelling hematophagous Diptera and their involvement in pathogen transmission, and finally discusses new challenges and future research directions.
Host-pathogen interaction in Fusarium oxysporum infections: where do we stand?
Husaini, Amjad M; Sakina, Aafreen; Cambay, Souliha R
2018-03-16
Fusarium oxysporum, a ubiquitous soil-borne pathogen causes devastating vascular wilt in more than 100 plant species and ranks fifth among top ten fungal plant pathogens. It has emerged as a human pathogen too, causing infections in immune-compromised patients. It is, therefore, important to gain insight into the molecular processes involved in the pathogenesis of this trans-kingdom pathogen. A complex network comprising of interconnected and over lapping signal pathways; mitogen-activated protein kinase (MAPK) signaling pathways, Ras proteins, G-protein signaling components and their downstream pathways, components of the velvet (LaeA/VeA/VelB) complex and cAMP pathways, is involved in perceiving the host. This network regulates the expression of various pathogenicity genes. Plants have however evolved an elaborate protection system to combat this attack. They too possess intricate mechanisms at molecular level, which once triggered by pathogen attack transduce signals to activate defense response. This review focuses on understanding and presenting a wholistic picture of the molecular mechanisms of F. oxysporum-host interactions in plant immunity.
Biphasic zinc compartmentalisation in a human fungal pathogen.
Crawford, Aaron C; Lehtovirta-Morley, Laura E; Alamir, Omran; Niemiec, Maria J; Alawfi, Bader; Alsarraf, Mohammad; Skrahina, Volha; Costa, Anna C B P; Anderson, Andrew; Yellagunda, Sujan; Ballou, Elizabeth R; Hube, Bernhard; Urban, Constantin F; Wilson, Duncan
2018-05-01
Nutritional immunity describes the host-driven manipulation of essential micronutrients, including iron, zinc and manganese. To withstand nutritional immunity and proliferate within their hosts, pathogenic microbes must express efficient micronutrient uptake and homeostatic systems. Here we have elucidated the pathway of cellular zinc assimilation in the major human fungal pathogen Candida albicans. Bioinformatics analysis identified nine putative zinc transporters: four cytoplasmic-import Zip proteins (Zrt1, Zrt2, Zrt3 and orf19.5428) and five cytoplasmic-export ZnT proteins (orf19.1536/Zrc1, orf19.3874, orf19.3769, orf19.3132 and orf19.52). Only Zrt1 and Zrt2 are predicted to localise to the plasma membrane and here we demonstrate that Zrt2 is essential for C. albicans zinc uptake and growth at acidic pH. In contrast, ZRT1 expression was found to be highly pH-dependent and could support growth of the ZRT2-null strain at pH 7 and above. This regulatory paradigm is analogous to the distantly related pathogenic mould, Aspergillus fumigatus, suggesting that pH-adaptation of zinc transport may be conserved in fungi and we propose that environmental pH has shaped the evolution of zinc import systems in fungi. Deletion of C. albicans ZRT2 reduced kidney fungal burden in wild type, but not in mice lacking the zinc-chelating antimicrobial protein calprotectin. Inhibition of zrt2Δ growth by neutrophil extracellular traps was calprotectin-dependent. This suggests that, within the kidney, C. albicans growth is determined by pathogen-Zrt2 and host-calprotectin. As well as serving as an essential micronutrient, zinc can also be highly toxic and we show that C. albicans deals with this potential threat by rapidly compartmentalising zinc within vesicular stores called zincosomes. In order to understand mechanistically how this process occurs, we created deletion mutants of all five ZnT-type transporters in C. albicans. Here we show that, unlike in Saccharomyces cerevisiae, C. albicans Zrc1 mediates zinc tolerance via zincosomal zinc compartmentalisation. This novel transporter was also essential for virulence and liver colonisation in vivo. In summary, we show that zinc homeostasis in a major human fungal pathogen is a multi-stage process initiated by Zrt1/Zrt2-cellular import, followed by Zrc1-dependent intracellular compartmentalisation.
Candida albicans orf19.3727 encodes phytase activity and is essential for human tissue damage
Fong, Wing-Ping; Samaranayake, Lakshman Perera
2017-01-01
Candida albicans is a clinically important human fungal pathogen. We previously identified the presence of cell-associated phytase activity in C. albicans. Here, we reveal for the first time, that orf19.3727 contributes to phytase activity in C. albicans and ultimately to its virulence potency. Compared with its wild type counterpart, disruption of C. albicans orf19.3727 led to decreased phytase activity, reduced ability to form hyphae, attenuated in vitro adhesion, and reduced ability to penetrate human epithelium, which are the major virulence attributes of this yeast. Thus, orf19.3727 of C. albicans plays a key role in fungal pathogenesis. Further, our data uncover a putative novel strategy for anti-Candidal drug design through inhibition of phytase activity of this common pathogen. PMID:29216308
Petruzzelli, Sabina; Congiu, Antonio; Gallamini, Michele; Pompei, Raffaello
2014-04-01
Lasers are commonly used in several fields of medicine as a complementary therapy for internal medicine, surgery and also diagnostics. The efficacy of ultra-low level laser therapy (ULLLT) at power levels around 0.15 mW/cm(2) has been demonstrated both in in vitro experiments and in the clinical environment. This work used an ULLLT laser source to analyze its efficacy on Staphylococcus aureus adhesion to cells and on its ability to produce pathogenic factors. Laser stimulation succeeded in impairing the binding of S. aureus to primary human cells in culture and in inhibiting the expression of coagulase, one of the main staphylococcal pathogenic factors. The importance of the extracellular matrix (ECM) and the modification of the ECM redox potential in these activities were also evidenced.
Diarrheagenic Escherichia coli
Nataro, James P.; Kaper, James B.
1998-01-01
Escherichia coli is the predominant nonpathogenic facultative flora of the human intestine. Some E. coli strains, however, have developed the ability to cause disease of the gastrointestinal, urinary, or central nervous system in even the most robust human hosts. Diarrheagenic strains of E. coli can be divided into at least six different categories with corresponding distinct pathogenic schemes. Taken together, these organisms probably represent the most common cause of pediatric diarrhea worldwide. Several distinct clinical syndromes accompany infection with diarrheagenic E. coli categories, including traveler’s diarrhea (enterotoxigenic E. coli), hemorrhagic colitis and hemolytic-uremic syndrome (enterohemorrhagic E. coli), persistent diarrhea (enteroaggregative E. coli), and watery diarrhea of infants (enteropathogenic E. coli). This review discusses the current level of understanding of the pathogenesis of the diarrheagenic E. coli strains and describes how their pathogenic schemes underlie the clinical manifestations, diagnostic approach, and epidemiologic investigation of these important pathogens. PMID:9457432
Protein kinase A and fungal virulence: a sinister side to a conserved nutrient sensing pathway.
Fuller, Kevin K; Rhodes, Judith C
2012-01-01
Diverse fungal species are the cause of devastating agricultural and human diseases. As successful pathogenesis is dependent upon the ability of the fungus to adapt to the nutritional and chemical environment of the host, the understanding of signaling pathways required for such adaptation will provide insights into the virulence of these pathogens and the potential identification of novel targets for antifungal intervention. The cAMP-PKA signaling pathway is well conserved across eukaryotes. In the nonpathogenic yeast, S. cerevisiae, PKA is activated in response to extracellular nutrients and subsequently regulates metabolism and growth. Importantly, this pathway is also a regulator of pathogenesis, as defects in PKA signaling lead to an attenuation of virulence in diverse plant and human pathogenic fungi. This review will compare and contrast PKA signaling in S. cerevisiae vs. various pathogenic species and provide a framework for the role of this pathway in regulating fungal virulence.
USDA-ARS?s Scientific Manuscript database
Fusarium (Hypocreales, Nectriaceae) is one of the most economically important and systematically challenging groups of mycotoxigenic phytopathogens and emergent human pathogens. We conducted maximum likelihood (ML), maximum parsimony (MP) and Bayesian (B) analyses on partial RNA polymerase largest (...
Maurer-Stroh, Sebastian; Lee, Raphael T C; Gunalan, Vithiagaran; Eisenhaber, Frank
2013-05-01
A characteristic difference between highly and non-highly pathogenic avian influenza strains is the presence of an extended, often multibasic, cleavage motif insertion in the hemagglutinin protein. Such motif is found in H7N3 strains from chicken farm outbreaks in 2012 in Mexico. Through phylogenetic, sequence and structural analysis, we try to shed light on the role, prevalence, likelihood of appearance and origin of the inserted cleavage motifs in these H7N3 avian influenza strains. The H7N3 avian influenza strain which caused outbreaks in chicken farms in June/July 2012 in Mexico has a new extended cleavage site which is the likely reason for its high pathogenicity in these birds. This cleavage site appears to have been naturally acquired and was not present in the closest low pathogenic precursors. Structural modeling shows that insertion of a productive cleavage site is quite flexible to accept insertions of different length and with sequences from different possible origins. Different from recent cleavage site insertions, the origin of the insert here is not from the viral genome but from host 28S ribosomal RNA (rRNA) instead. This is a novelty for a natural acquisition as a similar insertion has so far only been observed in a laboratory strain before. Given the abundance of viral and host RNA in infected cells, the acquisition of a pathogenicity-enhancing extended cleavage site through a similar route by other low-pathogenic avian strains in future does not seem unlikely. Important for surveillance of these H7N3 strains, the structural sites known to enhance mammalian airborne transmission are dominated by the characteristic avian residues and the risk of human to human transmission should currently be low but should be monitored for future changes accordingly. This highly pathogenic H7N3 avian influenza strain acquired a novel extended cleavage site which likely originated from recombination with 28S rRNA from the avian host. Notably, this new virus can infect humans but currently lacks critical host receptor adaptations that would facilitate human to human transmission.
Voyich, Jovanka M; Sturdevant, Daniel E; Braughton, Kevin R; Kobayashi, Scott D; Lei, Benfang; Virtaneva, Kimmo; Dorward, David W; Musser, James M; DeLeo, Frank R
2003-02-18
Group A Streptococcus (GAS) evades polymorphonuclear leukocyte (PMN) phagocytosis and killing to cause human disease, including pharyngitis and necrotizing fasciitis (flesh-eating syndrome). We show that GAS genes differentially regulated during phagocytic interaction with human PMNs comprise a global pathogen-protective response to innate immunity. GAS prophage genes and genes involved in virulence, oxidative stress, cell wall biosynthesis, and gene regulation were up-regulated during PMN phagocytosis. Genes encoding novel secreted proteins were up-regulated, and the proteins were produced during human GAS infections. We discovered an essential role for the Ihk-Irr two-component regulatory system in evading PMN-mediated killing and promoting host-cell lysis, processes that would facilitate GAS pathogenesis. Importantly, the irr gene was highly expressed during human GAS pharyngitis. We conclude that a complex pathogen genetic program circumvents human innate immunity to promote disease. The gene regulatory program revealed by our studies identifies previously undescribed potential vaccine antigens and targets for therapeutic interventions designed to control GAS infections.
Kilian, Mogens; Riley, David R; Jensen, Anders; Brüggemann, Holger; Tettelin, Hervé
2014-07-22
The bacterium Streptococcus pneumoniae is one of the leading causes of fatal infections affecting humans. Intriguingly, phylogenetic analysis shows that the species constitutes one evolutionary lineage in a cluster of the otherwise commensal Streptococcus mitis strains, with which humans live in harmony. In a comparative analysis of 35 genomes, including phylogenetic analyses of all predicted genes, we have shown that the pathogenic pneumococcus has evolved into a master of genomic flexibility while lineages that evolved into the nonpathogenic S. mitis secured harmonious coexistence with their host by stabilizing an approximately 15%-reduced genome devoid of many virulence genes. Our data further provide evidence that interspecies gene transfer between S. pneumoniae and S. mitis occurs in a unidirectional manner, i.e., from S. mitis to S. pneumoniae. Import of genes from S. mitis and other mitis, anginosus, and salivarius group streptococci ensured allelic replacements and antigenic diversification and has been driving the evolution of the remarkable structural diversity of capsular polysaccharides of S. pneumoniae. Our study explains how the unique structural diversity of the pneumococcal capsule emerged and conceivably will continue to increase and reveals a striking example of the fragile border between the commensal and pathogenic lifestyles. While genomic plasticity enabling quick adaptation to environmental stress is a necessity for the pathogenic streptococci, the commensal lifestyle benefits from stability. Importance: One of the leading causes of fatal infections affecting humans, Streptococcus pneumoniae, and the commensal Streptococcus mitis are closely related obligate symbionts associated with hominids. Faced with a shortage of accessible hosts, the two opposing lifestyles evolved in parallel. We have shown that the nonpathogenic S. mitis secured harmonious coexistence with its host by stabilizing a reduced genome devoid of many virulence genes. Meanwhile, the pathogenic pneumococcus evolved into a master of genomic flexibility and imports genes from S. mitis and other related streptococci. This process ensured antigenic diversification and has been driving the evolution of the remarkable structural diversity of capsular polysaccharides of S. pneumoniae, which conceivably will continue to increase and present a challenge to disease prevention. Copyright © 2014 Kilian et al.
Jian, Jiahui; Beno, Sarah M.; Wiedmann, Martin
2018-01-01
ABSTRACT While some species in the Bacillus cereus group are well-characterized human pathogens (e.g., B. anthracis and B. cereus sensu stricto), the pathogenicity of other species (e.g., B. pseudomycoides) either has not been characterized or is presently not well understood. To provide an updated characterization of the pathogenic potential of species in the B. cereus group, we classified a set of 52 isolates, including 8 type strains and 44 isolates from dairy-associated sources, into 7 phylogenetic clades and characterized them for (i) the presence of toxin genes, (ii) phenotypic characteristics used for identification, and (iii) cytotoxicity to human epithelial cells. Overall, we found that B. cereus toxin genes are broadly distributed but are not consistently present within individual species and/or clades. After growth at 37°C, isolates within a clade did not typically show a consistent cytotoxicity phenotype, except for isolates in clade VI (B. weihenstephanensis/B. mycoides), where none of the isolates were cytotoxic, and isolates in clade I (B. pseudomycoides), which consistently displayed cytotoxic activity. Importantly, our study highlights that B. pseudomycoides is cytotoxic toward human cells. Our results indicate that the detection of toxin genes does not provide a reliable approach to predict the pathogenic potential of B. cereus group isolates, as the presence of toxin genes is not always consistent with cytotoxicity phenotype. Overall, our results suggest that isolates from multiple B. cereus group clades have the potential to cause foodborne illness, although cytotoxicity is not always consistently found among isolates within each clade. IMPORTANCE Despite the importance of the Bacillus cereus group as a foodborne pathogen, characterizations of the pathogenic potential of all B. cereus group species were lacking. We show here that B. pseudomycoides (clade I), which has been considered a harmless environmental microorganism, produces toxins and exhibits a phenotype consistent with the production of pore-forming toxins. Furthermore, B. mycoides/B. weihenstephanensis isolates (clade VI) did not show cytotoxicity when grown at 37°C, despite carrying multiple toxin genes. Overall, we show that the current standard methods to characterize B. cereus group isolates and to detect the presence of toxin genes are not reliable indicators of species, phylogenetic clades, or an isolate's cytotoxic capacity, suggesting that novel methods are still needed for differentiating pathogenic from nonpathogenic species within the B. cereus group. Our results also contribute data that are necessary to facilitate risk assessments and a better understanding as to which B. cereus group species are likely to cause foodborne illness. PMID:29330180
Williams, Simon H; Che, Xiaoyu; Paulick, Ashley; Guo, Cheng; Lee, Bohyun; Muller, Dorothy; Uhlemann, Anne-Catrin; Lowy, Franklin D; Corrigan, Robert M; Lipkin, W Ian
2018-04-17
House mice ( Mus musculus ) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella , Salmonella , Clostridium difficile , and diarrheagenic Escherichia coli Furthermore, genes mediating antimicrobial resistance to fluoroquinolones ( qnrB ) and β-lactam drugs ( bla SHV and bla ACT/MIR ) were widely distributed. Culture and molecular strain typing of C. difficile revealed that mice harbor ribotypes associated with human disease, and screening of kidney samples demonstrated genetic evidence of pathogenic Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment. IMPORTANCE Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes. Copyright © 2018 Williams et al.
Leptospiral uveitis - there is more to it than meets the eye!
Verma, A; Stevenson, B
2012-09-01
Leptospirosis, caused by pathogenic species of genus Leptospira, is a highly prevalent zoonotic disease throughout many parts of the world, and an important emerging disease within the United States. Uveitis is a common complication of systemic infection in humans. A similar condition in horses is characterized by recurrent bouts of inflammation. In this article, we review advances in our understanding of leptospiral uveitis and its pathogenic mechanisms. © 2012 Blackwell Verlag GmbH.
Lu, Ding; McDowell, Julia Z.; Davis, George M.; Spear, Robert C.; Remais, Justin V.
2012-01-01
Environmental models, often applied to questions on the fate and transport of chemical hazards, have recently become important in tracing certain environmental pathogens to their upstream sources of contamination. These tools, such as first order decay models applied to contaminants in surface waters, offer promise for quantifying the fate and transport of pathogens with multiple environmental stages and/or multiple hosts, in addition to those pathogens whose environmental stages are entirely waterborne. Here we consider the fate and transport capabilities of the human schistosome Schistosoma japonicum, which exhibits two waterborne stages and is carried by an amphibious intermediate snail host. We present experimentally-derived dispersal estimates for the intermediate snail host and fate and transport estimates for the passive downstream diffusion of cercariae, the waterborne, human-infective parasite stage. Using a one dimensional advective transport model exhibiting first-order decay, we simulate the added spatial reach and relative increase in cercarial concentrations that dispersing snail hosts contribute to downstream sites. Simulation results suggest that snail dispersal can substantially increase the concentrations of cercariae reaching downstream locations, relative to no snail dispersal, effectively putting otherwise isolated downstream sites at increased risk of exposure to cercariae from upstream sources. The models developed here can be applied to other infectious diseases with multiple life-stages and hosts, and have important implications for targeted ecological control of disease spread. PMID:23162675
The Biology of Neisseria Adhesins
Hung, Miao-Chiu; Christodoulides, Myron
2013-01-01
Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these exposed epithelia is dependent on a repertoire of diverse bacterial molecules, extending not only from the surface of the bacteria but also found within the outer membrane. During invasive disease, pathogenic Neisseriae also interact with immune effector cells, vascular endothelia and the meninges. Neisseria adhesion involves the interplay of these multiple surface factors and in this review we discuss the structure and function of these important molecules and the nature of the host cell receptors and mechanisms involved in their recognition. We also describe the current status for recently identified Neisseria adhesins. Understanding the biology of Neisseria adhesins has an impact not only on the development of new vaccines but also in revealing fundamental knowledge about human biology. PMID:24833056
Vite-Garín, Tania; Estrada-Bárcenas, Daniel Alfonso; Cifuentes, Joaquín; Taylor, Maria Lucia
2014-01-01
Advances in the classification of the human pathogen Histoplasma capsulatum (H. capsulatum) (ascomycete) are sustained by the results of several genetic analyses that support the high diversity of this dimorphic fungus. The present mini-review highlights the great genetic plasticity of H. capsulatum. Important records with different molecular tools, mainly single- or multi-locus sequence analyses developed with this fungus, are discussed. Recent phylogenetic data with a multi-locus sequence analysis using 5 polymorphic loci support a new clade and/or phylogenetic species of H. capsulatum for the Americas, which was associated with fungal isolates obtained from the migratory bat Tadarida brasiliensis. 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.
Aspergillus Niger Genomics: Past, Present and into the Future
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baker, Scott E.
2006-09-01
Aspergillus niger is a filamentous ascomycete fungus that is ubiquitous in the environment and has been implicated in opportunistic infections of humans. In addition to its role as an opportunistic human pathogen, A. niger is economically important as a fermentation organism used for the production of citric acid. Industrial citric acid production by A. niger represents one of the most efficient, highest yield bioprocesses in use currently by industry. The genome size of A. niger is estimated to be between 35.5 and 38.5 megabases (Mb) divided among eight chromosomes/linkage groups that vary in size from 3.5 - 6.6 Mb. Currently,more » there are three independent A. niger genome projects, an indication of the economic importance of this organism. The rich amount of data resulting from these multiple A. niger genome sequences will be used for basic and applied research programs applicable to fermentation process development, morphology and pathogenicity.« less
A mouse model of Salmonella typhi infection
Mathur, Ramkumar; Oh, Hyunju; Zhang, Dekai; Park, Sung-Gyoo; Seo, Jin; Koblansky, Alicia; Hayden, Matthew S.; Ghosh, Sankar
2012-01-01
Salmonella spp. are gram-negative flagellated bacteria that can cause food and water-borne gastroenteritis and typhoid fever in humans. We now report that flagellin from Salmonella spp. is recognized in mouse intestine by Toll-like receptor 11 (TLR11). Absence of TLR11 renders mice more susceptible to infection by S. typhimurium, with increased dissemination of the bacteria and enhanced lethality. Unlike S. typhimurium, S. typhi, a human obligatory pathogen that causes typhoid fever, is normally unable to infect mice. TLR11 is expressed in mice but not in humans, and remarkably, we find that tlr11−/− mice are efficiently infected with orally-administered S. typhi. We also find that tlr11−/− mice can be immunized against S. typhi. Therefore, tlr11−/− mice represent the first small animal model for the study of the immune response to S. typhi, and for the development of vaccines against this important human pathogen. PMID:23101627
Wood, James L. N.; Leach, Melissa; Waldman, Linda; MacGregor, Hayley; Fooks, Anthony R.; Jones, Kate E.; Restif, Olivier; Dechmann, Dina; Hayman, David T. S.; Baker, Kate S.; Peel, Alison J.; Kamins, Alexandra O.; Fahr, Jakob; Ntiamoa-Baidu, Yaa; Suu-Ire, Richard; Breiman, Robert F.; Epstein, Jonathan H.; Field, Hume E.; Cunningham, Andrew A.
2012-01-01
Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation. PMID:22966143
Chlamydia cell biology and pathogenesis.
Elwell, Cherilyn; Mirrashidi, Kathleen; Engel, Joanne
2016-06-01
Chlamydia spp. are important causes of human disease for which no effective vaccine exists. These obligate intracellular pathogens replicate in a specialized membrane compartment and use a large arsenal of secreted effectors to survive in the hostile intracellular environment of the host. In this Review, we summarize the progress in decoding the interactions between Chlamydia spp. and their hosts that has been made possible by recent technological advances in chlamydial proteomics and genetics. The field is now poised to decipher the molecular mechanisms that underlie the intimate interactions between Chlamydia spp. and their hosts, which will open up many exciting avenues of research for these medically important pathogens.
Chlamydia cell biology and pathogenesis
Elwell, Cherilyn; Mirrashidi, Kathleen; Engel, Joanne
2016-01-01
Chlamydia spp. are important causes of human disease for which no effective vaccine exists. These obligate intracellular pathogens replicate in a specialized membrane compartment and use a large arsenal of secreted effectors to survive in the hostile intracellular environment of the host. In this Review, we summarize the progress in decoding the interactions between Chlamydia spp. and their hosts that has been made possible by recent technological advances in chlamydial proteomics and genetics. The field is now poised to decipher the molecular mechanisms that underlie the intimate interactions between Chlamydia spp. and their hosts, which will open up many exciting avenues of research for these medically important pathogens. PMID:27108705
Draft genome sequence of Enterococcus faecium strain LMG 8148.
Michiels, Joran E; Van den Bergh, Bram; Fauvart, Maarten; Michiels, Jan
2016-01-01
Enterococcus faecium, traditionally considered a harmless gut commensal, is emerging as an important nosocomial pathogen showing increasing rates of multidrug resistance. We report the draft genome sequence of E. faecium strain LMG 8148, isolated in 1968 from a human in Gothenburg, Sweden. The draft genome has a total length of 2,697,490 bp, a GC-content of 38.3 %, and 2,402 predicted protein-coding sequences. The isolation of this strain predates the emergence of E. faecium as a nosocomial pathogen. Consequently, its genome can be useful in comparative genomic studies investigating the evolution of E. faecium as a pathogen.
Nano/Micro and Spectroscopic Approaches to Food Pathogen Detection
NASA Astrophysics Data System (ADS)
Cho, Il-Hoon; Radadia, Adarsh D.; Farrokhzad, Khashayar; Ximenes, Eduardo; Bae, Euiwon; Singh, Atul K.; Oliver, Haley; Ladisch, Michael; Bhunia, Arun; Applegate, Bruce; Mauer, Lisa; Bashir, Rashid; Irudayaraj, Joseph
2014-06-01
Despite continuing research efforts, timely and simple pathogen detection with a high degree of sensitivity and specificity remains an elusive goal. Given the recent explosion of sensor technologies, significant strides have been made in addressing the various nuances of this important global challenge that affects not only the food industry but also human health. In this review, we provide a summary of the various ongoing efforts in pathogen detection and sample preparation in areas related to Fourier transform infrared and Raman spectroscopy, light scattering, phage display, micro/nanodevices, and nanoparticle biosensors. We also discuss the advantages and potential limitations of the detection methods and suggest next steps for further consideration.
Prevalence of Rickettsia species in Dermacentor variabilis ticks from Ontario, Canada.
Wood, Heidi; Dillon, Liz; Patel, Samir N; Ralevski, Filip
2016-07-01
Relatively little is known about the prevalence of rickettsial species in Dermacentor ticks in eastern Canada. In this study, Dermacentor ticks from the province of Ontario, Canada, were tested for the presence of spotted fever group rickettsial (SFGR) species, Coxiella burnetii and Francisella tularensis. Rickettsia rickettsii was not detected in any ticks tested, but R. montanensis was detected at a prevalence of 2.2% in D. variabilis (17/778). Two other SFGR species, R. parkeri and Candidatus R. andeanae, were detected individually in 2 Amblyomma maculatum ticks. Rickettsia peacockii, a non-pathogenic endosymbiont, was detected in two D. andersonii ticks. Given the highly abundant nature of D. variabilis, surveillance for human pathogens in this species of tick has important public health implications, but the lack of detection of known human pathogens indicates a low risk of infection via this tick species in Ontario. However, the detection of R. parkeri in an adventive A. maculatum tick indicates that health care providers should be aware of the possibility of spotted fever rickettsioses in individuals with a history of travel outside of Ontario and symptoms compatible with a spotted fever rickettsiosis. Coxiella burnetii and Francisella tularensis, human pathogens also potentially transmitted by D. variabilis, were not detected in a subset of the ticks. Copyright © 2016 Elsevier GmbH. All rights reserved.
Evolution of Influenza A Virus by Mutation and Re-Assortment
Shao, Wenhan; Li, Xinxin; Goraya, Mohsan Ullah; Wang, Song; Chen, Ji-Long
2017-01-01
Influenza A virus (IAV), a highly infectious respiratory pathogen, has continued to be a significant threat to global public health. To complete their life cycle, influenza viruses have evolved multiple strategies to interact with a host. A large number of studies have revealed that the evolution of influenza A virus is mainly mediated through the mutation of the virus itself and the re-assortment of viral genomes derived from various strains. The evolution of influenza A virus through these mechanisms causes worldwide annual epidemics and occasional pandemics. Importantly, influenza A virus can evolve from an animal infected pathogen to a human infected pathogen. The highly pathogenic influenza virus has resulted in stupendous economic losses due to its morbidity and mortality both in human and animals. Influenza viruses fall into a category of viruses that can cause zoonotic infection with stable adaptation to human, leading to sustained horizontal transmission. The rapid mutations of influenza A virus result in the loss of vaccine optimal efficacy, and challenge the complete eradication of the virus. In this review, we highlight the current understanding of influenza A virus evolution caused by the mutation and re-assortment of viral genomes. In addition, we discuss the specific mechanisms by which the virus evolves. PMID:28783091
Vergara-Alert, Júlia; Vidal, Enric; Bensaid, Albert; Segalés, Joaquim
2017-06-01
Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013-2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV), which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV), associated with severe pneumonia, arose in the Kingdom of Saudi Arabia. Until December 2016, MERS has accounted for more than 1800 cases and 35% fatality rate. Finding an animal model of disease is key to develop vaccines or antivirals against such emerging pathogens and to understand its pathogenesis. Knowledge of the potential role of domestic livestock and other animal species in the transmission of pathogens is of importance to understand the epidemiology of the disease. Little is known about MERS-CoV animal host range. In this paper, experimental data on potential hosts for MERS-CoV is reviewed. Advantages and limitations of different animal models are evaluated in relation to viral pathogenesis and transmission studies. Finally, the relevance of potential new target species is discussed.
The use of pseudotypes to study viruses, virus sero-epidemiology and vaccination.
Bentley, Emma M; Mather, Stuart T; Temperton, Nigel J
2015-06-12
The globalization of the world's economies, accompanied by increasing international travel, changing climates, altered human behaviour and demographics is leading to the emergence of different viral diseases, many of which are highly pathogenic and hence are considered of great public and animal health importance. To undertake basic research and therapeutic development, many of these viruses require handling by highly trained staff in BSL-3/4 facilities not readily available to the majority of the global R&D community. In order to circumvent the enhanced biosafety requirement, the development of non-pathogenic, replication-defective pseudotyped viruses is an effective and established solution to permit the study of many aspects of virus biology in a low containment biosafety level (BSL)-1/2 laboratory. Under the spectre of the unfolding Ebola crisis, this timely conference (the second to be organised by the Viral Pseudotype Unit, www.viralpseudotypeunit.info*) discusses the recent advances in pseudotype technology and how it is revolutionizing the study of important human and animal pathogens (human and avian influenza viruses, rabies/lyssaviruses, HIV, Marburg and Ebola viruses). Key topics addressed in this conference include the exploitation of pseudotypes for serology and serosurveillance, immunogenicity testing of current and next-generation vaccines and new pseudotype assay formats (multiplexing, kit development). The first pseudotype-focused Euroscicon conference organised by the Viral Pseudotype Unit was recently reviewed [1]. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.
Mire, Chad E.; Satterfield, Benjamin A.; Geisbert, Joan B.; Agans, Krystle N.; Borisevich, Viktoriya; Yan, Lianying; Chan, Yee-Peng; Cross, Robert W.; Fenton, Karla A.; Broder, Christopher C.; Geisbert, Thomas W.
2016-01-01
Nipah virus (NiV) is a paramyxovirus that causes severe disease in humans and animals. There are two distinct strains of NiV, Malaysia (NiVM) and Bangladesh (NiVB). Differences in transmission patterns and mortality rates suggest that NiVB may be more pathogenic than NiVM. To investigate pathogenic differences between strains, 4 African green monkeys (AGM) were exposed to NiVM and 4 AGMs were exposed to NiVB. While NiVB was uniformly lethal, only 50% of NiVM-infected animals succumbed to infection. Histopathology of lungs and spleens from NiVB-infected AGMs was significantly more severe than NiVM-infected animals. Importantly, a second study utilizing 11 AGMs showed that the therapeutic window for human monoclonal antibody m102.4, previously shown to rescue AGMs from NiVM infection, was much shorter in NiVB-infected AGMs. Together, these data show that NiVB is more pathogenic in AGMs under identical experimental conditions and suggests that postexposure treatments may need to be NiV strain specific for optimal efficacy. PMID:27484128
Kirsch, Petra; Jores, Jörg; Wieler, Lothar H
2004-01-01
Many bacterial virulence attributes, like toxins, adhesins, invasins, iron uptake systems, are encoded within specific regions of the bacterial genome. These in size varying regions are termed pathogenicity islands (PAIs) since they confer pathogenic properties to the respective micro-organism. Per definition PAIs are exclusively found in pathogenic strains and are often inserted near transfer-RNA genes. Nevertheless, non-pathogenic bacteria also possess foreign DNA elements that confer advantageous features, leading to improved fitness. These additional DNA elements as well as PAIs are termed genomic islands and were acquired during bacterial evolution. Significant G+C content deviation in pathogenicity islands with respect to the rest of the genome, the presence of direct repeat sequences at the flanking regions, the presence of integrase gene determinants as other mobility features,the particular insertion site (tRNA gene) as well as the observed genetic instability suggests that pathogenicity islands were acquired by horizontal gene transfer. PAIs are the fascinating proof of the plasticity of bacterial genomes. PAIs were originally described in human pathogenic Escherichia (E.) coli strains. In the meantime PAIs have been found in various pathogenic bacteria of humans, animals and even plants. The Locus of Enterocyte Effacement (LEE) is one particular widely distributed PAI of E coli. In addition, it also confers pathogenicity to the related species Citrobacter (C.) rodentium and Escherichia (E.) alvei. The LEE is an important virulence feature of several animal pathogens. It is an obligate PAI of all animal and human enteropathogenic E. coli (EPEC), and most enterohaemorrhegic E. coli (EHEC) also harbor the LEE. The LEE encodes a type III secretion system, an adhesion (intimin) that mediates the intimate contact between the bacterium and the epithelial cell, as well as various proteins which are secreted via the type III secretion system. The LEE encoded virulence features are responsible for the formation of so called attaching and effacing (AE) lesions in the intestinal epithelium. Due to its wide distribution in animal pathogens, LEE encoded antigens are suitable vaccine antigens. Acquisition and structure of the LEE pathogenicity island is the crucial point of numerous investigations. However, the evolution of the LEE, its origin and further spread in E. coli, are far from being resolved.
Hall, Miquette; Chattaway, Marie A.; Reuter, Sandra; Savin, Cyril; Strauch, Eckhard; Carniel, Elisabeth; Connor, Thomas; Van Damme, Inge; Rajakaruna, Lakshani; Rajendram, Dunstan; Jenkins, Claire; Thomson, Nicholas R.
2014-01-01
The genus Yersinia is a large and diverse bacterial genus consisting of human-pathogenic species, a fish-pathogenic species, and a large number of environmental species. Recently, the phylogenetic and population structure of the entire genus was elucidated through the genome sequence data of 241 strains encompassing every known species in the genus. Here we report the mining of this enormous data set to create a multilocus sequence typing-based scheme that can identify Yersinia strains to the species level to a level of resolution equal to that for whole-genome sequencing. Our assay is designed to be able to accurately subtype the important human-pathogenic species Yersinia enterocolitica to whole-genome resolution levels. We also report the validation of the scheme on 386 strains from reference laboratory collections across Europe. We propose that the scheme is an important molecular typing system to allow accurate and reproducible identification of Yersinia isolates to the species level, a process often inconsistent in nonspecialist laboratories. Additionally, our assay is the most phylogenetically informative typing scheme available for Y. enterocolitica. PMID:25339391
The International Congress on Toxoplasmosis.
Weiss, Louis M; Kim, Kami
2004-03-09
Toxoplasma gondii is an important pathogen in both veterinary and human medicine. Infection during pregnancy can result in fetal transmission and a congenital infection syndrome. In immune-compromised hosts reactivation of latent infection can result in encephalitis. It has been estimated that as many as one-third of the human population harbours this zoonosis. The Seventh International Congress on Toxoplasmosis, organised by Louis M. Weiss and Kami Kim (Albert Einstein College of Medicine, Bronx, NY) was held on 23-27 May 2003 in Tarrytown, New York. At this meeting 133 investigators from 14 countries presented 102 papers on research involving this model Apicomplexan parasite. The presented research covered the epidemiology, immunology, cellular biology and molecular biology of this pathogen.
Use of media and public-domain Internet sources for detection and assessment of plant health threats
Thomas, Carla S.; Nelson, Noele P.; Jahn, Gary C.; Niu, Tianchan; Hartley, David M.
2011-01-01
Event-based biosurveillance is a recognized approach to early warning and situational awareness of emerging health threats. In this study, we build upon previous human and animal health work to develop a new approach to plant pest and pathogen surveillance. We show that monitoring public domain electronic media for indications and warning of epidemics and associated social disruption can provide information about the emergence and progression of plant pest infestation or disease outbreak. The approach is illustrated using a case study, which describes a plant pest and pathogen epidemic in China and Vietnam from February 2006 to December 2007, and the role of ducks in contributing to zoonotic virus spread in birds and humans. This approach could be used as a complementary method to traditional plant pest and pathogen surveillance to aid global and national plant protection officials and political leaders in early detection and timely response to significant biological threats to plant health, economic vitality, and social stability. This study documents the inter-relatedness of health in human, animal, and plant populations and emphasizes the importance of plant health surveillance. PMID:24149031
Thomas, Carla S; Nelson, Noele P; Jahn, Gary C; Niu, Tianchan; Hartley, David M
2011-09-05
Event-based biosurveillance is a recognized approach to early warning and situational awareness of emerging health threats. In this study, we build upon previous human and animal health work to develop a new approach to plant pest and pathogen surveillance. We show that monitoring public domain electronic media for indications and warning of epidemics and associated social disruption can provide information about the emergence and progression of plant pest infestation or disease outbreak. The approach is illustrated using a case study, which describes a plant pest and pathogen epidemic in China and Vietnam from February 2006 to December 2007, and the role of ducks in contributing to zoonotic virus spread in birds and humans. This approach could be used as a complementary method to traditional plant pest and pathogen surveillance to aid global and national plant protection officials and political leaders in early detection and timely response to significant biological threats to plant health, economic vitality, and social stability. This study documents the inter-relatedness of health in human, animal, and plant populations and emphasizes the importance of plant health surveillance.
Xu, Jianping; Yan, Zhun; Guo, Hong
2009-06-01
The inheritance of mitochondrial genes and genomes are uniparental in most sexual eukaryotes. This pattern of inheritance makes mitochondrial genomes in natural populations effectively clonal. Here, we examined the mitochondrial population genetics of the emerging human pathogenic fungus Cryptococcus gattii. The DNA sequences for five mitochondrial DNA fragments were obtained from each of 50 isolates belonging to two evolutionary divergent lineages, VGI and VGII. Our analyses revealed a greater sequence diversity within VGI than that within VGII, consistent with observations of the nuclear genes. The combined analyses of all five gene fragments indicated significant divergence between VGI and VGII. However, the five individual genealogies showed different relationships among the isolates, consistent with recent hybridization and mitochondrial gene transfer between the two lineages. Population genetic analyses of the multilocus data identified evidence for predominantly clonal mitochondrial population structures within both lineages. Interestingly, there were clear signatures of recombination among mitochondrial genes within the VGII lineage. Our analyses suggest historical mitochondrial genome divergence within C. gattii, but there is evidence for recent hybridization and recombination in the mitochondrial genome of this important human yeast pathogen.
Zika Virus as an Emerging Global Pathogen
Beckham, J. David; Pastula, Daniel M.; Massey, Aaron; Tyler, Kenneth L.
2016-01-01
IMPORTANCE Zika virus (ZIKV) is an emerging arthropod-borne virus (arbovirus) in the genus Flavivirus that has caused a widespread outbreak of febrile illness, is associated with neurological disease, and has spread across the Pacific to the Americas in a short period. OBSERVATIONS In this review, we discuss what is currently known about ZIKV, neuroimmunologic complications, and the impact on global human health. Zika virus spread across Africa and Asia in part owing to unique genomic evolutionary conditions and pressures resulting in specific human disease manifestations, complications, and pathogenesis. Recent data suggest that acute ZIKV infection in pregnant women may result in acute infection of fetal tissue and brain tissue, causing microcephaly and potentially severe debilitation of the infant or even death of the fetus. Cases of acute ZIKV are also associated with Guillain-Barré syndrome. With the increased number of cases, new complications such as ocular involvement and sexual transmission have been reported. CONCLUSIONS AND RELEVANCE Zika virus is an emerging viral pathogen with significant consequences on human health throughout the world. Ongoing research into this pathogen is urgently needed to produce viable vaccine and therapeutic options. PMID:27183312
Swe, Pearl M; Zakrzewski, Martha; Kelly, Andrew; Krause, Lutz; Fischer, Katja
2014-01-01
The resident skin microbiota plays an important role in restricting pathogenic bacteria, thereby protecting the host. Scabies mites (Sarcoptes scabiei) are thought to promote bacterial infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. Epidemiological studies in humans confirm increased incidence of impetigo, generally caused by Staphylococcus aureus and Streptococcus pyogenes, secondary to the epidermal infestation with the parasitic mite. It is therefore possible that mite infestation could alter the healthy skin microbiota making way for the opportunistic pathogens. A longitudinal study to test this hypothesis in humans is near impossible due to ethical reasons. In a porcine model we generated scabies infestations closely resembling the disease manifestation in humans and investigated the scabies associated changes in the skin microbiota over the course of a mite infestation. In a 21 week trial, skin scrapings were collected from pigs infected with S. scabies var. suis and scabies-free control animals. A total of 96 skin scrapings were collected before, during infection and after acaricide treatment, and analyzed by bacterial 16S rDNA tag-encoded FLX-titanium amplicon pyrosequencing. We found significant changes in the epidermal microbiota, in particular a dramatic increase in Staphylococcus correlating with the onset of mite infestation in animals challenged with scabies mites. This increase persisted beyond treatment from mite infection and healing of skin. Furthermore, the staphylococci population shifted from the commensal S. hominis on the healthy skin prior to scabies mite challenge to S. chromogenes, which is increasingly recognized as being pathogenic, coinciding with scabies infection in pigs. In contrast, all animals in the scabies-free cohort remained relatively free of Staphylococcus throughout the trial. This is the first experimental in vivo evidence supporting previous assumptions that establishment of pathogens follow scabies infection. Our findings provide an explanation for a biologically important aspect of the disease pathogenesis. The methods developed from this pig trial will serve as a guide to analyze human clinical samples. Studies building on this will offer implications for development of novel intervention strategies against the mites and the secondary infections.
Swe, Pearl M.; Zakrzewski, Martha; Kelly, Andrew; Krause, Lutz; Fischer, Katja
2014-01-01
Background The resident skin microbiota plays an important role in restricting pathogenic bacteria, thereby protecting the host. Scabies mites (Sarcoptes scabiei) are thought to promote bacterial infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. Epidemiological studies in humans confirm increased incidence of impetigo, generally caused by Staphylococcus aureus and Streptococcus pyogenes, secondary to the epidermal infestation with the parasitic mite. It is therefore possible that mite infestation could alter the healthy skin microbiota making way for the opportunistic pathogens. A longitudinal study to test this hypothesis in humans is near impossible due to ethical reasons. In a porcine model we generated scabies infestations closely resembling the disease manifestation in humans and investigated the scabies associated changes in the skin microbiota over the course of a mite infestation. Methodology/Principal Findings In a 21 week trial, skin scrapings were collected from pigs infected with S. scabies var. suis and scabies-free control animals. A total of 96 skin scrapings were collected before, during infection and after acaricide treatment, and analyzed by bacterial 16S rDNA tag-encoded FLX-titanium amplicon pyrosequencing. We found significant changes in the epidermal microbiota, in particular a dramatic increase in Staphylococcus correlating with the onset of mite infestation in animals challenged with scabies mites. This increase persisted beyond treatment from mite infection and healing of skin. Furthermore, the staphylococci population shifted from the commensal S. hominis on the healthy skin prior to scabies mite challenge to S. chromogenes, which is increasingly recognized as being pathogenic, coinciding with scabies infection in pigs. In contrast, all animals in the scabies-free cohort remained relatively free of Staphylococcus throughout the trial. Conclusions/Significance This is the first experimental in vivo evidence supporting previous assumptions that establishment of pathogens follow scabies infection. Our findings provide an explanation for a biologically important aspect of the disease pathogenesis. The methods developed from this pig trial will serve as a guide to analyze human clinical samples. Studies building on this will offer implications for development of novel intervention strategies against the mites and the secondary infections. PMID:24875186
The medically important aerobic actinomycetes: epidemiology and microbiology.
McNeil, M M; Brown, J M
1994-01-01
The aerobic actinomycetes are soil-inhabiting microorganisms that occur worldwide. In 1888, Nocard first recognized the pathogenic potential of this group of microorganisms. Since then, several aerobic actinomycetes have been a major source of interest for the commercial drug industry and have proved to be extremely useful microorganisms for producing novel antimicrobial agents. They have also been well known as potential veterinary pathogens affecting many different animal species. The medically important aerobic actinomycetes may cause significant morbidity and mortality, in particular in highly susceptible severely immunocompromised patients, including transplant recipients and patients infected with human immunodeficiency virus. However, the diagnosis of these infections may be difficult, and effective antimicrobial therapy may be complicated by antimicrobial resistance. The taxonomy of these microorganisms has been problematic. In recent revisions of their classification, new pathogenic species have been recognized. The development of additional and more reliable diagnostic tests and of a standardized method for antimicrobial susceptibility testing and the application of molecular techniques for the diagnosis and subtyping of these microorganisms are needed to better diagnose and treat infected patients and to identify effective control measures for these unusual pathogens. We review the epidemiology and microbiology of the major medically important aerobic actinomycetes. Images PMID:7923055
Pathogen transport in groundwater systems: contrasts with traditional solute transport
NASA Astrophysics Data System (ADS)
Hunt, Randall J.; Johnson, William P.
2017-06-01
Water quality affects many aspects of water availability, from precluding use to societal perceptions of fit-for-purpose. Pathogen source and transport processes are drivers of water quality because they have been responsible for numerous outbreaks resulting in large economic losses due to illness and, in some cases, loss of life. Outbreaks result from very small exposure (e.g., less than 20 viruses) from very strong sources (e.g., trillions of viruses shed by a single infected individual). Thus, unlike solute contaminants, an acute exposure to a very small amount of contaminated water can cause immediate adverse health effects. Similarly, pathogens are larger than solutes. Thus, interactions with surfaces and settling become important even as processes important for solutes such as diffusion become less important. These differences are articulated in "Colloid Filtration Theory", a separate branch of pore-scale transport. Consequently, understanding pathogen processes requires changes in how groundwater systems are typically characterized, where the focus is on the leading edges of plumes and preferential flow paths, even if such features move only a very small fraction of the aquifer flow. Moreover, the relatively short survival times of pathogens in the subsurface require greater attention to very fast (<10 year) flow paths. By better understanding the differences between pathogen and solute transport mechanisms discussed here, a more encompassing view of water quality and source water protection is attained. With this more holistic view and theoretical understanding, better evaluations can be made regarding drinking water vulnerability and the relation between groundwater and human health.
2012-01-01
Background Streptococcus canis is an important opportunistic pathogen of dogs and cats that can also infect a wide range of additional mammals including cows where it can cause mastitis. It is also an emerging human pathogen. Results Here we provide characterization of the first genome sequence for this species, strain FSL S3-227 (milk isolate from a cow with an intra-mammary infection). A diverse array of putative virulence factors was encoded by the S. canis FSL S3-227 genome. Approximately 75% of these gene sequences were homologous to known Streptococcal virulence factors involved in invasion, evasion, and colonization. Present in the genome are multiple potentially mobile genetic elements (MGEs) [plasmid, phage, integrative conjugative element (ICE)] and comparison to other species provided convincing evidence for lateral gene transfer (LGT) between S. canis and two additional bovine mastitis causing pathogens (Streptococcus agalactiae, and Streptococcus dysgalactiae subsp. dysgalactiae), with this transfer possibly contributing to host adaptation. Population structure among isolates obtained from Europe and USA [bovine = 56, canine = 26, and feline = 1] was explored. Ribotyping of all isolates and multi locus sequence typing (MLST) of a subset of the isolates (n = 45) detected significant differentiation between bovine and canine isolates (Fisher exact test: P = 0.0000 [ribotypes], P = 0.0030 [sequence types]), suggesting possible host adaptation of some genotypes. Concurrently, the ancestral clonal complex (54% of isolates) occurred in many tissue types, all hosts, and all geographic locations suggesting the possibility of a wide and diverse niche. Conclusion This study provides evidence highlighting the importance of LGT in the evolution of the bacteria S. canis, specifically, its possible role in host adaptation and acquisition of virulence factors. Furthermore, recent LGT detected between S. canis and human bacteria (Streptococcus urinalis) is cause for concern, as it highlights the possibility for continued acquisition of human virulence factors for this emerging zoonotic pathogen. PMID:23244770
Exploring Other Genomes: Bacteria.
ERIC Educational Resources Information Center
Flannery, Maura C.
2001-01-01
Points out the importance of genomes other than the human genome project and provides information on the identified bacterial genomes Pseudomonas aeuroginosa, Leprosy, Cholera, Meningitis, Tuberculosis, Bubonic Plague, and plant pathogens. Considers the computer's use in genome studies. (Contains 14 references.) (YDS)
Molecular phylogeny of Entomophthoromycota
USDA-ARS?s Scientific Manuscript database
The Entomophthoromycota is a ubiquitous group of fungi best known as pathogens of a wide variety of economically important insect pests, arachnids, and other soil invertebrates, a smaller number of parasites of reptiles, vertebrates (including humans), macromycetes, fern gametophytes, and desmid alg...
Parasites and fungi as risk factors for human and animal health.
Góralska, Katarzyna; Błaszkowska, Joanna
2015-01-01
Recent literature data suggests that parasitic and fungal diseases, which pose a threat to both human and animal health, remain a clinical, diagnostic and therapeutic problem. Attention is increasingly paid to the role played by natural microbiota in maintaining homeostasis in humans. A particular emphasis is placed on the possibility of manipulating the human microbiota (permanent, transient, pathogenic) and macrobiota (e.g., Trichuris suis) to support the treatment of selected diseases such as Crohn's disease, obesity, diabetes and cancer. Emphasis is placed on important medical species whose infections not only impair health but can also be life threatening, such as Plasmodium falciparum, Echinococcus multilocularis and Baylisascaris procyonis, which expand into areas which have so far been uninhabited. This article also presents the epidemiology, diagnosis and treatment of opportunistic parasitoses imported from the tropics, which spread across large groups of people through human-to-human transmission (Enterobius vermicularis, Sarcoptes scabiei). It also discusses the problem of environmentally-conditioned parasitoses, particularly their etiological factors associated with food contaminated with invasive forms (Trichinella sp., Toxoplasma gondii). The analysis also concerns the presence of developmental forms of geohelminths (Toxocara sp.) and ectoparasites (ticks), which are vectors of serious human diseases (Lyme borreliosis, anaplasmosis, babesiosis), in the environment. Mycological topics contains rare cases of mycoses environmentally conditioned (CNS aspergillosis) and transmissions of these pathogens in a population of hospitalized individuals, as well as seeking new methods used to treat mycoses.
Lee, Cheonghoon; Agidi, Senyo; Marion, Jason W; Lee, Jiyoung
2012-08-01
The genus Arcobacter has been associated with human illness and fecal contamination by humans and animals. To better characterize the health risk posed by this emerging waterborne pathogen, we investigated the occurrence of Arcobacter spp. in Lake Erie beach waters. During the summer of 2010, water samples were collected 35 times from the Euclid, Villa Angela, and Headlands (East and West) beaches, located along Ohio's Lake Erie coast. After sample concentration, Arcobacter was quantified by real-time PCR targeting the Arcobacter 23S rRNA gene. Other fecal genetic markers (Bacteroides 16S rRNA gene [HuBac], Escherichia coli uidA gene, Enterococcus 23S rRNA gene, and tetracycline resistance genes) were also assessed. Arcobacter was detected frequently at all beaches, and both the occurrence and densities of Arcobacter spp. were higher at the Euclid and Villa Angela beaches (with higher levels of fecal contamination) than at the East and West Headlands beaches. The Arcobacter density in Lake Erie beach water was significantly correlated with the human-specific fecal marker HuBac according to Spearman's correlation analysis (r = 0.592; P < 0.001). Phylogenetic analysis demonstrated that most of the identified Arcobacter sequences were closely related to Arcobacter cryaerophilus, which is known to cause gastrointestinal diseases in humans. Since human-pathogenic Arcobacter spp. are linked to human-associated fecal sources, it is important to identify and manage the human-associated contamination sources for the prevention of Arcobacter-associated public health risks at Lake Erie beaches.
Fernandez, Carla; Lubar, Aristea A; Vinetz, Joseph M; Matthias, Michael A
2018-06-25
Leptospira licerasiae serovar Varillal, a group II intermediate pathogen species/serovar discovered in the Peruvian Amazon city of Iquitos, is commonly recognized in this region by sera from humans (at least 40% seroprevalence) without a known clinical history of leptospirosis. This high frequency of human seroreactivity remains unexplained. To test the hypothesis that the oral route of infection might explain the high rate of human seroreactivity against L. licerasiae , an experimental infection model using Rattus norvegicus was developed, given that rats were one of the original reservoir hosts identified as being colonized by this leptospire. Sprague-Dawley rats were experimentally exposed via mucosa, direct gastric gavage, or parenteral inoculation with nine different isolates of L. licerasiae originally isolated from Peruvian humans, peridomiciliary rodents, and wildlife. As shown by quantitative polymerase chain reaction of kidney tissue, Leptospira infection via these routes of infection was equally successful. Importantly, the data show that L. licerasiae infects R. norvegicus via the oral route demonstration, leading to renal colonization. Not only do these findings confirm the infectiousness of group II Leptospira , but also they underscore the potential importance of oral as well as mucosal and transcutaneous routes of Leptospira infection.
Mina, Michael J.; McCullers, Jonathan A.; Klugman, Keith P.
2014-01-01
ABSTRACT Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. PMID:24549845
Global Warming Will Bring New Fungal Diseases for Mammals
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
The poultry red mite (Dermanyssus gallinae): a potential vector of pathogenic agents.
Valiente Moro, Claire; De Luna, Carlos J; Tod, Alexander; Guy, Jonathan H; Sparagano, Olivier A E; Zenner, Lionel
2009-06-01
The poultry red mite, D. gallinae has been involved in the transmission of many pathogenic agents, responsible for serious diseases both in animals and humans. Nowadays, few effective methods are available to control the ectoparasite in poultry farms. Consequently, this is an emerging problem which must be taken into account to maintain good health in commercial egg production. This paper addresses the vector capacity of the ectoparasite with special emphasis on salmonellae, pathogenic agents responsible for many of the most important outbreaks of food-borne diseases worlwide. It has been experimentally shown that D. gallinae could act as a biological vector of S. enteritidis and natural carriage of these bacteria by the mite on poultry premises has also been reported. It was also found that D. gallinae carried other pathogens such as E. coli, Shigella sp., and Staphylococcus, thus increasing the list of pathogenic agents potentially transmitted by the mite.
Cationic Antimicrobial Peptide Resistance Mechanisms of Streptococcal Pathogens
LaRock, Christopher N.; Nizet, Victor
2015-01-01
Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. PMID:25701232
Pathogenic adaptations to host-derived antibacterial copper
Chaturvedi, Kaveri S.; Henderson, Jeffrey P.
2014-01-01
Recent findings suggest that both host and pathogen manipulate copper content in infected host niches during infections. In this review, we summarize recent developments that implicate copper resistance as an important determinant of bacterial fitness at the host-pathogen interface. An essential mammalian nutrient, copper cycles between copper (I) (Cu+) in its reduced form and copper (II) (Cu2+) in its oxidized form under physiologic conditions. Cu+ is significantly more bactericidal than Cu2+ due to its ability to freely penetrate bacterial membranes and inactivate intracellular iron-sulfur clusters. Copper ions can also catalyze reactive oxygen species (ROS) generation, which may further contribute to their toxicity. Transporters, chaperones, redox proteins, receptors and transcription factors and even siderophores affect copper accumulation and distribution in both pathogenic microbes and their human hosts. This review will briefly cover evidence for copper as a mammalian antibacterial effector, the possible reasons for this toxicity, and pathogenic resistance mechanisms directed against it. PMID:24551598
Reye, Anna L; Stegniy, Valentina; Mishaeva, Nina P; Velhin, Sviataslau; Hübschen, Judith M; Ignatyev, George; Muller, Claude P
2013-01-01
Worldwide, ticks are important vectors of human and animal pathogens. Besides Lyme Borreliosis, a variety of other bacterial and protozoal tick-borne infections are of medical interest in Europe. In this study, 553 questing and feeding Ixodes ricinus (n = 327) and Dermacentor reticulatus ticks (n = 226) were analysed by PCR for Borrelia, Rickettsia, Anaplasma, Coxiella, Francisella and Babesia species. Overall, the pathogen prevalence in ticks was 30.6% for I. ricinus and 45.6% for D. reticulatus. The majority of infections were caused by members of the spotted-fever group rickettsiae (24.4%), 9.4% of ticks were positive for Borrelia burgdorferi sensu lato, with Borrelia afzelii being the most frequently detected species (40.4%). Pathogens with low prevalence rates in ticks were Anaplasma phagocytophilum (2.2%), Coxiella burnetii (0.9%), Francisella tularensis subspecies (0.7%), Bartonella henselae (0.7%), Babesia microti (0.5%) and Babesia venatorum (0.4%). On a regional level, hotspots of pathogens were identified for A. phagocytophilum (12.5-17.2%), F. tularensis ssp. (5.5%) and C. burnetii (9.1%), suggesting established zoonotic cycles of these pathogens at least at these sites. Our survey revealed a high burden of tick-borne pathogens in questing and feeding I. ricinus and D. reticulatus ticks collected in different regions in Belarus, indicating a potential risk for humans and animals. Identified hotspots of infected ticks should be included in future surveillance studies, especially when F. tularensis ssp. and C. burnetii are involved.
Contamination of produce with human pathogens: sources and solutions
USDA-ARS?s Scientific Manuscript database
Outbreaks of foodborne illnesses associated with the presence of human pathogens have led to increased concern about the prevalence of pathogens in the environment and the vulnerability of fresh produce to contamination by these pathogens. As the FDA strives to mandate treatments to reduce pathogen...
Vayssier-Taussat, Muriel; Kazimirova, Maria; Hubalek, Zdenek; Hornok, Sándor; Farkas, Robert; Cosson, Jean-François; Bonnet, Sarah; Vourch, Gwenaël; Gasqui, Patrick; Mihalca, Andrei Daniel; Plantard, Olivier; Silaghi, Cornelia; Cutler, Sally; Rizzoli, Annapaola
2015-01-01
Ticks, as vectors of several notorious zoonotic pathogens, represent an important and increasing threat for human and animal health in Europe. Recent applications of new technology revealed the complexity of the tick microbiome, which may affect its vectorial capacity. Appreciation of these complex systems is expanding our understanding of tick-borne pathogens, leading us to evolve a more integrated view that embraces the ‘pathobiome’; the pathogenic agent integrated within its abiotic and biotic environments. In this review, we will explore how this new vision will revolutionize our understanding of tick-borne diseases. We will discuss the implications in terms of future research approaches that will enable us to efficiently prevent and control the threat posed by ticks. PMID:26610021
Ras-Mediated Signal Transduction and Virulence in Human Pathogenic Fungi
Fortwendel, Jarrod R.
2013-01-01
Signal transduction pathways regulating growth and stress responses are areas of significant study in the effort to delineate pathogenic mechanisms of fungi. In-depth knowledge of signal transduction events deepens our understanding of how a fungal pathogen is able to sense changes in the environment and respond accordingly by modulation of gene expression and re-organization of cellular activities to optimize fitness. Members of the Ras protein family are important regulators of growth and differentiation in eukaryotic organisms, and have been the focus of numerous studies exploring fungal pathogenesis. Here, the current data regarding Ras signal transduction are reviewed for three major pathogenic fungi: Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus. Particular emphasis is placed on Ras-protein interactions during control of morphogenesis, stress response and virulence. PMID:24855584
Pathogenic Mechanisms and Host Interactions in Staphylococcus epidermidis Device-Related Infection.
Sabaté Brescó, Marina; Harris, Llinos G; Thompson, Keith; Stanic, Barbara; Morgenstern, Mario; O'Mahony, Liam; Richards, R Geoff; Moriarty, T Fintan
2017-01-01
Staphylococcus epidermidis is a permanent member of the normal human microbiota, commonly found on skin and mucous membranes. By adhering to tissue surface moieties of the host via specific adhesins, S. epidermidis is capable of establishing a lifelong commensal relationship with humans that begins early in life. In its role as a commensal organism, S. epidermidis is thought to provide benefits to human host, including out-competing more virulent pathogens. However, largely due to its capacity to form biofilm on implanted foreign bodies, S. epidermidis has emerged as an important opportunistic pathogen in patients receiving medical devices. S. epidermidis causes approximately 20% of all orthopedic device-related infections (ODRIs), increasing up to 50% in late-developing infections. Despite this prevalence, it remains underrepresented in the scientific literature, in particular lagging behind the study of the S. aureus . This review aims to provide an overview of the interactions of S. epidermidis with the human host, both as a commensal and as a pathogen. The mechanisms retained by S. epidermidis that enable colonization of human skin as well as invasive infection, will be described, with a particular focus upon biofilm formation. The host immune responses to these infections are also described, including how S. epidermidis seems to trigger low levels of pro-inflammatory cytokines and high levels of interleukin-10, which may contribute to the sub-acute and persistent nature often associated with these infections. The adaptive immune response to S. epidermidis remains poorly described, and represents an area which may provide significant new discoveries in the coming years.
Laroche, Maureen; Berenger, Jean-Michel; Mediannikov, Oleg; Raoult, Didier; Parola, Philippe
2017-01-01
Background Among the Reduviidae family, triatomines are giant blood-sucking bugs. They are well known in Central and South America where they transmit Trypanosoma cruzi to mammals, including humans, through their feces. This parasitic protozoan is the causative agent of Chagas disease, a major public health issue in endemic areas. Because of the medical and economic impact of Chagas disease, the presence of other arthropod-borne pathogens in triatomines was rarely investigated. Methodology/Principal findings In this study, seven triatomines species involved in the transmission of T. cruzi were molecularly screened for the presence of known pathogens generally associated with arthropods, such as Rickettsia, Bartonella, Anaplasmataceae, Borrelia species and Coxiella burnetii. Of all included triatomine species, only Eratyrus mucronatus specimens tested positive for Bartonella species for 56% of tested samples. A new genotype of Bartonella spp. was detected in 13/23 Eratyrus mucronatus specimens, an important vector of T. cruzi to humans. This bacterium was further characterized by sequencing fragments of the ftsZ, gltA and rpoB genes. Depending on the targeted gene, this agent shares 84% to 91% of identity with B. bacilliformis, the agent of Carrion’s disease, a deadly sandfly-borne infectious disease endemic in South America. It is also closely related to animal pathogens such as B. bovis and B. chomelii. Conclusions As E. mucronatus is an invasive species that occasionally feeds on humans, the presence of potentially pathogenic Bartonella-infected bugs could present another risk for human health, along with the T. cruzi issue. PMID:28095503
MERS, SARS and other coronaviruses as causes of pneumonia.
Yin, Yudong; Wunderink, Richard G
2018-02-01
Human coronaviruses (HCoVs) have been considered to be relatively harmless respiratory pathogens in the past. However, after the outbreak of the severe acute respiratory syndrome (SARS) and emergence of the Middle East respiratory syndrome (MERS), HCoVs have received worldwide attention as important pathogens in respiratory tract infection. This review focuses on the epidemiology, pathogenesis and clinical characteristics among SARS-coronaviruses (CoV), MERS-CoV and other HCoV infections. © 2017 Asian Pacific Society of Respirology.
Glycoconjugates in human milk: protecting infants from disease.
Peterson, Robyn; Cheah, Wai Yuen; Grinyer, Jasmine; Packer, Nicolle
2013-12-01
Breastfeeding is known to have many health benefits for a newborn. Not only does human milk provide an excellent source of nutrition, it also contains components that protect against infection from a wide range of pathogens. Some of the protective properties of human milk can be attributed to the immunoglobulins. Yet, there is another level of defense provided by the "sweet" protective agents that human milk contains, including free oligosaccharides, glycoproteins and glycolipids. Sugar epitopes in human milk are similar to the glycan receptors that serve as pathogen adhesion sites in the human gastrointestinal tract and other epithelial cell surfaces; hence, the milk glycans can competitively bind to and remove the disease-causing microorganisms before they cause infection. The protective value of free oligosaccharides in human milk has been well researched and documented. Human milk glycoconjugates have received less attention but appear to play an equally important role. Here, we bring together the breadth of research that has focused on the protective mechanisms of human milk glycoconjugates, with a particular focus on the glycan moieties that may play a role in disease prevention. In addition, human milk glycoconjugates are compared with bovine milk glycoconjugates in terms of their health benefits for the human infant.
Blocking transmission of vector-borne diseases.
Schorderet-Weber, Sandra; Noack, Sandra; Selzer, Paul M; Kaminsky, Ronald
2017-04-01
Vector-borne diseases are responsible for significant health problems in humans, as well as in companion and farm animals. Killing the vectors with ectoparasitic drugs before they have the opportunity to pass on their pathogens could be the ideal way to prevent vector borne diseases. Blocking of transmission might work when transmission is delayed during blood meal, as often happens in ticks. The recently described systemic isoxazolines have been shown to successfully prevent disease transmission under conditions of delayed pathogen transfer. However, if the pathogen is transmitted immediately at bite as it is the case with most insects, blocking transmission becomes only possible if ectoparasiticides prevent the vector from landing on or, at least, from biting the host. Chemical entities exhibiting repellent activity in addition to fast killing, like pyrethroids, could prevent pathogen transmission even in cases of immediate transfer. Successful blocking depends on effective action in the context of the extremely diverse life-cycles of vectors and vector-borne pathogens of medical and veterinary importance which are summarized in this review. This complexity leads to important parameters to consider for ectoparasiticide research and when considering the ideal drug profile for preventing disease transmission. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Obaidat, Mohammad M; Bani Salman, Alaa E
2017-03-01
This study determined the prevalence and antimicrobial resistance of human-specific ( Shigella spp.) and zoonotic ( Salmonella enterica ) foodborne pathogens in internationally traded seafood. Sixty-four Salmonella and 61 Shigella isolates were obtained from 330 imported fresh fish samples from Egypt, Yemen, and India. The pathogens were isolated on selective media, confirmed by PCR, and tested for antimicrobial resistance. Approximately 79 and 98% of the Salmonella and Shigella isolates, respectively, exhibited resistance to at least one antimicrobial, and 8 and 49% exhibited multidrug resistance (resistance to three or more antimicrobial classes). Generally, Salmonella exhibited high resistance to amoxicillin-clavulanic acid, cephalothin, streptomycin, and ampicillin; very low resistance to kanamycin, tetracycline, gentamicin, chloramphenicol, nalidixic acid, sulfamethoxazole-trimethoprim, and ciprofloxacin; and no resistance to ceftriaxone. Meanwhile, Shigella spp. exhibited high resistance to tetracycline, amoxicillin-clavulanic acid, cephalothin, streptomycin, and ampicillin; low resistance to kanamycin, nalidixic acid, sulfamethoxazole-trimethoprim, and ceftriaxone; and very low resistance to gentamicin and ciprofloxacin. Salmonella isolates exhibited 14 resistance profiles, Shigella isolates 42. This study is novel in showing that a human-specific pathogen has higher antimicrobial resistance percentages and more diverse profiles than a zoonotic pathogen. Thus, the impact of antimicrobial use in humans is as significant as, if not more significant than, it is in animals in spreading antibiotic resistance through food. This study also demonstrates that locally derived antimicrobial resistance can spread and pose a public health risk worldwide through seafood trade and that high resistance would make a possible outbreak difficult to control. So, capacity building and monitoring harvest water areas are encouraged in fish producing countries.
Van Damme, I; De Zutter, L; Jacxsens, L; Nauta, M J
2017-06-01
This study aimed to evaluate the effect of different processing scenarios along the farm-to-fork chain on the contamination of minced pork with human pathogenic Y. enterocolitica. A modular process risk model (MPRM) was used to perform the assessment of the concentrations of pathogenic Y. enterocolitica in minced meat produced in industrial meat processing plants. The model described the production of minced pork starting from the contamination of pig carcasses with pathogenic Y. enterocolitica just before chilling. The endpoints of the assessment were (i) the proportion of 0.5 kg minced meat packages that contained pathogenic Y. enterocolitica and (ii) the proportion of 0.5 kg minced meat packages that contained more than 10³ pathogenic Y. enterocolitica at the end of storage, just before consumption of raw pork or preparation. Comparing alternative scenarios to the baseline model showed that the initial contamination and different decontamination procedures of carcasses have an important effect on the proportion of highly contaminated minced meat packages at the end of storage. The addition of pork cheeks and minimal quantities of tonsillar tissue into minced meat also had a large effect on the endpoint estimate. Finally, storage time and temperature at consumer level strongly influenced the number of highly contaminated packages. Copyright © 2016 Elsevier Ltd. All rights reserved.
Li, Liping; Wang, Rui; Huang, Yan; Huang, Ting; Luo, Fuguang; Huang, Weiyi; Yang, Xiuying; Lei, Aiying; Chen, Ming; Gan, Xi
2018-01-01
Group B streptococcus (GBS) is the major pathogen causing diseases in neonates, pregnant/puerperal women, cows and fish. Recent studies have shown that GBS may be infectious across hosts and some fish GBS strain might originate from human. The purpose of this study is to investigate the genetic relationship of CC103 strains that recently emerged in cows and humans, and explore the pathogenicity of clinical GBS isolates from human to tilapia. Ninety-two pathogenic GBS isolates were identified from 19 patients with different diseases and their evolution and pathogenicity to tilapia were analyzed. The multilocus sequence typing revealed that clonal complex (CC) 103 strain was isolated from 21.74% (20/92) of patients and ST485 strain was from 14.13% (13/92) patients with multiple diseases including neonates. Genomic evolution analysis showed that both bovine and human CC103 strains alternately form independent evolutionary branches. Three CC67 isolates carried gbs2018-C gene and formed one evolutionary branch with ST61 and ST67 strains that specifically infect dairy cows. Studies of interspecies transmission to tilapia found that 21/92 (22.83%) isolates including all ST23 isolates were highly pathogenic to tilapia and demonstrated that streptococci could break through the blood-brain barrier into brain tissue. In conclusions, CC103 strains are highly prevalent among pathogenic GBS from humans and have evolved into the highly pathogenic ST485 strains specifically infecting humans. The CC67 strains isolated from cows are able to infect humans through evolutionary events of acquiring CC17-specific type C gbs2018 gene and others. Human-derived ST23 pathogenic GBS strains are highly pathogenic to tilapia. PMID:29467722
Błaszkowska, Joanna; Wójcik, Anna
2012-01-01
Current issues concerning Parasitology and Mycology with regard to diseases of the skin and its appendages are presented. Aspects of diagnostics, clinical picture and therapy of skin and nail mycoses, as well as difficulties in the diagnosis and treatment of both native parasitoses (toxoplasmosis) and imported human tropical parasitoses (malaria, filariosis) have been emphasised. The clinical importance of environmental mould fungi in nosocomial infections and fungal meningitis, as well as selected properties of fungi isolated from patients with head and neck neoplasms treated by radiotherapy are discussed. Other mycological topics include the characteristics of newly-synthesized thiosemicarbazides and thiadiazoles as potential drugs against toxoplasmosis and their biological activity against Toxoplasma gondii tachyzoites, selected molecular mechanisms of resistance to azoles, Candida albicans strains and a new tool (barcoding DNA) for describing the biodiversity of potential allergenic molds. The importance of environmental factors in pathogenesis of mycoses and parasitoses is noted. The characteristics of pathogenic fungi isolated from natural ponds in Bialystok and potentially pathogenic yeast-like fungi isolated from children's recreation areas in Lodz are presented. The ongoing problem of anthropozoonoses is considered, as are the roles of stray cats and dogs in contaminating soil with the developing forms of intestinal parasites. The characteristics of the human microbiome, including population composition, activity and their importance in normal human physiology, are presented, as are the major goals of the Human Microbiome Project initiated by National Institutes of Health (NIH).
Yu, Jinghua; Kuo, Sherwin; Coda, Alvin; Jiang, Yong; Gallo, Richard L.; Huang, Chun-Ming
2013-01-01
Bacterial interference creates an ecological competition between commensal and pathogenic bacteria. Through fermentation of milk with gut-friendly bacteria, yogurt is an excellent aid to balance the bacteriological ecosystem in the human intestine. Here, we demonstrate that fermentation of glycerol with Propionibacterium acnes (P. acnes), a skin commensal bacterium, can function as a skin probiotic for in vitro and in vivo growth suppression of USA300, the most prevalent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). We also promote the notion that inappropriate use of antibiotics may eliminate the skin commensals, making it more difficult to fight pathogen infection. This study warrants further investigation to better understand the role of fermentation of skin commensals in infectious disease and the importance of the human skin microbiome in skin health. PMID:23405142
Zahedi, Alireza; Paparini, Andrea; Jian, Fuchun; Robertson, Ian; Ryan, Una
2016-04-01
Cryptosporidium is an enteric parasite that is transmitted via the faecal-oral route, water and food. Humans, wildlife and domestic livestock all potentially contribute Cryptosporidium to surface waters. Human encroachment into natural ecosystems has led to an increase in interactions between humans, domestic animals and wildlife populations. Increasing numbers of zoonotic diseases and spill over/back of zoonotic pathogens is a consequence of this anthropogenic disturbance. Drinking water catchments and water reservoir areas have been at the front line of this conflict as they can be easily contaminated by zoonotic waterborne pathogens. Therefore, the epidemiology of zoonotic species of Cryptosporidium in free-ranging and captive wildlife is of increasing importance. This review focuses on zoonotic Cryptosporidium species reported in global wildlife populations to date, and highlights their significance for public health and the water industry.
Significance of Fecal Coliform-Positive Klebsiella1
Bagley, Susan T.; Seidler, Ramon J.
1977-01-01
A total of 191 Klebsiella pneumoniae isolates of human clinical, bovine mastitis, and a wide variety of environmental sources were tested for fecal coliform (FC) response with the membrane filtration and most probable number techniques. Twenty-seven Escherichia coli cultures of human clinical and environmental origins were also tested. Eighty-five percent (49/58) of known pathogenic K. pneumoniae were FC positive, compared with 16% (19/120) of the environmental strains. E. coli results indicated 93% (13/14) of the clinical and 85% (11/13) of the environmental strains as FC positive. There was no significant difference in the incidence of FC-positive cultures between pathogenic Klebsiella and E. coli. pH measurements of K. pneumoniae and E. coli cultures growing in m-FC broth at 44.5°C revealed three distinct pH ranges correlating with colony morphology. β-Galactosidase assays of Klebsiella and E. coli cultures at 44.5°C indicated all were able to hydrolyze lactose, even if they were FC negative by the membrane filtration or most probable number techniques. The FC response pattern appears stable in K. pneumoniae. Three pathogenic cultures showed no change in FC responses after 270 generations of growth in sterile pulp mill effluent. Since K. pneumoniae is carried in the gastrointestinal tract of humans and animals and 85% of the tested pathogenic strains were FC positive, the isolation of FC-positive Klebsiella organisms from the environment would indicate their fecal or clinical origin or both. The added fact that K. pneumoniae is an opportunistic pathogen of increasing importance makes the occurrence of FC-positive environmental Klebsiella, particularly in large numbers, a potential human and animal health hazard. PMID:18086
Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen Pneumocystis.
Cissé, Ousmane H; Ma, Liang; Wei Huang, Da; Khil, Pavel P; Dekker, John P; Kutty, Geetha; Bishop, Lisa; Liu, Yueqin; Deng, Xilong; Hauser, Philippe M; Pagni, Marco; Hirsch, Vanessa; Lempicki, Richard A; Stajich, Jason E; Cuomo, Christina A; Kovacs, Joseph A
2018-05-08
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. IMPORTANCE Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. Pneumocystis , a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, Pneumocystis can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different Pneumocystis species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that Pneumocystis may have undergone recent host shifts. The results demonstrate that Pneumocystis strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.
Innate Immune Signaling Activated by MDR Bacteria in the Airway
Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice
2015-01-01
Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation. PMID:26582515
Romanowska, Magdalena; Nowak, Iwona; Brydak, Lidia; Wojtyla, Andrzej
2009-01-01
Since 1997, human infections with highly pathogenic zoonotic avian influenza viruses have shown that the risk of influenza pandemic is significant. In Europe, infections caused by the highly pathogenic avian influenza A(H7N7) virus were confirmed in the human population in 2003 in the Netherlands. Moreover, outbreaks of A(H5N1) infections were observed in wild and farm birds in different European regions, including Poland in 2006-2008. This study presents 16 patients in Poland from whom clinical specimens were collected and tested for A(H5N1) highly pathogenic avian influenza. This article shows the results of laboratory tests and discusses the legitimacy of the collection and testing of the specimens. All patients were negative for A(H5N1) infection. Nevertheless, only two patients met clinical and epidemiological criteria from the avian influenza case definition. The conclusion is that there is still a strong necessity for increasing the awareness of medical and laboratory staff, as well as the awareness of some occupational groups about human infections with avian influenza viruses, including the importance of seasonal influenza vaccination. It should also be emphasized that in the case of patients suspected of being infected with avian influenza, the information about clinical symptoms is insufficient and must be accompanied by a wide epidemiological investigation.
Kohl, Alain; Pondeville, Emilie; Schnettler, Esther; Crisanti, Andrea; Supparo, Clelia; Christophides, George K.; Kersey, Paul J.; Maslen, Gareth L.; Takken, Willem; Koenraadt, Constantianus J. M.; Oliva, Clelia F.; Busquets, Núria; Abad, F. Xavier; Failloux, Anna-Bella; Levashina, Elena A.; Wilson, Anthony J.; Veronesi, Eva; Pichard, Maëlle; Arnaud Marsh, Sarah; Simard, Frédéric; Vernick, Kenneth D.
2016-01-01
Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector–pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations. PMID:27677378
Lima, Patrícia de Sousa; Chung, Dawoon; Bailão, Alexandre Melo; Cramer, Robert A; Soares, Célia Maria de Almeida
2015-12-01
Hypoxic microenvironments are generated during fungal infection. It has been described that to survive in the human host, fungi must also tolerate and overcome in vivo microenvironmental stress conditions including low oxygen tension; however nothing is known how Paracoccidioides species respond to hypoxia. The genus Paracoccidioides comprises human thermal dimorphic fungi and are causative agents of paracoccidioidomycosis (PCM), an important mycosis in Latin America. In this work, a detailed hypoxia characterization was performed in Paracoccidioides. Using NanoUPLC-MSE proteomic approach, we obtained a total of 288 proteins differentially regulated in 12 and 24 h of hypoxia, providing a global view of metabolic changes during this stress. In addition, a functional characterization of the homologue to the most important molecule involved in hypoxia responses in other fungi, the SREBP (sterol regulatory element binding protein) was performed. We observed that Paracoccidioides species have a functional homologue of SREBP, named here as SrbA, detected by using a heterologous genetic approach in the srbA null mutant in Aspergillus fumigatus. Paracoccidioides srbA (PbsrbA), in addition to involvement in hypoxia, is probable involved in iron adaptation and azole drug resistance responses. In this study, the hypoxia was characterized in Paracoccidioides. The first results can be important for a better understanding of the fungal adaptation to the host and improve the arsenal of molecules for the development of alternative treatment options in future, since molecules related to fungal adaptation to low oxygen levels are important to virulence and pathogenesis in human pathogenic fungi.
Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection
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
Epigenetic regulation of development and pathogenesis in fungal plant pathogens.
Dubey, Akanksha; Jeon, Junhyun
2017-08-01
Evidently, epigenetics is at forefront in explaining the mechanisms underlying the success of human pathogens and in the identification of pathogen-induced modifications within host plants. However, there is a lack of studies highlighting the role of epigenetics in the modulation of the growth and pathogenicity of fungal plant pathogens. In this review, we attempt to highlight and discuss the role of epigenetics in the regulation of the growth and pathogenicity of fungal phytopathogens using Magnaporthe oryzae, a devastating fungal plant pathogen, as a model system. With the perspective of wide application in the understanding of the development, pathogenesis and control of other fungal pathogens, we attempt to provide a synthesized view of the epigenetic studies conducted on M. oryzae to date. First, we discuss the mechanisms of epigenetic modifications in M. oryzae and their impact on fungal development and pathogenicity. Second, we highlight the unexplored epigenetic mechanisms and areas of research that should be considered in the near future to construct a holistic view of epigenetic functioning in M. oryzae and other fungal plant pathogens. Importantly, the development of a complete understanding of the modulation of epigenetic regulation in fungal pathogens can help in the identification of target points to combat fungal pathogenesis. © 2016 BSPP AND JOHN WILEY & SONS LTD.
Wang, George C; Dash, Pradyot; McCullers, Jonathan A; Doherty, Peter C; Thomas, Paul G
2012-04-04
A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8⁺ TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV)-specific CD8⁺ T cells recovered directly ex vivo. We found that CD8⁺ TCRαβ repertoire diversity, but not the size of the CD8⁺ T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8⁺ T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.
Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway
Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter
2017-01-01
The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination. PMID:28553281
Litschko, Christa; Oldrini, Davide; Budde, Insa; Berger, Monika; Meens, Jochen; Gerardy-Schahn, Rita; Berti, Francesco; Schubert, Mario; Fiebig, Timm
2018-05-29
Group 2 capsule polymers represent crucial virulence factors of Gram-negative pathogenic bacteria. They are synthesized by enzymes called capsule polymerases. In this report, we describe a new family of polymerases that combine glycosyltransferase and hexose- and polyol-phosphate transferase activity to generate complex poly(oligosaccharide phosphate) and poly(glycosylpolyol phosphate) polymers, the latter of which display similarity to wall teichoic acid (WTA), a cell wall component of Gram-positive bacteria. Using modeling and multiple-sequence alignment, we showed homology between the predicted polymerase domains and WTA type I biosynthesis enzymes, creating a link between Gram-negative and Gram-positive cell wall biosynthesis processes. The polymerases of the new family are highly abundant and found in a variety of capsule-expressing pathogens such as Neisseria meningitidis , Actinobacillus pleuropneumoniae , Haemophilus influenzae , Bibersteinia trehalosi , and Escherichia coli with both human and animal hosts. Five representative candidates were purified, their activities were confirmed using nuclear magnetic resonance (NMR) spectroscopy, and their predicted folds were validated by site-directed mutagenesis. IMPORTANCE Bacterial capsules play an important role in the interaction between a pathogen and the immune system of its host. During the last decade, capsule polymerases have become attractive tools for the production of capsule polymers applied as antigens in glycoconjugate vaccine formulations. Conventional production of glycoconjugate vaccines requires the cultivation of the pathogen and thus the highest biosafety standards, leading to tremendous costs. With regard to animal husbandry, where vaccines could avoid the extensive use of antibiotics, conventional production is not sufficiently cost-effective. In contrast, enzymatic synthesis of capsule polymers is pathogen-free and fast, offers high stereo- and regioselectivity, and works with high efficacy. The new capsule polymerase family described here vastly increases the toolbox of enzymes available for biotechnology purposes. Representatives are abundantly found in human pathogens but also in animal pathogens, paving the way for the exploitation of polymerases for the development of a new generation of vaccines for animal husbandry. Copyright © 2018 Litschko et al.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-24
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2001-D-0066] (Formerly Docket No. 2001D-0107) Expedited Review for New Animal Drug Applications for Human Pathogen... Review for New Animal Drug Applications for Human Pathogen Reduction Claims.'' The guidance predates the...
An Efficient, Rapid, and Recyclable System for CRISPR-Mediated Genome Editing in Candida albicans.
Nguyen, Namkha; Quail, Morgan M F; Hernday, Aaron D
2017-01-01
Candida albicans is the most common fungal pathogen of humans. Historically, molecular genetic analysis of this important pathogen has been hampered by the lack of stable plasmids or meiotic cell division, limited selectable markers, and inefficient methods for generating gene knockouts. The recent development of clustered regularly interspaced short palindromic repeat(s) (CRISPR)-based tools for use with C. albicans has opened the door to more efficient genome editing; however, previously reported systems have specific limitations. We report the development of an optimized CRISPR-based genome editing system for use with C. albicans . Our system is highly efficient, does not require molecular cloning, does not leave permanent markers in the genome, and supports rapid, precise genome editing in C. albicans . We also demonstrate the utility of our system for generating two independent homozygous gene knockouts in a single transformation and present a method for generating homozygous wild-type gene addbacks at the native locus. Furthermore, each step of our protocol is compatible with high-throughput strain engineering approaches, thus opening the door to the generation of a complete C. albicans gene knockout library. IMPORTANCE Candida albicans is the major fungal pathogen of humans and is the subject of intense biomedical and discovery research. Until recently, the pace of research in this field has been hampered by the lack of efficient methods for genome editing. We report the development of a highly efficient and flexible genome editing system for use with C. albicans . This system improves upon previously published C. albicans CRISPR systems and enables rapid, precise genome editing without the use of permanent markers. This new tool kit promises to expedite the pace of research on this important fungal pathogen.
NASA Astrophysics Data System (ADS)
Zhao, Youbo; Monroy, Guillermo L.; You, Sixian; Shelton, Ryan L.; Nolan, Ryan M.; Tu, Haohua; Chaney, Eric J.; Boppart, Stephen A.
2016-10-01
We investigate and demonstrate the feasibility of using a combined Raman scattering (RS) spectroscopy and low-coherence interferometry (LCI) probe to differentiate microbial pathogens and improve our diagnostic ability of ear infections [otitis media (OM)]. While the RS probe provides noninvasive molecular information to identify and differentiate infectious microorganisms, the LCI probe helps to identify depth-resolved structural information as well as to guide and monitor positioning of the Raman spectroscopy beam for relatively longer signal acquisition times. A series of phantom studies, including the use of human middle ear effusion samples, were performed to mimic the conditions of in vivo investigations. These were also conducted to validate the feasibility of using this combined RS/LCI probe for point-of-care diagnosis of the infectious pathogen(s) in OM patients. This work establishes important parameters for future in vivo investigations of fast and accurate determination and diagnosis of infectious microorganisms in OM patients, potentially improving the efficacy and outcome of OM treatments, and importantly reducing the misuse of antibiotics in the presence of viral infections.
Zhao, Youbo; Monroy, Guillermo L; You, Sixian; Shelton, Ryan L; Nolan, Ryan M; Tu, Haohua; Chaney, Eric J; Boppart, Stephen A
2016-10-01
We investigate and demonstrate the feasibility of using a combined Raman scattering (RS) spectroscopy and low-coherence interferometry (LCI) probe to differentiate microbial pathogens and improve our diagnostic ability of ear infections [otitis media (OM)]. While the RS probe provides noninvasive molecular information to identify and differentiate infectious microorganisms, the LCI probe helps to identify depth-resolved structural information as well as to guide and monitor positioning of the Raman spectroscopy beam for relatively longer signal acquisition times. A series of phantom studies, including the use of human middle ear effusion samples, were performed to mimic the conditions of in vivo investigations. These were also conducted to validate the feasibility of using this combined RS/LCI probe for point-of-care diagnosis of the infectious pathogen(s) in OM patients. This work establishes important parameters for future in vivo investigations of fast and accurate determination and diagnosis of infectious microorganisms in OM patients, potentially improving the efficacy and outcome of OM treatments, and importantly reducing the misuse of antibiotics in the presence of viral infections.
Ruiz-Fons, F
2017-02-01
Many wild swine populations in different parts of the World have experienced an unprecedented demographic explosion that may result in increased exposure of humans to wild swine zoonotic pathogens. Interactions between humans and wild swine leading to pathogen transmission could come from different ways, being hunters and game professionals the most exposed to acquiring infections from wild swine. However, increasing human settlements in semi-natural areas, outdoor activities, socio-economic changes and food habits may increase the rate of exposure to wild swine zoonotic pathogens and to potentially emerging pathogens from wild swine. Frequent and increasing contact rate between humans and wild swine points to an increasing chance of zoonotic pathogens arising from wild swine to be transmitted to humans. Whether this frequent contact could lead to new zoonotic pathogens emerging from wild swine to cause human epidemics or emerging disease outbreaks is difficult to predict, and assessment should be based on thorough epidemiologic surveillance. Additionally, several gaps in knowledge on wild swine global population dynamics trends and wild swine-zoonotic pathogen interactions should be addressed to correctly assess the potential role of wild swine in the emergence of diseases in humans. In this work, viruses such as hepatitis E virus, Japanese encephalitis virus, Influenza virus and Nipah virus, and bacteria such as Salmonella spp., Shiga toxin-producing Escherichia coli, Campylobacter spp. and Leptospira spp. have been identified as the most prone to be transmitted from wild swine to humans on the basis of geographic spread in wild swine populations worldwide, pathogen circulation rates in wild swine populations, wild swine population trends in endemic areas, susceptibility of humans to infection, transmissibility from wild swine to humans and existing evidence of wild swine-human transmission events. © 2015 Blackwell Verlag GmbH.
Mechanism and function of type IV secretion during infection of the human host
Gonzalez-Rivera, Christian; Bhatty, Minny; Christie, Peter J.
2015-01-01
Bacterial pathogens employ type IV secretion systems (T4SSs) for various purposes to aid in survival and proliferation in eukaryotic host. One large T4SS subfamily, the conjugation systems, confers a selective advantage to the invading pathogen in clinical settings through dissemination of antibiotic resistance genes and virulence traits. Besides their intrinsic importance as principle contributors to the emergence of multiply drug-resistant ‘superbugs’, detailed studies of these highly tractable systems have generated important new insights into the mode of action and architectures of paradigmatic T4SSs as a foundation for future efforts aimed at suppressing T4SS machine function. Over the past decade, extensive work on the second large T4SS subfamily, the effector translocators, has identified a myriad of mechanisms employed by pathogens to subvert, subdue, or bypass cellular processes and signaling pathways of the host cell. An overarching theme in the evolution of many effectors is that of molecular mimicry. These effectors carry domains similar to those of eukaryotic proteins and exert their effects through stealthy interdigitation of cellular pathways, often with the outcome not of inducing irreversible cell damage but rather of reversibly modulating cellular functions. This chapter summarizes the major developments for the actively studied pathogens with an emphasis on the structural and functional diversity of the T4SSs and the emerging common themes surrounding effector function in the human host. PMID:27337453
Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum.
Vinayak, Sumiti; Pawlowic, Mattie C; Sateriale, Adam; Brooks, Carrie F; Studstill, Caleb J; Bar-Peled, Yael; Cipriano, Michael J; Striepen, Boris
2015-07-23
Recent studies into the global causes of severe diarrhoea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrhoeal pathogen after rotavirus. Diarrhoeal disease is estimated to be responsible for 10.5% of overall child mortality. Cryptosporidium is also an opportunistic pathogen in the contexts of human immunodeficiency virus (HIV)-caused AIDS and organ transplantation. There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger: malnourished children and immunocompromised patients. Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes a lack of systems for continuous culture, facile animal models, and molecular genetic tools. Here we describe an experimental framework to genetically modify this important human pathogen. We established and optimized transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we developed a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, and in vivo selection for aminoglycoside resistance. We derived reporter parasites suitable for in vitro and in vivo drug screening, and we evaluated the basis of drug susceptibility by gene knockout. We anticipate that the ability to genetically engineer this parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection, and the role of parasite genes in these processes is now open to rigorous investigation.
Pet roundworms and hookworms: a continuing need for global worming.
Traversa, Donato
2012-05-10
Ascarids and ancylostomatids are the most important parasites affecting dogs and cats worldwide, in terms of diffusion and risk for animal and human health. Different misconceptions have led the general public and pet owners to minimize the importance of these intestinal worms. A low grade of interest is also registered among veterinary professions, although there is a significant merit in keeping our guard up against these parasites. This article reviews current knowledge of ascarids and ancylostomatids, with a special focus on pathogenicity, epidemiology and control methods in veterinary and human medicine.
Pet roundworms and hookworms: A continuing need for global worming
2012-01-01
Ascarids and ancylostomatids are the most important parasites affecting dogs and cats worldwide, in terms of diffusion and risk for animal and human health. Different misconceptions have led the general public and pet owners to minimize the importance of these intestinal worms. A low grade of interest is also registered among veterinary professions, although there is a significant merit in keeping our guard up against these parasites. This article reviews current knowledge of ascarids and ancylostomatids, with a special focus on pathogenicity, epidemiology and control methods in veterinary and human medicine. PMID:22574783
Toxicity and metabolism of nitroalkanes and substituted nitroalkanes
USDA-ARS?s Scientific Manuscript database
A series of low molecular weight nitro- containing compounds has recently been discovered to have a variety of biological activities including the reduction of anaerobic methane production in ruminant animals and activity against economically important human pathogens, including Salmonella sp. and s...
GENOME ANALYSIS OF BURKHOLDERIA CEPACIA AC1100
Burkholderia cepacia is an important organism in bioremediation of environmental pollutants and it is also of increasing interest as a human pathogen. The genomic organization of B. cepacia is being studied in order to better understand its unusual adaptive capacity and genome pl...
Baddal, Buket; Muzzi, Alessandro; Censini, Stefano; Calogero, Raffaele A; Torricelli, Giulia; Guidotti, Silvia; Taddei, Anna R; Covacci, Antonello; Pizza, Mariagrazia; Rappuoli, Rino; Soriani, Marco; Pezzicoli, Alfredo
2015-11-17
The ability to adhere and adapt to the human respiratory tract mucosa plays a pivotal role in the pathogenic lifestyle of nontypeable Haemophilus influenzae (NTHi). However, the temporal events associated with a successful colonization have not been fully characterized. In this study, by reconstituting the ciliated human bronchial epithelium in vitro, we monitored the global transcriptional changes in NTHi and infected mucosal epithelium simultaneously for up to 72 h by dual RNA sequencing. The initial stage of colonization was characterized by the binding of NTHi to ciliated cells. Temporal profiling of host mRNA signatures revealed significant dysregulation of the target cell cytoskeleton elicited by bacterial infection, with a profound effect on the intermediate filament network and junctional complexes. In response to environmental stimuli of the host epithelium, NTHi downregulated its central metabolism and increased the expression of transporters, indicating a change in the metabolic regime due to the availability of host substrates. Concurrently, the oxidative environment generated by infected cells instigated bacterial expression of stress-induced defense mechanisms, including the transport of exogenous glutathione and activation of the toxin-antitoxin system. The results of this analysis were validated by those of confocal microscopy, Western blotting, Bio-plex, and real-time quantitative reverse transcription-PCR (qRT-PCR). Notably, as part of our screening for novel signatures of infection, we identified a global profile of noncoding transcripts that are candidate small RNAs (sRNAs) regulated during human host infection in Haemophilus species. Our data, by providing a robust and comprehensive representation of the cross talk between the host and invading pathogen, provides important insights into NTHi pathogenesis and the development of efficacious preventive strategies. Simultaneous monitoring of infection-linked transcriptome alterations in an invading pathogen and its target host cells represents a key strategy for identifying regulatory responses that drive pathogenesis. In this study, we report the progressive events of NTHi colonization in a highly differentiated model of ciliated bronchial epithelium. Genome-wide transcriptome maps of NTHi during infection provided mechanistic insights into bacterial adaptive responses to the host niche, with modulation of the central metabolism as an important signature of the evolving milieu. Our data indicate that infected epithelia respond by substantial alteration of the cytoskeletal network and cytokine repertoire, revealing a dynamic cross talk that is responsible for the onset of inflammation. This work significantly enhances our understanding of the means by which NTHi promotes infection on human mucosae and reveals novel strategies exploited by this important pathogen to cause invasive disease. Copyright © 2015 Baddal et al.
Infection strategies of enteric pathogenic Escherichia coli
Clements, Abigail; Young, Joanna C.; Constantinou, Nicholas; Frankel, Gad
2012-01-01
Enteric Escherichia coli (E. coli) are both natural flora of humans and important pathogens causing significant morbidity and mortality worldwide. Traditionally enteric E. coli have been divided into 6 pathotypes, with further pathotypes often proposed. In this review we suggest expansion of the enteric E. coli into 8 pathotypes to include the emerging pathotypes of adherent invasive E. coli (AIEC) and Shiga-toxin producing enteroaggregative E. coli (STEAEC). The molecular mechanisms that allow enteric E. coli to colonize and cause disease in the human host are examined and for two of the pathotypes that express a type 3 secretion system (T3SS) we discuss the complex interplay between translocated effectors and manipulation of host cell signaling pathways that occurs during infection. PMID:22555463
Chang, S C; Macêdo, D P C; Souza-Motta, C M; Oliveira, N T
2013-08-12
Fusarium verticillioides is a pathogen of agriculturally important crops, especially maize. It is considered one of the most important pathogens responsible for fumonisin contamination of food products, which causes severe, chronic, and acute intoxication in humans and animals. Moreover, it is recognized as a cause of localized infections in immunocompetent patients and disseminated infections among severely immunosuppressed patients. Several molecular tools have been used to analyze the intraspecific variability of fungi. The objective of this study was to use molecular markers to compare pathogenic isolates of F. verticillioides and isolates of the same species obtained from clinical samples of patients with Fusarium mycoses. The molecular markers that we used were inter-simple sequence repeat markers (primers GTG5 and GACA4), intron splice site primer (primer EI1), random amplified polymorphic DNA marker (primer OPW-6), and restriction fragment length polymorphism-internal transcribed spacer (ITS) from rDNA. From the data obtained, clusters were generated based on the UPGMA clustering method. The amplification products obtained using primers ITS4 and ITS5 and loci ITS1-5.8-ITS2 of the rDNA yielded fragments of approximately 600 bp for all the isolates. Digestion of the ITS region fragment using restriction enzymes such as EcoRI, DraI, BshI, AluI, HaeIII, HinfI, MspI, and PstI did not permit differentiation among pathogenic and clinical isolates. The inter-simple sequence repeat, intron splice site primer, and random amplified polymorphic DNA markers presented high genetic homogeneity among clinical isolates in contrast to the high variability found among the phytopathogenic isolates of F. verticillioides.
Leptospira Species in Feral Cats and Black Rats from Western Australia and Christmas Island.
Dybing, Narelle A; Jacobson, Caroline; Irwin, Peter; Algar, David; Adams, Peter J
2017-05-01
Leptospirosis is a neglected, re-emerging bacterial disease with both zoonotic and conservation implications. Rats and livestock are considered the usual sources of human infection, but all mammalian species are capable of carrying Leptospira spp. and transmitting pathogenic leptospires in their urine, and uncertainty remains about the ecology and transmission dynamics of Leptospira in different regions. In light of a recent case of human leptospirosis on tropical Christmas Island, this study aimed to investigate the role of introduced animals (feral cats and black rats) as carriers of pathogenic Leptospira spp. on Christmas Island and to compare this with two different climatic regions of Western Australia (one island and one mainland). Kidney samples were collected from black rats (n = 68) and feral cats (n = 59) from Christmas Island, as well as feral cats from Dirk Hartog Island (n = 23) and southwest Western Australia (n = 59). Molecular (PCR) screening detected pathogenic leptospires in 42.4% (95% confidence interval 29.6-55.9) of cats and 2.9% (0.4-10.2) of rats from Christmas Island. Sequencing of cat- and rat-positive samples from Christmas Island showed 100% similarity for Leptospira interrogans. Pathogenic leptospires were not detected in cats from Dirk Hartog Island or southwest Western Australia. These findings were consistent with previous reports of higher Leptospira spp. prevalence in tropical regions compared with arid and temperate regions. Despite the abundance of black rats on Christmas Island, feral cats appear to be the more important reservoir species for the persistence of pathogenic L. interrogans on the island. This research highlights the importance of disease surveillance and feral animal management to effectively control potential disease transmission.
Mechanisms of genome evolution of Streptococcus.
Andam, Cheryl P; Hanage, William P
2015-07-01
The genus Streptococcus contains 104 recognized species, many of which are associated with human or animal hosts. A globally prevalent human pathogen in this group is Streptococcus pneumoniae (the pneumococcus). While being a common resident of the upper respiratory tract, it is also a major cause of otitis media, pneumonia, bacteremia and meningitis, accounting for a high burden of morbidity and mortality worldwide. Recent findings demonstrate the importance of recombination and selection in driving the population dynamics and evolution of different pneumococcal lineages, allowing them to successfully evade the impacts of selective pressures such as vaccination and antibiotic treatment. We highlight the ability of pneumococci to respond to these pressures through processes including serotype replacement, capsular switching and horizontal gene transfer (HGT) of antibiotic resistance genes. The challenge in controlling this pathogen also lies in the exceptional genetic and phenotypic variation among different pneumococcal lineages, particularly in terms of their pathogenicity and resistance to current therapeutic strategies. The widespread use of pneumococcal conjugate vaccines, which target only a small subset of the more than 90 pneumococcal serotypes, provides us with a unique opportunity to elucidate how the processes of selection and recombination interact to generate a remarkable level of plasticity and heterogeneity in the pneumococcal genome. These processes also play an important role in the emergence and spread of multi-resistant strains, which continues to pose a challenge in disease control and/or eradication. The application of population of genomic approaches at different spatial and temporal scales will help improve strategies to control this global pathogen, and potentially other pathogenic streptococci. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Hosseini, Parviez R; Mills, James N; Prieur-Richard, Anne-Hélène; Ezenwa, Vanessa O; Bailly, Xavier; Rizzoli, Annapaola; Suzán, Gerardo; Vittecoq, Marion; García-Peña, Gabriel E; Daszak, Peter; Guégan, Jean-François; Roche, Benjamin
2017-06-05
Biodiversity is of critical value to human societies, but recent evidence that biodiversity may mitigate infectious-disease risk has sparked controversy among researchers. The majority of work on this topic has focused on direct assessments of the relationship between biodiversity and endemic-pathogen prevalence, without disentangling intervening mechanisms; thus study outcomes often differ, fuelling more debate. Here, we suggest two critical changes to the approach researchers take to understanding relationships between infectious disease, both endemic and emerging, and biodiversity that may help clarify sources of controversy. First, the distinct concepts of hazards versus risks need to be separated to determine how biodiversity and its drivers may act differently on each. This distinction is particularly important since it illustrates that disease emergence drivers in humans could be quite different to the general relationship between biodiversity and transmission of endemic pathogens. Second, the interactive relationship among biodiversity, anthropogenic change and zoonotic disease risk, including both direct and indirect effects, needs to be recognized and accounted for. By carefully disentangling these interactions between humans' activities and pathogen circulation in wildlife, we suggest that conservation efforts could mitigate disease risks and hazards in novel ways that complement more typical disease control efforts.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. © 2017 The Author(s).
Diversity of the Epsilonproteobacteria Dsb (disulfide bond) systems
Bocian-Ostrzycka, Katarzyna M.; Grzeszczuk, Magdalena J.; Dziewit, Lukasz; Jagusztyn-Krynicka, Elżbieta K.
2015-01-01
The bacterial proteins of the Dsb family—important components of the post-translational protein modification system—catalyze the formation of disulfide bridges, a process that is crucial for protein structure stabilization and activity. Dsb systems play an essential role in the assembly of many virulence factors. Recent rapid advances in global analysis of bacteria have thrown light on the enormous diversity among bacterial Dsb systems. While the Escherichia coli disulfide bond-forming system is quite well understood, the mechanisms of action of Dsb systems in other bacteria, including members of class Epsilonproteobacteria that contain pathogenic and non-pathogenic bacteria colonizing extremely diverse ecological niches, are poorly characterized. Here we present a review of current knowledge on Epsilonproteobacteria Dsb systems. We have focused on the Dsb systems of Campylobacter spp. and Helicobacter spp. because our knowledge about Dsb proteins of Wolinella and Arcobacter spp. is still scarce and comes mainly from bioinformatic studies. Helicobacter pylori is a common human pathogen that colonizes the gastric epithelium of humans with severe consequences. Campylobacter spp. is a leading cause of zoonotic enteric bacterial infections in most developed and developing nations. We focus on various aspects of the diversity of the Dsb systems and their influence on pathogenicity, particularly because Dsb proteins are considered as potential targets for a new class of anti-virulence drugs to treat human infections by Campylobacter or Helicobacter spp. PMID:26106374
Ma, Jiawen; Hu, Yue; Villegas, Eric N.; Xiao, Lihua
2018-01-01
Cryptosporidiosis, giardiasis, and microsporidiosis are important waterborne diseases. In the standard for wastewater treatment plant (WWTP) effluents in China and other countries, the fecal coliform count is the only microbial indicator, raising concerns about the potential for pathogen transmission through WWTP effluent reuse. In this study, we collected 50 effluent samples (30 L/sample) from three municipal WWTPs in Shanghai, China, and analyzed for Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi by microscopy and/or polymerase chain reaction (PCR). Moreover, propidium monoazide (PMA)-PCR was used to assess the viability of oocysts/cysts. The microscopy and PCR-positive rates for Cryptosporidium spp. were 62% and 40%, respectively. The occurrence rates of G. duodenalis were 96% by microscopy and 92–100% by PCR analysis of three genetic loci. Furthermore, E. bieneusi was detected in 70% (35/50) of samples by PCR. Altogether, 10 Cryptosporidium species or genotypes, two G. duodenalis genotypes, and 11 E. bieneusi genotypes were found, most of which were human-pathogenic. The chlorine dioxide disinfection employed in WWTP1 and WWTP3 failed to inactivate the residual pathogens; 93% of the samples from WWTP1 and 83% from WWTP3 did not meet the national standard on fecal coliform levels. Thus, urban WWTP effluents often contain residual waterborne human pathogens. PMID:27280607
Hosseini, Parviez R.; Mills, James N.; Prieur-Richard, Anne-Hélène; Bailly, Xavier; Rizzoli, Annapaola; Suzán, Gerardo; Vittecoq, Marion; Daszak, Peter; Guégan, Jean-François
2017-01-01
Biodiversity is of critical value to human societies, but recent evidence that biodiversity may mitigate infectious-disease risk has sparked controversy among researchers. The majority of work on this topic has focused on direct assessments of the relationship between biodiversity and endemic-pathogen prevalence, without disentangling intervening mechanisms; thus study outcomes often differ, fuelling more debate. Here, we suggest two critical changes to the approach researchers take to understanding relationships between infectious disease, both endemic and emerging, and biodiversity that may help clarify sources of controversy. First, the distinct concepts of hazards versus risks need to be separated to determine how biodiversity and its drivers may act differently on each. This distinction is particularly important since it illustrates that disease emergence drivers in humans could be quite different to the general relationship between biodiversity and transmission of endemic pathogens. Second, the interactive relationship among biodiversity, anthropogenic change and zoonotic disease risk, including both direct and indirect effects, needs to be recognized and accounted for. By carefully disentangling these interactions between humans' activities and pathogen circulation in wildlife, we suggest that conservation efforts could mitigate disease risks and hazards in novel ways that complement more typical disease control efforts. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’. PMID:28438918
Innate Immunity to H5N1 Influenza Viruses in Humans
Ramos, Irene; Fernandez-Sesma, Ana
2012-01-01
Avian influenza virus infections in the human population are rare due to their inefficient direct human-to-human transmission. However, when humans are infected, a strong inflammatory response is usually induced, characterized by elevated levels of cytokines and chemokines in serum, believed to be important in the severe pathogenesis that develops in a high proportion of these patients. Extensive research has been performed to understand the molecular viral mechanisms involved in the H5N1 pathogenesis in humans, providing interesting insights about the virus-host interaction and the regulation of the innate immune response by these highly pathogenic viruses. In this review we summarize and discuss the most important findings in this field, focusing mainly on H5N1 virulence factors and their impact on the modulation of the innate immunity in humans. PMID:23342363
The coastal environment and human health: microbial indicators, pathogens, sentinels and reservoirs
Stewart, Jill R; Gast, Rebecca J; Fujioka, Roger S; Solo-Gabriele, Helena M; Meschke, J Scott; Amaral-Zettler, Linda A; del Castillo, Erika; Polz, Martin F; Collier, Tracy K; Strom, Mark S; Sinigalliano, Christopher D; Moeller, Peter DR; Holland, A Fredrick
2008-01-01
Innovative research relating oceans and human health is advancing our understanding of disease-causing organisms in coastal ecosystems. Novel techniques are elucidating the loading, transport and fate of pathogens in coastal ecosystems, and identifying sources of contamination. This research is facilitating improved risk assessments for seafood consumers and those who use the oceans for recreation. A number of challenges still remain and define future directions of research and public policy. Sample processing and molecular detection techniques need to be advanced to allow rapid and specific identification of microbes of public health concern from complex environmental samples. Water quality standards need to be updated to more accurately reflect health risks and to provide managers with improved tools for decision-making. Greater discrimination of virulent versus harmless microbes is needed to identify environmental reservoirs of pathogens and factors leading to human infections. Investigations must include examination of microbial community dynamics that may be important from a human health perspective. Further research is needed to evaluate the ecology of non-enteric water-transmitted diseases. Sentinels should also be established and monitored, providing early warning of dangers to ecosystem health. Taken together, this effort will provide more reliable information about public health risks associated with beaches and seafood consumption, and how human activities can affect their exposure to disease-causing organisms from the oceans. PMID:19025674
Pathogen transport in groundwater systems: Contrasts with traditional solute transport
Hunt, Randall J.; Johnson, William P.
2017-01-01
Water quality affects many aspects of water availability, from precluding use to societal perceptions of fit-for-purpose. Pathogen source and transport processes are drivers of water quality because they have been responsible for numerous outbreaks resulting in large economic losses due to illness and, in some cases, loss of life. Outbreaks result from very small exposure (e.g., less than 20 viruses) from very strong sources (e.g., trillions of viruses shed by a single infected individual). Thus, unlike solute contaminants, an acute exposure to a very small amount of contaminated water can cause immediate adverse health effects. Similarly, pathogens are larger than solutes. Thus, interactions with surfaces and settling become important even as processes important for solutes such as diffusion become less important. These differences are articulated in “Colloid Filtration Theory”, a separate branch of pore-scale transport. Consequently, understanding pathogen processes requires changes in how groundwater systems are typically characterized, where the focus is on the leading edges of plumes and preferential flow paths, even if such features move only a very small fraction of the aquifer flow. Moreover, the relatively short survival times of pathogens in the subsurface require greater attention to very fast (<10 year) flow paths. By better understanding the differences between pathogen and solute transport mechanisms discussed here, a more encompassing view of water quality and source water protection is attained. With this more holistic view and theoretical understanding, better evaluations can be made regarding drinking water vulnerability and the relation between groundwater and human health.
Swei, Andrea; Ostfeld, Richard S; Lane, Robert S; Briggs, Cheryl J
2011-05-01
Invasive species, including pathogens, can have important effects on local ecosystems, including indirect consequences on native species. This study focuses on the effects of an invasive plant pathogen on a vertebrate community and Ixodes pacificus, the vector of the Lyme disease pathogen (Borrelia burgdorferi) in California. Phytophthora ramorum, the causative agent of sudden oak death, is a non-native pathogen killing trees in California and Oregon. We conducted a multi-year study using a gradient of SOD-caused disturbance to assess the impact on the dusky-footed woodrat (Neotoma fuscipes) and the deer mouse (Peromyscus maniculatus), two reservoir hosts of B. burgdorferi, as well as the impact on the Columbian black-tailed deer (Odocoileus hemionus columbianus) and the western fence lizard (Sceloporus occidentalis), both of which are important hosts for I. pacificus but are not pathogen reservoirs. Abundances of P. maniculatus and S. occidentalis were positively correlated with greater SOD disturbance, whereas N. fuscipes abundance was negatively correlated. We did not find a change in space use by O. hemionus. Our data show that SOD has a positive impact on the density of nymphal ticks, which is expected to increase the risk of human exposure to Lyme disease all else being equal. A positive correlation between SOD disturbance and the density of nymphal ticks was expected given increased abundances of two important hosts: deer mice and western fence lizards. However, further research is needed to integrate the direct effects of SOD on ticks, for example via altered abiotic conditions with host-mediated indirect effects.
Condron, Robin; Farrokh, Choreh; Jordan, Kieran; McClure, Peter; Ross, Tom; Cerf, Olivier
2015-01-02
Studies on the heat resistance of dairy pathogens are a vital part of assessing the safety of dairy products. However, harmonized methodology for the study of heat resistance of food pathogens is lacking, even though there is a need for such harmonized experimental design protocols and for harmonized validation procedures for heat treatment studies. Such an approach is of particular importance to allow international agreement on appropriate risk management of emerging potential hazards for human and animal health. This paper is working toward establishment of a harmonized protocol for the study of the heat resistance of pathogens, identifying critical issues for establishment of internationally agreed protocols, including a harmonized framework for reporting and interpretation of heat inactivation studies of potentially pathogenic microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.
An Update on the Hazards and Risks of Forensic Anthropology, Part I: Human Remains.
Roberts, Lindsey G; Dabbs, Gretchen R; Spencer, Jessica R
2016-01-01
This work reviews the hazards and risks of practicing forensic anthropology in North America, with a focus on pathogens encountered through contact with unpreserved human remains. Since the publication of Galloway and Snodgrass' seminal paper concerning the hazards of forensic anthropology, research has provided new information about known pathogen hazards, and regulating authorities have updated recommendations for the recognition and treatment of several infections. Additionally, forensic anthropology has gained popularity, exposing an increased number of students and practitioners to these hazards. Current data suggest many occupational exposures to blood or body fluids go unreported, especially among students, highlighting the need for this discussion. For each pathogen and associated disease, this work addresses important history, reviews routes of exposure, provides an overview of symptoms and treatments, lists decontamination procedures, and presents data on postmortem viability. Personal protection and laboratory guidelines should be established and enforced in conjunction with the consideration of these data. © 2015 American Academy of Forensic Sciences.
Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.
Mielczarek, Ewelina; Blaszkowska, Joanna
2016-08-01
Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.
Antimicrobial Mechanisms of Macrophages and the Immune Evasion Strategies of Staphylococcus aureus
Flannagan, Ronald S.; Heit, Bryan; Heinrichs, David E.
2015-01-01
Habitually professional phagocytes, including macrophages, eradicate microbial invaders from the human body without overt signs of infection. Despite this, there exist select bacteria that are professional pathogens, causing significant morbidity and mortality across the globe and Staphylococcus aureus is no exception. S. aureus is a highly successful pathogen that can infect virtually every tissue that comprises the human body causing a broad spectrum of diseases. The profound pathogenic capacity of S. aureus can be attributed, in part, to its ability to elaborate a profusion of bacterial effectors that circumvent host immunity. Macrophages are important professional phagocytes that contribute to both the innate and adaptive immune response, however from in vitro and in vivo studies, it is evident that they fail to eradicate S. aureus. This review provides an overview of the antimicrobial mechanisms employed by macrophages to combat bacteria and describes the immune evasion strategies and some representative effectors that enable S. aureus to evade macrophage-mediated killing. PMID:26633519
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
Predators indirectly control vector-borne disease: linking predator-prey and host-pathogen models.
Moore, Sean M; Borer, Elizabeth T; Hosseini, Parviez R
2010-01-06
Pathogens transmitted by arthropod vectors are common in human populations, agricultural systems and natural communities. Transmission of these vector-borne pathogens depends on the population dynamics of the vector species as well as its interactions with other species within the community. In particular, predation may be sufficient to control pathogen prevalence indirectly via the vector. To examine the indirect effect of predators on vectored-pathogen dynamics, we developed a theoretical model that integrates predator-prey and host-pathogen theory. We used this model to determine whether predation can prevent pathogen persistence or alter the stability of host-pathogen dynamics. We found that, in the absence of predation, pathogen prevalence in the host increases with vector fecundity, whereas predation on the vector causes pathogen prevalence to decline, or even become extinct, with increasing vector fecundity. We also found that predation on a vector may drastically slow the initial spread of a pathogen. The predator can increase host abundance indirectly by reducing or eliminating infection in the host population. These results highlight the importance of studying interactions that, within the greater community, may alter our predictions when studying disease dynamics. From an applied perspective, these results also suggest situations where an introduced predator or the natural enemies of a vector may slow the rate of spread of an emerging vector-borne pathogen.
Lis-Kuberka, Jolanta; Orczyk-Pawiłowicz, Magdalena
2015-07-22
Human milk is extremely complex secretion rich in biologically active glycoconjugates including free oligosaccharides, glycoproteins, glycolipids, and glycosaminoglycans. Alpha1-2-fucosylated glycoconjugates of human milk are component of the innate immune system and provide an additional defense for infants. Participation of fucosylated glycotopes in the inhibition of infections caused by some bacteria and/or viruses rely on blocking of lectin-receptors of pathogen. Free fucosylated glycoconjugates present in milk are recognized and bound by the lectin-receptors of bacteria and/or viruses, and prevent pathogens adhesion to host epithelial cells and development of infection. So far, the efficacy of fucosylated glycoconjugates of human milk in the inhibition of adhesion has been confirmed for Escherichia coli, Campylobacter jejuni, Salmonella enterica, Rotaviruses, HIV, and Noroviruses. In this process the secretor/nonsecretor status of mother plays an important role. This is particularly important for the women who are nonsecretors and whose milk does not contain α1-2-fucosylated glycoconjugates and has reduced anti-microbial properties. Fucosylated glycoconjugates of milk are also one of the energy sources for physiological bacterial flora (Bifidobacterium), and have a positive impact on the intestinal peristalsis, and indirectly stimulate the central nervous system of infants. Furthermore, compared to human milk, the content of fucosylated glycoconjugates of cow’s milk is very low and does not provide adequate protection. This fact is particularly important in terms of nutrition and should be taken into consideration when artificial mixtures based on cows’ milk are used. The paper presents the current state of knowledge on human milk glycoconjugates, particularly on α1-2-fucosylated free oligosaccharides and glycoproteins, and discusses the significance of fucosylated glycoconjugates of human milk in the nutrition of newborns and infants.
Knight-Jones, T J D; Mylrea, G E; Kahn, S
2010-12-01
In this short study, expert opinion and a literature review were used to identify the pathogens that should be prioritised by the World Organisation for Animal Health (OIE) for the development of future standards for animal production food safety. Prioritisation was based on a pathogen's impact on human health and amenability to control using on-farm measures. As the OIE mandate includes alleviation of global poverty, the study focused on developing countries and those with 'in-transition' economies. The regions considered were Eastern Europe, Asia, the Middle East, Africa and South America. Salmonella (from species other than poultry) and pathogenic Escherichia coli were considered to be top priorities. Brucella spp., Echinococcus granulosus and Staphylococcus aureus were also mentioned by experts. As Salmonella, and to a lesser extent pathogenic E. coli, can be controlled by on-farm measures, these pathogens should be considered for prioritisation in future standard setting. On-farm control measures for Brucella spp. will be addressed in 2010-2011 in a review of the OLE Terrestrial Animal/Health Code chapter on brucellosis. In Africa, E. granulosus, the causative agent of hydatidosis, was estimated to have the greatest impact of all pathogens that could potentially be transmitted by food (i.e. via contamination). It was also listed for the Middle East and thought to be of importance by both South American experts consulted. Taenia saginata was thought to be of importance in South America and Africa and by one expert in the Middle East.
[The pigeon tick, Argas reflexus, and hazard for human health].
Khoury, Cristina; Maroli, Michele
2004-01-01
The massive presence of the pigeon (Columba livia f. domestica) in urban areas not only is cause of serious aesthetic damages as decline of squares, of churches, of statues and buildings, but often creates many hygienic and medical problems. The pigeon, in fact, can transmit a great number of pathogenic agents and also be infested by several ectoparasites. Among these, Argas reflexus (Acari: Argasidae), the well known pigeon tick, is the most important ectoparasite that can involve also human health. Buildings infested by A. reflexus and attacks by this tick species to man are frequently reported, with an increasing interest for human health. In fact the pigeon tick bites can induce anaphylactic reactions for the presence of allergens, and as vector, the tick can also transmit some pathogens. This review deals with actual knowledge on the distribution, eco-biology, vector competence, prevention and control of A. reflexus in Italy.
New technologies, human-microbe interactions, and the search for previously unrecognized pathogens.
Relman, David A
2002-12-01
Evidence suggests that a significant number of clinically important microbial pathogens remain unrecognized. Observations from the natural world, from patterns of disease in human populations, from the bedside, and from the clinical laboratory all contribute to this body of evidence. A variety of acute and chronic neurologic syndromes illustrate this point; despite features of infection, most cases of aseptic meningitis, encephalitis, and cerebral vasculitis cannot be assigned a microbiologic diagnosis. The development and clinical application of molecular methods have led to the discovery of novel members of the endogenous normal flora as well as putative disease agents. Current challenges include the establishment of criteria for disease causation and further characterization of the human microbiome during states of health. These challenges and the goal of understanding microbial contributions to inflammatory disease may be addressed effectively through the thoughtful integration of modern technologies and clinical insight.
Parasite Zoonoses and Wildlife: Emerging Issues
Thompson, R.C. Andrew; Kutz, Susan J.; Smith, Andrew
2009-01-01
The role of wildlife as important sources, reservoirs and amplifiers of emerging human and domestic livestock pathogens, in addition to well recognized zoonoses of public health significance, has gained considerable attention in recent years. However, there has been little attention given to the transmission and impacts of pathogens of human origin, particularly protozoan, helminth and arthropod parasites, on wildlife. Substantial advances in molecular technologies are greatly improving our ability to follow parasite flow among host species and populations and revealing valuable insights about the interactions between cycles of transmission. Here we present several case studies of parasite emergence, or risk of emergence, in wildlife, as a result of contact with humans or anthropogenic activities. For some of these parasites, there is growing evidence of the serious consequences of infection on wildlife survival, whereas for others, there is a paucity of information about their impact. PMID:19440409
Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines
2017-01-01
Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use. PMID:28775971
Prevalence and diversity of human pathogenic rickettsiae in urban versus rural habitats, Hungary.
Szekeres, Sándor; Docters van Leeuwen, Arieke; Rigó, Krisztina; Jablonszky, Mónika; Majoros, Gábor; Sprong, Hein; Földvári, Gábor
2016-02-01
Tick-borne rickettsioses belong to the important emerging infectious diseases worldwide. We investigated the potential human exposure to rickettsiae by determining their presence in questing ticks collected in an urban park of Budapest and a popular hunting and recreational forest area in southern Hungary. Differences were found in the infectious risk between the two habitats. Rickettsia monacensis and Rickettsia helvetica were identified with sequencing in questing Ixodes ricinus, the only ticks species collected in the city park. Female I. ricinus had a particularly high prevalence of R. helvetica (45%). Tick community was more diverse in the rural habitat with Dermacentor reticulatus ticks having especially high percentage (58%) of Rickettsia raoultii infection. We conclude that despite the distinct eco-epidemiological traits, the risk (hazard and exposure) of acquiring human pathogenic rickettsial infections in both the urban and the rural study sites exists.
Ståhle, Magnus U; Brandhorst, Daniel; Korsgren, Olle; Knutson, Folke
2011-01-01
Serum is regarded as an essential supplement to promote survival and growth of cells during culture. However, the potential risk of transmitting diseases disqualifies the use of serum for clinical cell therapy in most countries. Hence, most clinical cell therapy programs have replaced human serum with human serum albumin, which can result in inferior quality of released cell products. Photochemical treatment of different blood products utilizing Intercept® technology has been shown to inactivate a broad variety of pathogens of RNA and DNA origin. The present study assesses the feasibility of using pathogen-inactivated, blood group-compatible serum for use in human pancreatic islet culture. Isolated human islets were cultured at 37°C for 3-4 days in CMRL 1066 supplemented with 10% of either pathogen-inactivated or nontreated human serum. Islet quality assessment included glucose-stimulated insulin release (perifusion), ADP/ATP ratio, cytokine expression, and posttransplant function in diabetic nude mice. No differences were found between islets cultured in pathogen-inactivated or control serum regarding stimulated insulin release, intracellular insulin content, and ADP/ATP ratio. Whether media was supplemented with treated or nontreated serum, islet expression of IL-6, IL-8, MCP-1, or tissue factor was not affected. The final diabetes-reversal rate of mice receiving islets cultured in pathogen-inactivated or nontreated serum was 78% and 87%, respectively (NS). As reported here, pathogen-inactivated human serum does not affect viability or functional integrity of cultured human islets. The implementation of this technology for RNA- and DNA-based pathogen inactivation should enable reintroduction of human serum for clinical cell therapy.
Farajollahi, Ary; Fonseca, Dina M; Kramer, Laura D; Marm Kilpatrick, A
2011-10-01
The transmission of vector-borne pathogens is greatly influenced by the ecology of their vector, which is in turn shaped by genetic ancestry, the environment, and the hosts that are fed on. One group of vectors, the mosquitoes in the Culex pipiens complex, play key roles in the transmission of a range of pathogens including several viruses such as West Nile and St. Louis encephalitis viruses, avian malaria (Plasmodium spp.), and filarial worms. The Cx. pipiens complex includes Culex pipiens pipiens with two forms, pipiens and molestus, Culex pipiens pallens, Culex quinquefasciatus, Culex australicus, and Culex globocoxitus. While several members of the complex have limited geographic distributions, Cx. pipienspipiens and Cx. quinquefasciatus are found in all known urban and sub-urban temperate and tropical regions, respectively, across the world, where they are often principal disease vectors. In addition, hybrids are common in areas of overlap. Although gaps in our knowledge still remain, the advent of genetic tools has greatly enhanced our understanding of the history of speciation, domestication, dispersal, and hybridization. We review the taxonomy, genetics, evolution, behavior, and ecology of members of the Cx. pipiens complex and their role in the transmission of medically important pathogens. The adaptation of Cx. pipiens complex mosquitoes to human-altered environments led to their global distribution through dispersal via humans and, combined with their mixed feeding patterns on birds and mammals (including humans), increased the transmission of several avian pathogens to humans. We highlight several unanswered questions that will increase our ability to control diseases transmitted by these mosquitoes. Copyright © 2011 Elsevier B.V. All rights reserved.
The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes
Hu, Yongfei; Yang, Xi; Li, Jing; Lv, Na; Liu, Fei; Wu, Jun; Lin, Ivan Y. C.; Wu, Na; Gao, George F.
2016-01-01
ABSTRACT Horizontally acquired antibiotic resistance genes (ARGs) in bacteria are highly mobile and have been ranked as principal risk resistance determinants. However, the transfer network of the mobile resistome and the forces driving mobile ARG transfer are largely unknown. Here, we present the whole profile of the mobile resistome in 23,425 bacterial genomes and explore the effects of phylogeny and ecology on the recent transfer (≥99% nucleotide identity) of mobile ARGs. We found that mobile ARGs are mainly present in four bacterial phyla and are significantly enriched in Proteobacteria. The recent mobile ARG transfer network, which comprises 703 bacterial species and 16,859 species pairs, is shaped by the bacterial phylogeny, while an ecological barrier also exists, especially when interrogating bacteria colonizing different human body sites. Phylogeny is still a driving force for the transfer of mobile ARGs between farm animals and the human gut, and, interestingly, the mobile ARGs that are shared between the human and animal gut microbiomes are also harbored by diverse human pathogens. Taking these results together, we suggest that phylogeny and ecology are complementary in shaping the bacterial mobile resistome and exert synergistic effects on the development of antibiotic resistance in human pathogens. IMPORTANCE The development of antibiotic resistance threatens our modern medical achievements. The dissemination of antibiotic resistance can be largely attributed to the transfer of bacterial mobile antibiotic resistance genes (ARGs). Revealing the transfer network of these genes in bacteria and the forces driving the gene flow is of great importance for controlling and predicting the emergence of antibiotic resistance in the clinic. Here, by analyzing tens of thousands of bacterial genomes and millions of human and animal gut bacterial genes, we reveal that the transfer of mobile ARGs is mainly controlled by bacterial phylogeny but under ecological constraints. We also found that dozens of ARGs are transferred between the human and animal gut and human pathogens. This work demonstrates the whole profile of mobile ARGs and their transfer network in bacteria and provides further insight into the evolution and spread of antibiotic resistance in nature. PMID:27613679
Mwamuye, Micky M; Kariuki, Edward; Omondi, David; Kabii, James; Odongo, David; Masiga, Daniel; Villinger, Jandouwe
2017-02-01
Ticks are important vectors of emerging and re-emerging zoonoses, the majority of which originate from wildlife. In recent times, this has become a global public health concern that necessitates surveillance of both known and unknown tick-borne pathogens likely to be future disease threats, as well as their tick vectors. We carried out a survey of the diversity of ticks and tick-borne pathogens in Kenya's Shimba Hills National Reserve (SHNR), an area with intensified human-livestock-wildlife interactions, where we collected 4297 questing ticks (209 adult ticks, 586 nymphs and 3502 larvae). We identified four tick species of two genera (Amblyomma eburneum, Amblyomma tholloni, Rhipicephalus maculatus and a novel Rhipicephalus sp.) based on both morphological characteristics and molecular analysis of 16S rRNA, internal transcribed spacer 2 (ITS 2) and cytochrome oxidase subunit 1 (CO1) genes. We pooled the ticks (3-8 adults, 8-15 nymphs or 30 larvae) depending on species and life-cycle stages, and screened for bacterial, arboviral and protozoal pathogens using PCR with high-resolution melting analysis and sequencing of unique melt profiles. We report the first molecular detection of Anaplasma phagocytophilum, a novel Rickettsia-like and Ehrlichia-like species, in Rh. maculatus ticks. We also detected Ehrlichia chaffeensis, Coxiella sp., Rickettsia africae and Theileria velifera in Am. eburneum ticks for the first time. Our findings demonstrate previously unidentified tick-pathogen relationships and a unique tick diversity in the SHNR that may contribute to livestock, and possibly human, morbidity in the region. This study highlights the importance of routine surveillance in similar areas to elucidate disease transmission dynamics, as a critical component to inform the development of better tick-borne disease diagnosis, prevention and control measures. Copyright © 2016 Elsevier GmbH. All rights reserved.
Conspicuous impacts of inconspicuous hosts on the Lyme disease epidemic.
Brisson, Dustin; Dykhuizen, Daniel E; Ostfeld, Richard S
2008-01-22
Emerging zoonotic pathogens are a constant threat to human health throughout the world. Control strategies to protect public health regularly fail, due in part to the tendency to focus on a single host species assumed to be the primary reservoir for a pathogen. Here, we present evidence that a diverse set of species can play an important role in determining disease risk to humans using Lyme disease as a model. Host-targeted public health strategies to control the Lyme disease epidemic in North America have focused on interrupting Borrelia burgdorferi sensu stricto (ss) transmission between blacklegged ticks and the putative dominant reservoir species, white-footed mice. However, B. burgdorferi ss infects more than a dozen vertebrate species, any of which could transmit the pathogen to feeding ticks and increase the density of infected ticks and Lyme disease risk. Using genetic and ecological data, we demonstrate that mice are neither the primary host for ticks nor the primary reservoir for B. burgdorferi ss, feeding 10% of all ticks and 25% of B. burgdorferi-infected ticks. Inconspicuous shrews feed 35% of all ticks and 55% of infected ticks. Because several important host species influence Lyme disease risk, interventions directed at a multiple host species will be required to control this epidemic.
Douville, Christopher; Masica, David L; Stenson, Peter D; Cooper, David N; Gygax, Derek M; Kim, Rick; Ryan, Michael; Karchin, Rachel
2016-01-01
Insertion/deletion variants (indels) alter protein sequence and length, yet are highly prevalent in healthy populations, presenting a challenge to bioinformatics classifiers. Commonly used features--DNA and protein sequence conservation, indel length, and occurrence in repeat regions--are useful for inference of protein damage. However, these features can cause false positives when predicting the impact of indels on disease. Existing methods for indel classification suffer from low specificities, severely limiting clinical utility. Here, we further develop our variant effect scoring tool (VEST) to include the classification of in-frame and frameshift indels (VEST-indel) as pathogenic or benign. We apply 24 features, including a new "PubMed" feature, to estimate a gene's importance in human disease. When compared with four existing indel classifiers, our method achieves a drastically reduced false-positive rate, improving specificity by as much as 90%. This approach of estimating gene importance might be generally applicable to missense and other bioinformatics pathogenicity predictors, which often fail to achieve high specificity. Finally, we tested all possible meta-predictors that can be obtained from combining the four different indel classifiers using Boolean conjunctions and disjunctions, and derived a meta-predictor with improved performance over any individual method. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.
Iannitti, Rossana G.; Napolioni, Valerio; Oikonomou, Vasilis; De Luca, Antonella; Galosi, Claudia; Pariano, Marilena; Massi-Benedetti, Cristina; Borghi, Monica; Puccetti, Matteo; Lucidi, Vincenzina; Colombo, Carla; Fiscarelli, Ersilia; Lass-Flörl, Cornelia; Majo, Fabio; Cariani, Lisa; Russo, Maria; Porcaro, Luigi; Ricciotti, Gabriella; Ellemunter, Helmut; Ratclif, Luigi; De Benedictis, Fernando Maria; Talesa, Vincenzo Nicola; Dinarello, Charles A.; van de Veerdonk, Frank L.; Romani, Luigina
2016-01-01
Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurrs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF. PMID:26972847
Iannitti, Rossana G; Napolioni, Valerio; Oikonomou, Vasilis; De Luca, Antonella; Galosi, Claudia; Pariano, Marilena; Massi-Benedetti, Cristina; Borghi, Monica; Puccetti, Matteo; Lucidi, Vincenzina; Colombo, Carla; Fiscarelli, Ersilia; Lass-Flörl, Cornelia; Majo, Fabio; Cariani, Lisa; Russo, Maria; Porcaro, Luigi; Ricciotti, Gabriella; Ellemunter, Helmut; Ratclif, Luigi; De Benedictis, Fernando Maria; Talesa, Vincenzo Nicola; Dinarello, Charles A; van de Veerdonk, Frank L; Romani, Luigina
2016-03-14
Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF.
Molecular Epidemiology of Human Intestinal Amoebas in Iran
Hooshyar, H; Rostamkhani, P; Rezaian, M
2012-01-01
Many microscopic-based epidemiological surveys on the prevalence of human intestinal pathogenic and non-pathogenic protozoa including intestinal amoeba performed in Iran show a high prevalence of human intestinal amoeba in different parts of Iran. Such epidemiological studies on amoebiasis are confusing, mainly due to recently appreciated distinction between the Entamoeba histolytica, E. dispar and E. moshkovskii. Differential diagnosis can be done by some methods such as PCR-based methods, monoclonal antibodies and the analysis of isoenzyme typing, however the molecular study of these protozoa in Iran is low. Based on molecular studies, it seems that E. dispar is predominant species especially in the central and northern areas of Iran and amoebiasis due to E. histolytica is a rare infection in the country. It is suggested that infection with E. moshkovskii may be common among Iranians. Considering the importance of molecular epidemiology of amoeba in Iran and also the current data, the present study reviews the data currently available on the molecular distribution of intestinal human amoeba in Iran. PMID:23193500
Nutritional Requirements and Their Importance for Virulence of Pathogenic Cryptococcus Species
Watkins, Rhys A.; Johnston, Simon A.
2017-01-01
Cryptococcus sp. are basidiomycete yeasts which can be found widely, free-living in the environment. Interactions with natural predators, such as amoebae in the soil, are thought to have promoted the development of adaptations enabling the organism to survive inside human macrophages. Infection with Cryptococcus in humans occurs following inhalation of desiccated yeast cells or spore particles and may result in fatal meningoencephalitis. Human disease is caused almost exclusively by the Cryptococcus neoformans species complex, which predominantly infects immunocompromised patients, and the Cryptococcus gattii species complex, which is capable of infecting immunocompetent individuals. The nutritional requirements of Cryptococcus are critical for its virulence in animals. Cryptococcus has evolved a broad range of nutrient acquisition strategies, many if not most of which also appear to contribute to its virulence, enabling infection of animal hosts. In this review, we summarise the current understanding of nutritional requirements and acquisition in Cryptococcus and offer perspectives to its evolution as a significant pathogen of humans. PMID:28974017
Cellular and Molecular Interactions of Rhabdoviruses with their Insect and Plant Hosts
USDA-ARS?s Scientific Manuscript database
The rhabdoviruses form a large family (Rhabdoviridae) whose host ranges include humans, other vertebrates, invertebrates, and plants. There are about 75 plant-infecting rhabdoviruses described, several of which are economically important pathogens that are persistently transmitted to their plant ho...
SELENIUM-DEFICIENCY MODIFIES INFLUENZA INFECTION OF DIFFERENTIATED HUMAN BRONCHIAL EPITHELIAL CELLS
The nutritional status of the host is important in the defense against invading pathogens. Many studies regarding the effects of host nutritional status on the immune response have demonstrated that suboptimal host nutrition results in impaired host immunity and increased suscept...
USDA-ARS?s Scientific Manuscript database
Understanding of plant-bacterial interactions is of critical importance for developing effective control measures against infectious diseases caused by foodborne human pathogens. However, limitations of existing scientific tools to access and evaluate natural plant tissues, and the large variations ...
Chapter 2. Assessing the importance of zoonotic waterborne pathogens
USDA-ARS?s Scientific Manuscript database
Cryptosporidium, an apicomplexan protozoan, is reported to infect persons in 106 countries and more than 150 species of other mammals worldwide. Estimates of prevalence in humans vary greatly because reporting is not universally required, diagnostic methods vary greatly, and many persons have no acc...
2016-02-01
To prevent transmission of bloodborne pathogens, it is important that health care providers adhere to standard precautions, follow fundamental infection-control principles, and use appropriate procedural techniques. All obstetrician-gynecologists who provide clinical care should receive the hepatitis B virus vaccine series. The Society for Healthcare Epidemiology of America has established guidelines for the management of health care providers who are infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV). The guidelines categorize representative obstetric and gynecologic procedures according to level of risk of bloodborne pathogen transmission and include recommendations for health care provider clinical activities, based on these categories and viral burden. It is important to note that when no restrictions are recommended, careful supervision should be carried out as highlighted. These recommendations provide a framework within which to consider such cases; however, each case should be independently considered in context by the expert review panel.
Small molecule inhibition of apicomplexan FtsH1 disrupts plastid biogenesis in human pathogens.
Amberg-Johnson, Katherine; Hari, Sanjay B; Ganesan, Suresh M; Lorenzi, Hernan A; Sauer, Robert T; Niles, Jacquin C; Yeh, Ellen
2017-08-18
The malaria parasite Plasmodium falciparum and related apicomplexan pathogens contain an essential plastid organelle, the apicoplast, which is a key anti-parasitic target. Derived from secondary endosymbiosis, the apicoplast depends on novel, but largely cryptic, mechanisms for protein/lipid import and organelle inheritance during parasite replication. These critical biogenesis pathways present untapped opportunities to discover new parasite-specific drug targets. We used an innovative screen to identify actinonin as having a novel mechanism-of-action inhibiting apicoplast biogenesis. Resistant mutation, chemical-genetic interaction, and biochemical inhibition demonstrate that the unexpected target of actinonin in P. falciparum and Toxoplasma gondii is FtsH1, a homolog of a bacterial membrane AAA+ metalloprotease. Pf FtsH1 is the first novel factor required for apicoplast biogenesis identified in a phenotypic screen. Our findings demonstrate that FtsH1 is a novel and, importantly, druggable antimalarial target. Development of FtsH1 inhibitors will have significant advantages with improved drug kinetics and multistage efficacy against multiple human parasites.
Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies.
Bocharov, Eduard V; Lesovoy, Dmitry M; Goncharuk, Sergey A; Goncharuk, Marina V; Hristova, Kalina; Arseniev, Alexander S
2013-11-05
Fibroblast growth factor receptor 3 (FGFR3) transduces biochemical signals via lateral dimerization in the plasma membrane, and plays an important role in human development and disease. Eight different pathogenic mutations, implicated in cancers and growth disorders, have been identified in the FGFR3 transmembrane segment. Here, we describe the dimerization of the FGFR3 transmembrane domain in membrane-mimicking DPC/SDS (9/1) micelles. In the solved NMR structure, the two transmembrane helices pack into a symmetric left-handed dimer, with intermolecular stacking interactions occurring in the dimer central region. Some pathogenic mutations fall within the helix-helix interface, whereas others are located within a putative alternative interface. This implies that although the observed dimer structure is important for FGFR3 signaling, the mechanism of FGFR3-mediated transduction across the membrane is complex. We propose an FGFR3 signaling mechanism that is based on the solved structure, available structures of isolated soluble FGFR domains, and published biochemical and biophysical data. Copyright © 2013 Elsevier Ltd. All rights reserved.
Developments in Fungal Taxonomy
Guarro, Josep; Gené, Josepa; Stchigel, Alberto M.
1999-01-01
Fungal infections, especially those caused by opportunistic species, have become substantially more common in recent decades. Numerous species cause human infections, and several new human pathogens are discovered yearly. This situation has created an increasing interest in fungal taxonomy and has led to the development of new methods and approaches to fungal biosystematics which have promoted important practical advances in identification procedures. However, the significance of some data provided by the new approaches is still unclear, and results drawn from such studies may even increase nomenclatural confusion. Analyses of rRNA and rDNA sequences constitute an important complement of the morphological criteria needed to allow clinical fungi to be more easily identified and placed on a single phylogenetic tree. Most of the pathogenic fungi so far described belong to the kingdom Fungi; two belong to the kingdom Chromista. Within the Fungi, they are distributed in three phyla and in 15 orders (Pneumocystidales, Saccharomycetales, Dothideales, Sordariales, Onygenales, Eurotiales, Hypocreales, Ophiostomatales, Microascales, Tremellales, Poriales, Stereales, Agaricales, Schizophyllales, and Ustilaginales). PMID:10398676
Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication
König, Renate; Zhou, Yingyao; Elleder, Daniel; Diamond, Tracy L.; Bonamy, Ghislain M.C.; Irelan, Jeffrey T.; Chiang, Chih-yuan; Tu, Buu P.; De Jesus, Paul D.; Lilley, Caroline E.; Seidel, Shannon; Opaluch, Amanda M.; Caldwell, Jeremy S.; Weitzman, Matthew D.; Kuhen, Kelli L.; Bandyopadhyay, Sourav; Ideker, Trey; Orth, Anthony P.; Miraglia, Loren J.; Bushman, Frederic D.; Young, John A.; Chanda, Sumit K.
2008-01-01
Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection. PMID:18854154
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hast, Michael A.; Beese, Lorena S.
2008-11-21
Protein geranylgeranyltransferase-I (GGTase-I) catalyzes the transfer of a 20-carbon isoprenoid lipid to the sulfur of a cysteine residue located near the C terminus of numerous cellular proteins, including members of the Rho superfamily of small GTPases and other essential signal transduction proteins. In humans, GGTase-I and the homologous protein farnesyltransferase (FTase) are targets of anticancer therapeutics because of the role small GTPases play in oncogenesis. Protein prenyltransferases are also essential for many fungal and protozoan pathogens that infect humans, and have therefore become important targets for treating infectious diseases. Candida albicans, a causative agent of systemic fungal infections in immunocompromisedmore » individuals, is one pathogen for which protein prenylation is essential for survival. Here we present the crystal structure of GGTase-I from C. albicans (CaGGTase-I) in complex with its cognate lipid substrate, geranylgeranylpyrophosphate. This structure provides a high-resolution picture of a non-mammalian protein prenyltransferase. There are significant variations between species in critical areas of the active site, including the isoprenoid-binding pocket, as well as the putative product exit groove. These differences indicate the regions where specific protein prenyltransferase inhibitors with antifungal activity can be designed.« less
Structural Model for Covalent Adhesion of the Streptococcus pyogenes Pilus through a Thioester Bond*
Linke-Winnebeck, Christian; Paterson, Neil G.; Young, Paul G.; Middleditch, Martin J.; Greenwood, David R.; Witte, Gregor; Baker, Edward N.
2014-01-01
The human pathogen Streptococcus pyogenes produces pili that are essential for adhesion to host surface receptors. Cpa, the adhesin at the pilus tip, was recently shown to have a thioester-containing domain. The thioester bond is believed to be important in adhesion, implying a mechanism of covalent attachment analogous to that used by human complement factors. Here, we have characterized a second active thioester-containing domain on Cpa, the N-terminal domain of Cpa (CpaN). Expression of CpaN in Escherichia coli gave covalently linked dimers. These were shown by x-ray crystallography and mass spectrometry to comprise two CpaN molecules cross-linked by the polyamine spermidine following reaction with the thioester bonds. This cross-linked CpaN dimer provides a model for the covalent attachment of Cpa to target receptors and thus the streptococcal pilus to host cells. Similar thioester domains were identified in cell wall proteins of other Gram-positive pathogens, suggesting that thioester domains are more widely used and provide a mechanism of adhesion by covalent bonding to target molecules on host cells that mimics that used by the human complement system to eliminate pathogens. PMID:24220033
Asymptomatic Carriage of Group A Streptococcus Is Associated with Elimination of Capsule Production
Jewell, Brittany E.; Olsen, Randall J.; Shelburne, Samuel A.; Fittipaldi, Nahuel; Beres, Stephen B.; Musser, James M.
2014-01-01
Humans commonly carry pathogenic bacteria asymptomatically, but despite decades of study, the underlying molecular contributors remain poorly understood. Here, we show that a group A streptococcus carriage strain contains a frameshift mutation in the hasA gene resulting in loss of hyaluronic acid capsule biosynthesis. This mutation was repaired by allelic replacement, resulting in restoration of capsule production in the isogenic derivative strain. The “repaired” isogenic strain was significantly more virulent than the carriage strain in a mouse model of necrotizing fasciitis and had enhanced growth ex vivo in human blood. Importantly, the repaired isogenic strain colonized the mouse oropharynx with significantly greater bacterial burden and had significantly reduced ability to internalize into cultured epithelial cells than the acapsular carriage strain. We conducted full-genome sequencing of 81 strains cultured serially from 19 epidemiologically unrelated human subjects and discovered the common theme that mutations negatively affecting capsule biosynthesis arise in vivo in the has operon. The significantly decreased capsule production is a key factor contributing to the molecular détente between pathogen and host. Our discoveries suggest a general model for bacterial pathogens in which mutations that downregulate or ablate virulence factor production contribute to carriage. PMID:25024363
Sato, Mitsuharu; Watthanaworawit, Wanitda; Ling, Clare L.; Mauduit, Marjorie; Malleret, Benoît; Grüner, Anne-Charlotte; Tan, Rosemary; Nosten, François H.; Snounou, Georges; Rénia, Laurent; Ng, Lisa F. P.
2014-01-01
Tropical pathogens often cause febrile illnesses in humans and are responsible for considerable morbidity and mortality. The similarities in clinical symptoms provoked by these pathogens make diagnosis difficult. Thus, early, rapid and accurate diagnosis will be crucial in patient management and in the control of these diseases. In this study, a microfluidic lab-on-chip integrating multiplex molecular amplification and DNA microarray hybridization was developed for simultaneous detection and species differentiation of 26 globally important tropical pathogens. The analytical performance of the lab-on-chip for each pathogen ranged from 102 to 103 DNA or RNA copies. Assay performance was further verified with human whole blood spiked with Plasmodium falciparum and Chikungunya virus that yielded a range of detection from 200 to 4×105 parasites, and from 250 to 4×107 PFU respectively. This lab-on-chip was subsequently assessed and evaluated using 170 retrospective patient specimens in Singapore and Thailand. The lab-on-chip had a detection sensitivity of 83.1% and a specificity of 100% for P. falciparum; a sensitivity of 91.3% and a specificity of 99.3% for P. vivax; a positive 90.0% agreement and a specificity of 100% for Chikungunya virus; and a positive 85.0% agreement and a specificity of 100% for Dengue virus serotype 3 with reference methods conducted on the samples. Results suggested the practicality of an amplification microarray-based approach in a field setting for high-throughput detection and identification of tropical pathogens. PMID:25078474
Airborne pathogens from dairy manure aerial irrigation and the human health risk
Borchardt, Mark A.; Burch, Tucker R
2016-01-01
Dairy manure, like the fecal excrement from any domesticated or wild animal, can contain pathogens capable of infecting humans and causing illness or even death. Pathogens in dairy manure can be broadly divided into categories of taxonomy or infectiousness. Dividing by taxonomy there are three pathogen groups in dairy manure: viruses (e.g., bovine rotavirus), bacteria (e.g., Salmonella species), and protozoa (e.g., Cryptosporidium parvum). There are two categories of infectiousness for pathogens found in animals: those that are zoonotic and those that are not. A zoonotic pathogen is one that can infect both human and animal hosts. Some zoonotic pathogens found in dairy manure cause illness in both hosts (e.g., Salmonella) while other zoonotic pathogens, like Escherichia coli O157:H7, (enterohemorrhagic E. coli (EHEC)) cause illness only in humans. As a general rule, the gastrointestinal viruses found in dairy manure are not zoonotic. While there are exceptions (e.g., rare reports of bovine rotavirus infecting children), for the most part the viruses in dairy manure are not a human health concern. The primary concerns are the zoonotic bacteria and protozoa in dairy manure.
Disseminated Geotrichum candidum infection.
Kassamali, H; Anaissie, E; Ro, J; Rolston, K; Kantarjian, H; Fainstein, V; Bodey, G P
1987-01-01
The pathogenicity of the fungus Geotrichum candidum in humans has not been clearly defined. A patient with acute leukemia who developed a fatal disseminated G. candidum infection while neutropenic is described. At autopsy examination, this patient was misdiagnosed on the basis of histopathology as having disseminated candidiasis until G. candidum was isolated from postmortem culture specimens. The emergence of this organism as an occasional pathogen in leukemic patients is of interest and illustrates the importance of obtaining fungal cultures. There is a need for more effective drugs for antifungal prophylaxis and therapy. PMID:3477570
Species-Level Identification of Orthopoxviruses with an Oligonucleotide Microchip
Lapa, Sergey; Mikheev, Maxim; Shchelkunov, Sergei; Mikhailovich, Vladimir; Sobolev, Alexander; Blinov, Vladimir; Babkin, Igor; Guskov, Alexander; Sokunova, Elena; Zasedatelev, Alexander; Sandakhchiev, Lev; Mirzabekov, Andrei
2002-01-01
A method for species-specific detection of orthopoxviruses pathogenic for humans and animals is described. The method is based on hybridization of a fluorescently labeled amplified DNA specimen with the oligonucleotide DNA probes immobilized on a microchip (MAGIChip). The probes identify species-specific sites within the crmB gene encoding the viral analogue of tumor necrosis factor receptor, one of the most important determinants of pathogenicity in this genus of viruses. The diagnostic procedure takes 6 h and does not require any sophisticated equipment (a portable fluorescence reader can be used). PMID:11880388
Vödisch, Martin; Albrecht, Daniela; Lessing, Franziska; Schmidt, André D; Winkler, Robert; Guthke, Reinhard; Brakhage, Axel A; Kniemeyer, Olaf
2009-03-01
The filamentous fungus Aspergillus fumigatus has become the most important airborne fungal pathogen causing life-threatening infections in immunosuppressed patients. We established a 2-D reference map for A. fumigatus. Using MALDI-TOF-MS/MS, we identified 381 spots representing 334 proteins. Proteins involved in cellular metabolism, protein synthesis, transport processes and cell cycle were most abundant. Furthermore, we established a protocol for the isolation of mitochondria of A. fumigatus and developed a mitochondrial proteome reference map. 147 proteins represented by 234 spots were identified.
Mok, Chris Ka Pun; Lee, Horace Hok Yeung; Lestra, Maxime; Nicholls, John Malcolm; Chan, Michael Chi Wai; Sia, Sin Fun; Zhu, Huachen; Poon, Leo Lit Man; Guan, Yi
2014-01-01
ABSTRACT A novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus. In this study, we determined the contribution of PB2-E627K in H7N9 virus to its pathogenicity in mammalian hosts. In addition, the compensatory role of the PB2 mutations T271A, Q591K, and D701N in H7N9 virus was investigated. We characterized the activity of polymerase complexes with these PB2 mutations and found that they enhance the polymerase activity in human 293T cells. The rescued mutants enhanced growth in mammalian cells in vitro. Mice infected with the H7N9 mutant containing the avian signature protein PB2-627E showed a marked decrease in disease severity (weight loss) and pathology compared to mice infected with the wild-type strain (PB2-627K) or other PB2 mutants. Also, mutants with PB2-627E showed lower virus replication and proinflammatory cytokine responses in the lungs of the virus-infected mice, which may contribute to pathogenicity. Our results suggest that these amino acid substitutions contribute to mouse pathogenicity and mammalian adaptation. IMPORTANCE A novel avian H7N9 influenza A virus emerged in east China in 2013 to cause zoonotic human disease associated with significant mortality. It is important to understand the viral genetic markers of mammalian adaptation and disease severity in this H7N9 virus. Since many human (but not avian) H7N9 virus isolates have an amino acid substitution at position E627K in the polymerase basic protein 2 (PB2) gene, we investigated the role of this and other functionally related mutations for polymerase activity in vitro, virus replication competence, and pathogenicity in the mouse model. We found that E627K and functionally related mutations are associated with increased polymerase activity, increased viral replication competence, and increased disease severity in mice. PMID:24403592
Shimabukuro, Paloma Helena Fernandes; de Andrade, Andrey José; Galati, Eunice Aparecida Bianchi
2017-01-01
Abstract Phlebotomine sand flies are dipteran insects of medical importance because many species are involved in the transmission of pathogens between human and non-human animals. A total of 530 American species of sand flies is presented in an updated checklist, along with their author(s) and year of publication using the classification by Galati (1995, 2003). Distribution by country is also provided. PMID:28794674
Ma, Y; Zhang, Z B; Cao, L; Lu, J Y; Li, K B; Su, W Z; Li, T G; Yang, Z C; Wang, M
2018-06-10
Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.
Sung, Anne A; Gromek, Samantha M; Balunas, Marcy J
2017-08-11
Marine natural product drug discovery has begun to play an important role in the treatment of disease, with several recently approved drugs. In addition, numerous microbial natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces , due to their metabolic diversity for production of biologically active secondary metabolites. However, many secondary metabolites cannot be produced under laboratory conditions because growth conditions in flask culture differ from conditions in the natural environment. Various experimental conditions (e.g., mixed fermentation) have been attempted to increase yields of previously described metabolites, cause production of previously undetected metabolites, and increase antibiotic activity. Adult ascidians-also known as tunicates-are sessile marine invertebrates, making them vulnerable to predation and therefore are hypothesized to use host-associated bacteria that produce biologically active secondary metabolites for chemical defense. A marine-derived Streptomyces sp. strain PTY087I2 was isolated from a Panamanian tunicate and subsequently co-cultured with human pathogens including Bacillus subtilis , methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa , followed by extraction. Co-culture of Streptomyces sp. PTY087I2 with each of these human pathogens resulted in increased production of three antibiotics: granaticin, granatomycin D, and dihydrogranaticin B, as well as several analogues seen via molecular networking. In addition, co-cultures resulted in strongly enhanced biological activity against the Gram positive human pathogens used in these experiments. Expanded utilization of co-culture experiments to allow for competitive interactions may enhance metabolite production and further our understanding of these microbial interactions.
Bactericidal activity of the human skin fatty acid cis-6-hexadecanoic acid on Staphylococcus aureus.
Cartron, Michaël L; England, Simon R; Chiriac, Alina Iulia; Josten, Michaele; Turner, Robert; Rauter, Yvonne; Hurd, Alexander; Sahl, Hans-Georg; Jones, Simon; Foster, Simon J
2014-07-01
Human skin fatty acids are a potent aspect of our innate defenses, giving surface protection against potentially invasive organisms. They provide an important parameter in determining the ecology of the skin microflora, and alterations can lead to increased colonization by pathogens such as Staphylococcus aureus. Harnessing skin fatty acids may also give a new avenue of exploration in the generation of control measures against drug-resistant organisms. Despite their importance, the mechanism(s) whereby skin fatty acids kill bacteria has remained largely elusive. Here, we describe an analysis of the bactericidal effects of the major human skin fatty acid cis-6-hexadecenoic acid (C6H) on the human commensal and pathogen S. aureus. Several C6H concentration-dependent mechanisms were found. At high concentrations, C6H swiftly kills cells associated with a general loss of membrane integrity. However, C6H still kills at lower concentrations, acting through disruption of the proton motive force, an increase in membrane fluidity, and its effects on electron transfer. The design of analogues with altered bactericidal effects has begun to determine the structural constraints on activity and paves the way for the rational design of new antistaphylococcal agents. Copyright © 2014 Cartron et al.
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.
Lee, Young Ah; Nam, Young Hee; Min, Arim; Kim, Kyeong Ah; Nozaki, Tomoyoshi; Saito-Nakano, Yumiko; Mirelman, David; Shin, Myeong Heon
2014-01-01
Entamoeba histolytica is an extracellular tissue parasite causing colitis and occasional liver abscess in humans. E. histolytica-derived secretory products (SPs) contain large amounts of cysteine proteases (CPs), one of the important amoebic virulence factors. Although tissue-residing mast cells play an important role in the mucosal inflammatory response to this pathogen, it is not known whether the SPs induce mast cell activation. In this study, when human mast cells (HMC-1 cells) were stimulated with SPs collected from pathogenic wild-type amoebae, interleukin IL-8 mRNA expression and production were significantly increased compared with cells incubated with medium alone. Inhibition of CP activity in the SPs with heat or the CP inhibitor E64 resulted in significant reduction of IL-8 production. Moreover, SPs obtained from inhibitors of cysteine protease (ICP)-overexpressing amoebae with low CP activity showed weaker stimulatory effects on IL-8 production than the wild-type control. Preincubation of HMC-1 cells with antibodies to human protease-activated receptor 2 (PAR2) did not affect the SP-induced IL-8 production. These results suggest that cysteine proteases in E. histolytica-derived secretory products stimulate mast cells to produce IL-8 via a PAR2-independent mechanism, which contributes to IL-8-mediated tissue inflammatory responses during the early phase of human amoebiasis. © Y.A. Lee et al., published by EDP Sciences, 2014.
Skelly, Chris; Weinstein, Phil
2003-01-01
Campylobacteriosis, like many human diseases, has its own ecology in which the propagation of human infection and disease depends on pathogen survival and finding new hosts in order to replicate and sustain the pathogen population. The complexity of this process, a process common to other enteric pathogens, has hampered control efforts. Many unknowns remain, resulting in a poorly understood disease ecology. To provide structure to these unknowns and help direct further research and intervention, we propose an eco-environmental modeling approach for campylobacteriosis. This modeling approach follows the pathogen population as it moves through the environments that define the physical structure of its ecology. In this paper, we term the ecologic processes and environments through which these populations move "pathogen survival trajectories." Although such a modeling approach could have veterinary applications, our emphasis is on human campylobacteriosis and focuses on human exposures to Campylobacter through feces, food, and aquatic environments. The pathogen survival trajectories that lead to human exposure include ecologic filters that limit population size, e.g., cooking food to kill Campylobacter. Environmental factors that influence the size of the pathogen reservoirs include temperature, nutrient availability, and moisture availability during the period of time the pathogen population is moving through the environment between infected and susceptible hosts. We anticipate that the modeling approach proposed here will work symbiotically with traditional epidemiologic and microbiologic research to help guide and evaluate the acquisition of new knowledge about the ecology, eventual intervention, and control of campylobacteriosis. PMID:12515674
Dileep, V; Kumar, H S; Kumar, Y; Nishibuchi, M; Karunasagar, Indrani; Karunasagar, Iddya
2003-01-01
To study the incidence of Vibrio parahaemolyticus in seafoods, water and sediment by molecular techniques vs conventional microbiological methods. Of 86 samples analysed, 28 recorded positive for V. parahaemolyticus by conventional microbiological method, while 53 were positive by the toxR-targeted PCR, performed directly on enrichment broth lysates. While one sample of molluscan shellfish was positive for tdh gene, trh gene was detected in three enrichment broths of molluscan shellfish. Direct application of PCR to enrichment broths will be useful for the rapid and sensitive detection of potentially pathogenic strains of V. parahemolyticus in seafoods. Vibrio parahaemolyticus is an important human pathogen responsible for food-borne gastroenteritis world-wide. As, both pathogenic and non-pathogenic strains of V. parahaemolyticus exist in the seafood, application of PCR specific for the virulence genes (tdh & trh) will help in detection of pathogenic strains of V. parahaemolyticus and consequently reduce the risk of food-borne illness.
Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens.
LaRock, Christopher N; Nizet, Victor
2015-11-01
Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Copyright © 2015 Elsevier B.V. All rights reserved.
Aardema, H.; Luijnenburg, E. M.; Salm, E. F.; Bijlmer, H. A.; Visser, C. E.; Van't Wout, J. W.
2005-01-01
Melioidosis is an infectious disease caused by Burkholderia pseudomallei. It is endemic in South East Asia and tropical regions of Northern Australia. Sporadic cases have been described elsewhere. In this article we present a case of acute pulmonary melioidosis with fatal outcome imported from Brazil. The most common pathogen causing severe community-acquired pneumonia in Brazil is Streptococcus pneumoniae. Other possible pathogens include Legionella spp., Mycoplasma pneumonia, Gram-negative rods and viruses. There are few reports of melioidosis in the Americas. This article represents the second known human case of melioidosis from Brazil. Recognition of melioidosis as a possible cause of severe pneumonia, even if a patient has not been travelling in a highly endemic area, is important because of the therapeutic consequences. The epidemiology of melioidosis will be reviewed. PMID:16181507
Khurana, Surender; Chung, Ka Yan; Coyle, Elizabeth M; Meijer, Adam; Golding, Hana
2016-10-15
Infections with H7 highly pathogenic avian influenza (HPAI) viruses remain a major public health concern. Adaptation of low-pathogenic H7N7 to highly pathogenic H7N7 in Europe in 2015 raised further alarm for a potential pandemic. An in-depth understanding of antibody responses to HPAI H7 virus following infection in humans could provide important insight into virus gene expression as well as define key protective and serodiagnostic targets. Here we used whole-genome gene fragment phage display libraries (GFPDLs) expressing peptides of 15 to 350 amino acids across the complete genome of the HPAI H7N7 A/Netherlands/33/03 virus. The hemagglutinin (HA) antibody epitope repertoires of 15 H7N7-exposed humans identified clear differences between individuals with no hemagglutination inhibition (HI) titers (<1:10) and those with HI titers of >1:40. Several potentially protective H7N7 epitopes close to the HA receptor binding domain (RBD) and neuraminidase (NA) catalytic site were identified. Surface plasmon resonance (SPR) analysis identified a strong correlation between HA1 (but not HA2) binding antibodies and H7N7 HI titers. A proportion of HA1 binding in plasma was contributed by IgA antibodies. Antibodies against the N7 neuraminidase were less frequent but targeted sites close to the sialic acid binding site. Importantly, we identified strong antibody reactivity against PA-X, a putative virulence factor, in most H7N7-exposed individuals, providing the first evidence for in vivo expression of PA-X and its recognition by the immune system during human influenza A virus infection. This knowledge can help inform the development and selection of the most effective countermeasures for prophylactic as well as therapeutic treatments of HPAI H7N7 avian influenza virus. An outbreak of pathogenic H7N7 virus occurred in poultry farms in The Netherlands in 2003. Severe outcome included conjunctivitis, influenza-like illness, and one lethal infection. In this study, we investigated convalescent-phase sera from H7N7-exposed individuals by using a whole-genome phage display library (H7N7-GFPDL) to explore the complete repertoire of post-H7N7-exposure antibodies. PA-X is a recently identified influenza virus virulence protein generated by ribosomal frameshifting in segment 3 of influenza virus coding for PA. However, PA-X expression during influenza virus infection in humans is unknown. We identified strong antibody reactivity against PA-X in most H7N7-exposed individuals (but not in unexposed adults), providing the first evidence for in vivo expression of PA-X and its recognition by the immune system during human infection with pathogenic H7N7 avian influenza virus. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Cryptosporidiosis, giardiasis, and microsporidiosis are important waterborne diseases. In the standard for wastewater treatment plant (WWTP) effluents in China and other countries, fecal coliform is the only microbial indicator, raising concerns about the potential for pathogen t...
Persistence of salmonella Typhimurium in Nopal
USDA-ARS?s Scientific Manuscript database
Having documented information available on the capability of Salmonella to remain in the cladode tissue it is important to understand the role of nopal on the lifecycle of enteropathogenic bacteria in humans, as well as for management and control programs of theses pathogens in plants. Because of th...
Evidence of aneuploidy modulating aflatoxigenicity in Aspergillus flavus
USDA-ARS?s Scientific Manuscript database
Aspergillus flavus is a well-known pathogen of many important agricultural commodities and is a major producer of aflatoxins, which are carcinogenic polyketides that pose a serious health risk to humans and animals. Aflatoxin contamination in peanut exports worldwide accounts for as much as $450 mi...
A taxonomic and phylogenetic re-appraisal of the genus Curvularia
USDA-ARS?s Scientific Manuscript database
Species of Curvularia are important plant and human pathogens worldwide. In this study, the genus Curvularia is re-assessed based on molecular phylogenetic analysis and morphological observations of available isolates and specimens. A multi-gene phylogenetic tree inferred from ITS, TEF and GPDH gene...
Molecular biology of tick Acetylcholinesterases – a minireview
USDA-ARS?s Scientific Manuscript database
Ticks are important hematophagous arthropod ectoparasites and like mosquitoes, are vectors for a wide variety of human and animal pathogens. Ticks have significant world-wide health and economic impacts. In the U.S., major impacts include the ability of the blacklegged tick, Ixodes scapularis, to tr...
Comparative Fecal Metagenomics Unveils Unique Functional Capacity of the Swine Gut
Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health and to food and water safety due to the presence of human pathogens in pig feces. Limited information on the physiological...
PaPrBaG: A machine learning approach for the detection of novel pathogens from NGS data
NASA Astrophysics Data System (ADS)
Deneke, Carlus; Rentzsch, Robert; Renard, Bernhard Y.
2017-01-01
The reliable detection of novel bacterial pathogens from next-generation sequencing data is a key challenge for microbial diagnostics. Current computational tools usually rely on sequence similarity and often fail to detect novel species when closely related genomes are unavailable or missing from the reference database. Here we present the machine learning based approach PaPrBaG (Pathogenicity Prediction for Bacterial Genomes). PaPrBaG overcomes genetic divergence by training on a wide range of species with known pathogenicity phenotype. To that end we compiled a comprehensive list of pathogenic and non-pathogenic bacteria with human host, using various genome metadata in conjunction with a rule-based protocol. A detailed comparative study reveals that PaPrBaG has several advantages over sequence similarity approaches. Most importantly, it always provides a prediction whereas other approaches discard a large number of sequencing reads with low similarity to currently known reference genomes. Furthermore, PaPrBaG remains reliable even at very low genomic coverages. CombiningPaPrBaG with existing approaches further improves prediction results.
A new view to intracellular pathogens and host responses in the South of Spain.
García-del Portillo, Francisco; Cossart, Pascale
2012-03-01
A workshop on 'The Biology of Intracellular Bacterial Pathogens' was held last October in a venue of the International University of Andalusia (UNIA) located in the World Historic Heritage town of Baeza, in the South of Spain. This Workshop gathered leading scientists from around the world to discuss their latest findings related to the mechanisms that intracellular pathogens use to subvert and manipulate host cell functions. The workshop focused on novel aspects that imprint current research in this discipline, including the heterogeneous behaviour of the pathogen at the population level, the host determinants that modulate susceptibility to the infection, the search for new drugs to combat these particular types of infections and also cutting edge technologies based on new imaging approaches and the use of microfluidics. Discussion on these topics provided new insights into the biology of these pathogens and enriched the field with new ideas for understanding why colonization of the intracellular niche of eukaryotic cells is a preferred strategy used by important human pathogens. Copyright © 2012 EMBO Molecular Medicine.
Borrelia miyamotoi, Other Vector-Borne Agents in Cat Blood and Ticks in Eastern Maryland.
Shannon, Avery B; Rucinsky, Renee; Gaff, Holly D; Brinkerhoff, R Jory
2017-12-01
We collected blood and tick samples in eastern Maryland to quantify vector-borne pathogen exposure and infection in healthy cats and to assess occupational disease risk to veterinary professionals and others who regularly interact with household pets. Thirty-six percent of healthy cats parasitized by ticks at time of examination (9/25) were exposed to, and 14% of bloods (7/49) tested PCR-positive for, at least one vector-borne pathogen including several bloods and ticks with Borrelia miyamotoi, a recently recognized tick-borne zoonotic bacterium. There was no indication that high tick burdens were associated with exposure to vector-borne pathogens. Our results underscore the potential importance of cats to human vector-borne disease risk.
Kinetoplastids: related protozoan pathogens, different diseases
Stuart, Ken; Brun, Reto; Croft, Simon; Fairlamb, Alan; Gürtler, Ricardo E.; McKerrow, Jim; Reed, Steve; Tarleton, Rick
2008-01-01
Kinetoplastids are a group of flagellated protozoans that include the species Trypanosoma and Leishmania, which are human pathogens with devastating health and economic effects. The sequencing of the genomes of some of these species has highlighted their genetic relatedness and underlined differences in the diseases that they cause. As we discuss in this Review, steady progress using a combination of molecular, genetic, immunologic, and clinical approaches has substantially increased understanding of these pathogens and important aspects of the diseases that they cause. Consequently, the paths for developing additional measures to control these “neglected diseases” are becoming increasingly clear, and we believe that the opportunities for developing the drugs, diagnostics, vaccines, and other tools necessary to expand the armamentarium to combat these diseases have never been better. PMID:18382742
Chaves, Edilânia Gomes Araújo; Weber, Simone Schneider; Báo, Sonia Nair; Pereira, Luiz Augusto; Bailão, Alexandre Melo; Borges, Clayton Luiz; Soares, Célia Maria de Almeida
2015-02-27
Despite being important thermal dimorphic fungi causing Paracoccidioidomycosis, the pathogenic mechanisms that underlie the genus Paracoccidioides remain largely unknown. Microbial pathogens express molecules that can interact with human plasminogen, a protein from blood plasma, which presents fibrinolytic activity when activated into plasmin. Additionally, plasmin exhibits the ability of degrading extracellular matrix components, favoring the pathogen spread to deeper tissues. Previous work from our group demonstrated that Paracoccidioides presents enolase, as a protein able to bind and activate plasminogen, increasing the fibrinolytic activity of the pathogen, and the potential for adhesion and invasion of the fungus to host cells. By using proteomic analysis, we aimed to identify other proteins of Paracoccidioides with the ability of binding to plasminogen. In the present study, we employed proteomic analysis of the secretome, in order to identify plasminogen-binding proteins of Paracoccidioides, Pb01. Fifteen proteins were present in the fungal secretome, presenting the ability to bind to plasminogen. Those proteins are probable targets of the fungus interaction with the host; thus, they could contribute to the invasiveness of the fungus. For validation tests, we selected the protein fructose 1,6-bisphosphate aldolase (FBA), described in other pathogens as a plasminogen-binding protein. The protein FBA at the fungus surface and the recombinant FBA (rFBA) bound human plasminogen and promoted its conversion to plasmin, potentially increasing the fibrinolytic capacity of the fungus, as demonstrated in fibrin degradation assays. The addition of rFBA or anti-rFBA antibodies was capable of reducing the interaction between macrophages and Paracoccidioides, possibly by blocking the binding sites for FBA. These data reveal the possible participation of the FBA in the processes of cell adhesion and tissue invasion/dissemination of Paracoccidioides. These data indicate that Paracoccidioides is a pathogen that has several plasminogen-binding proteins that likely play important roles in pathogen-host interaction. In this context, FBA is a protein that might be involved somehow in the processes of invasion and spread of the fungus during infection.
Genetic Factors Influence Serological Measures of Common Infections
Rubicz, Rohina; Leach, Charles T.; Kraig, Ellen; Dhurandhar, Nikhil V.; Duggirala, Ravindranath; Blangero, John; Yolken, Robert; Göring, Harald H.H.
2011-01-01
Background/Aims Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and −2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses. Results Serological phenotypes were significantly heritable for most pathogens (h2 = 0.17–0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c2 = 0.10–0.32). The underlying genetic etiology appears to be largely different for most pathogens. Conclusions Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance. PMID:21996708
Gervasi, T; Lo Curto, R; Minniti, E; Narbad, A; Mayer, M J
2014-10-01
Clostridium perfringens is frequently found in food and the environment and produces potent toxins that have a negative impact on both human and animal health and particularly on the poultry industry. Lactobacillus johnsonii FI9785, isolated from the chicken gastrointestinal tract, has been demonstrated to exclude Cl. perfringens in poultry. We have investigated the interaction of wild-type Lact. johnsonii FI9785 or an engineered strain expressing a cell wall-hydrolysing endolysin with Cl. perfringens in vitro, using a batch culture designed to simulate human gastrointestinal tract conditions. Co-culture experiments indicated that acid production by Lact. johnsonii is important in pathogen control. The co-culture of the endolysin-secreting Lact. johnsonii with Cl. perfringens showed that the engineered strain had the potential to control the pathogen, but the ability to reduce Cl. perfringens numbers was not consistent. Results obtained indicate that survival of high numbers of Lact. johnsonii will be essential for effective pathogen control. Significance and impact of the study: The bacterium Lactobacillus johnsonii FI9785 reduces numbers of the pathogen Clostridium perfringens in vitro. Biocontrol was improved by engineering the strain to produce and export a cell wall-hydrolysing endolysin, but good survival of the producer strain is essential. The production of bacteriophage endolysins by commensal bacteria has the potential to improve competitive exclusion of pathogens in the gastrointestinal tract. © 2014 The Society for Applied Microbiology.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-26
... ENVIRONMENTAL PROTECTION AGENCY [FRL-9311-4] Problem Formulation for Human Health Risk Assessments of Pathogens in Land-Applied Biosolids AGENCY: Environmental Protection Agency (EPA). ACTION: Notice... Formulation for Human Health Risk Assessments of Pathogens in Land-Applied Biosolids'' EPA/600/R-08/035F...
Jobbins, S E; Sanderson, C E; Alexander, K A
2014-03-01
Leptospirosis is the most widespread zoonosis in the world. In northern Botswana, humans live in close proximity to a diversity of wildlife and peridomestic rodents and may be exposed to a variety of zoonotic pathogens. Little is known regarding the occurrence and epidemiology of L. interrogans in Africa despite the recognized global importance of this zoonotic disease and the threat it poses to public health. In Botswana, banded mongooses (Mungos mungo) live in close proximity to humans across protected and unprotected landscapes and may be a useful sentinel species for assessing the occurrence of zoonotic organisms, such as L. interrogans. We utilized PCR to screen banded mongoose kidneys for leptospiral DNA and identified 41.5% prevalence of renal carriage of L. interrogans (exact binomial 95% CI 27.7-56.7%, n = 41). Renal carriage was also detected in one Selous' mongoose (Paracynictis selousi). This is the first published confirmation of carriage of L. interrogans in either species. This is also the first report of L. interrogans occurrence in northern Botswana and the only report of this organism in a wildlife host in the country. Pathogenic Leptospira are usually transmitted indirectly to humans through soil or water contaminated with infected urine. Other avenues, such as direct contact between humans and wildlife, as well as consumption of mongooses and other wildlife as bushmeat, may pose additional exposure risk and must be considered in public health management of this newly identified zoonotic disease threat. There is a critical need to characterize host species involvement and pathogen transmission dynamics, including human-wildlife interactions that may increase human exposure potential and infection risk. We recommend that public health strategy be modified to include sensitization of medical practitioners to the presence of L. interrogans in the region, the potential for human infection, and implementation of clinical screening. This study illustrates the need for increased focus on neglected zoonotic diseases as they present an important threat to public health. © 2013 Blackwell Verlag GmbH.
Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines
Pizzuto, Matteo S.; Silic-Benussi, Micol; Pavone, Silvia; Ciminale, Vincenzo; Capua, Ilaria
2014-01-01
ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of human cancer, with dismal survival rates due to late-stage diagnoses and a lack of efficacious therapies. Building on the observation that avian influenza A viruses (IAVs) have a tropism for the pancreas in vivo, the present study was aimed at testing the efficacy of IAVs as oncolytic agents for killing human PDA cell lines. Receptor characterization confirmed that human PDA cell lines express the alpha-2,3- and the alpha-2,6-linked glycan receptor for avian and human IAVs, respectively. PDA cell lines were sensitive to infection by human and avian IAV isolates, which is consistent with this finding. Growth kinetic experiments showed preferential virus replication in PDA cells over that in a nontransformed pancreatic ductal cell line. Finally, at early time points posttreatment, infection with IAVs caused higher levels of apoptosis in PDA cells than gemcitabine and cisplatin, which are the cornerstone of current therapies for PDA. In the BxPC-3 PDA cell line, apoptosis resulted from the engagement of the intrinsic mitochondrial pathway. Importantly, IAVs did not induce apoptosis in nontransformed pancreatic ductal HPDE6 cells. Using a model based on the growth of a PDA cell line as a xenograft in SCID mice, we also show that a slightly pathogenic avian IAV significantly inhibited tumor growth following intratumoral injection. Taken together, these results are the first to suggest that IAVs may hold promise as future agents of oncolytic virotherapy against pancreatic ductal adenocarcinomas. IMPORTANCE Despite intensive studies aimed at designing new therapeutic approaches, PDA still retains the most dismal prognosis among human cancers. In the present study, we provide the first evidence indicating that avian IAVs of low pathogenicity display a tropism for human PDA cells, resulting in viral RNA replication and a potent induction of apoptosis in vitro and antitumor effects in vivo. These results suggest that slightly pathogenic IAVs may prove to be effective for oncolytic virotherapy of PDA and provide grounds for further studies to develop specific and targeted viruses, with the aim of testing their efficacy in clinical contexts. PMID:24899201
Dannemann, Michael; Andrés, Aida M.; Kelso, Janet
2016-01-01
Pathogens and the diseases they cause have been among the most important selective forces experienced by humans during their evolutionary history. Although adaptive alleles generally arise by mutation, introgression can also be a valuable source of beneficial alleles. Archaic humans, who lived in Europe and Western Asia for more than 200,000 years, were probably well adapted to this environment and its local pathogens. It is therefore conceivable that modern humans entering Europe and Western Asia who admixed with them obtained a substantial immune advantage from the introgression of archaic alleles. Here we document a cluster of three Toll-like receptors (TLR6-TLR1-TLR10) in modern humans that carries three distinct archaic haplotypes, indicating repeated introgression from archaic humans. Two of these haplotypes are most similar to the Neandertal genome, and the third haplotype is most similar to the Denisovan genome. The Toll-like receptors are key components of innate immunity and provide an important first line of immune defense against bacteria, fungi, and parasites. The unusually high allele frequencies and unexpected levels of population differentiation indicate that there has been local positive selection on multiple haplotypes at this locus. We show that the introgressed alleles have clear functional effects in modern humans; archaic-like alleles underlie differences in the expression of the TLR genes and are associated with reduced microbial resistance and increased allergic disease in large cohorts. This provides strong evidence for recurrent adaptive introgression at the TLR6-TLR1-TLR10 locus, resulting in differences in disease phenotypes in modern humans. PMID:26748514
Migrating microbes: what pathogens can tell us about population movements and human evolution.
Houldcroft, Charlotte J; Ramond, Jean-Baptiste; Rifkin, Riaan F; Underdown, Simon J
2017-08-01
The biology of human migration can be observed from the co-evolutionary relationship with infectious diseases. While many pathogens are brief, unpleasant visitors to human bodies, others have the ability to become life-long human passengers. The story of a pathogen's genetic code may, therefore, provide insight into the history of its human host. The evolution and distribution of disease in Africa is of particular interest, because of the deep history of human evolution in Africa, the presence of a variety of non-human primates, and tropical reservoirs of emerging infectious diseases. This study explores which pathogens leave traces in the archaeological record, and whether there are realistic prospects that these pathogens can be recovered from sub-Saharan African archaeological contexts. Three stories are then presented of germs on a journey. The first is the story of HIV's spread on the back of colonialism and the railway networks over the last 150 years. The second involves the spread of Schistosoma mansoni, a parasite which shares its history with the trans-Atlantic slave trade and the origins of fresh-water fishing. Finally, we discuss the tantalising hints of hominin migration and interaction found in the genome of human herpes simplex virus 2. Evidence from modern African pathogen genomes can provide data on human behaviour and migration in deep time and contribute to the improvement of human quality-of-life and longevity.
The Alphavirus Exit Pathway: What We Know and What We Wish We Knew
2018-01-01
Alphaviruses are enveloped positive sense RNA viruses and include serious human pathogens, such as the encephalitic alphaviruses and Chikungunya virus. Alphaviruses are transmitted to humans primarily by mosquito vectors and include species that are classified as emerging pathogens. Alphaviruses assemble highly organized, spherical particles that bud from the plasma membrane. In this review, we discuss what is known about the alphavirus exit pathway during a cellular infection. We describe the viral protein interactions that are critical for virus assembly/budding and the host factors that are involved, and we highlight the recent discovery of cell-to-cell transmission of alphavirus particles via intercellular extensions. Lastly, we discuss outstanding questions in the alphavirus exit pathway that may provide important avenues for future research. PMID:29470397
Mapping the evolutionary trajectories of morbilliviruses: what, where and whither.
Nambulli, Sham; Sharp, Claire R; Acciardo, Andrew S; Drexler, J Felix; Duprex, W Paul
2016-02-01
Morbilliviruses are pathogens of humans and other animals. Live attenuated morbillivirus vaccines have been used to end endemic transmission of measles virus (MV) in many parts of the developed world and to eradicate rinderpest virus. Entry is mediated by two different receptors which govern virus lymphotropism and epitheliotropism. Morbillivirus transmissibility is unparalleled and MV represents the most infectious human pathogen on earth. Their evolutionary origins remain obscure and their potential for adaption to new hosts is poorly understood. It has been suggested that MV could be eradicated. Therefore it is imperative to dissect barriers which restrict cross species infections. This is important as ecological studies identify novel morbilliviruses in a vast number of small mammals and carnivorous predators. Copyright © 2016 Elsevier B.V. All rights reserved.
Whiley, H; Keegan, A; Fallowfield, H; Bentham, R
2015-06-01
Water reuse has become increasingly important for sustainable water management. Currently, its application is primarily constrained by the potential health risks. Presently there is limited knowledge regarding the presence and fate of opportunistic pathogens along reuse water distribution pipelines. In this study opportunistic human pathogens Legionella spp., L. pneumophila and Mycobacterium avium complex were detected using real-time polymerase chain reaction along two South Australian reuse water distribution pipelines at maximum concentrations of 10⁵, 10³ and 10⁵ copies/mL, respectively. During the summer period of sampling the concentration of all three organisms significantly increased (P < 0.05) along the pipeline, suggesting multiplication and hence viability. No seasonality in the decrease in chlorine residual along the pipelines was observed. This suggests that the combination of reduced chlorine residual and increased water temperature promoted the presence of these opportunistic pathogens.
The proportional lack of archaeal pathogens: Do viruses/phages hold the key?
Gill, Erin E; Brinkman, Fiona S L
2011-01-01
Although Archaea inhabit the human body and possess some characteristics of pathogens, there is a notable lack of pathogenic archaeal species identified to date. We hypothesize that the scarcity of disease-causing Archaea is due, in part, to mutually-exclusive phage and virus populations infecting Bacteria and Archaea, coupled with an association of bacterial virulence factors with phages or mobile elements. The ability of bacterial phages to infect Bacteria and then use them as a vehicle to infect eukaryotes may be difficult for archaeal viruses to evolve independently. Differences in extracellular structures between Bacteria and Archaea would make adsorption of bacterial phage particles onto Archaea (i.e. horizontal transfer of virulence) exceedingly hard. If phage and virus populations are indeed exclusive to their respective host Domains, this has important implications for both the evolution of pathogens and approaches to infectious disease control. PMID:21328413
Neutrophil evasion strategies by Streptococcus pneumoniae and Staphylococcus aureus.
Lewis, Megan L; Surewaard, Bas G J
2018-03-01
Humans are well equipped to defend themselves against bacteria. The innate immune system employs diverse mechanisms to recognize, control and initiate a response that can destroy millions of different microbes. Microbes that evade the sophisticated innate immune system are able to escape detection and could become pathogens. The pathogens Streptococcus pneumoniae and Staphylococcus aureus are particularly successful due to the development of a wide variety of virulence strategies for bacterial pathogenesis and they invest significant efforts towards mechanisms that allow for neutrophil evasion. Neutrophils are a primary cellular defense and can rapidly kill invading microbes, which is an indispensable function for maintaining host health. This review compares the key features of Streptococcus pneumoniae and Staphylococcus aureus in epidemiology, with a specific focus on virulence mechanisms utilized to evade neutrophils in bacterial pathogenesis. It is important to understand the complex interactions between pathogenic bacteria and neutrophils so that we can disrupt the ability of pathogens to cause disease.
The evolution of sex-specific virulence in infectious diseases
Úbeda, Francisco; Jansen, Vincent A. A.
2016-01-01
Fatality rates of infectious diseases are often higher in men than women. Although this difference is often attributed to a stronger immune response in women, we show that differences in the transmission routes that the sexes provide can result in evolution favouring pathogens with sex-specific virulence. Because women can transmit pathogens during pregnancy, birth or breast-feeding, pathogens adapt, evolving lower virulence in women. This can resolve the long-standing puzzle on progression from Human T-cell Lymphotropic Virus Type 1 (HTLV-1) infection to lethal Adult T-cell Leukaemia (ATL); a progression that is more likely in Japanese men than women, while it is equally likely in Caribbean women and men. We argue that breastfeeding, being more prolonged in Japan than in the Caribbean, may have driven the difference in virulence between the two populations. Our finding signifies the importance of investigating the differences in genetic expression profile of pathogens in males and females. PMID:27959327
Sequestration of host metabolism by an intracellular pathogen.
Gehre, Lena; Gorgette, Olivier; Perrinet, Stéphanie; Prevost, Marie-Christine; Ducatez, Mathieu; Giebel, Amanda M; Nelson, David E; Ball, Steven G; Subtil, Agathe
2016-03-16
For intracellular pathogens, residence in a vacuole provides a shelter against cytosolic host defense to the cost of limited access to nutrients. The human pathogen Chlamydia trachomatis grows in a glycogen-rich vacuole. How this large polymer accumulates there is unknown. We reveal that host glycogen stores shift to the vacuole through two pathways: bulk uptake from the cytoplasmic pool, and de novo synthesis. We provide evidence that bacterial glycogen metabolism enzymes are secreted into the vacuole lumen through type 3 secretion. Our data bring strong support to the following scenario: bacteria co-opt the host transporter SLC35D2 to import UDP-glucose into the vacuole, where it serves as substrate for de novo glycogen synthesis, through a remarkable adaptation of the bacterial glycogen synthase. Based on these findings we propose that parasitophorous vacuoles not only offer protection but also provide a microorganism-controlled metabolically active compartment essential for redirecting host resources to the pathogens.
Mylonakis, Eleftherios; Casadevall, Arturo; Ausubel, Frederick M
2007-07-27
Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.
The evolution of sex-specific virulence in infectious diseases.
Úbeda, Francisco; Jansen, Vincent A A
2016-12-13
Fatality rates of infectious diseases are often higher in men than women. Although this difference is often attributed to a stronger immune response in women, we show that differences in the transmission routes that the sexes provide can result in evolution favouring pathogens with sex-specific virulence. Because women can transmit pathogens during pregnancy, birth or breast-feeding, pathogens adapt, evolving lower virulence in women. This can resolve the long-standing puzzle on progression from Human T-cell Lymphotropic Virus Type 1 (HTLV-1) infection to lethal Adult T-cell Leukaemia (ATL); a progression that is more likely in Japanese men than women, while it is equally likely in Caribbean women and men. We argue that breastfeeding, being more prolonged in Japan than in the Caribbean, may have driven the difference in virulence between the two populations. Our finding signifies the importance of investigating the differences in genetic expression profile of pathogens in males and females.
Biofilms and the survival of opportunistic pathogens in recycled water
NASA Technical Reports Server (NTRS)
Boyle, M.; Ford, T.; Maki, J. S.; Mitchell, R.
1991-01-01
Microorganisms are likely to develop an organic film on pipes, water reservoirs and filters used for waste water reclamation during extended missions in space. These biofilms can serve to protect and concentrate potentially pathogenic microorganisms. Our investigation has emphasized the survival strategy of opportunistic pathogenic bacteria in distilled water. Pseudomonas aeruginosa and Staphylococcus aureus were used as test organisms. Cultures were incubated at 10 degrees, 25 degrees, and 37 degrees C. No viable Staphylococcus cells were detected after the first week of incubation. P. aeruginosa, however, survived in distilled water up to 5 months at all three temperatures tested. The starved cells were able to form a biofilm layer on stainless steel. The cells exhibited a negative surface charge. The charge may be involved in the adhesion of this bacterium to metal substrata. We are currently investigating the importance of adhesion in the survival of this and other potential human pathogens found in water recycling systems.
Horton, Katherine C; Dueger, Erica L; Kandeel, Amr; Abdallat, Mohamed; El-Kholy, Amani; Al-Awaidy, Salah; Kohlani, Abdul Hakim; Amer, Hanaa; El-Khal, Abel Latif; Said, Mayar; House, Brent; Pimentel, Guillermo; Talaat, Maha
2017-01-01
Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1-3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens-influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. Viral respiratory pathogens are common among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is important to monitor changes in the etiology, seasonality and severity of pathogens of interest.
Müller, Gabriela L.; Tuttobene, Marisel; Altilio, Matías; Martínez Amezaga, Maitena; Nguyen, Meaghan; Cribb, Pamela; Cybulski, Larisa E.; Ramírez, María Soledad; Altabe, Silvia
2017-01-01
ABSTRACT Light sensing in chemotrophic bacteria has been relatively recently ascertained. In the human pathogen Acinetobacter baumannii, light modulates motility, biofilm formation, and virulence through the blue-light-sensing-using flavin (BLUF) photoreceptor BlsA. In addition, light can induce a reduction in susceptibility to certain antibiotics, such as minocycline and tigecycline, in a photoreceptor-independent manner. In this work, we identified new traits whose expression levels are modulated by light in this pathogen, which comprise not only important determinants related to pathogenicity and antibiotic resistance but also metabolic pathways, which represents a novel concept for chemotrophic bacteria. Indeed, the phenylacetic acid catabolic pathway and trehalose biosynthesis were modulated by light, responses that completely depend on BlsA. We further show that tolerance to some antibiotics and modulation of antioxidant enzyme levels are also influenced by light, likely contributing to bacterial persistence in adverse environments. Also, we present evidence indicating that surfactant production is modulated by light. Finally, the expression of whole pathways and gene clusters, such as genes involved in lipid metabolism and genes encoding components of the type VI secretion system, as well as efflux pumps related to antibiotic resistance, was differentially induced by light. Overall, our results indicate that light modulates global features of the A. baumannii lifestyle. IMPORTANCE The discovery that nonphototrophic bacteria respond to light constituted a novel concept in microbiology. In this context, we demonstrated that light could modulate aspects related to bacterial virulence, persistence, and resistance to antibiotics in the human pathogen Acinetobacter baumannii. In this work, we present the novel finding that light directly regulates metabolism in this chemotrophic bacterium. Insights into the mechanism show the involvement of the photoreceptor BlsA. In addition, tolerance to antibiotics and catalase levels are also influenced by light, likely contributing to bacterial persistence in adverse environments, as is the expression of the type VI secretion system and efflux pumps. Overall, a profound influence of light on the lifestyle of A. baumannii is suggested to occur. PMID:28289081
Müller, Gabriela L; Tuttobene, Marisel; Altilio, Matías; Martínez Amezaga, Maitena; Nguyen, Meaghan; Cribb, Pamela; Cybulski, Larisa E; Ramírez, María Soledad; Altabe, Silvia; Mussi, María Alejandra
2017-05-15
Light sensing in chemotrophic bacteria has been relatively recently ascertained. In the human pathogen Acinetobacter baumannii , light modulates motility, biofilm formation, and virulence through the blue-light-sensing-using flavin (BLUF) photoreceptor BlsA. In addition, light can induce a reduction in susceptibility to certain antibiotics, such as minocycline and tigecycline, in a photoreceptor-independent manner. In this work, we identified new traits whose expression levels are modulated by light in this pathogen, which comprise not only important determinants related to pathogenicity and antibiotic resistance but also metabolic pathways, which represents a novel concept for chemotrophic bacteria. Indeed, the phenylacetic acid catabolic pathway and trehalose biosynthesis were modulated by light, responses that completely depend on BlsA. We further show that tolerance to some antibiotics and modulation of antioxidant enzyme levels are also influenced by light, likely contributing to bacterial persistence in adverse environments. Also, we present evidence indicating that surfactant production is modulated by light. Finally, the expression of whole pathways and gene clusters, such as genes involved in lipid metabolism and genes encoding components of the type VI secretion system, as well as efflux pumps related to antibiotic resistance, was differentially induced by light. Overall, our results indicate that light modulates global features of the A. baumannii lifestyle. IMPORTANCE The discovery that nonphototrophic bacteria respond to light constituted a novel concept in microbiology. In this context, we demonstrated that light could modulate aspects related to bacterial virulence, persistence, and resistance to antibiotics in the human pathogen Acinetobacter baumannii In this work, we present the novel finding that light directly regulates metabolism in this chemotrophic bacterium. Insights into the mechanism show the involvement of the photoreceptor BlsA. In addition, tolerance to antibiotics and catalase levels are also influenced by light, likely contributing to bacterial persistence in adverse environments, as is the expression of the type VI secretion system and efflux pumps. Overall, a profound influence of light on the lifestyle of A. baumannii is suggested to occur. Copyright © 2017 American Society for Microbiology.
Impacts of climate change on indirect human exposure to pathogens and chemicals from agriculture.
Boxall, Alistair B A; Hardy, Anthony; Beulke, Sabine; Boucard, Tatiana; Burgin, Laura; Falloon, Peter D; Haygarth, Philip M; Hutchinson, Thomas; Kovats, R Sari; Leonardi, Giovanni; Levy, Leonard S; Nichols, Gordon; Parsons, Simon A; Potts, Laura; Stone, David; Topp, Edward; Turley, David B; Walsh, Kerry; Wellington, Elizabeth M H; Williams, Richard J
2009-04-01
Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. In this review, we used expert input and considered literature on climate change; health effects resulting from exposure to pathogens and chemicals arising from agriculture; inputs of chemicals and pathogens to agricultural systems; and human exposure pathways for pathogens and chemicals in agricultural systems. We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes.
Sykes, Melissa L.; Jones, Amy J.; Shelper, Todd B.; Simpson, Moana; Lang, Rebecca; Poulsen, Sally-Ann; Sleebs, Brad E.
2017-01-01
ABSTRACT Open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages in vitro. Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this in vitro biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research. PMID:28674055
Duffy, Sandra; Sykes, Melissa L; Jones, Amy J; Shelper, Todd B; Simpson, Moana; Lang, Rebecca; Poulsen, Sally-Ann; Sleebs, Brad E; Avery, Vicky M
2017-09-01
Open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages in vitro Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this in vitro biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research. Copyright © 2017 Duffy et al.
Mechanisms of Antibiotic Resistance
Munita, Jose M.; Arias, Cesar A.
2015-01-01
Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291
Ciprandi, Alessandra; da Silva, Wanderson Marques; Santos, Agenor Valadares; de Castro Pimenta, Adriano Monteiro; Carepo, Marta Sofia Peixe; Schneider, Maria Paula Cruz; Azevedo, Vasco; Silva, Artur
2013-07-01
Chromobacterium violaceum is a beta-proteobacterium with high biotechnological potential, found in tropical environments. This bacterium causes opportunistic infections in both humans and animals, that can spread throughout several tissues, quickly leading to the death of the host. Genomic studies identified potential mechanisms of pathogenicity but no further studies were done to confirm the expression of these systems. In this study 36 unique protein entries were identified in databank from a two-dimensional profile of C. violaceum secreted proteins. Chromobacterium violaceum exoproteomic preliminary studies confirmed the production of proteins identified as virulence factors (such as a collagenase, flagellum proteins, metallopeptidases, and toxins), allowing us to better understand its pathogenicity mechanisms. Biotechnologically interesting proteins (such as chitinase and chitosanase) were also identified among the secreted proteins, as well as proteins involved in the transport and capture of amino acids, carbohydrates, and oxidative stress protection. Overall, the secreted proteins identified provide us important insights on pathogenicity mechanisms, biotechnological potential, and environment adaptation of C. violaceum.
Manore, Carrie A; Hickmann, Kyle S; Hyman, James M; Foppa, Ivo M; Davis, Justin K; Wesson, Dawn M; Mores, Christopher N
2015-01-01
Mosquito-borne diseases cause significant public health burden and are widely re-emerging or emerging. Understanding, predicting, and mitigating the spread of mosquito-borne disease in diverse populations and geographies are ongoing modelling challenges. We propose a hybrid network-patch model for the spread of mosquito-borne pathogens that accounts for individual movement through mosquito habitats, extending the capabilities of existing agent-based models (ABMs) to include vector-borne diseases. The ABM are coupled with differential equations representing 'clouds' of mosquitoes in patches accounting for mosquito ecology. We adapted an ABM for humans using this method and investigated the importance of heterogeneity in pathogen spread, motivating the utility of models of individual behaviour. We observed that the final epidemic size is greater in patch models with a high risk patch frequently visited than in a homogeneous model. Our hybrid model quantifies the importance of the heterogeneity in the spread of mosquito-borne pathogens, guiding mitigation strategies.
PCR-based Approaches for the Detection of Clinical Methicillin-resistant Staphylococcus aureus
Liu, Ying; Zhang, Jiang; Ji, Yinduo
2016-01-01
Staphylococcus aureus is an important pathogen that can cause a variety of infections, including superficial and systematic infections, in humans and animals. The persistent emergence of multidrug resistant S. aureus, particularly methicillin-resistant S. aureus, has caused dramatically economic burden and concerns in the public health due to limited options of treatment of MRSA infections. In order to make a correct choice of treatment for physicians and understand the prevalence of MRSA, it is extremely critical to precisely and timely diagnose the pathogen that induces a specific infection of patients and to reveal the antibiotic resistant profile of the pathogen. In this review, we outlined different PCR-based approaches that have been successfully utilized for the rapid detection of S. aureus, including MRSA and MSSA, directly from various clinical specimens. The sensitivity and specificity of detections were pointed out. Both advantages and disadvantages of listed approaches were discussed. Importantly, an alternative approach is necessary to further confirm the detection results from the molecular diagnostic assays. PMID:27335617
Lu, Xin; Liang, Weili; Wang, Yunduan; Xu, Jialiang
2014-01-01
Vibrio fluvialis is an important food-borne pathogen that causes diarrheal illness and sometimes extraintestinal infections in humans. In this study, we sequenced the genome of a clinical V. fluvialis strain and determined its phylogenetic relationships with other Vibrio species by comparative genomic analysis. We found that the closest relationship was between V. fluvialis and V. furnissii, followed by those with V. cholerae and V. mimicus. Moreover, based on genome comparisons and gene complementation experiments, we revealed genetic mechanisms of the biochemical tests that differentiate V. fluvialis from closely related species. Importantly, we identified a variety of genes encoding potential virulence factors, including multiple hemolysins, transcriptional regulators, and environmental survival and adaptation apparatuses, and the type VI secretion system, which is indicative of complex regulatory pathways modulating pathogenesis in this organism. The availability of V. fluvialis genome sequences may promote our understanding of pathogenic mechanisms for this emerging pathogen. PMID:24441165
Genetic Recombination between Human and Animal Parasites Creates Novel Strains of Human Pathogen
Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick
2015-01-01
Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT. PMID:25816228
Genetic recombination between human and animal parasites creates novel strains of human pathogen.
Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick
2015-03-01
Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.
Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus
Barnard, Karen N.; Ossiboff, Robert J.; Khedri, Zahra; Feng, Kurtis H.; Yu, Hai; Chen, Xi; Varki, Ajit
2017-01-01
ABSTRACT Sialic acids (Sias) are important glycans displayed on the cells and tissues of many different animals and are frequent targets for binding and modification by pathogens, including influenza viruses. Influenza virus hemagglutinins bind Sias during the infection of their normal hosts, while the encoded neuraminidases and/or esterases remove or modify the Sia to allow virion release or to prevent rebinding. Sias naturally occur in a variety of modified forms, and modified Sias can alter influenza virus host tropisms through their altered interactions with the viral glycoproteins. However, the distribution of modified Sia forms and their effects on pathogen-host interactions are still poorly understood. Here we used probes developed from viral Sia-binding proteins to detect O-acetylated (4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl) Sias displayed on the tissues of some natural or experimental hosts for influenza viruses. These modified Sias showed highly variable displays between the hosts and tissues examined. The 9-O-acetyl (and 7,9-) modified Sia forms were found on cells and tissues of many hosts, including mice, humans, ferrets, guinea pigs, pigs, horses, dogs, as well as in those of ducks and embryonated chicken egg tissues and membranes, although in variable amounts. The 4-O-acetyl Sias were found in the respiratory tissues of fewer animals, being primarily displayed in the horse and guinea pig, but were not detected in humans or pigs. The results suggest that these Sia variants may influence virus tropisms by altering and selecting their cell interactions. IMPORTANCE Sialic acids (Sias) are key glycans that control or modulate many normal cell and tissue functions while also interacting with a variety of pathogens, including many different viruses. Sias are naturally displayed in a variety of different forms, with modifications at several positions that can alter their functional interactions with pathogens. In addition, Sias are often modified or removed by enzymes such as host or pathogen esterases or sialidases (neuraminidases), and Sia modifications can alter those enzymatic activities to impact pathogen infections. Sia chemical diversity in different hosts and tissues likely alters the pathogen-host interactions and influences the outcome of infection. Here we explored the display of 4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl modified Sia forms in some target tissues for influenza virus infection in mice, humans, birds, guinea pigs, ferrets, swine, horses, and dogs, which encompass many natural and laboratory hosts of those viruses. PMID:28904995
Tilton, Susan C.; Menachery, Vineet D.; Gralinski, Lisa E.; Schäfer, Alexandra; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Chang, Jean; Luna, Maria L.; Long, Casey E.; Shukla, Anil K.; Bankhead, Armand R.; Burkett, Susan E.; Zornetzer, Gregory; Tseng, Chien-Te Kent; Metz, Thomas O.; Pickles, Raymond; McWeeney, Shannon; Smith, Richard D.; Katze, Michael G.; Waters, Katrina M.; Baric, Ralph S.
2013-01-01
The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo. PMID:23365422
Senghore, Madikay; Bayliss, Sion C; Kwambana-Adams, Brenda A; Foster-Nyarko, Ebenezer; Manneh, Jainaba; Dione, Michel; Badji, Henry; Ebruke, Chinelo; Doughty, Emma L; Thorpe, Harry A; Jasinska, Anna J; Schmitt, Christopher A; Cramer, Jennifer D; Turner, Trudy R; Weinstock, George; Freimer, Nelson B; Pallen, Mark J; Feil, Edward J; Antonio, Martin
2016-10-01
Staphylococcus aureus is an important pathogen of humans and animals. We genome sequenced 90 S. aureus isolates from The Gambia: 46 isolates from invasive disease in humans, 13 human carriage isolates, and 31 monkey carriage isolates. We inferred multiple anthroponotic transmissions of S. aureus from humans to green monkeys (Chlorocebus sabaeus) in The Gambia over different time scales. We report a novel monkey-associated clade of S. aureus that emerged from a human-to-monkey switch estimated to have occurred 2,700 years ago. Adaptation of this lineage to the monkey host is accompanied by the loss of phage-carrying genes that are known to play an important role in human colonization. We also report recent anthroponotic transmission of the well-characterized human lineages sequence type 6 (ST6) and ST15 to monkeys, probably because of steadily increasing encroachment of humans into the monkeys' habitat. Although we have found no evidence of transmission of S. aureus from monkeys to humans, as the two species come into ever-closer contact, there might be an increased risk of additional interspecies exchanges of potential pathogens. The population structures of Staphylococcus aureus in humans and monkeys in sub-Saharan Africa have been previously described using multilocus sequence typing (MLST). However, these data lack the power to accurately infer details regarding the origin and maintenance of new adaptive lineages. Here, we describe the use of whole-genome sequencing to detect transmission of S. aureus between humans and nonhuman primates and to document the genetic changes accompanying host adaptation. We note that human-to-monkey switches tend to be more common than the reverse and that a novel monkey-associated clade is likely to have emerged from such a switch approximately 2,700 years ago. Moreover, analysis of the accessory genome provides important clues as to the genetic changes underpinning host adaptation and, in particular, shows that human-to-monkey switches tend to be associated with the loss of genes known to confer adaptation to the human host. Copyright © 2016 Senghore et al.
A Viral-Human Interactome Based on Structural Motif-Domain Interactions Captures the Human Infectome
Guo, Xianwu; Rodríguez-Pérez, Mario A.
2013-01-01
Protein interactions between a pathogen and its host are fundamental in the establishment of the pathogen and underline the infection mechanism. In the present work, we developed a single predictive model for building a host-viral interactome based on the identification of structural descriptors from motif-domain interactions of protein complexes deposited in the Protein Data Bank (PDB). The structural descriptors were used for searching, in a database of protein sequences of human and five clinically important viruses; therefore, viral and human proteins sharing a descriptor were predicted as interacting proteins. The analysis of the host-viral interactome allowed to identify a set of new interactions that further explain molecular mechanism associated with viral infections and showed that it was able to capture human proteins already associated to viral infections (human infectome) and non-infectious diseases (human diseasome). The analysis of human proteins targeted by viral proteins in the context of a human interactome showed that their neighbors are enriched in proteins reported with differential expression under infection and disease conditions. It is expected that the findings of this work will contribute to the development of systems biology for infectious diseases, and help guide the rational identification and prioritization of novel drug targets. PMID:23951184
Label-free SERS detection of Salmonella Typhimurium on DNA aptamer modified AgNR substrates
USDA-ARS?s Scientific Manuscript database
A straightforward label-free method based on aptamer binding and surface enhanced Raman specstroscopy (SERS) has been developed for the detection of Salmonella Typhimurium, an important foodborne pathogen that causes gastroenteritis in both humans and animals. Surface of the SERS-active silver nanor...
Patterns and processes of Mycobacterium bovis evolution revealed by phylogenomic analyses
USDA-ARS?s Scientific Manuscript database
Mycobacterium bovis is an important animal pathogen worldwide that parasitizes wild and domesticated vertebrate livestock as well as humans. A comparison of the five M. bovis complete genomes from UK, South Korea, Brazil and USA revealed four novel large-scale structural variations of at least 2,000...
USDA-ARS?s Scientific Manuscript database
The fractured Silurian dolomite aquifer is an important, but vulnerable, source of drinking water in northeast Wisconsin. Areas underlain by the Silurian dolomite aquifer are extremely vulnerable to groundwater contamination from various land-use activities, especially the disposal of human wastewat...
USDA-ARS?s Scientific Manuscript database
Commensal E. coli inhabit the large intestines of humans and animals and are important in maintaining normal intestinal homeostasis. There are also many groups of disease-causing E. coli, including diarrheagenic and extra-intestinal pathogenic E. coli (ExPEC). There are approximately O188 somatic O...
Water quality of four major lakes in Mississippi, USA: Impacts on human and aquatic ecosystem health
USDA-ARS?s Scientific Manuscript database
Harmful algal blooms (HABs), harmful microorganisms (pathogens) and toxic metals represent three major agents of water quality deterioration. Better water quality is of utmost importance to water bodies that provide recreational opportunities, even better quality is expected in the water bodies that...
USDA-ARS?s Scientific Manuscript database
The secondary screwworm, Cochliomyia macellaria (F.), is an important blowfly species affecting both livestock and humans. It can transmit pathogenic disease agents mechanically and is an agent of facultative myiasis, which leads to economic losses. The adult flies are attracted to decomposing carca...
Managing Abiotic Factors of Compost to Increase Soilborne Disease Suppression
ERIC Educational Resources Information Center
Griffin, Deirdre E.
2012-01-01
Soilborne pathogens can devastate crops, causing economic losses for farmers due to reduced yields and expensive management practices. Fumigants and fungicides have harmful impacts on the surrounding environment and can be toxic to humans. Therefore, alternative methods of disease management are important. The disease suppressive abilities of…
Lineage and genogroup-defining single nucleotide polymorphisms of Escherichia coli 0157:H7
USDA-ARS?s Scientific Manuscript database
Escherichia coli O157:H7 is a zoonotic human pathogen for which cattle are an important reservoir host. Using both previously published and new sequencing data, a 48-locus single nucleotide polymorphism (SNP) based typing panel was developed that redundantly identified eleven genogroups that span ...
USDA-ARS?s Scientific Manuscript database
Aspergillus section Nidulantes is a speciose group of microscopic fungi whose species are important in indoor air quality, food spoilage, mycotoxin production and human pathogenicity. We assembled as many species from the section as possible with either type specimens or protologues for analysis. DN...
USDA-ARS?s Scientific Manuscript database
Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, which can cause serious illnesses, including hemorrhagic colitis and hemolytic uremic syndrome. To examine if pigs are potential animal reservoirs for human STEC infections, we conducted a longitudinal cohort study in ...
The blood DNA virome in 8,000 humans.
Moustafa, Ahmed; Xie, Chao; Kirkness, Ewen; Biggs, William; Wong, Emily; Turpaz, Yaron; Bloom, Kenneth; Delwart, Eric; Nelson, Karen E; Venter, J Craig; Telenti, Amalio
2017-03-01
The characterization of the blood virome is important for the safety of blood-derived transfusion products, and for the identification of emerging pathogens. We explored non-human sequence data from whole-genome sequencing of blood from 8,240 individuals, none of whom were ascertained for any infectious disease. Viral sequences were extracted from the pool of sequence reads that did not map to the human reference genome. Analyses sifted through close to 1 Petabyte of sequence data and performed 0.5 trillion similarity searches. With a lower bound for identification of 2 viral genomes/100,000 cells, we mapped sequences to 94 different viruses, including sequences from 19 human DNA viruses, proviruses and RNA viruses (herpesviruses, anelloviruses, papillomaviruses, three polyomaviruses, adenovirus, HIV, HTLV, hepatitis B, hepatitis C, parvovirus B19, and influenza virus) in 42% of the study participants. Of possible relevance to transfusion medicine, we identified Merkel cell polyomavirus in 49 individuals, papillomavirus in blood of 13 individuals, parvovirus B19 in 6 individuals, and the presence of herpesvirus 8 in 3 individuals. The presence of DNA sequences from two RNA viruses was unexpected: Hepatitis C virus is revealing of an integration event, while the influenza virus sequence resulted from immunization with a DNA vaccine. Age, sex and ancestry contributed significantly to the prevalence of infection. The remaining 75 viruses mostly reflect extensive contamination of commercial reagents and from the environment. These technical problems represent a major challenge for the identification of novel human pathogens. Increasing availability of human whole-genome sequences will contribute substantial amounts of data on the composition of the normal and pathogenic human blood virome. Distinguishing contaminants from real human viruses is challenging.
Kanungo, Reba; Shashikala; Karunasagar, I; Srinivasan, S; Sheela, Devi; Venkatesh, K; Anitha, P
2007-12-01
Potentially pathogenic members of the Vibrionaceae family including Vibrio cholerae and Vibrio parahemolyticus were isolated from domestic sources of drinking water in coastal villages following sea water inundation during the tsunami in Southern India. Phenotypic and genotypic studies were done to confirm the identity and detection of toxins. Vibrio-gyr (gyrase B gene) was detected in all sixteen vibrio isolates. Toxin regulating genes i.e.: ctx gene, tdh gene, and trh gene, however were not detected in any of the strains, thereby ruling out presence of toxins which could endanger human life. Other potentially pathogenic bacteria Aeromonas and Plesiomonas were also isolated from hand pumps and wells, in a few localities. There was no immediate danger in the form of an outbreak or sporadic gastroenteritis at the time of the study. Timely chlorination and restoration of potable water supply to the flood affected population by governmental and nongovernmental agencies averted waterborne gastroenteritis. Assessment of quality of water and detection of potential virulent organisms is an important public health activity following natural disasters. This work highlights the importance of screening water sources for potentially pathogenic microorganisms after natural disasters to avert outbreaks of gastroenteritis and other infectious diseases.
Duscher, Tanja; Hodžić, Adnan; Glawischnig, Walter; Duscher, Georg G
2017-04-01
The neozoan species raccoon dog (Nyctereutes procyonoides) and raccoon (Procyon lotor) are widespread in Europe and potential vectors of many diseases that can threaten human and domestic animal health. Facing a further spread of these species, it is important to know about (i) pathogens imported and/or (ii) pathogens acquired in the new habitat. Thus, we investigated the parasite fauna of wild raccoon dogs and raccoons from Austria, at the edge of their new distribution range. The eight examined raccoons were nearly free of pathogens including Baylisascaris procyonis, and thus assumed to have a low epidemiological impact, so far. Out of ten raccoon dog specimens, we found one from western Austria to be infected with Echinococcus multilocularis and another three from the eastern wetland regions to harbour adults of Alaria alata. Furthermore, we detected Babesia cf. microti in five of eight raccoon dogs all over Austria but none of our samples were tested positive for Trichinella spp. Nevertheless, the raccoon dog seems to be a relevant host, at least for the zoonotic pathogens E. multilocularis and A. alata, and we suggest to further monitor the raccoon dogs parasite fauna.
Molecular Tools To Study Preharvest Food Safety Challenges.
Kumar, Deepak; Thakur, Siddhartha
2018-02-01
Preharvest food safety research and activities have advanced over time with the recognition of the importance and complicated nature of the preharvest phase of food production. In developed nations, implementation of preharvest food safety procedures along with strict monitoring and containment at various postharvest stages such as slaughter, processing, storage, and distribution have remarkably reduced the burden of foodborne pathogens in humans. Early detection and adequate surveillance of pathogens at the preharvest stage is of the utmost importance to ensure a safe meat supply. There is an urgent need to develop rapid, cost-effective, and point-of-care diagnostics which could be used at the preharvest stage and would complement postmortem and other quality checks performed at the postharvest stage. With newer methods and technologies, more efforts need to be directed toward developing rapid, sensitive, and specific methods for detection or screening of foodborne pathogens at the preharvest stage. In this review, we will discuss the molecular methods available for detection and molecular typing of bacterial foodborne pathogens at the farm. Such methods include conventional techniques such as endpoint PCR, real-time PCR, DNA microarray, and more advanced techniques such as matrix-assisted layer desorption ionization-time of flight mass spectrometry and whole-genome sequencing.
Zhao, Youbo; Monroy, Guillermo L.; You, Sixian; Shelton, Ryan L.; Nolan, Ryan M.; Tu, Haohua; Chaney, Eric J.; Boppart, Stephen A.
2016-01-01
Abstract. We investigate and demonstrate the feasibility of using a combined Raman scattering (RS) spectroscopy and low-coherence interferometry (LCI) probe to differentiate microbial pathogens and improve our diagnostic ability of ear infections [otitis media (OM)]. While the RS probe provides noninvasive molecular information to identify and differentiate infectious microorganisms, the LCI probe helps to identify depth-resolved structural information as well as to guide and monitor positioning of the Raman spectroscopy beam for relatively longer signal acquisition times. A series of phantom studies, including the use of human middle ear effusion samples, were performed to mimic the conditions of in vivo investigations. These were also conducted to validate the feasibility of using this combined RS/LCI probe for point-of-care diagnosis of the infectious pathogen(s) in OM patients. This work establishes important parameters for future in vivo investigations of fast and accurate determination and diagnosis of infectious microorganisms in OM patients, potentially improving the efficacy and outcome of OM treatments, and importantly reducing the misuse of antibiotics in the presence of viral infections. PMID:27802456
Severity of Bovine Tuberculosis Is Associated with Co-Infection with Common Pathogens in Wild Boar
Risco, David; Serrano, Emmanuel; Fernández-Llario, Pedro; Cuesta, Jesús M.; Gonçalves, Pilar; García-Jiménez, Waldo L.; Martínez, Remigio; Cerrato, Rosario; Velarde, Roser; Gómez, Luis; Segalés, Joaquím; Hermoso de Mendoza, Javier
2014-01-01
Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under controlled conditions. Furthermore, more research including other important pathogens, such as gastro-intestinal nematodes, will be necessary to complete this picture. PMID:25350002
Evaluation of Gulf Coast Ticks (Acari: Ixodidae) for Ehrlichia and Anaplasma Species.
Allerdice, Michelle E J; Hecht, Joy A; Karpathy, Sandor E; Paddock, Christopher D
2017-03-01
Amblyomma maculatum Koch (the Gulf Coast tick) is an aggressive, human-biting ixodid tick distributed throughout much of the southeastern United States and is the primary vector for Rickettsia parkeri, an emerging human pathogen. Amblyomma maculatum has diverse host preferences that include white-tailed deer, a known reservoir for Ehrlichia and Anaplasma species, including the human pathogens E. ewingii and E. chaffeensis. To examine more closely the potential role of A. maculatum in the maintenance of various pathogenic Ehrlichia and Anaplasma species, we screened DNA samples from 493 questing adult A. maculatum collected from six U.S. states using broad-range Anaplasmataceae and Ehrlichia genus-specific PCR assays. Of the samples tested, four (0.8%) were positive for DNA of Ehrlichia ewingii, one (0.2%) was positive for Anaplasma platys, and one (0.2%) was positive for a previously unreported Ehrlichia species closely related to Ehrlichia muris and an uncultivated Ehrlichia species from Haemaphysalis longicornis ticks in Japan. No ticks contained DNA of Ehrlichia chaffeensis, Ehrlichia canis, the Panola Mountain Ehrlichia, or Anaplasma phagocytophilum. This is the first identification of E. ewingii, A. platys, and the novel Ehrlichia in questing Gulf Coast ticks; nonetheless the low prevalence of these agents suggests that A. maculatum is not likely an important vector of these zoonotic pathogens. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.
Bansod, Sunita Dashrath; Bawaskar, Manisha Subrashrao; Gade, Aniket Krishnarao; Rai, Mahendra Kumar
2015-08-01
Many scientists have focused their research on the role of nanotechnology for the control of human pathogens, but there are also many topical pathogens present in animals, which infect animals and transfer to humans. Topical therapy is extremely important for the management of dermatological condition in animals. Therefore, the present study aims to evaluate the efficacy of biogenic silver nanoparticles (AgNPs) in combination with herbal oils against animal skin infections which may be responsible for causing infections in human beings. Here, the authors synthesised and characterised the AgNPs from Azadirachta indica. The oils were extracted from medicinal plants including Cymbopogon citratus, Cymbopogon martini, Eucalyptus globules, A. indica and Ocimum sanctum and the antifungal and antibacterial activity of plant oils along with AgNPs were evaluated. An excision wound model was used for the study of wound healing activity in rabbits. AgNPs functionalised oil has demonstrated remarkable antimicrobial activity against pathogens present on the skin of animals. The nano-functionalised antimicrobial oils were used in the formulation of shampoo, soap and ointment for veterinary dermatology. Antimicrobial products of plant origin with AgNPs are valuable, safe and have a specific role in controlling diseases. The authors believe that this approach will be a good alternative therapy to solve the continuous antibiotic resistance developed by many bacterial pathogens and will be utilised in various animal contacting areas in medicine.
Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi
2011-01-01
Background Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans. Results 97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales (Coccidioides species) and the mould Aspergillus fumigatus. The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species. Conclusions Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens. PMID:21247460
Stromberg, Zachary R; Johnson, James R; Fairbrother, John M; Kilbourne, Jacquelyn; Van Goor, Angelica; Curtiss, Roy; Mellata, Melha
2017-01-01
Extraintestinal pathogenic Escherichia coli (ExPEC) strains are important pathogens that cause diverse diseases in humans and poultry. Some E. coli isolates from chicken feces contain ExPEC-associated virulence genes, so appear potentially pathogenic; they conceivably could be transmitted to humans through handling and/or consumption of contaminated meat. However, the actual extraintestinal virulence potential of chicken-source fecal E. coli is poorly understood. Here, we assessed whether fecal E. coli isolates from healthy production chickens could cause diseases in a chicken model of avian colibacillosis and three rodent models of ExPEC-associated human infections. From 304 E. coli isolates from chicken fecal samples, 175 E. coli isolates were screened by PCR for virulence genes associated with human-source ExPEC or avian pathogenic E. coli (APEC), an ExPEC subset that causes extraintestinal infections in poultry. Selected isolates genetically identified as ExPEC and non-ExPEC isolates were assessed in vitro for virulence-associated phenotypes, and in vivo for disease-causing ability in animal models of colibacillosis, sepsis, meningitis, and urinary tract infection. Among the study isolates, 13% (40/304) were identified as ExPEC; the majority of these were classified as APEC and uropathogenic E. coli, but none as neonatal meningitis E. coli. Multiple chicken-source fecal ExPEC isolates resembled avian and human clinical ExPEC isolates in causing one or more ExPEC-associated illnesses in experimental animal infection models. Additionally, some isolates that were classified as non-ExPEC were able to cause ExPEC-associated illnesses in animal models, and thus future studies are needed to elucidate their mechanisms of virulence. These findings show that E. coli isolates from chicken feces contain ExPEC-associated genes, exhibit ExPEC-associated in vitro phenotypes, and can cause ExPEC-associated infections in animal models, and thus may pose a health threat to poultry and consumers.
Johnson, James R.; Fairbrother, John M.; Kilbourne, Jacquelyn; Van Goor, Angelica; Curtiss, Roy; Mellata, Melha
2017-01-01
Extraintestinal pathogenic Escherichia coli (ExPEC) strains are important pathogens that cause diverse diseases in humans and poultry. Some E. coli isolates from chicken feces contain ExPEC-associated virulence genes, so appear potentially pathogenic; they conceivably could be transmitted to humans through handling and/or consumption of contaminated meat. However, the actual extraintestinal virulence potential of chicken-source fecal E. coli is poorly understood. Here, we assessed whether fecal E. coli isolates from healthy production chickens could cause diseases in a chicken model of avian colibacillosis and three rodent models of ExPEC-associated human infections. From 304 E. coli isolates from chicken fecal samples, 175 E. coli isolates were screened by PCR for virulence genes associated with human-source ExPEC or avian pathogenic E. coli (APEC), an ExPEC subset that causes extraintestinal infections in poultry. Selected isolates genetically identified as ExPEC and non-ExPEC isolates were assessed in vitro for virulence-associated phenotypes, and in vivo for disease-causing ability in animal models of colibacillosis, sepsis, meningitis, and urinary tract infection. Among the study isolates, 13% (40/304) were identified as ExPEC; the majority of these were classified as APEC and uropathogenic E. coli, but none as neonatal meningitis E. coli. Multiple chicken-source fecal ExPEC isolates resembled avian and human clinical ExPEC isolates in causing one or more ExPEC-associated illnesses in experimental animal infection models. Additionally, some isolates that were classified as non-ExPEC were able to cause ExPEC-associated illnesses in animal models, and thus future studies are needed to elucidate their mechanisms of virulence. These findings show that E. coli isolates from chicken feces contain ExPEC-associated genes, exhibit ExPEC-associated in vitro phenotypes, and can cause ExPEC-associated infections in animal models, and thus may pose a health threat to poultry and consumers. PMID:28671990
Lipsitch, Marc; Levinson, Meira
2015-01-01
This paper proposes an ethical framework for evaluating biosafety risks of gain-of-function (GOF) experiments that create novel strains of influenza expected to be virulent and transmissible in humans, so-called potential pandemic pathogens (PPP). Such research raises ethical concerns because of the risk that accidental release from a laboratory could lead to extensive or even global spread of a virulent pathogen. Biomedical research ethics has focused largely on human subjects research, while biosafety concerns about accidental infections, seen largely as a problem of occupational health, have been ignored. GOF/PPP research is an example of a small but important class of research where biosafety risks threaten public health, well beyond the small number of persons conducting the research. We argue that bioethical principles that ordinarily apply only to human subjects research should also apply to research that threatens public health, even if, as in GOF/PPP studies, the research involves no human subjects. Specifically we highlight the Nuremberg Code’s requirements of “fruitful results for the good of society, unprocurable by other methods,” and proportionality of risk and humanitarian benefit, as broad ethical principles that recur in later documents on research ethics and should also apply to certain types of research not involving human subjects. We address several potential objections to this view, and conclude with recommendations for bringing these ethical considerations into policy development. PMID:26320212
REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants.
Ioannidis, Nilah M; Rothstein, Joseph H; Pejaver, Vikas; Middha, Sumit; McDonnell, Shannon K; Baheti, Saurabh; Musolf, Anthony; Li, Qing; Holzinger, Emily; Karyadi, Danielle; Cannon-Albright, Lisa A; Teerlink, Craig C; Stanford, Janet L; Isaacs, William B; Xu, Jianfeng; Cooney, Kathleen A; Lange, Ethan M; Schleutker, Johanna; Carpten, John D; Powell, Isaac J; Cussenot, Olivier; Cancel-Tassin, Geraldine; Giles, Graham G; MacInnis, Robert J; Maier, Christiane; Hsieh, Chih-Lin; Wiklund, Fredrik; Catalona, William J; Foulkes, William D; Mandal, Diptasri; Eeles, Rosalind A; Kote-Jarai, Zsofia; Bustamante, Carlos D; Schaid, Daniel J; Hastie, Trevor; Ostrander, Elaine A; Bailey-Wilson, Joan E; Radivojac, Predrag; Thibodeau, Stephen N; Whittemore, Alice S; Sieh, Weiva
2016-10-06
The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p < 10 -12 ) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies <0.5%. The area under the receiver operating characteristic curve (AUC) for REVEL was 0.046-0.182 higher in an independent test set of 935 recent SwissVar disease variants and 123,935 putatively neutral exome sequencing variants and 0.027-0.143 higher in an independent test set of 1,953 pathogenic and 2,406 benign variants recently reported in ClinVar than the AUCs for other ensemble methods. We provide pre-computed REVEL scores for all possible human missense variants to facilitate the identification of pathogenic variants in the sea of rare variants discovered as sequencing studies expand in scale. Copyright © 2016 American Society of Human Genetics. All rights reserved.
Cryptosporidiosis, giardiasis, and microsporidiosis are important waterborne diseases. In thestandard for wastewater treatment plant (WWTP) effluents in China and other countries, fecalcoliform is the only microbial indicator, raising concerns about the potential for pathogentransmission through WWPT effluent reuse. In this study, we collected 50 effluent samples(30 L/sample) from three municipal WWTPs in Shanghai, China and analyzed for Cryptosporidiumspp., Giardia duodenalis and Enterocytozoon bieneusi by microscopy and/or PCR. Moreover,propidium monoazide (PMA)-PCR was used to assess the viability of oocysts/cysts. The microscopyand PCR-positive rates for Cryptosporidium spp. were 62% and 40%, respectively. The occurrencerates of G. duodenalis were 96% by microscopy and 92??100% by PCR analysis of three genetic loci.Furthermore, E. bieneusi was detected in 70% (35/50) of samples by PCR. Altogether, tenCryptosporidium species or genotypes, two G. duodenalis genotypes, and 11 E. bieneusi genotypeswere found, most of which were human-pathogenic. The chlorine dioxide disinfection employed inWWTP1 and WWTP3 failed to inactivate the residual pathogens; 93% of the samples from WWTP1 and83% from WWTP3 did not meet the national standard on fecal coliform levels. Thus, urban WWTPeffluents often contain residual waterborne human pathogens.This dataset is associated with the following publication:Ma, J., Y. Feng, Y. Hu, E. Villegas , and L. Xiao. Human infective potentia
The consequences of human actions on risks for infectious diseases: a review
Lindahl, Johanna F.; Grace, Delia
2015-01-01
The human population is growing, requiring more space for food production, and needing more animals to feed it. Emerging infectious diseases are increasing, causing losses in both human and animal lives, as well as large costs to society. Many factors are contributing to disease emergence, including climate change, globalization and urbanization, and most of these factors are to some extent caused by humans. Pathogens may be more or less prone to emergence in themselves, and rapidly mutating viruses are more common among the emerging pathogens. The climate-sensitive vector-borne diseases are likely to be emerging due to climate changes and environmental changes, such as increased irrigation. This review lists the factors within pathogens that make them prone to emergence, and the modes of transmission that are affected. The anthropogenic changes contributing to disease emergence are described, as well as how they directly and indirectly cause either increased numbers of susceptible or exposed individuals, or cause increased infectivity. Many actions may have multiple direct or indirect effects, and it may be difficult to assess what the consequences may be. In addition, most anthropogenic drivers are related to desired activities, such as logging, irrigation, trade, and travelling, which the society is requiring. It is important to research more about the indirect and direct effects of the different actions to understand both the benefits and the risks. PMID:26615822
Antimicrobial activity of an aspartic protease from Salpichroa origanifolia fruits.
Díaz, M E; Rocha, G F; Kise, F; Rosso, A M; Guevara, M G; Parisi, M G
2018-05-08
Plant proteases play a fundamental role in several processes like growth, development and in response to biotic and abiotic stress. In particular, aspartic proteases (AP) are expressed in different plant organs and have antimicrobial activity. Previously, we purified an AP from Salpichroa origanifolia fruits called salpichroin. The aim of this work was to determine the cytotoxic activity of this enzyme on selected plant and human pathogens. For this purpose, the growth of the selected pathogens was analysed after exposure to different concentrations of salpichroin. The results showed that the enzyme was capable of inhibiting Fusarium solani and Staphylococcus aureus in a dose-dependent manner. It was determined that 1·2 μmol l -1 of salpichroin was necessary to inhibit 50% of conidial germination, and the minimal bactericidal concentration was between 1·9 and 2·5 μmol l -1 . Using SYTOX Green dye we were able to demonstrate that salpichroin cause membrane permeabilization. Moreover, the enzyme treated with its specific inhibitor pepstatin A did not lose its antibacterial activity. This finding demonstrates that the cytotoxic activity of salpichroin is due to the alteration of the cell plasma membrane barrier but not due to its proteolytic activity. Antimicrobial activity of the AP could represent a potential alternative for the control of pathogens that affect humans or crops of economic interest. This study provides insights into the antimicrobial activity of an aspartic protease isolated from Salpichroa origanifolia fruits on plant and human pathogens. The proteinase inhibited Fusarium solani and Staphylococcus aureus in a dose-dependent manner due to the alteration of the cell plasma membrane barrier but not due to its proteolytic activity. Antimicrobial activity of salpichroin suggests its potential applications as an important tool for the control of pathogenic micro-organisms affecting humans and crops of economic interest. Therefore, it would represent a new alternative to avoid the problems of environmental pollution and antimicrobial resistance. © 2018 The Society for Applied Microbiology.
Wu, Hong-Yan; Zhang, Xiao-Lian; Pan, Qin; Wu, Jianguo
2005-11-01
Salmonella enterica serovar Typhi (S. Typhi) is an important pathogen which infects humans exclusively and causes typhoid or enteric fever. Recently it has been discovered that type IVB pili, encoded by the S. Typhi pil operon located in the major pathogenicity island, may be important in the pathogenesis of epidemic enteric fever. To further investigate the roles of type IVB pili of S. Typhi, a 12-mer peptide (RQERSSLSKPVV), binding to the structural protein PilS of the type IVB pili of S. Typhi, was isolated with a ribosome display system. This peptide was designated as peptide R. We found that peptide R inhibited adhesion to/invasion of human monocytic THP-1 cells by piliated S. Typhi bacteria, but had no effects on nonpiliated S. Typhi bacteria. A random 12-mer peptide, of size and solubility equal to peptide R, served as a control on the specificity of peptide R. The specific interaction and binding equilibrium between the 12-mer peptide R and PilS protein was determined by isothermal titration calorimetry (ITC) and a binding constant Ka determined to be between 0.4 x 10(5) and 2.2 x 10(5)L mol(-1). Our findings suggest that the type IV pili-binding peptide R holds potential as an antibacterial peptide effective against S. Typhi infections, both in terms of prevention and therapeutic treatment. The data further provide insights into the understanding of the pathogenic roles of the type IVB pili of S. Typhi.
Pathogen Reduction in Human Plasma Using an Ultrashort Pulsed Laser
Tsen, Shaw-Wei D.; Kingsley, David H.; Kibler, Karen; Jacobs, Bert; Sizemore, Sara; Vaiana, Sara M.; Anderson, Jeanne; Tsen, Kong-Thon; Achilefu, Samuel
2014-01-01
Pathogen reduction is a viable approach to ensure the continued safety of the blood supply against emerging pathogens. However, the currently licensed pathogen reduction techniques are ineffective against non-enveloped viruses such as hepatitis A virus, and they introduce chemicals with concerns of side effects which prevent their widespread use. In this report, we demonstrate the inactivation of both enveloped and non-enveloped viruses in human plasma using a novel chemical-free method, a visible ultrashort pulsed laser. We found that laser treatment resulted in 2-log, 1-log, and 3-log reductions in human immunodeficiency virus, hepatitis A virus, and murine cytomegalovirus in human plasma, respectively. Laser-treated plasma showed ≥70% retention for most coagulation factors tested. Furthermore, laser treatment did not alter the structure of a model coagulation factor, fibrinogen. Ultrashort pulsed lasers are a promising new method for chemical-free, broad-spectrum pathogen reduction in human plasma. PMID:25372037
Shin, So Youn; Kwon, Kye Chul; Park, Jong Woo; Kim, Ji Myung; Shin, So Young; Koo, Sun Hoe
2012-01-01
Bacterial meningitis is an infectious disease with high rates of mortality and high frequency of severe sequelae. Early identification of causative bacterial and viral pathogens is important for prompt and proper treatment of meningitis and for prevention of life-threatening clinical outcomes. In the present study, we evaluated the value of the Seeplex Meningitis ACE Detection kit (Seegene Inc., Korea), a newly developed multiplex PCR kit employing dual priming oligonucleotide methods, for diagnosing acute meningitis. Analytical sensitivity of the kit was studied using reference strains for each pathogen targeted by the kit, while it's analytical specificity was studied using the human genome DNA and 58 clinically well-identified reference strains. For clinical validation experiment, we used 27 control cerebrospinal fluid (CSF) samples and 78 clinical CSF samples collected from patients at the time of diagnosis of acute meningitis. The lower detection limits ranged from 10(1) copies/µL to 5×10(1) copies/µL for the 12 viral and bacterial pathogens targeted. No cross-reaction was observed. In the validation study, high detection rate of 56.4% was obtained. None of the control samples tested positive, i.e., false-positive results were absent. The Seeplex Meningitis ACE Detection kit showed high sensitivity, specificity, and detection rate for the identification of pathogens in clinical CSF samples. This kit may be useful for rapid identification of important acute meningitis-causing pathogens.
Shin, So Youn; Kwon, Kye Chul; Park, Jong Woo; Kim, Ji Myung; Shin, So Young
2012-01-01
Background Bacterial meningitis is an infectious disease with high rates of mortality and high frequency of severe sequelae. Early identification of causative bacterial and viral pathogens is important for prompt and proper treatment of meningitis and for prevention of life-threatening clinical outcomes. In the present study, we evaluated the value of the Seeplex Meningitis ACE Detection kit (Seegene Inc., Korea), a newly developed multiplex PCR kit employing dual priming oligonucleotide methods, for diagnosing acute meningitis. Methods Analytical sensitivity of the kit was studied using reference strains for each pathogen targeted by the kit, while it's analytical specificity was studied using the human genome DNA and 58 clinically well-identified reference strains. For clinical validation experiment, we used 27 control cerebrospinal fluid (CSF) samples and 78 clinical CSF samples collected from patients at the time of diagnosis of acute meningitis. Results The lower detection limits ranged from 101 copies/µL to 5×101 copies/µL for the 12 viral and bacterial pathogens targeted. No cross-reaction was observed. In the validation study, high detection rate of 56.4% was obtained. None of the control samples tested positive, i.e., false-positive results were absent. Conclusions The Seeplex Meningitis ACE Detection kit showed high sensitivity, specificity, and detection rate for the identification of pathogens in clinical CSF samples. This kit may be useful for rapid identification of important acute meningitis-causing pathogens. PMID:22259778
Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages
Fabri, Mario; Stenger, Steffen; Shin, Dong-Min; Yuk, Jae-Min; Liu, Philip T.; Realegeno, Susan; Lee, Hye-Mi; Krutzik, Stephan R.; Schenk, Mirjam; Sieling, Peter A.; Teles, Rosane; Montoya, Dennis; Iyer, Shankar S.; Bruns, Heiko; Lewinsohn, David M.; Hollis, Bruce W.; Hewison, Martin; Adams, John S.; Steinmeyer, Andreas; Zügel, Ulrich; Cheng, Genhong; Jo, Eun-Kyeong; Bloom, Barry R.; Modlin, Robert L.
2012-01-01
Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection. PMID:21998409
Westenius, Veera; Mäkelä, Sanna M; Ziegler, Thedi; Julkunen, Ilkka; Österlund, Pamela
2014-12-01
Avian influenza A (H9N2) viruses have occasionally been identified in humans with upper respiratory tract infections. The novel H7N9/2013 virus identified in China shows that a low pathogenic avian influenza (LPAI) virus can be highly pathogenic in humans. Therefore, it is important to understand virus-host cell interactions and immune responses triggered by LPAI viruses in humans. We found that LPAI A/Hong Kong/1073/99 (H9N2) virus replicated efficiently in human dendritic cells (DCs). The H9N2 virus induced strong IFN gene expression although with different kinetics than seasonal influenza A/Beijing/353/89 (H3N2) virus. IFN inducible antiviral proteins were produced in H9N2 virus-infected cells at the same level as in H3N2 infection. The H9N2 virus was extremely sensitive to the antiviral actions of type I IFNs. These results indicate that the avian influenza H9N2 virus is inducing a strong antiviral IFN response in human DCs. Copyright © 2014 Elsevier Inc. All rights reserved.
Joshi, Manju B.; Rogers, Matthew E.; Shakarian, Alison M.; Yamage, Mat; Al-Harthi, Saeed A.; Bates, Paul A.; Dwyer, Dennis M.
2010-01-01
SUMMARY Chitinases have been implicated to be of importance in the life cycle development and transmission of a variety of parasitic organisms. Using a molecular approach, we identified and characterized the structure of a single copy LmexCht1-chitinase gene from the primitive trypanosomatid pathogen of humans, Leishmania mexicana. The LmexCht1 encodes an ~50 kDa protein, with well-conserved substrate-binding and catalytic domains characteristic of members of the Chitinase-18 protein family. Further, we showed that LmexCht1 mRNA is constitutively expressed by both the insect vector (i.e. promastigote) and mammalian (i.e. amastigote) life cycle developmental forms of this protozoan parasite. Interestingly, however, amastigotes were found to secrete/release ~ >2-4 fold higher levels of chitinase activity during their growth in vitro than promastigotes. Moreover, a homologous episomal-expression system was devised and used to express an epitope–tagged LmexCht1 chimeric construct in these parasites. Expression of the LmexCht1 chimera was verified in these transfectants by RT-PCR, Western blots and indirect immunofluorescence analyses. Further, results of coupled-immunoprecipitation/ enzyme activity experiments demonstrated that the LmexCht1 chimeric protein was secreted/released by these transfected L. mexicana parasites and that it possessed functional chitinase enzyme activity. Such transfectants were also evaluated for their infectivity both in human macrophages in vitro and in two different strains of mice. Results of those experiments demonstrated that the LmexCht1 transfectants survived significantly better in human macrophages and also produced significantly larger lesions in mice than control parasites. Taken together, our results indicate that the LmexCht1-chimera afforded a definitive survival advantage to the parasite within these mammalian hosts. Thus, the LmexCht1 could potentially represent a new virulence determinant in the mammalian phase of this important human pathogen PMID:15561707
Ecological fitness and virulence features of Vibrio parahaemolyticus in estuarine environments.
Lovell, Charles R
2017-03-01
Vibrio parahaemolyticus is a commonly encountered and highly successful organism in marine ecosystems. It is a fast-growing, extremely versatile copiotroph that is active over a very broad range of conditions. It frequently occurs suspended in the water column (often attached to particles or zooplankton), and is a proficient colonist of submerged surfaces. This organism is an important pathogen of animals ranging from microcrustaceans to humans and is a causative agent of seafood-associated food poisoning. This review examines specific ecological adaptations of V. parahaemolyticus, including its broad tolerances to temperature and salinity, its utilization of a wide variety of organic carbon and energy sources, and its pervasive colonization of suspended and stationary materials that contribute to its success and ubiquity in temperate and tropical estuarine ecosystems. Several virulence-related features are examined, in particular the thermostable direct hemolysin (TDH), the TDH-related hemolysin (TRH), and the type 3 secretion system, and the possible importance of these features in V. parahaemolyticus pathogenicity is explored. The impact of new and much more effective PCR primers on V. parahaemolyticus detection and our views of virulent strain abundance are also described. It is clear that strains carrying the canonical virulence genes are far more common than previously thought, which opens questions regarding the role of these genes in pathogenesis. It is also clear that virulence is an evolving feature of V. parahaemolyticus and that novel combinations of virulence factors can lead to emergent virulence in which a strain that is markedly more pathogenic evolves and propagates to produce an outbreak. The effects of global climate change on the frequency of epidemic disease, the geographic distribution of outbreaks, and the human impacts of V. parahaemolyticus are increasing and this review provides information on why this ubiquitous human pathogen has increased its footprint and its significance so dramatically.
Korves, T M; Piceno, Y M; Tom, L M; Desantis, T Z; Jones, B W; Andersen, G L; Hwang, G M
2013-02-01
Air travel can rapidly transport infectious diseases globally. To facilitate the design of biosensors for infectious organisms in commercial aircraft, we characterized bacterial diversity in aircraft air. Samples from 61 aircraft high-efficiency particulate air (HEPA) filters were analyzed with a custom microarray of 16S rRNA gene sequences (PhyloChip), representing bacterial lineages. A total of 606 subfamilies from 41 phyla were detected. The most abundant bacterial subfamilies included bacteria associated with humans, especially skin, gastrointestinal and respiratory tracts, and with water and soil habitats. Operational taxonomic units that contain important human pathogens as well as their close, more benign relatives were detected. When compared to 43 samples of urban outdoor air, aircraft samples differed in composition, with higher relative abundance of Firmicutes and Gammaproteobacteria lineages in aircraft samples, and higher relative abundance of Actinobacteria and Betaproteobacteria lineages in outdoor air samples. In addition, aircraft and outdoor air samples differed in the incidence of taxa containing human pathogens. Overall, these results demonstrate that HEPA filter samples can be used to deeply characterize bacterial diversity in aircraft air and suggest that the presence of close relatives of certain pathogens must be taken into account in probe design for aircraft biosensors. A biosensor that could be deployed in commercial aircraft would be required to function at an extremely low false alarm rate, making an understanding of microbial background important. This study reveals a diverse bacterial background present on aircraft, including bacteria closely related to pathogens of public health concern. Furthermore, this aircraft background is different from outdoor air, suggesting different probes may be needed to detect airborne contaminants to achieve minimal false alarm rates. This study also indicates that aircraft HEPA filters could be used with other molecular techniques to further characterize background bacteria and in investigations in the wake of a disease outbreak. © 2012 John Wiley & Sons A/S.
Mora, Azucena; López, Cecilia; Dabhi, Ghizlane; Blanco, Miguel; Blanco, Jesús E; Alonso, María Pilar; Herrera, Alexandra; Mamani, Rosalía; Bonacorsi, Stéphane; Moulin-Schouleur, Maryvonne; Blanco, Jorge
2009-07-07
Extraintestinal pathogenic Escherichia coli (ExPEC) strains of serotype O1:K1:H7/NM are frequently implicated in neonatal meningitis, urinary tract infections and septicemia in humans. They are also commonly isolated from colibacillosis in poultry. Studies to determine the similarities of ExPEC from different origins have indicated that avian strains potentially have zoonotic properties. A total of 59 ExPEC O1:K1:H7/NM isolates (21 from avian colibacillosis, 15 from human meningitis, and 23 from human urinary tract infection and septicemia) originated from four countries were characterized by phylogenetic PCR grouping, Multilocus Sequence Typing (MLST), Pulsed Field Gel Electrophoresis (PFGE) and genotyping based on several genes known for their association with ExPEC or avian pathogenic Escherichia coli (APEC) virulence.APEC and human ExPEC isolates differed significantly in their assignments to phylogenetic groups, being phylogroup B2 more prevalent among APEC than among human ExPEC (95% vs. 53%, P = 0.001), whereas phylogroup D was almost exclusively associated with human ExPEC (47% vs. 5%, P = 0.0000). Seven virulence genes showed significant differences, being fimAvMT78 and sat genes linked to human isolates, while papGII, tsh, iron, cvaC and iss were significantly associated to APEC. By MLST, 39 of 40 ExPEC belonging to phylogroup B2, and 17 of 19 belonging to phylogroup D exhibited the Sequence Types (STs) ST95 and ST59, respectively. Additionally, two novel STs (ST1013 and ST1006) were established. Considering strains sharing the same ST, phylogenetic group, virulence genotype and PFGE cluster to belong to the same subclone, five subclones were detected; one of those grouped six strains of human and animal origin from two countries. Present results reveal that the clonal group B2 O1:K1:H7/NM ST95, detected in strains of animal and human origin, recovered from different dates and geographic sources, provides evidence that some APEC isolates may act as potential pathogens for humans and, consequently, poultry as a foodborne source, suggesting no host specificity for this type of isolates. A novel and important finding has been the detection of the clonal group D O1:K1:H7/NM ST59 almost exclusively in humans, carrying pathogenic genes linked to the phylogenetic group D. This finding would suggest D O1:K1:H7/NM ST59 as a host specific pathotype for humans.
A Unified Framework for the Infection Dynamics of Zoonotic Spillover and Spread.
Lo Iacono, Giovanni; Cunningham, Andrew A; Fichet-Calvet, Elisabeth; Garry, Robert F; Grant, Donald S; Leach, Melissa; Moses, Lina M; Nichols, Gordon; Schieffelin, John S; Shaffer, Jeffrey G; Webb, Colleen T; Wood, James L N
2016-09-01
A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.e. transmission of pathogens from animals to humans, and 'stuttering transmission', i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir.
A Unified Framework for the Infection Dynamics of Zoonotic Spillover and Spread
Cunningham, Andrew A.; Fichet-Calvet, Elisabeth; Garry, Robert F.; Grant, Donald S.; Leach, Melissa; Moses, Lina M.; Nichols, Gordon; Schieffelin, John S.; Shaffer, Jeffrey G.; Webb, Colleen T.; Wood, James L. N.
2016-01-01
A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: ‘spillover’, i.e. transmission of pathogens from animals to humans, and ‘stuttering transmission’, i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir. PMID:27588425
Water microbiology. Bacterial pathogens and water.
Cabral, João P S
2010-10-01
Water is essential to life, but many people do not have access to clean and safe drinking water and many die of waterborne bacterial infections. In this review a general characterization of the most important bacterial diseases transmitted through water-cholera, typhoid fever and bacillary dysentery-is presented, focusing on the biology and ecology of the causal agents and on the diseases' characteristics and their life cycles in the environment. The importance of pathogenic Escherichia coli strains and emerging pathogens in drinking water-transmitted diseases is also briefly discussed. Microbiological water analysis is mainly based on the concept of fecal indicator bacteria. The main bacteria present in human and animal feces (focusing on their behavior in their hosts and in the environment) and the most important fecal indicator bacteria are presented and discussed (focusing on the advantages and limitations of their use as markers). Important sources of bacterial fecal pollution of environmental waters are also briefly indicated. In the last topic it is discussed which indicators of fecal pollution should be used in current drinking water microbiological analysis. It was concluded that safe drinking water for all is one of the major challenges of the 21st century and that microbiological control of drinking water should be the norm everywhere. Routine basic microbiological analysis of drinking water should be carried out by assaying the presence of Escherichia coli by culture methods. Whenever financial resources are available, fecal coliform determinations should be complemented with the quantification of enterococci. More studies are needed in order to check if ammonia is reliable for a preliminary screening for emergency fecal pollution outbreaks. Financial resources should be devoted to a better understanding of the ecology and behavior of human and animal fecal bacteria in environmental waters.
Water Microbiology. Bacterial Pathogens and Water
Cabral, João P. S.
2010-01-01
Water is essential to life, but many people do not have access to clean and safe drinking water and many die of waterborne bacterial infections. In this review a general characterization of the most important bacterial diseases transmitted through water—cholera, typhoid fever and bacillary dysentery—is presented, focusing on the biology and ecology of the causal agents and on the diseases’ characteristics and their life cycles in the environment. The importance of pathogenic Escherichia coli strains and emerging pathogens in drinking water-transmitted diseases is also briefly discussed. Microbiological water analysis is mainly based on the concept of fecal indicator bacteria. The main bacteria present in human and animal feces (focusing on their behavior in their hosts and in the environment) and the most important fecal indicator bacteria are presented and discussed (focusing on the advantages and limitations of their use as markers). Important sources of bacterial fecal pollution of environmental waters are also briefly indicated. In the last topic it is discussed which indicators of fecal pollution should be used in current drinking water microbiological analysis. It was concluded that safe drinking water for all is one of the major challenges of the 21st century and that microbiological control of drinking water should be the norm everywhere. Routine basic microbiological analysis of drinking water should be carried out by assaying the presence of Escherichia coli by culture methods. Whenever financial resources are available, fecal coliform determinations should be complemented with the quantification of enterococci. More studies are needed in order to check if ammonia is reliable for a preliminary screening for emergency fecal pollution outbreaks. Financial resources should be devoted to a better understanding of the ecology and behavior of human and animal fecal bacteria in environmental waters. PMID:21139855
Auffret, Marc D; Dewhurst, Richard J; Duthie, Carol-Anne; Rooke, John A; John Wallace, R; Freeman, Tom C; Stewart, Robert; Watson, Mick; Roehe, Rainer
2017-12-11
The emergence and spread of antimicrobial resistance is the most urgent current threat to human and animal health. An improved understanding of the abundance of antimicrobial resistance genes and genes associated with microbial colonisation and pathogenicity in the animal gut will have a major role in reducing the contribution of animal production to this problem. Here, the influence of diet on the ruminal resistome and abundance of pathogenicity genes was assessed in ruminal digesta samples taken from 50 antibiotic-free beef cattle, comprising four cattle breeds receiving two diets containing different proportions of concentrate. Two hundred and four genes associated with antimicrobial resistance (AMR), colonisation, communication or pathogenicity functions were identified from 4966 metagenomic genes using KEGG identification. Both the diversity and abundance of these genes were higher in concentrate-fed animals. Chloramphenicol and microcin resistance genes were dominant in samples from forage-fed animals (P < 0.001), while aminoglycoside and streptomycin resistances were enriched in concentrate-fed animals. The concentrate-based diet also increased the relative abundance of Proteobacteria, which includes many animal and zoonotic pathogens. A high ratio of Proteobacteria to (Firmicutes + Bacteroidetes) was confirmed as a good indicator for rumen dysbiosis, with eight cases all from concentrate-fed animals. Finally, network analysis demonstrated that the resistance/pathogenicity genes are potentially useful as biomarkers for health risk assessment of the ruminal microbiome. Diet has important effects on the complement of AMR genes in the rumen microbial community, with potential implications for human and animal health.
Detection of Pathogen Exposure in African Buffalo Using Non-Specific Markers of Inflammation
Glidden, Caroline K.; Beechler, Brianna; Buss, Peter Erik; Charleston, Bryan; de Klerk-Lorist, Lin-Mari; Maree, Francois Frederick; Muller, Timothy; Pérez-Martin, Eva; Scott, Katherine Anne; van Schalkwyk, Ockert Louis; Jolles, Anna
2018-01-01
Detecting exposure to new or emerging pathogens is a critical challenge to protecting human, domestic animal, and wildlife health. Yet, current techniques to detect infections typically target known pathogens of humans or economically important animals. In the face of the current surge in infectious disease emergence, non-specific disease surveillance tools are urgently needed. Tracking common host immune responses indicative of recent infection may have potential as a non-specific diagnostic approach for disease surveillance. The challenge to immunologists is to identify the most promising markers, which ideally should be highly conserved across pathogens and host species, become upregulated rapidly and consistently in response to pathogen invasion, and remain elevated beyond clearance of infection. This study combined an infection experiment and a longitudinal observational study to evaluate the utility of non-specific markers of inflammation [NSMI; two acute phase proteins (haptoglobin and serum amyloid A), two pro-inflammatory cytokines (IFNγ and TNF-α)] as indicators of pathogen exposure in a wild mammalian species, African buffalo (Syncerus caffer). Specifically, in the experimental study, we asked (1) How quickly do buffalo mount NSMI responses upon challenge with an endemic pathogen, foot-and-mouth disease virus; (2) for how long do NSMI remain elevated after viral clearance and; (3) how pronounced is the difference between peak NSMI concentration and baseline NSMI concentration? In the longitudinal study, we asked (4) Are elevated NSMI associated with recent exposure to a suite of bacterial and viral respiratory pathogens in a wild population? Among the four NSMI that we tested, haptoglobin showed the strongest potential as a surveillance marker in African buffalo: concentrations quickly and consistently reached high levels in response to experimental infection, remaining elevated for almost a month. Moreover, elevated haptoglobin was indicative of recent exposure to two respiratory pathogens assessed in the longitudinal study. We hope this work motivates studies investigating suites of NSMI as indicators for pathogen exposure in a broader range of both pathogen and host species, potentially transforming how we track disease burden in natural populations. PMID:29375568
Impacts of Climate Change on Indirect Human Exposure to Pathogens and Chemicals from Agriculture
Boxall, Alistair B.A.; Hardy, Anthony; Beulke, Sabine; Boucard, Tatiana; Burgin, Laura; Falloon, Peter D.; Haygarth, Philip M.; Hutchinson, Thomas; Kovats, R. Sari; Leonardi, Giovanni; Levy, Leonard S.; Nichols, Gordon; Parsons, Simon A.; Potts, Laura; Stone, David; Topp, Edward; Turley, David B.; Walsh, Kerry; Wellington, Elizabeth M.H.; Williams, Richard J.
2009-01-01
Objective Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources In this review, we used expert input and considered literature on climate change; health effects resulting from exposure to pathogens and chemicals arising from agriculture; inputs of chemicals and pathogens to agricultural systems; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes. PMID:19440487
Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation
Wagener, Jeanette; Malireddi, R. K. Subbarao; Lenardon, Megan D.; Köberle, Martin; Vautier, Simon; MacCallum, Donna M.; Biedermann, Tilo; Schaller, Martin; Netea, Mihai G.; Kanneganti, Thirumala-Devi; Brown, Gordon D.; Brown, Alistair J. P.; Gow, Neil A. R.
2014-01-01
Chitin is an essential structural polysaccharide of fungal pathogens and parasites, but its role in human immune responses remains largely unknown. It is the second most abundant polysaccharide in nature after cellulose and its derivatives today are widely used for medical and industrial purposes. We analysed the immunological properties of purified chitin particles derived from the opportunistic human fungal pathogen Candida albicans, which led to the selective secretion of the anti-inflammatory cytokine IL-10. We identified NOD2, TLR9 and the mannose receptor as essential fungal chitin-recognition receptors for the induction of this response. Chitin reduced LPS-induced inflammation in vivo and may therefore contribute to the resolution of the immune response once the pathogen has been defeated. Fungal chitin also induced eosinophilia in vivo, underpinning its ability to induce asthma. Polymorphisms in the identified chitin receptors, NOD2 and TLR9, predispose individuals to inflammatory conditions and dysregulated expression of chitinases and chitinase-like binding proteins, whose activity is essential to generate IL-10-inducing fungal chitin particles in vitro, have also been linked to inflammatory conditions and asthma. Chitin recognition is therefore critical for immune homeostasis and is likely to have a significant role in infectious and allergic disease. Authors Summary Chitin is the second most abundant polysaccharide in nature after cellulose and an essential component of the cell wall of all fungal pathogens. The discovery of human chitinases and chitinase-like binding proteins indicates that fungal chitin is recognised by cells of the human immune system, shaping the immune response towards the invading pathogen. We show that three immune cell receptors– the mannose receptor, NOD2 and TLR9 recognise chitin and act together to mediate an anti-inflammatory response via secretion of the cytokine IL-10. This mechanism may prevent inflammation-based damage during fungal infection and restore immune balance after an infection has been cleared. By increasing the chitin content in the cell wall pathogenic fungi may influence the immune system in their favour, by down-regulating protective inflammatory immune responses. Furthermore, gene mutations and dysregulated enzyme activity in the described chitin recognition pathway are implicated in inflammatory conditions such as Crohn's Disease and asthma, highlighting the importance of the discovered mechanism in human health. PMID:24722226
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.
Iraola, Gregorio; Forster, Samuel C; Kumar, Nitin; Lehours, Philippe; Bekal, Sadjia; García-Peña, Francisco J; Paolicchi, Fernando; Morsella, Claudia; Hotzel, Helmut; Hsueh, Po-Ren; Vidal, Ana; Lévesque, Simon; Yamazaki, Wataru; Balzan, Claudia; Vargas, Agueda; Piccirillo, Alessandra; Chaban, Bonnie; Hill, Janet E; Betancor, Laura; Collado, Luis; Truyers, Isabelle; Midwinter, Anne C; Dagi, Hatice T; Mégraud, Francis; Calleros, Lucía; Pérez, Ruben; Naya, Hugo; Lawley, Trevor D
2017-11-08
Campylobacter fetus is a venereal pathogen of cattle and sheep, and an opportunistic human pathogen. It is often assumed that C. fetus infection occurs in humans as a zoonosis through food chain transmission. Here we show that mammalian C. fetus consists of distinct evolutionary lineages, primarily associated with either human or bovine hosts. We use whole-genome phylogenetics on 182 strains from 17 countries to provide evidence that C. fetus may have originated in humans around 10,500 years ago and may have "jumped" into cattle during the livestock domestication period. We detect C. fetus genomes in 8% of healthy human fecal metagenomes, where the human-associated lineages are the dominant type (78%). Thus, our work suggests that C. fetus is an unappreciated human intestinal pathobiont likely spread by human to human transmission. This genome-based evolutionary framework will facilitate C. fetus epidemiology research and the development of improved molecular diagnostics and prevention schemes for this neglected pathogen.
A Novel Protective Vaccine Antigen from the Core Escherichia coli Genome
Moriel, Danilo G.; Tan, Lendl; Goh, Kelvin G. K.; Ipe, Deepak S.; Lo, Alvin W.; Peters, Kate M.
2016-01-01
ABSTRACT Escherichia coli is a versatile pathogen capable of causing intestinal and extraintestinal infections that result in a huge burden of global human disease. The diversity of E. coli is reflected by its multiple different pathotypes and mosaic genome composition. E. coli strains are also a major driver of antibiotic resistance, emphasizing the urgent need for new treatment and prevention measures. Here, we used a large data set comprising 1,700 draft and complete genomes to define the core and accessory genome of E. coli and demonstrated the overlapping relationship between strains from different pathotypes. In combination with proteomic investigation, this analysis revealed core genes that encode surface-exposed or secreted proteins that represent potential broad-coverage vaccine antigens. One of these antigens, YncE, was characterized as a conserved immunogenic antigen able to protect against acute systemic infection in mice after vaccination. Overall, this work provides a genomic blueprint for future analyses of conserved and accessory E. coli genes. The work also identified YncE as a novel antigen that could be exploited in the development of a vaccine against all pathogenic E. coli strains—an important direction given the high global incidence of infections caused by multidrug-resistant strains for which there are few effective antibiotics. IMPORTANCE E. coli is a multifaceted pathogen of major significance to global human health and an important contributor to increasing antibiotic resistance. Given the paucity of therapies still effective against multidrug-resistant pathogenic E. coli strains, novel treatment and prevention strategies are urgently required. In this study, we defined the core and accessory components of the E. coli genome by examining a large collection of draft and completely sequenced strains available from public databases. This data set was mined by employing a reverse-vaccinology approach in combination with proteomics to identify putative broadly protective vaccine antigens. One such antigen was identified that was highly immunogenic and induced protection in a mouse model of bacteremia. Overall, our study provides a genomic and proteomic framework for the selection of novel vaccine antigens that could mediate broad protection against pathogenic E. coli. PMID:27904885
Development of a CRISPR-Cas9 System for Efficient Genome Editing of Candida lusitaniae.
Norton, Emily L; Sherwood, Racquel K; Bennett, Richard J
2017-01-01
Candida lusitaniae is a member of the Candida clade that includes a diverse group of fungal species relevant to both human health and biotechnology. This species exhibits a full sexual cycle to undergo interconversion between haploid and diploid forms. C. lusitaniae is also an emerging opportunistic pathogen that can cause serious bloodstream infections in the clinic and yet has often proven to be refractory to facile genetic manipulations. In this work, we develop a clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (Cas9) system to enable genome editing of C. lusitaniae . We demonstrate that expression of CRISPR-Cas9 components under species-specific promoters is necessary for efficient gene targeting and can be successfully applied to multiple genes in both haploid and diploid isolates. Gene deletion efficiencies with CRISPR-Cas9 were further enhanced in C. lusitaniae strains lacking the established nonhomologous end joining (NHEJ) factors Ku70 and DNA ligase 4. These results indicate that NHEJ plays an important role in directing the repair of DNA double-strand breaks (DSBs) in C. lusitaniae and that removal of this pathway increases integration of gene deletion templates by homologous recombination. The described approaches significantly enhance the ability to perform genetic studies in, and promote understanding of, this emerging human pathogen and model sexual species. IMPORTANCE The ability to perform efficient genome editing is a key development for detailed mechanistic studies of a species. Candida lusitaniae is an important member of the Candida clade and is relevant both as an emerging human pathogen and as a model for understanding mechanisms of sexual reproduction. We highlight the development of a CRISPR-Cas9 system for efficient genome manipulation in C. lusitaniae and demonstrate the importance of species-specific promoters for expression of CRISPR components. We also demonstrate that the NHEJ pathway contributes to non-template-mediated repair of DNA DSBs and that removal of this pathway enhances efficiencies of gene targeting by CRISPR-Cas9. These results therefore establish important genetic tools for further exploration of C. lusitaniae biology.
Space Tourism and Safety from Infection
NASA Astrophysics Data System (ADS)
Ilyin, V. K.; Tiurina, D. A.; Usanova, N. A.; Starkova, L. V.; Soloviova, Z. O.; Morozova, Ju. A.; Kirjukhina, N. V.; Webb, A.
This paper highlights the major scenarios of the microbiological changes which occur in the human organism in space missions, i.e. the increasing of the conventional pathogen population share in human microflora and changes in antibiotic susceptibility, and substantiates compatible countermeasures based on probiotics consumption. Special attention is given to the prospects of the consumption of probiotics made of strains which are representative of human commensurate microflora for the support of resistance during a space journey. It is a most important technique and one which will be acceptable for space tourists.
Potential in vitro antimicrobial efficacy of Holigarna arnottiana (Hook F).
Manilal, Aseer; Idhayadhulla, Akbar
2014-01-01
To explore the in vitro antimicrobial potential of Holigarna arnottiana (H. arnottiana) against human and shrimp pathogenic bacteria and use GC-MS analysis to elucidate its antimicrobial principles. In the present study, organic extract of H. arnottiana was examined for in vitro antimicrobial potency against five clinical human pathogens, seven species of human type culture pathogens, six pathogenic Vibrio strains isolated from moribund tiger shrimp (Penaeus monodon) and seven type cultures (Microbial Type Culture Collection, MTCC) of prominent shrimp pathogens. The extraction of H. arnottiana with ethyl acetate yielded bioactive crude extract that efficiently repressed the growth of all tested pathogens. Among the pathogens tested, shrimp pathogens were the most susceptible organisms while clinical pathogens were found to be a little resistant. The chemical constituents of the H. arnottiana were analysed by GC-MS which revealed the presence of major compounds such as 3,7,11,15-tetramethyl-2-hexadecen-1-o1 (42.1%), 1-lodo-2-methylundecane (34.5%) and squalene (11.1%) which might have a functional role in the chemical defence against microbial invasion. Based on the finding it could be inferred that H. arnottiana would be a reliable source for developing shrimp and human bio-therapeutics in future. Copyright © 2014 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.
Potential in vitro antimicrobial efficacy of Holigarna arnottiana (Hook F)
Manilal, Aseer; Idhayadhulla, Akbar
2014-01-01
Objective To explore the in vitro antimicrobial potential of Holigarna arnottiana (H. arnottiana) against human and shrimp pathogenic bacteria and use GC-MS analysis to elucidate its antimicrobial principles. Methods In the present study, organic extract of H. arnottiana was examined for in vitro antimicrobial potency against five clinical human pathogens, seven species of human type culture pathogens, six pathogenic Vibrio strains isolated from moribund tiger shrimp (Penaeus monodon) and seven type cultures (Microbial Type Culture Collection, MTCC) of prominent shrimp pathogens. Results The extraction of H. arnottiana with ethyl acetate yielded bioactive crude extract that efficiently repressed the growth of all tested pathogens. Among the pathogens tested, shrimp pathogens were the most susceptible organisms while clinical pathogens were found to be a little resistant. The chemical constituents of the H. arnottiana were analysed by GC-MS which revealed the presence of major compounds such as 3,7,11,15-tetramethyl-2-hexadecen-1-o1 (42.1%), 1-lodo-2-methylundecane (34.5%) and squalene (11.1%) which might have a functional role in the chemical defence against microbial invasion. Conclusions Based on the finding it could be inferred that H. arnottiana would be a reliable source for developing shrimp and human bio-therapeutics in future. PMID:24144126
Elbahesh, Husni; Schughart, Klaus
2016-05-19
Influenza A viruses (IAV) are zoonotic pathogens that pose a major threat to human and animal health. Influenza virus disease severity is influenced by viral virulence factors as well as individual differences in host response. We analyzed gene expression changes in the blood of infected mice using a previously defined set of signature genes that was derived from changes in the blood transcriptome of IAV-infected human volunteers. We found that the human signature was reproduced well in the founder strains of the Collaborative Cross (CC) mice, thus demonstrating the relevance and importance of mouse experimental model systems for studying human influenza disease.