Risks Posed by Reston, the Forgotten Ebolavirus

PubMed Central

Cantoni, Diego; Hamlet, Arran; Michaelis, Martin; Wass, Mark N.

2016-01-01

ABSTRACT Out of the five members of the Ebolavirus family, four cause life-threatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans. Amino acid sequence differences between RESTV and the other Ebolaviruses are found in all nine Ebolavirus proteins, though no one residue appears sufficient to confer pathogenicity. Changes in the glycoprotein contribute to differences in Ebolavirus pathogenicity but are not sufficient to confer pathogenicity on their own. Similarly, differences in VP24 and VP35 affect viral immune evasion and are associated with changes in human pathogenicity. A recent in silico analysis systematically determined the functional consequences of sequence variations between RESTV and human-pathogenic Ebolaviruses. Multiple positions in VP24 were differently conserved between RESTV and the other Ebolaviruses and may alter human pathogenicity. In conclusion, the factors that determine the pathogenicity of Ebolaviruses in humans remain insufficiently understood. An improved understanding of these pathogenicity-determining factors is of crucial importance for disease prevention and for the early detection of emergent and potentially human-pathogenic RESTVs. PMID:28066813

Life-threatening Cerebral Edema Caused by Acute Occlusion of a Superior Vena Cava Stent

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

Sofue, Keitaro, E-mail: keitarosofue@yahoo.co.jp; Takeuchi, Yoshito, E-mail: yotake62@qg8.so-net.ne.jp; Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp

A71-year-old man with advanced lung cancer developed a life-threatening cerebral edema caused by the acute occlusion of a superior vena cava (SVC) stent and was successfully treated by an additional stent placement. Although stent occlusion is a common early complication, no life-threatening situations have been reported until now. Our experience highlights the fact that acute stent occlusion can potentially lead to the complete venous shutdown of the SVC, resulting in life-threatening cerebral edema, after SVC stent placement. Immediate diagnosis and countermeasures are required.

Animal models of polymicrobial pneumonia

PubMed Central

Hraiech, Sami; Papazian, Laurent; Rolain, Jean-Marc; Bregeon, Fabienne

2015-01-01

Pneumonia is one of the leading causes of severe and occasionally life-threatening infections. The physiopathology of pneumonia has been extensively studied, providing information for the development of new treatments for this condition. In addition to in vitro research, animal models have been largely used in the field of pneumonia. Several models have been described and have provided a better understanding of pneumonia under different settings and with various pathogens. However, the concept of one pathogen leading to one infection has been challenged, and recent flu epidemics suggest that some pathogens exhibit highly virulent potential. Although “two hits” animal models have been used to study infectious diseases, few of these models have been described in pneumonia. Therefore the aims of this review were to provide an overview of the available literature in this field, to describe well-studied and uncommon pathogen associations, and to summarize the major insights obtained from this information. PMID:26170617

A PR-1-like Protein of Fusarium oxysporum Functions in Virulence on Mammalian Hosts*

PubMed Central

Prados-Rosales, Rafael C.; Roldán-Rodríguez, Raquel; Serena, Carolina; López-Berges, Manuel S.; Guarro, Josep; Martínez-del-Pozo, Álvaro; Di Pietro, Antonio

2012-01-01

The pathogenesis-related PR-1-like protein family comprises secreted proteins from the animal, plant, and fungal kingdoms whose biological function remains poorly understood. Here we have characterized a PR-1-like protein, Fpr1, from Fusarium oxysporum, an ubiquitous fungal pathogen that causes vascular wilt disease on a wide range of plant species and can produce life-threatening infections in immunocompromised humans. Fpr1 is secreted and proteolytically processed by the fungus. The fpr1 gene is required for virulence in a disseminated immunodepressed mouse model, and its function depends on the integrity of the proposed active site of PR-1-like proteins. Fpr1 belongs to a gene family that has expanded in plant pathogenic Sordariomycetes. These results suggest that secreted PR-1-like proteins play important roles in fungal pathogenicity. PMID:22553200

Cryptosporidiosis Drug Discovery: Opportunities and Challenges.

PubMed

Manjunatha, Ujjini H; Chao, Alexander T; Leong, F Joel; Diagana, Thierry T

2016-08-12

The apicomplexan parasite Cryptosporidium is the second most important diarrheal pathogen causing life-threatening diarrhea in children, which is also associated with long-term growth faltering and cognitive deficiency. Cryptosporidiosis is a parasitic disease of public health concern caused by Cryptosporidium parvum and Cryptosporidium hominis. Currently, nitazoxanide is the only approved treatment for cryptosporidium infections. Unfortunately, it has limited efficacy in the most vulnerable patients, thus there is an urgent need for a safe and efficacious cryptosporidiosis drug. In this work, we present our current perspectives on the target product profile for novel cryptosporidiosis therapies and the perceived challenges and possible mitigation plans at different stages in the cryptosporidiosis drug discovery process.

Lipids and flaviviruses, present and future perspectives for the control of dengue, Zika, and West Nile viruses.

PubMed

Martín-Acebes, Miguel A; Vázquez-Calvo, Ángela; Saiz, Juan-Carlos

2016-10-01

Flaviviruses are emerging arthropod-borne pathogens that cause life-threatening diseases such as yellow fever, dengue, West Nile encephalitis, tick-borne encephalitis, Kyasanur Forest disease, tick-borne encephalitis, or Zika disease. This viral genus groups >50 viral species of small enveloped plus strand RNA virus that are phylogenetically closely related to hepatitis C virus. Importantly, the flavivirus life cycle is intimately associated to host cell lipids. Along this line, flaviviruses rearrange intracellular membranes from the endoplasmic-reticulum of the infected cells to develop adequate platforms for viral replication and particle biogenesis. Moreover, flaviviruses dramatically orchestrate a profound reorganization of the host cell lipid metabolism to create a favorable environment for viral multiplication. Consistently, recent work has shown the importance of specific lipid classes in flavivirus infections. For instances, fatty acid synthesis is linked to viral replication, phosphatidylserine and phosphatidylethanolamine are involved on the entry of flaviviruses, sphingolipids (ceramide and sphingomyelin) play a key role on virus assembly and pathogenesis, and cholesterol is essential for innate immunity evasion in flavivirus-infected cells. Here, we revise the current knowledge on the interactions of the flaviviruses with the cellular lipid metabolism to identify potential targets for future antiviral development aimed to combat these relevant health-threatening pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevention of Infectious Complications in Patients With Chronic Granulomatous Disease.

PubMed

Slack, Maria A; Thomsen, Isaac P

2018-05-09

Chronic granulomatous disease (CGD) is a primary immunodeficiency that confers a markedly increased risk of bacterial and fungal infections caused by certain opportunistic pathogens. Current evidence supports the use of prophylactic antibacterial, antifungal, and immunomodulatory therapies designed to prevent serious or life-threatening infections in patients with CGD. In this review, we discuss current strategies for the prevention of infections in children and adults with CGD and the evidence that supports those strategies. In addition, we address current challenges and opportunities for future research in this important area.

Broad-Spectrum Molecular Detection of Fungal Nucleic Acids by PCR-Based Amplification Techniques.

PubMed

Czurda, Stefan; Lion, Thomas

2017-01-01

Over the past decade, the incidence of life-threatening invasive fungal infections has dramatically increased. Infections caused by hitherto rare and emerging fungal pathogens are associated with significant morbidity and mortality among immunocompromised patients. These observations render the coverage of a broad range of clinically relevant fungal pathogens highly important. The so-called panfungal or, perhaps more correctly, broad-range nucleic acid amplification techniques do not only facilitate sensitive detection of all clinically relevant fungal species but are also rapid and can be applied to analyses of any patient specimens. They have therefore become valuable diagnostic tools for sensitive screening of patients at risk of invasive fungal infections. This chapter summarizes the currently available molecular technologies employed in testing of a wide range of fungal pathogens, and provides a detailed workflow for patient screening by broad-spectrum nucleic acid amplification techniques.

Bacteremia caused by a rare pathogen - Chromobacterium violaceum: a case report from Nepal.

PubMed

Parajuli, Narayan Prasad; Bhetwal, Anjeela; Ghimire, Sumitra; Maharjan, Anjila; Shakya, Shreena; Satyal, Deepa; Pandit, Roshan; Khanal, Puspa Raj

2016-01-01

Chromobacterium violaceum is a gram negative saprophytic bacterium, prevalent in tropical and subtropical climates. Infections caused by C. violaceum are very uncommon, yet it can cause severe systemic infections with higher mortality when entered into the bloodstream through open wound. A case of symptomatic bacteremia in a woman caused by C. violaceum was identified recently at a tertiary care teaching hospital in Nepal. Timely diagnosis by microbiological methods and rapid administration of antimicrobials led to a successful treatment of this life-threatening infection in this case. From this experience, we suggest to include this bacterium in the differential diagnosis of sepsis, especially when abraded skin is exposed to soil or stagnant water in tropical areas. The precise antimicrobial selection and timely administration should be considered when this infection is suspected.

Endemic Scrub Typhus in South America.

PubMed

Weitzel, Thomas; Dittrich, Sabine; López, Javier; Phuklia, Weerawat; Martinez-Valdebenito, Constanza; Velásquez, Katia; Blacksell, Stuart D; Paris, Daniel H; Abarca, Katia

2016-09-08

Scrub typhus is a life-threatening zoonosis caused by Orientia tsutsugamushi organisms that are transmitted by the larvae of trombiculid mites. Endemic scrub typhus was originally thought to be confined to the so called "tsutsugamushi triangle" within the Asia-Pacific region. In 2006, however, two individual cases were detected in the Middle East and South America, which suggested that the pathogen was present farther afield. Here, we report three autochthonous cases of scrub typhus caused by O. tsutsugamushi acquired on Chiloé Island in southern Chile, which suggests the existence of an endemic focus in South America. (Funded by the Chilean Comisión Nacional de Investigación Científica y Tecnológica and the Wellcome Trust.).

[Reduced number of fatal and life-threatening reactions to food. Reporting by the medical profession has resulted in effective measures].

PubMed

Foucard, Tony; Yman, Ingrid Malmheden; Nordvall, Lennart

The results from the Swedish system for reporting severe and fatal reactions caused by food for the period 1993-96 were published in Lakartidningen in 1997. We now report the results for the period 1997-2003. The number of fatal cases has decreased from 1.75 to 0.86 per year and the number of life-threatening cases from 3 to I per year. The most gratifying result was the large decrease in severe reactions caused by soy, from 3 deaths and 6 life-threatening cases during the first 4-year period to just one life-threatening case during the following 7-year period. This reduction is probably largely due to an increased awareness of identified risk persons, but also to a reduced use of soy protein. The ongoing study illustrates the usefulness of a national system for reporting severe and fatal reactions caused by food.

Current and emerging techniques for antibiotic susceptibility tests.

PubMed

Syal, Karan; Mo, Manni; Yu, Hui; Iriya, Rafael; Jing, Wenwen; Guodong, Sui; Wang, Shaopeng; Grys, Thomas E; Haydel, Shelley E; Tao, Nongjian

2017-01-01

Infectious diseases caused by bacterial pathogens are a worldwide burden. Serious bacterial infection-related complications, such as sepsis, affect over a million people every year with mortality rates ranging from 30% to 50%. Crucial clinical microbiology laboratory responsibilities associated with patient management and treatment include isolating and identifying the causative bacterium and performing antibiotic susceptibility tests (ASTs), which are labor-intensive, complex, imprecise, and slow (taking days, depending on the growth rate of the pathogen). Considering the life-threatening condition of a septic patient and the increasing prevalence of antibiotic-resistant bacteria in hospitals, rapid and automated diagnostic tools are needed. This review summarizes the existing commercial AST methods and discusses some of the promising emerging AST tools that will empower humans to win the evolutionary war between microbial genes and human wits.

Current and emerging techniques for antibiotic susceptibility tests

PubMed Central

Syal, Karan; Mo, Manni; Yu, Hui; Iriya, Rafael; Jing, Wenwen; Guodong, Sui; Wang, Shaopeng; Grys, Thomas E.; Haydel, Shelley E.; Tao, Nongjian

2017-01-01

Infectious diseases caused by bacterial pathogens are a worldwide burden. Serious bacterial infection-related complications, such as sepsis, affect over a million people every year with mortality rates ranging from 30% to 50%. Crucial clinical microbiology laboratory responsibilities associated with patient management and treatment include isolating and identifying the causative bacterium and performing antibiotic susceptibility tests (ASTs), which are labor-intensive, complex, imprecise, and slow (taking days, depending on the growth rate of the pathogen). Considering the life-threatening condition of a septic patient and the increasing prevalence of antibiotic-resistant bacteria in hospitals, rapid and automated diagnostic tools are needed. This review summarizes the existing commercial AST methods and discusses some of the promising emerging AST tools that will empower humans to win the evolutionary war between microbial genes and human wits. PMID:28638468

Staphylococcus aureus pathogenesis in diverse host environments

PubMed Central

Balasubramanian, Divya; Harper, Lamia; Shopsin, Bo; Torres, Victor J.

2017-01-01

Abstract Staphylococcus aureus is an eminent human pathogen that can colonize the human host and cause severe life-threatening illnesses. This bacterium can reside in and infect a wide range of host tissues, ranging from superficial surfaces like the skin to deeper tissues such as in the gastrointestinal tract, heart and bones. Due to its multifaceted lifestyle, S. aureus uses complex regulatory networks to sense diverse signals that enable it to adapt to different environments and modulate virulence. In this minireview, we explore well-characterized environmental and host cues that S. aureus responds to and describe how this pathogen modulates virulence in response to these signals. Lastly, we highlight therapeutic approaches undertaken by several groups to inhibit both signaling and the cognate regulators that sense and transmit these signals downstream. PMID:28104617

Interleukin-13 associates with life-threatening rhinovirus infections in infants and young children.

PubMed

Caballero, Mauricio T; Hijano, Diego R; Acosta, Patricio L; Mateu, Cecilia G; Marcone, Débora N; Linder, Jodell E; Talarico, Laura B; Elder, John M; Echavarria, Marcela; Miller, Eva Kathryn; Polack, Fernando P

2018-04-17

Delineate risk factors associated with severe hypoxemia (O 2 sat ≤87%) in infants and children younger than 2 years hospitalized with single pathogen HRV infection. Prospective study in a yearly catchment population of 56 560 children <2 years old between 2011 and 2013 in Argentina. All children with respiratory signs and O 2 sat <93% on admission were included. HRV infections were identified by reverse transcriptase-polymerase chain reaction. Epidemiologic, clinical, viral, and immunological risk factors were assessed. Among 5012 hospitalized patients, HRV was detected as a single pathogen in 347 (6.92%) subjects. Thirty-two (9.2%) had life-threatening disease. Traditional risk factors for severe bronchiolitis did not affect severity of illness. HRV viral load, HRV groups, and type II and III interferons did not associate with severe hypoxemia. Interleukin-13 Levels in respiratory secretions at the time of admission (OR = 7.43 (3-18.4); P < 0.001 for IL-13 >10 pg/mL) predisposed to life-threatening disease. Targeted interventions against IL-13 should be evaluated to decrease severity of HRV illness in infancy and early childhood. © 2018 Wiley Periodicals, Inc.

Innate immunity and gut-microbe mutualism in Drosophila.

PubMed

Ryu, Ji-Hwan; Ha, Eun-Mi; Lee, Won-Jae

2010-04-01

Metazoan guts face a wide variety of microorganisms upon exposure to the environment, including beneficial symbionts, non-symbionts, food-borne microbes and life-threatening pathogens. Recent evidence has shown that the innate immunity of gut epithelia, such as anti-microbial peptide- and reactive oxygen species-based immune systems, actively participate in gut-microbe homeostasis by shaping the commensal community while efficiently eliminating unwanted bacteria. Therefore, elucidation of the regulatory mechanism by which gut innate immunity occurs at the molecular level will provide a novel perspective of gut-microbe mutualisms as well as of gut diseases caused by alterations in the innate immunity.

Purulent pericarditis and pneumonia caused by Streptococcus equi subsp. zooepidemicus.

PubMed

Held, Jürgen; Schmitz, Roland; van der Linden, Mark; Nührenberg, Thomas; Häcker, Georg; Neumann, Franz-Josef

2014-02-01

Purulent pericarditis is a life-threatening disease that usually manifests following bacteraemia or through spreading from an intrathoracic focus. Only a few cases of this disease have been reported with Lancefield group C streptococci as aetiological agents, and the primary focus in these infections remains unknown. We report a case of purulent pericarditis with septic and cardiogenic shock, caused by Streptococcus equi subsp. zooepidemicus (group C) in a 51-year-old patient. The pathogen was possibly contracted through contact with horses. Most probably, it caused initially pneumonia before spreading to the pericardium, either directly or via the bloodstream. A combined therapeutic approach, consisting of antibiotic therapy and repeated pericardial drainage, was necessary to ensure a clinical cure. After discharge, long-term follow-up for development of constrictive pericarditis is considered mandatory.

MRSA Information for Patients

MedlinePlus

... untreated, they can lead to serious problems including sepsis , a life-threatening reaction to severe infection in ... the body and cause life-threatening problems including sepsis . Top of Page What Are Some of the ...

Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus Pneumocystis jirovecii.

PubMed

Schmid-Siegert, Emanuel; Richard, Sophie; Luraschi, Amanda; Mühlethaler, Konrad; Pagni, Marco; Hauser, Philippe M

2017-11-07

Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose by Pneumocystis jirovecii This uncultivable fungus is an obligate pulmonary pathogen that in immunocompromised individuals causes pneumonia, a major life-threatening infection. Long-read PacBio sequencing was used to assemble a core of subtelomeres of a single P. jirovecii strain from a bronchoalveolar lavage fluid specimen from a single patient. A total of 113 genes encoding surface proteins were identified, including 28 pseudogenes. These genes formed a subtelomeric gene superfamily, which included five families encoding adhesive glycosylphosphatidylinositol (GPI)-anchored glycoproteins and one family encoding excreted glycoproteins. Numerical analyses suggested that diversification of the glycoproteins relies on mosaic genes created by ectopic recombination and occurs only within each family. DNA motifs suggested that all genes are expressed independently, except those of the family encoding the most abundant surface glycoproteins, which are subject to mutually exclusive expression. PCR analyses showed that exchange of the expressed gene of the latter family occurs frequently, possibly favored by the location of the genes proximal to the telomere because this allows concomitant telomere exchange. Our observations suggest that (i) the P. jirovecii cell surface is made of a complex mixture of different surface proteins, with a majority of a single isoform of the most abundant glycoprotein, (ii) genetic mosaicism within each family ensures variation of the glycoproteins, and (iii) the strategy of the fungus consists of the continuous production of new subpopulations composed of cells that are antigenically different. IMPORTANCE Pneumocystis jirovecii is a fungus causing severe pneumonia in immunocompromised individuals. It is the second most frequent life-threatening invasive fungal infection. We have studied the mechanisms of antigenic variation used by this pathogen to escape the human immune system, a strategy commonly used by pathogenic microorganisms. Using a new DNA sequencing technology generating long reads, we could characterize the highly repetitive gene families encoding the proteins that are present on the cellular surface of this pest. These gene families are localized in the regions close to the ends of all chromosomes, the subtelomeres. Such chromosomal localization was found to favor genetic recombinations between members of each gene family and to allow diversification of these proteins continuously over time. This pathogen seems to use a strategy of antigenic variation consisting of the continuous production of new subpopulations composed of cells that are antigenically different. Such a strategy is unique among human pathogens. Copyright © 2017 Schmid-Siegert et al.

Identification of virulence determinants of the human pathogenic fungi Aspergillus fumigatus and Candida albicans by proteomics.

PubMed

Kniemeyer, Olaf; Schmidt, André D; Vödisch, Martin; Wartenberg, Dirk; Brakhage, Axel A

2011-06-01

Both fungi Candida albicans and Aspergillus fumigatus can cause a number of life-threatening systemic infections in humans. The commensal yeast C. albicans is one of the main causes of nosocomial fungal infectious diseases, whereas the filamentous fungus A. fumigatus has become one of the most prevalent airborne fungal pathogens. Early diagnosis of these fungal infections is challenging, only a limited number of antifungals for treatment are available, and the molecular details of pathogenicity are hardly understood. The completion of both the A. fumigatus and C. albicans genome sequence provides the opportunity to improve diagnosis, to define new drug targets, to understand the functions of many uncharacterised proteins, and to study protein regulation on a global scale. With the application of proteomic tools, particularly two-dimensional gel electrophoresis and LC/MS-based methods, a comprehensive overview about the proteins of A. fumigatus and C. albicans present or induced during environmental changes and stress conditions has been obtained in the past 5 years. However, for the discovery of further putative virulence determinants, more sensitive and targeted proteomic methods have to be applied. Here, we review the recent proteome data generated for A. fumigatus and C. albicans that are related to factors required for pathogenicity. Copyright © 2011 Elsevier GmbH. All rights reserved.

Rhodococcus equi: the many facets of a pathogenic actinomycete.

PubMed

Vázquez-Boland, José A; Giguère, Steeve; Hapeshi, Alexia; MacArthur, Iain; Anastasi, Elisa; Valero-Rello, Ana

2013-11-29

Rhodococcus equi is a soil-dwelling pathogenic actinomycete that causes pulmonary and extrapulmonary pyogranulomatous infections in a variety of animal species and people. Young foals are particularly susceptible and develop a life-threatening pneumonic disease that is endemic at many horse-breeding farms worldwide. R. equi is a facultative intracellular parasite of macrophages that replicates within a modified phagocytic vacuole. Its pathogenicity depends on a virulence plasmid that promotes intracellular survival by preventing phagosome-lysosome fusion. Species-specific tropism of R. equi for horses, pigs and cattle appears to be determined by host-adapted virulence plasmid types. Molecular epidemiological studies of these plasmids suggest that human R. equi infection is zoonotic. Analysis of the recently determined R. equi genome sequence has identified additional virulence determinants on the bacterial chromosome. This review summarizes our current understanding of the clinical aspects, biology, pathogenesis and immunity of this fascinating microbe with plasmid-governed infectivity. Copyright © 2013 Elsevier B.V. All rights reserved.

Profiling a killer, the development of Cryptococcus neoformans

PubMed Central

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

The first 30 years of Shiga toxin-producing Escherichia coli in cattle production: Preharvest intervention strategies

USDA-ARS?s Scientific Manuscript database

Cattle are naturally colonized with foodborne pathogenic bacteria, including Shiga toxin-producing E. coli (STEC). While these foodborne pathogens threaten food safety, they also cause human illnesses via cross contamination of other foods, the water supply, and via direct animal contact. Pre-harv...

Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes

PubMed Central

Hiller, Ekkehard; Istel, Fabian; Tscherner, Michael; Brunke, Sascha; Ames, Lauren; Firon, Arnaud; Green, Brian; Cabral, Vitor; Marcet-Houben, Marina; Jacobsen, Ilse D.; Quintin, Jessica; Seider, Katja; Frohner, Ingrid; Glaser, Walter; Jungwirth, Helmut; Bachellier-Bassi, Sophie; Chauvel, Murielle; Zeidler, Ute; Ferrandon, Dominique; Gabaldón, Toni; Hube, Bernhard; d'Enfert, Christophe; Rupp, Steffen; Cormack, Brendan; Haynes, Ken; Kuchler, Karl

2014-01-01

The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes. PMID:24945925

Streptococcus suis - The "Two Faces" of a Pathobiont in the Porcine Respiratory Tract.

PubMed

Vötsch, Désirée; Willenborg, Maren; Weldearegay, Yenehiwot B; Valentin-Weigand, Peter

2018-01-01

Streptococcus (S.) suis is a frequent early colonizer of the upper respiratory tract of pigs. In fact, it is difficult to find S. suis -free animals under natural conditions, showing the successful adaptation of this pathogen to its porcine reservoir host. On the other hand, S. suis can cause life-threatening diseases and represents the most important bacterial cause of meningitis in pigs worldwide. Notably, S. suis can also cause zoonotic infections, such as meningitis, septicemia, endocarditis, and other diseases in humans. In Asia, it is classified as an emerging zoonotic pathogen and currently considered as one of the most important causes of bacterial meningitis in adults. The "two faces" of S. suis , one of a colonizing microbe and the other of a highly invasive pathogen, have raised many questions concerning the interpretation of diagnostic detection and the definition of virulence. Thus, one major research challenge is the identification of virulence-markers which allow differentiation of commensal and virulent strains. This is complicated by the high phenotypic and genotypic diversity of S. suis , as reflected by the occurrence of (at least) 33 capsular serotypes. In this review, we present current knowledge in the context of S. suis as a highly diverse pathobiont in the porcine respiratory tract that can exploit disrupted host homeostasis to flourish and promote inflammatory processes and invasive diseases in pigs and humans.

Streptococcus suis – The “Two Faces” of a Pathobiont in the Porcine Respiratory Tract

PubMed Central

Vötsch, Désirée; Willenborg, Maren; Weldearegay, Yenehiwot B.; Valentin-Weigand, Peter

2018-01-01

Streptococcus (S.) suis is a frequent early colonizer of the upper respiratory tract of pigs. In fact, it is difficult to find S. suis-free animals under natural conditions, showing the successful adaptation of this pathogen to its porcine reservoir host. On the other hand, S. suis can cause life-threatening diseases and represents the most important bacterial cause of meningitis in pigs worldwide. Notably, S. suis can also cause zoonotic infections, such as meningitis, septicemia, endocarditis, and other diseases in humans. In Asia, it is classified as an emerging zoonotic pathogen and currently considered as one of the most important causes of bacterial meningitis in adults. The “two faces” of S. suis, one of a colonizing microbe and the other of a highly invasive pathogen, have raised many questions concerning the interpretation of diagnostic detection and the definition of virulence. Thus, one major research challenge is the identification of virulence-markers which allow differentiation of commensal and virulent strains. This is complicated by the high phenotypic and genotypic diversity of S. suis, as reflected by the occurrence of (at least) 33 capsular serotypes. In this review, we present current knowledge in the context of S. suis as a highly diverse pathobiont in the porcine respiratory tract that can exploit disrupted host homeostasis to flourish and promote inflammatory processes and invasive diseases in pigs and humans. PMID:29599763

Haemophilus parainfluenzae meningitis in an adult associated with acute otitis media.

PubMed

Cardines, Rita; Giufrè, Maria; Ciofi degli Atti, Marta Luisa; Accogli, Marisa; Mastrantonio, Paola; Cerquetti, Marina

2009-04-01

A case of Haemophilus parainfluenzae meningitis in a woman with a 3-day history of acute otitis media is reported. Her medical history included bladder cancer surgery. Unequivocal identification of the isolate was obtained by using molecular techniques such as 16S rRNA sequencing besides to conventional culture methods. To investigate bacterial virulent traits possibly related to invasive properties, in vitro serum resistance of our isolate was analyzed, but it was found serum susceptible. Our study demonstrates that H. parainfluenzae can be considered an opportunistic pathogen able to cause life-threatening infections not only in children but also in patients with underlying conditions.

Viral Pneumonia in Patients with Hematologic Malignancy or Hematopoietic Stem Cell Transplantation.

PubMed

Vakil, Erik; Evans, Scott E

2017-03-01

Viral pneumonias in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation cause significant morbidity and mortality. Advances in diagnostic techniques have enabled rapid identification of respiratory viral pathogens from upper and lower respiratory tract samples. Lymphopenia, myeloablative and T-cell depleting chemotherapy, graft-versus-host disease, and other factors increase the risk of developing life-threatening viral pneumonia. Chest imaging is often nonspecific but may aid in diagnoses. Bronchoscopy with bronchoalveolar lavage is recommended in those at high risk for viral pneumonia who have new infiltrates on chest imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis

PubMed Central

Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

2015-01-01

Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of > 50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with > 99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. From the Clinical Editor Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. PMID:25791815

Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis.

PubMed

Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

2015-07-01

Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of >50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with >99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Cronobacter (Enterobacter) sakazakii

USDA-ARS?s Scientific Manuscript database

Cronobacter sakazakii has been identified as an infrequently isolated opportunistic pathogen. Over 120 cases of C. sakazakii-related illness have been reported and most reported cases are life-threatening infections. Many of these outbreaks have been linked the consumption of C. sakazakii-contamina...

Pathogenesis of group A streptococcal infections.

PubMed

Henningham, Anna; Barnett, Timothy C; Maamary, Peter G; Walker, Mark J

2012-05-01

Group A Streptococcus (GAS; Streptococcus pyogenes) is a human pathogen which causes significant morbidity and mortality globally. GAS typically infects the throat and skin of the host, causing mild infections such as pharyngitis and impetigo, in addition to life threatening conditions including necrotizing fasciitis, streptococcal toxic shock syndrome (STSS), and bacteremia. Repeated infection with GAS may result in the non-suppurative sequelae, acute rheumatic fever, and acute glomerulonephritis. GAS remains sensitive to the antibiotic penicillin which can be administered as a means to treat infection or as prophylaxis. However, issues with patient compliance and a growing concern over the possible emergence of resistant GAS strains may limit the usefulness of antibiotics in the future. A vaccine capable of preventing GAS infection may be the only effective way to control and eliminate GAS infection and disease.

Innate Immune Control of West Nile Virus Infection

PubMed Central

Arjona, Alvaro; Wang, Penghua; Montgomery, Ruth R.; Fikrig, Erol

2011-01-01

West Nile virus (WNV), from the Flaviviridae family, is a re-emerging zoonotic pathogen of medical importance. In humans, WNV infection may cause life-threatening meningoencephalitis or long-term neurologic sequelae. WNV is transmitted by Culex spp mosquitoes and both the arthropod vector and the mammalian host are equipped with antiviral innate immune mechanisms sharing a common phylogeny. As far as the current evidence is able to demonstrate, mosquitoes primarily rely on RNA interference, Toll, Imd and JAK-STAT signaling pathways for limiting viral infection, while mammals are provided with these and other more complex antiviral mechanisms involving antiviral effectors, inflammatory mediators, and cellular responses triggered by highly specialized pathogen detection mechanisms that often resemble their invertebrate ancestry. This mini-review summarizes our current understanding of how the innate immune systems of the vector and the mammalian host react to WNV infection and shape its pathogenesis. PMID:21790942

Global food and fibre security threatened by current inefficiencies in fungal identification.

PubMed

Crous, Pedro W; Groenewald, Johannes Z; Slippers, Bernard; Wingfield, Michael J

2016-12-05

Fungal pathogens severely impact global food and fibre crop security. Fungal species that cause plant diseases have mostly been recognized based on their morphology. In general, morphological descriptions remain disconnected from crucially important knowledge such as mating types, host specificity, life cycle stages and population structures. The majority of current fungal species descriptions lack even the most basic genetic data that could address at least some of these issues. Such information is essential for accurate fungal identifications, to link critical metadata and to understand the real and potential impact of fungal pathogens on production and natural ecosystems. Because international trade in plant products and introduction of pathogens to new areas is likely to continue, the manner in which fungal pathogens are identified should urgently be reconsidered. The technologies that would provide appropriate information for biosecurity and quarantine already exist, yet the scientific community and the regulatory authorities are slow to embrace them. International agreements are urgently needed to enforce new guidelines for describing plant pathogenic fungi (including key DNA information), to ensure availability of relevant data and to modernize the phytosanitary systems that must deal with the risks relating to trade-associated plant pathogens.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Author(s).

The pathogenesis, detection, and prevention of Vibrio parahaemolyticus

PubMed Central

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

2015-01-01

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

Sub-Inhibitory Concentrations of Trans-Cinnamaldehyde Attenuate Virulence in Cronobacter sakazakii in Vitro

PubMed Central

Amalaradjou, Mary Anne Roshni; Kim, Kwang Sik; Venkitanarayanan, Kumar

2014-01-01

Cronobacter sakazakii is a foodborne pathogen, which causes a life-threatening form of meningitis, necrotizing colitis and meningoencephalitis in neonates and children. Epidemiological studies implicate dried infant formula as the principal source of C. sakazakii. In this study, we investigated the efficacy of sub-inhibitory concentrations (SIC) of trans-cinnamaldehyde (TC), an ingredient in cinnamon, for reducing C. sakazakii virulence in vitro using cell culture, microscopy and gene expression assays. TC significantly (p ≤ 0.05) suppressed C. sakazakii adhesion to and invasion of human and rat intestinal epithelial cells, and human brain microvascular endothelial cells. In addition, TC inhibited C. sakazakii survival and replication in human macrophages. We also observed that TC reduced the ability of C. sakazakii to cause cell death in rat intestinal cells, by inhibiting nitric oxide production. Results from gene expression studies revealed that TC significantly downregulated the virulence genes critical for motility, host tissue adhesion and invasion, macrophage survival, and LPS (Lipopolysaccharide) synthesis in C. sakazakii. The efficacy of TC in attenuating these major virulence factors in C. sakazakii underscores its potential use in the prevention and/or control of infection caused by this pathogen. PMID:24837831

Sub-inhibitory concentrations of trans-cinnamaldehyde attenuate virulence in Cronobacter sakazakii in vitro.

PubMed

Amalaradjou, Mary Anne Roshni; Kim, Kwang Sik; Venkitanarayanan, Kumar

2014-05-15

Cronobacter sakazakii is a foodborne pathogen, which causes a life-threatening form of meningitis, necrotizing colitis and meningoencephalitis in neonates and children. Epidemiological studies implicate dried infant formula as the principal source of C. sakazakii. In this study, we investigated the efficacy of sub-inhibitory concentrations (SIC) of trans-cinnamaldehyde (TC), an ingredient in cinnamon, for reducing C. sakazakii virulence in vitro using cell culture, microscopy and gene expression assays. TC significantly (p ≤ 0.05) suppressed C. sakazakii adhesion to and invasion of human and rat intestinal epithelial cells, and human brain microvascular endothelial cells. In addition, TC inhibited C. sakazakii survival and replication in human macrophages. We also observed that TC reduced the ability of C. sakazakii to cause cell death in rat intestinal cells, by inhibiting nitric oxide production. Results from gene expression studies revealed that TC significantly downregulated the virulence genes critical for motility, host tissue adhesion and invasion, macrophage survival, and LPS (Lipopolysaccharide) synthesis in C. sakazakii. The efficacy of TC in attenuating these major virulence factors in C. sakazakii underscores its potential use in the prevention and/or control of infection caused by this pathogen.

White Paper: Recommendations on the Conduct of Superiority and Organism-Specific Clinical Trials of Antibacterial Agents for the Treatment of Infections Caused by Drug-Resistant Bacterial Pathogens

PubMed Central

2012-01-01

There is a critical need for new pathways to develop antibacterial agents to treat life-threatening infections caused by highly resistant bacteria. Traditionally, antibacterial agents have been studied in noninferiority clinical trials that focus on one site of infection (eg, pneumonia, intra-abdominal infection). Conduct of superiority trials for infections caused by highly antibiotic-resistant bacteria represents a new, and as yet, untested paradigm for antibacterial drug development. We sought to define feasible trial designs of antibacterial agents that could enable conduct of superiority and organism-specific clinical trials. These recommendations are the results of several years of active dialogue among the white paper's drafters as well as external collaborators and regulatory officials. Our goal is to facilitate conduct of new types of antibacterial clinical trials to enable development and ultimately approval of critically needed new antibacterial agents. PMID:22891041

The Role of Typhoid Toxin in Salmonella Typhi Virulence


PubMed Central

Chong, Alexander; Lee, Sohyoung; Yang, Yi-An; Song, Jeongmin

2017-01-01

Unlike many of the nontyphoidal Salmonella serovars such as S. Typhimurium that cause restricted gastroenteritis, Salmonella Typhi is unique in that it causes life-threatening typhoid fever in humans. Despite the vast difference in disease outcomes that S. Typhi and S. Typhimurium cause in humans, there are few genomic regions that are unique to S. Typhi. Of these regions, the most notable is the small locus encoding typhoid toxin, an AB toxin that has several distinct characteristics that contribute to S. Typhi’s pathogenicity. As a result, typhoid toxin and its role in S. Typhi virulence have been studied in an effort to gain insight into potential treatment and prevention strategies. Given the rise of multidrug-resistant strains, research in this area has become increasingly important. This article discusses the current understanding of typhoid toxin and potential directions for future research endeavors in order to better understand the contribution of typhoid toxin to S. Typhi virulence. PMID:28656014

Combining mass spectrometry, surface acoustic wave interaction analysis and cell viability assays for characterization of Shiga toxin subtypes of pathogenic Escherichia coli bacteria.

PubMed

Steil, Daniel; Pohlentz, Gottfried; Legros, Nadine; Mormann, Michael; Mellmann, Alexander; Karch, Helge; Müthing, Johannes

2018-06-25

Shiga toxin (Stx)-producing Escherichia coli (STEC) and enterohemorrhagic E. coli (EHEC) as a human-pathogenic subgroup of STEC are characterized by releasing Stx AB5-toxin as the major virulence factor. Worldwide disseminated EHEC strains cause sporadic infections and outbreaks in the human population and swine-pathogenic STEC strains represent greatly feared pathogens in pig breeding and fattening plants. Among the various Stx subtypes Stx1a and Stx2a are of eminent clinical importance in human infections being associated with life-threatening hemorrhagic colitis and hemolytic uremic syndrome, whereas Stx2e subtype is associated with porcine edema disease with generalized fatal outcome for the animals. Binding towards the glycosphingolipid globotriaosylceramide (Gb3Cer) is a common feature of all Stx subtypes analyzed so far. Here we report on the development of a matched strategy combining (i) miniaturized one-step affinity purification of native Stx subtypes from culture supernatant of bacterial wild-type strains using Gb3-functionalized magnetic beads, (ii) structural analysis and identification of Stx holotoxins by electrospray ionization ion mobility mass spectrometry (ESI MS) (iii), functional Stx-receptor real-time interaction analysis employing the surface acoustic wave technology (SAW), and (iv) Vero cell culture assays for determining Stx-caused cytotoxic effects. Structural investigations revealed diagnostic tryptic peptide ions for purified Stx1a, Stx2a and Stx2e, respectively, and functional analysis resulted in characteristic binding kinetics of each Stx subtype. Cytotoxicity studies revealed differing toxin-mediated cell damage ranked with Stx1a > Stx2a > Stx2e. Collectively, this matched procedure represents a promising clinical application for the characterization of life-endangering Stx subtypes at the protein level.

Detection of Bacterial Meningitis Pathogens by PCR-Mass Spectrometry in Cerebrospinal Fluid.

PubMed

Jing-Zi, Piao; Zheng-Xin, He; Wei-Jun, Chen; Yong-Qiang, Jiang

2018-06-01

Acute bacterial meningitis remains a life-threatening infectious disease with considerable morbidity and mortality. DNA-based detection methods are an urgent requisite for meningitis-causing bacterial pathogens for the prevention of outbreaks and control of infections. We proposed a novel PCR-mass spectrometry (PCR-Mass) assay for the simultaneous detection of four meningitis-causing agents, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Mycobacterium tuberculosis in the present study. A total of 138 cerebrospinal fluid (CSF) samples (including 56 CSF culture positive, 44 CSF culture negative, and 38 CSF control) were enrolled and analyzed by PCR/Mass. Results were compared to real-time PCR detection. These four targeting pathogens could be discriminated without cross-reaction by the accurate detection of the corresponding extension products with different masses. The limits of detection were 102 copies/reaction for S. pneumoniae, H. influenzae, and N. meningitidis and 103 for M. tuberculosis. The evaluation of the culture-positive CSF specimens from the meningitis patients provided an overall agreement rate of 85.7% with PCR-Mass and real-time PCR. The PCR-Mass was also able to detect the targeting pathogens from culture-negative CSF specimens from meningitis patients receiving early antibiotic treatment. PCR-Mass could be used for the molecular detection of bacterial meningitis and tuberculosis, especially when early antibiotic treatment has been administered to the suspected patients.

Biochemical characterization of a catalase from Vibrio vulnificus, a pathogen that causes gastroenteritis.

PubMed

Pei, Jihua; Wang, Haijun; Wu, Limin; Xia, Shenglong; Xu, Changlong; Zheng, Bo; Li, Tianya; Jiang, Yi

2017-01-01

Vibrio vulnificus is a virulent human pathogen causing gastroenteritis and possibly life threatening septicemia in patients. Most V. vulnificus are catalase positive and can deactivate peroxides, thus allowing them to survive within the host. In the study presented here, a catalase from V. vulnificus (CAT-Vv) was purified to homogeneity after expression in Escherichia coli. The kinetics and function of CAT-Vv were examined. CAT-Vv catalyzed the reduction of H 2 O 2 at an optimal pH of 7.5 and temperature of 35°C. The V max and K m values were 65.8±1.2 U/mg and 10.5±0.7 mM for H 2 O 2 , respectively. Mutational analysis suggests that amino acids involved in heme binding play a key role in the catalysis. Quantitative reverse transcription-PCR revealed that in V. vulnificus, transcription of CAT-Vv was upregulated by low salinity, heat, and oxidative stresses. This research gives new clues to help inhibit the growth of, and infection by V. vulnificus.

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

Shalev, Moran; Rozenberg, Haim; Smolkin, Boris

Leishmaniasis comprises an array of diseases caused by pathogenic species of Leishmania, resulting in a spectrum of mild to life-threatening pathologies. Currently available therapies for leishmaniasis include a limited selection of drugs. This coupled with the rather fast emergence of parasite resistance, presents a dire public health concern. Paromomycin (PAR), a broad-spectrum aminoglycoside antibiotic, has been shown in recent years to be highly efficient in treating visceral leishmaniasis (VL)—the life-threatening form of the disease. While much focus has been given to exploration of PAR activities in bacteria, its mechanism of action in Leishmania has received relatively little scrutiny and hasmore » yet to be fully deciphered. In the present study we present an X-ray structure of PAR bound to rRNA model mimicking its leishmanial binding target, the ribosomal A-site. We evaluate PAR inhibitory actions on leishmanial growth and ribosome function, as well as effects on auditory sensory cells, by comparing several structurally related natural and synthetic aminoglycoside derivatives. The results provide insights into the structural elements important for aminoglycoside inhibitory activities and selectivity for leishmanial cytosolic ribosomes, highlighting a novel synthetic derivative, compound 3, as a prospective therapeutic candidate for the treatment of VL.« less

Demonstrating the benefits of phytosanitary regulations: the case of ISPM 15

Treesearch

Eckehard G. Brockerhoff; Juliann E. Aukema; Joseph F. Cavey; Lynn J. Garrett; Robert A. Haack; Mark Kimberley; Andrew M. Liebhold; Frank L. Lowenstein; Carissa Marasas; Amelia Nuding; Lars Olson; Christa Speekmann; Michael Springborn; Christina Vieglais; James Turner

2011-01-01

Invasions of non-indigenous insects and pathogens threaten trees and forest ecosystems worldwide. For example, the arrival and spread of the pathogens causing chestnut blight and Dutch elm disease, along with the bark beetles vectoring the latter, had dramatic effects on North American forests. Despite our improved awareness of the risks associated with biological...

Toxic epidermal necrolysis

PubMed Central

Hoetzenecker, Wolfram; Mehra, Tarun; Saulite, Ieva; Glatz, Martin; Schmid-Grendelmeier, Peter; Guenova, Emmanuella; Cozzio, Antonio; French, Lars E.

2016-01-01

Toxic epidermal necrolysis (TEN) is a rare, life-threatening drug-induced skin disease with a mortality rate of approximately 30%. The clinical hallmark of TEN is a marked skin detachment caused by extensive keratinocyte cell death associated with mucosal involvement. The exact pathogenic mechanism of TEN is still uncertain. Recent advances in this field have led to the identification of several factors that might contribute to the induction of excessive apoptosis of keratinocytes. In addition, specific human leukocyte antigen types seem to be associated with certain drugs and the development of TEN. As well-controlled studies are lacking, patients are treated with various immunomodulators (e.g. intravenous immunoglobulin) in addition to the best supportive care. PMID:27239294

Future perspectives, applications and challenges of genomic epidemiology studies for food-borne pathogens: A case study of Enterohemorrhagic Escherichia coli (EHEC) of the O157:H7 serotype

PubMed Central

Eppinger, Mark; Cebula, Thomas A

2015-01-01

The shiga-toxin (Stx)-producing human pathogen Escherichia coli serotype O157:H7 is a highly pathogenic subgroup of Stx-producing E. coli (STEC) with food-borne etiology and bovine reservoir. Each year in the U. S., approximately 100,000 patients are infected with enterohemorrhagic E. coli (EHEC) of the O157:H7 serotype. This food-borne pathogen is a global public health threat responsible for widespread outbreaks of human disease. Since its initial discovery in 1982, O157:H7 has rapidly become the dominant EHEC serotype in North America. Hospitalization rates among patients as high as 50% have been reported for severe outbreaks of human disease. Symptoms of disease can rapidly deteriorate and progress to life-threatening complications such as Hemolytic Uremic Syndrome (HUS), the leading cause of kidney failure in children, or Hemorrhagic Colitis. In depth understanding of the genomic diversity that exists among currently circulating EHEC populations has broad applications for improved molecular-guided biosurveillance, outbreak preparedness, diagnostic risk assessment, and development of alternative toxin-suppressing therapeutics. PMID:25483335

Psoriasin, a novel anti-Candida albicans adhesin.

PubMed

Brauner, Annelie; Alvendal, Cathrin; Chromek, Milan; Stopsack, Konrad H; Ehrström, Sophia; Schröder, Jens M; Bohm-Starke, Nina

2018-05-07

Candida albicans belongs to the normal microbial flora on epithelial surfaces of humans. However, under certain, still not fully understood conditions, it can become pathogenic and cause a spectrum of diseases, from local infections to life-threatening septicemia. We investigated a panel of antimicrobial proteins and peptides (AMPs), potentially involved in mucosal immunity against this pathogen. Out of six studied AMPs, psoriasin was most up-regulated during a mucosal infection, an acute episode of recurrent Candida vulvovaginitis, although candidacidal activity has not been demonstrated. We here show that psoriasin binds to β-glucan, a basic component of the C. albicans cell wall, and thereby inhibits adhesion of the pathogen to surfaces and increases IL-8 production by mucosal epithelial cells. In conclusion, we show a novel mechanism of action of psoriasin. By inhibiting C. albicans adhesion and by enhancing cytokine production, psoriasin contributes to the immune response against C. albicans. The antimicrobial peptide psoriasin is highly up-regulated during a local mucosal infection, Candida albicans vulvovaginitis. Psoriasin binds to β-glucan in the Candida albicans cell wall and thereby inhibits adhesion of the pathogen. Binding of psoriasin to Candida albicans induces an immune response by mucosal epithelial cells.

Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

PubMed Central

Ghazaei, Ciamak

2018-01-01

Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species. PMID:29445617

Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

PubMed Central

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

Meningococcal B Vaccination (4CMenB) in Infants and Toddlers

PubMed Central

Esposito, Susanna; Tagliabue, Claudia; Bosis, Samantha

2015-01-01

Neisseria meningitidis is a Gram-negative pathogen that actively invades its human host and leads to the development of life-threatening pathologies. One of the leading causes of death in the world, N. meningitidis can be responsible for nearly 1,000 new infections per 100,000 subjects during an epidemic period. The bacterial species are classified into 12 serogroups, five of which (A, B, C, W, and Y) cause the majority of meningitides. The three purified protein conjugate vaccines currently available target serogroups A, C, W, and Y. Serogroup B has long been a challenge but the discovery of the complete genome sequence of an MenB strain has allowed the development of a specific four-component vaccine (4CMenB). This review describes the pathogenetic role of N. meningitidis and the recent literature concerning the new meningococcal vaccine. PMID:26351647

A substantial proportion of life-threatening injuries are sport-related.

PubMed

Meehan, William P; Mannix, Rebekah

2013-05-01

This study aimed to assess the proportion of all life-threatening injuries that are sport-related. We conducted a cross-sectional study of patients included in the National Hospital Ambulatory Medical Care Survey during the years 1999 to 2008. Life-threatening injuries were defined according to the International Classification of Diseases, Ninth Revision codes: skull fracture (800.x-802.xx, 803.x-804.xx), cervical spine fractures (805.xx-806.10), intracranial hemorrhage (852.xx-853.xx), traumatic pneumothorax/hemothorax (860.00-860.05), liver lacerations (864.xx), spleen lacerations (865.xx), aortic rupture (901.0; 902.0), gastric/duodenal rupture (537.89), heat stroke (992.0), and commotio cordis/heart contusion (861.01). Sport-related was defined by the external cause of injury codes, confirmed by text search. There were 300,394 observed emergency department visits during the study period. An estimated 0.5% (95% confidence interval [CI], 0.5%-0.6%) of all emergency department visits nationally were for life-threatening injuries. Of the life-threatening injuries, 14% (95% CI, 12%-17) were sport-related, representing 926,805 sport-related, life-threatening injuries nationally. A higher percentage (32%; 95% CI, 27%-38%) of life-threatening injuries sustained by children was sport-related when compared with adults (9%; 95% CI, 7%-11%). For adults aged 19 to 44 years, 12% (95% CI, 9%-15%) of life-threatening injuries were sport-related. For children aged 6 to 18 years, 39% (95% CI, 33%-46%) of life-threatening injuries were sport-related. Nearly a quarter (23%; 95% CI, 7%-55%) of pediatric cervical spine fractures was sport-related. The percentage of cervical spine fractures that were sport-related was lower for adults (7%; 95% CI, 4%-11%). Efforts should be made to prevent the number of sport-related, life-threatening injuries.

Efficacy of Heat Treatment for the Thousand Cankers Disease Vector and Pathogen in Small Black Walnut Logs

Treesearch

A. E. Mayfield; S. W. Fraedrich; A. Taylor; P. Merten; S. W. Myers

2014-01-01

Thousand cankers disease, caused by the walnut twig beetle (Pityophthorus juglandis Blackman) and an associated fungal pathogen (Geosmithia morbida M. Kolarõ´k, E. Freeland, C. Utley, and N. Tisserat), threatens the health and commercial use of eastern black walnut (Juglans nigra L.), one of the most economically...

Phosphate-Containing Polyethylene Glycol Polymers Prevent Lethal Sepsis by Multidrug-Resistant Pathogens

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

Zaborin, Alexander; Defazio, Jennifer; Kade, Matthew

The gastrointestinal tract is the primary site of colonization for multi-drug resistant healthcare associated pathogens (HAPs) that are the principal source and cause of life-threatening infections in critically ill patients. We previously identified a high molecular weight co-polymer (PEG15-20) with mucoadhesive and cytoprotective actions on the intestinal epithelium. In this report we covalently bonded phosphate (Pi) to PEG15-20 ( termed Pi-PEG15-20) to enhance its cytoprotective activity against microbial virulence activation and invasion based on our previous work showing that Pi is a key environmental cue regulating microbial virulence across pathogens of clinical importance to hospitalized patients. We demonstrated that Pi-PEG15-20more » can suppress phosphate-, iron-, and quorum sensing signal- mediated activation of bacterial virulence as well as inhibit intestinal epithelial IL-8 release during lipopolysaccharide (LPS) exposure. Pi-PEG15-20 also prevented mortality in C. elegans and mice exposed to several highly virulent and antibiotic(?)-resistant health care acquired pathogens (HAPs) while preserving the normal microbiota. Intestinal application Pi-PEG 15-20 has the potential to be a useful agent to prevent the pathogenic activation of microbes during critical illness where exposure to HAPs is ubiquitous.« less

Immunogold Nanoparticles for Rapid Plasmonic Detection of C. sakazakii.

PubMed

Aly, Mohamed A; Domig, Konrad J; Kneifel, Wolfgang; Reimhult, Erik

2018-06-25

Cronobacter sakazakii is a foodborne pathogen that can cause a rare, septicemia, life-threatening meningitis, and necrotizing enterocolitis in infants. In general, standard methods for pathogen detection rely on culture, plating, colony counting and polymerase chain reaction DNA-sequencing for identification, which are time, equipment and skill demanding. Recently, nanoparticle- and surface-based immunoassays have increasingly been explored for pathogen detection. We investigate the functionalization of gold nanoparticles optimized for irreversible and specific binding to C. sakazakii and their use for spectroscopic detection of the pathogen. We demonstrate how 40-nm gold nanoparticles grafted with a poly(ethylene glycol) brush and functionalized with polyclonal antibodies raised against C. sakazakii can be used to specifically target C. sakazakii . The strong extinction peak of the Au nanoparticle plasmon polariton resonance in the optical range is used as a label for detection of the pathogens. Individual binding of the nanoparticles to the C. sakazakii surface is also verified by transmission electron microscopy. We show that a high degree of surface functionalization with anti- C. sakazakii optimizes the detection and leads to a detection limit as low as 10 CFU/mL within 2 h using a simple cuvette-based UV-Vis spectrometric readout that has great potential for further optimization.

Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts

PubMed Central

Ma, Liang; Chen, Zehua; Huang, Da Wei; Kutty, Geetha; Ishihara, Mayumi; Wang, Honghui; Abouelleil, Amr; Bishop, Lisa; Davey, Emma; Deng, Rebecca; Deng, Xilong; Fan, Lin; Fantoni, Giovanna; Fitzgerald, Michael; Gogineni, Emile; Goldberg, Jonathan M.; Handley, Grace; Hu, Xiaojun; Huber, Charles; Jiao, Xiaoli; Jones, Kristine; Levin, Joshua Z.; Liu, Yueqin; Macdonald, Pendexter; Melnikov, Alexandre; Raley, Castle; Sassi, Monica; Sherman, Brad T.; Song, Xiaohong; Sykes, Sean; Tran, Bao; Walsh, Laura; Xia, Yun; Yang, Jun; Young, Sarah; Zeng, Qiandong; Zheng, Xin; Stephens, Robert; Nusbaum, Chad; Birren, Bruce W.; Azadi, Parastoo; Lempicki, Richard A.; Cuomo, Christina A.; Kovacs, Joseph A.

2016-01-01

Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses. PMID:26899007

Walnut twig beetle (Coleoptera: Curculionidae: Scolytinae) Colonization of eastern black walnut nursery trees

Treesearch

Jackson Audley; William E. Klingeman; Albert Mayfield; Scott Myers; Adam Taylor

2017-01-01

Thousand cankers disease, caused by the invasive bark beetle Pityophthorus juglandis Blackman and an associ-ated fungal pathogen Geosmithia morbida M. .Kolank , E. Freeland, C. Utley, N. Tisserat, currently threatens the health of eastern black walnut (Juglans nigra L.) in North America. Both the beetle and pathogen have ex- panded beyond their native range via...

Life-threatening complications associated with acute monocytic leukaemia after dental treatment.

PubMed

Koulocheris, P; Metzger, M C; Kesting, M R; Hohlweg-Majert, B

2009-03-01

It is highly recommended to conduct a prophylactic check for any dental problems on patients who suffer from leukaemia before chemotherapy begins. Bacteraemia caused by oral microflora may be very dangerous for patients with haematological malignancies. However, it should be noted that the prophylactic process itself might bring about life-threatening complications if there is only a short interval between dental treatment and the beginning of chemotherapy, or if the dental treatment is too aggressive. We present a case where this prophylactic procedure produced life-threatening complications for a patient with acute myeloid leukaemia.

Bordetella pertussis and pertactin-deficient clinical isolates: lessons for pertussis vaccines.

PubMed

Hegerle, Nicolas; Guiso, Nicole

2014-09-01

Bordetella pertussis causes whooping cough in humans, a highly transmissible respiratory disease life threatening for unvaccinated infants. Vaccination strategies were thus introduced worldwide with great success in developed countries reaching high vaccine coverage with efficacious vaccines. In the late 20th/early 21st century, acellular pertussis vaccines replaced whole cell pertussis vaccines but B. pertussis still circulates and evolves in humans, its only known reservoir. The latest transformation of this pathogen, and of its close relative Bordetella parapertussis, is the loss of pertactin production, a virulence factor included in different acellular pertussis vaccines. The real impact of this evolution on acellular pertussis vaccines efficacy and effectiveness should be assessed through standardized surveillance and isolation of B. pertussis and B. parapertussis worldwide.

Typhoid toxin provides a window into typhoid fever and the biology of Salmonella Typhi.

PubMed

Galán, Jorge E

2016-06-07

Salmonella Typhi is the cause of typhoid fever, a disease that has challenged humans throughout history and continues to be a major public health concern. Unlike infections with most other Salmonellae, which result in self-limiting gastroenteritis, typhoid fever is a life-threatening systemic disease. Furthermore, in contrast to most Salmonellae, which can infect a broad range of hosts, S. Typhi is a strict human pathogen. The unique features of S. Typhi pathogenesis and its stringent host specificity have been a long-standing puzzle. The discovery of typhoid toxin not only has provided major insight into these questions but also has offered unique opportunities to develop novel therapeutic and prevention strategies to combat typhoid fever.

Typhoid toxin provides a window into typhoid fever and the biology of Salmonella Typhi

PubMed Central

Galán, Jorge E.

2016-01-01

Salmonella Typhi is the cause of typhoid fever, a disease that has challenged humans throughout history and continues to be a major public health concern. Unlike infections with most other Salmonellae, which result in self-limiting gastroenteritis, typhoid fever is a life-threatening systemic disease. Furthermore, in contrast to most Salmonellae, which can infect a broad range of hosts, S. Typhi is a strict human pathogen. The unique features of S. Typhi pathogenesis and its stringent host specificity have been a long-standing puzzle. The discovery of typhoid toxin not only has provided major insight into these questions but also has offered unique opportunities to develop novel therapeutic and prevention strategies to combat typhoid fever. PMID:27222578

Development of Bioluminescent Cronobacter sakazakii ATCC 29544 in a Mouse Model.

PubMed

Wang, Xiwen; Li, Zhiping; Dong, Xiaolin; Chi, Hang; Wang, Guannan; Li, Jiakuan; Sun, Rui; Chen, Man; Zhang, Xinying; Wang, Yuanyuan; Qu, Han; Sun, Yu; Xia, Zhiping; Li, Qianxue

2015-05-01

Cronobacter sakazakii is an emerging pathogen that causes severe and life-threatening conditions including meningitis, bacteremia, and necrotizing enterocolitis. An animal model study for extrapolation of C. sakazakii infection can provide a better understanding of pathogenesis. However, methods for real-time monitoring of the course of C. sakazakii infection in living animals have been lacking. We developed a bioluminescent C. sakazakii strain (ATCC 29544) that can be used for real-time monitoring of C. sakazakii infection in BALB/c mice. C. sakazakii ATCC 29544 mainly colonized brain, liver, spleen, kidney, and gastrointestinal tract, as indicated by bioluminescence imaging. This work provides a novel approach for studying the progression of C. sakazakii infection and evaluating therapeutics in a living mouse model.

[Current status and perspectives of diagnosis and treatment of complications related to liver cirrhosis].

PubMed

Nan, Y M

2017-04-20

Liver cirrhosis is the severe period of chronic liver diseases, especially decompensated liver cirrhosis and its complications, such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, acute kidney injury, and hepatocellular carcinoma, which greatly affect patients' quality of life and even threaten their lives. Early prevention and treatment of the causes of development and progression and pathogenic mechanism may slow down or reverse liver cirrhosis and its severe complications. Once the disease progresses to portal hypertension and related complications, it is very important to select preventive measures for acute exacerbation of different complications, as well as the methods and timing for treatment in acute stage, which may help to save patients' lives and improve their prognosis.

Trichosporon asahii sepsis in a patient with pediatric malignancy.

PubMed

Ozkaya-Parlakay, Aslinur; Karadag-Oncel, Eda; Cengiz, Ali Bulent; Kara, Ates; Yigit, Atilla; Gucer, Safak; Gur, Deniz

2016-02-01

Trichosporon asahii is a rare opportunistic infection, especially in children, causing a life-threatening fungal infection underlying hematologic malignancies. Predisposing factors for infection with this pathogen are immunodeficiency including underlying malignancy, organ transplantation, extensive burns, human immunodeficiency virus infection, corticosteroid therapy, prosthetic valve surgery, and peritoneal dialysis. In the literature, a breakthrough under caspofungin, micafungin therapy is reported. In this article we report on a 16-year-old patient with Ewing sarcoma who had T. asahii sepsis. The patient died although he had been receiving caspofungin for less than 3 months and amphotericin B therapy for 3 days. A postmortem study of conchal tissues revealed T. asahii and mucormycosis histopathologically, and blood culture grew T. asahii. Copyright © 2013. Published by Elsevier B.V.

Methicillin-resistant Staphylococcus aureus--an overview.

PubMed

Eadon, H J; Pinney, R J

1991-12-01

Methicillin-resistant strains of Staphylococcus aureus (MRSA) cause life-threatening infections, but they are no more pathogenic than methicillin-sensitive strains. Difficulties occur because of incorrect or missed identification of MRSA, and hence inappropriate or ineffective treatment of infections. Therapeutic options are severely limited and the increasing spectrum of resistance in MRSA is worrying. However, new methods of detection and new agents for treatment are being developed in response to the challenge of MRSA. Whilst the organism is a problem and control measures are necessary to contain its spread, the outlook is not bleak. In the medium term, the development of new, effective anti-MRSA agents should prevent the threat of MRSA becoming any greater in the field of hospital infection control.

An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

PubMed Central

Chibucos, Marcus C.; Soliman, Sameh; Gebremariam, Teclegiorgis; Lee, Hongkyu; Daugherty, Sean; Orvis, Joshua; Shetty, Amol C.; Crabtree, Jonathan; Hazen, Tracy H.; Etienne, Kizee A.; Kumari, Priti; O'Connor, Timothy D.; Rasko, David A.; Filler, Scott G.; Fraser, Claire M.; Lockhart, Shawn R.; Skory, Christopher D.; Ibrahim, Ashraf S.; Bruno, Vincent M.

2016-01-01

Mucormycosis is a life-threatening infection caused by Mucorales fungi. Here we sequence 30 fungal genomes, and perform transcriptomics with three representative Rhizopus and Mucor strains and with human airway epithelial cells during fungal invasion, to reveal key host and fungal determinants contributing to pathogenesis. Analysis of the host transcriptional response to Mucorales reveals platelet-derived growth factor receptor B (PDGFRB) signaling as part of a core response to divergent pathogenic fungi; inhibition of PDGFRB reduces Mucorales-induced damage to host cells. The unique presence of CotH invasins in all invasive Mucorales, and the correlation between CotH gene copy number and clinical prevalence, are consistent with an important role for these proteins in mucormycosis pathogenesis. Our work provides insight into the evolution of this medically and economically important group of fungi, and identifies several molecular pathways that might be exploited as potential therapeutic targets. PMID:27447865

Parasitic scabies mites and associated bacteria joining forces against host complement defence.

PubMed

Swe, P M; Reynolds, S L; Fischer, K

2014-11-01

Scabies is a ubiquitous and contagious skin disease caused by the parasitic mite Sarcoptes scabiei Epidemiological studies have identified scabies as a causative agent for secondary skin infections caused by Staphylococcus aureus and Streptococcus pyogenes. This is an important notion, as such bacterial infections can lead to serious downstream life-threatening complications. As the complement system is the first line of host defence that confronts invading pathogens, both the mite and bacteria produce a large array of molecules that inhibit the complement cascades. It is hypothesised that scabies mite complement inhibitors may play an important role in providing a favourable micro-environment for the establishment of secondary bacterial infections. This review aims to bring together the current literature on complement inhibition by scabies mites and bacteria associated with scabies and to discuss the proposed molecular link between scabies and bacterial co-infections. © 2014 John Wiley & Sons Ltd.

Structural basis for selective targeting of leishmanial ribosomes: Aminoglycoside derivatives as promising therapeutics

DOE PAGES

Shalev, Moran; Rozenberg, Haim; Smolkin, Boris; ...

2015-08-11

Leishmaniasis comprises an array of diseases caused by pathogenic species of Leishmania, resulting in a spectrum of mild to life-threatening pathologies. Currently available therapies for leishmaniasis include a limited selection of drugs. This coupled with the rather fast emergence of parasite resistance, presents a dire public health concern. Paromomycin (PAR), a broad-spectrum aminoglycoside antibiotic, has been shown in recent years to be highly efficient in treating visceral leishmaniasis (VL)—the life-threatening form of the disease. While much focus has been given to exploration of PAR activities in bacteria, its mechanism of action in Leishmania has received relatively little scrutiny and hasmore » yet to be fully deciphered. In the present study we present an X-ray structure of PAR bound to rRNA model mimicking its leishmanial binding target, the ribosomal A-site. We evaluate PAR inhibitory actions on leishmanial growth and ribosome function, as well as effects on auditory sensory cells, by comparing several structurally related natural and synthetic aminoglycoside derivatives. The results provide insights into the structural elements important for aminoglycoside inhibitory activities and selectivity for leishmanial cytosolic ribosomes, highlighting a novel synthetic derivative, compound 3, as a prospective therapeutic candidate for the treatment of VL.« less

A Substantial Proportion of Life-Threatening Injuries are Sport-Related

PubMed Central

Meehan, William P.; Mannix, Rebekah

2013-01-01

Objective To assess the proportion of all life-threatening injuries that are sport-related. Methods We conducted a cross-sectional study of patients included in the National Hospital Ambulatory Medical Care Survey (NHAMCS) during the years 1999–2008. Life-threatening injuries were defined as International Classification of Diseases 9 codes: skull fracture [800.x–802.xx, 803.x–804.xx], cervical spine fractures [805.xx–806.10], intracranial hemorrhage [852.xx–853.xx], traumatic pneumothorax/hemothorax [860.00–860.05], liver lacerations [864.xx], spleen lacerations [865.xx], aortic rupture [901.0; 902.0], gastric/duodenal rupture [537.89], heat stroke [992.0], and commotio cordis/heart contusion [861.01]. Sport-related was defined by external cause of injury codes, confirmed by text search. Results There were 300,394 observed emergency department visits during the study period. An estimated 0.5% (95% CI, 0.5 – 0.6) of all ED visits nationally were for life-threatening injuries. Of life-threatening injuries, 14% (95% CI, 12 – 17) were sport-related, representing 926,805 sport-related, life-threatening injuries nationally. A higher percentage (32%; 95% CI, 27 – 38) of life-threatening injuries sustained by children was sport-related when compared with adults (9%; 95% CI, 7 – 11). For adults aged 19–44 years, 12% (95% CI, 9 – 15) of life-threatening injuries were sport-related. For children aged 6–18 years, 39% (95% CI, 33 – 46) of life-threatening injuries were sport-related. Nearly a quarter (23%; 95% CI, 7 – 55) of pediatric cervical spine fractures was sport-related. The percentage of cervical spine fractures that were sport-related was lower for adults (7%; 95% CI, 4 – 11). Conclusion Efforts should be made to prevent the number of sport-related, life-threatening injuries. PMID:23603654

FAST: Rapid determinations of antibiotic susceptibility phenotypes using label-free cytometry.

PubMed

Huang, Tzu-Hsueh; Tzeng, Yih-Ling; Dickson, Robert M

2018-05-07

Sepsis, a life-threatening immune response to blood infections (bacteremia), has a ∼30% mortality rate and is the 10th leading cause of US hospital deaths. The typical bacterial loads in adult septic patients are ≤100 bacterial cells (colony forming units, CFU) per ml blood, while pediatric patients exhibit only ∼1000 CFU/ml. Due to the low numbers, bacteria must be propagated through ∼24-hours blood cultures to generate sufficient CFUs for diagnosis and further analyses. Herein, we demonstrate that, unlike other rapid post-blood culture antibiotic susceptibility tests (ASTs), our phenotypic approach can drastically accelerate ASTs for the most common sepsis-causing gram-negative pathogens by circumventing long blood culture-based amplification. For all blood isolates of multi-drug resistant pathogens investigated (Escherichia coli, Klebsiella pneumoniae, and Acinetobacter nosocomialis), effective antibiotic(s) were readily identified within the equivalent of 8 hours from initial blood draw using <0.5 mL of adult blood per antibiotic. These methods should drastically improve patient outcomes by significantly reducing time to actionable treatment information and reduce the incidence of antibiotic resistance. © 2018 International Society for Advancement of Cytometry. © 2018 International Society for Advancement of Cytometry.

Hybrid microarray based on double biomolecular markers of DNA and carbohydrate for simultaneous genotypic and phenotypic detection of cholera toxin-producing Vibrio cholerae.

PubMed

Shin, Hwa Hui; Seo, Jeong Hyun; Kim, Chang Sup; Hwang, Byeong Hee; Cha, Hyung Joon

2016-05-15

Life-threatening diarrheal cholera is usually caused by water or food contaminated with cholera toxin-producing Vibrio cholerae. For the prevention and surveillance of cholera, it is crucial to rapidly and precisely detect and identify the etiological causes, such as V. cholerae and/or its toxin. In the present work, we propose the use of a hybrid double biomolecular marker (DBM) microarray containing 16S rRNA-based DNA capture probe to genotypically identify V. cholerae and GM1 pentasaccharide capture probe to phenotypically detect cholera toxin. We employed a simple sample preparation method to directly obtain genomic DNA and secreted cholera toxin as target materials from bacterial cells. By utilizing the constructed DBM microarray and prepared samples, V. cholerae and cholera toxin were detected successfully, selectively, and simultaneously; the DBM microarray was able to analyze the pathogenicity of the identified V. cholerae regardless of whether the bacteria produces toxin. Therefore, our proposed DBM microarray is a new effective platform for identifying bacteria and analyzing bacterial pathogenicity simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

Factors predicting life-threatening infections with respiratory syncytial virus in adult patients.

PubMed

Park, Se Yoon; Kim, Taeeun; Jang, Young Rock; Kim, Min-Chul; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2017-05-01

Respiratory syncytial virus (RSV) is a significant cause of acute respiratory illness with a clinical spectrum ranging from self-limiting upper respiratory infection to severe lower respiratory infection in elderly persons as well as young children. However, there are limited data on risk factors for life-threatening infections that could guide the appropriate use of antiviral agents in adult patients with RSV. We conducted a retrospective cohort study from October 2013 to September 2015. Adult patients with RSV who visited the emergency department were enrolled. Primary outcome was life-threatening infection (admission to intensive care unit, need for ventilator care or in-hospital death). A total of 227 patients were analysed. Thirty-four (15%) were classified as having life-threatening infections. By logistic regression, lower respiratory infection, chronic lung disease and bacterial co-infection were independent predictors of life-threatening infections. We developed a simple clinical scoring system using these variables (lower respiratory tract infection = score 4, chronic respiratory disease = score 3, bacterial co-infection = score 3 and fever ≥38 °C = score 2) to predict life-threatening infection. A score of >5 differentiated life-threatening RSV from non-life-threatening RSV with 82% sensitivity (95% CI, 66-93) and 72% specificity (95% CI, 65-78). The use of a clinical scoring system based on lower respiratory infection, chronic respiratory disease, bacterial co-infection and fever appears to be useful for outcome prediction and risk stratification in order to select patients who may need early antiviral therapy.

7 CFR 624.4 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... occurrence that could cause significant damage to property or threaten human life in the near future. (e)(1...) Exigency means those situations that demand immediate action to avoid potential loss of life or property..., cause new damages or the potential loss of life if action to remedy the situation is not taken...

7 CFR 624.4 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... occurrence that could cause significant damage to property or threaten human life in the near future. (e)(1...) Exigency means those situations that demand immediate action to avoid potential loss of life or property..., cause new damages or the potential loss of life if action to remedy the situation is not taken...

Applied genetic conservation of Hawaiian Acacia koa: an eco-regional approach

Treesearch

Nick Dudley; Tyler Jones; Robert James; Richard Sniezko; Jessica Wright; Christina Liang; Paul F. Gugger; Phil Cannon

2017-01-01

Koa (Acacia koa) is a valuable tree species economically, ecologically, and culturally in Hawaii. A vascular wilt disease of koa, caused by the fungal pathogen Fusarium oxysporum f. sp. koae (FOXY), causes high rates of mortality in field plantings and threatens native koa forests in Hawaii. Producing seeds with genetic resistance to FOXY is vital...

Colonization of cashew plants by Lasiodiplodia theobromae: Microscopical features

USDA-ARS?s Scientific Manuscript database

Lasiodiplodia theobromae is a phytopathogenic fungus causing gummosis, a threatening disease for cashew plants in Brazil. In an attempt to investigate the ultrastructural features of the pathogen colonization and its response to immunofluorescence labeling, light, confocal and electron microscope st...

Why Be Temperate: Lessons from Bacteriophage λ.

PubMed

Gandon, Sylvain

2016-05-01

Many pathogens have evolved the ability to induce latent infections of their hosts. The bacteriophage λ is a classical model for exploring the regulation and the evolution of latency. Here, I review recent experimental studies on phage λ that identify specific conditions promoting the evolution of lysogenic life cycles. In addition, I present specific adaptations of phage λ that allow this virus to react plastically to variations in the environment and to reactivate its lytic life cycle. All of these different examples are discussed in the light of evolutionary epidemiology theory to disentangle the different evolutionary forces acting on temperate phages. Understanding phage λ adaptations yield important insights into the evolution of latency in other microbes, including several life-threatening human pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel splicing mutation in GALT gene causing Galactosemia in Ecuadorian family.

PubMed

De Lucca, M; Barba, C; Casique, L

2017-07-01

Classic Galactosemia (OMIM 230400) is an autosomal recessive disorder of galactose metabolism caused by mutations in the galactose-1-phosphate uridyl transferase (GALT) gene. This disease caused by the inability to metabolize galactose is potentially life-threatening but its pathophysiology has not been clearly defined. GALT gene presents high allelic heterogeneity and around 336 variations have been identified. Here, we report the case of a patient with Classic Galactosemia who was detected during a neonatal screening in Ecuador. Molecular study revealed a mutation in GALT gene intron 1, c.82+3A>G in homozygous condition, this mutation has not been previously reported. This gene variation was not found in any of the 119 healthy Ecuadorian individuals used as control. Furthermore, the mutation was the only alteration detected in the propositus's GALT after sequencing all exons and introns of this gene. In silico modeling predicted that the mutation was pathogenic. Copyright © 2017. Published by Elsevier B.V.

Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb® sorbent porous polymer beads.

PubMed

Gruda, Maryann C; Ruggeberg, Karl-Gustav; O'Sullivan, Pamela; Guliashvili, Tamaz; Scheirer, Andrew R; Golobish, Thomas D; Capponi, Vincent J; Chan, Phillip P

2018-01-01

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system. Purified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead) device in vitro. Except for the TNF-α trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent. This study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions.

Genotypic, physiological, and biochemical characterization of potentially pathogenic Acanthamoeba isolated from the environment in Cairo, Egypt.

PubMed

Tawfeek, Gihan Mostafa; Bishara, Sawsan Abdel-Hamid; Sarhan, Rania Mohammad; ElShabrawi Taher, Eman; ElSaady Khayyal, Amira

2016-05-01

Acanthamoebae are the most common opportunistic amphizoic protozoa that cause life-threatening granulomatous amoebic encephalitis in immunocompromised individuals and sight-threatening amoebic keratitis (AK) in contact lens wearers. The present work aimed to determine the presence of Acanthamoeba isolates in different environmental sources: water, soil, and dust in Cairo, Egypt and to characterize the pathogenic potential of the isolated Acanthamoeba using physiological and biochemical assays as well as determination of the genotypes in an attempt to correlate pathogenicity with certain genotypes. The study included the collection of 22 corneal scrapings from patients complaining of symptoms and signs indicative of acanthamoeba keratitis (AK) and 75 environmental samples followed by cultivation on non-nutrient agar plates preseeded with E. coli. Positive samples for Acanthamoeba were subjected to osmo- and thermo-tolerance assays and zymography analysis. Potentially pathogenic isolates were subjected to PCR amplification using genus-specific primer pair. Isolates were classified at the genotype level based on the sequence analysis of Acanthamoeba 18S rRNA gene (diagnostic fragment 3). The total detection rate for Acanthamoeba in environmental samples was 33.3 %, 31.4 % in water, 40 % in soil, and 20 % in dust samples. Three and two Acanthamoeba isolates from water and soil sources, respectively, had the potential for pathogenicity as they exhibited full range of pathogenic traits. Other 12 isolates were designated as weak potential pathogens. Only ten of the environmental isolates were positive in PCR and were classified by genotype analysis into T4 genotype (70 %), T3 (10 %) and T5 (20 %). Potential pathogens belonged to genotypes T4 (from water) and T5 (from soil) while weak potential pathogens belonged to genotypes T3 (from water) and T4 (from water and soil). Additionally, T7 genotype was isolated from keratitis patients. There is a considerable variation in the response of Acanthamoeba members of the same genotype to pathogenicity indicator assays making correlation of pathogenicity with certain genotypes difficult. Presence of potentially pathogenic Acanthamoeba isolates in habitats related directly to human populations represent a risk for human health. Isolation of Acanthamoeba genotype T7 from AK cases, which is commonly considered as nonpathogenic, might draw the attention to other Acanthamoeba genotypes considered as non pathogenic and reevaluate their role in production of human infections. To our knowledge, this is the first study on the presence and distribution of Acanthamoeba genotypes in the environment, Cairo, Egypt.

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions.

PubMed

Hebecker, Betty; Vlaic, Sebastian; Conrad, Theresia; Bauer, Michael; Brunke, Sascha; Kapitan, Mario; Linde, Jörg; Hube, Bernhard; Jacobsen, Ilse D

2016-11-03

Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses.

Responses of innate immune cells to group A Streptococcus

PubMed Central

Fieber, Christina; Kovarik, Pavel

2014-01-01

Group A Streptococcus (GAS), also called Streptococcus pyogenes, is a Gram-positive beta-hemolytic human pathogen which causes a wide range of mostly self-limiting but also several life-threatening diseases. Innate immune responses are fundamental for defense against GAS, yet their activation by pattern recognition receptors (PRRs) and GAS-derived pathogen-associated molecular patterns (PAMPs) is incompletely understood. In recent years, the use of animal models together with the powerful tools of human molecular genetics began shedding light onto the molecular mechanisms of innate immune defense against GAS. The signaling adaptor MyD88 was found to play a key role in launching the immune response against GAS in both humans and mice, suggesting that PRRs of the Toll-like receptor (TLR) family are involved in sensing this pathogen. The specific TLRs and their ligands have yet to be identified. Following GAS recognition, induction of cytokines such as TNF and type I interferons (IFNs), leukocyte recruitment, phagocytosis, and the formation of neutrophil extracellular traps (NETs) have been recognized as key events in host defense. A comprehensive knowledge of these mechanisms is needed in order to understand their frequent failure against GAS immune evasion strategies. PMID:25325020

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

PubMed Central

Hebecker, Betty; Vlaic, Sebastian; Conrad, Theresia; Bauer, Michael; Brunke, Sascha; Kapitan, Mario; Linde, Jörg; Hube, Bernhard; Jacobsen, Ilse D.

2016-01-01

Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses. PMID:27808111

Evaluation of the Seeplex® Meningitis ACE Detection kit for the detection of 12 common bacterial and viral pathogens of acute meningitis.

PubMed

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.

Evaluation of the Seeplex® Meningitis ACE Detection Kit for the Detection of 12 Common Bacterial and Viral Pathogens of Acute Meningitis

PubMed Central

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

Ecosystem transformation by emerging infectious disease: loss of large tanoak from California forests

Treesearch

Richard C. Cobb; Joao A.N. Filipe; Ross K. Meentemeyer; Christopher A. Gilligan; David M. Rizzo

2012-01-01

1. Few pathogens are the sole or primary cause of species extinctions, but forest disease has caused spectacular declines in North American overstorey trees and restructured forest ecosystems at large spatial scales over the past 100 years. These events threaten biodiversity associated with impacted host trees and other resources valued by human societies even when...

Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen Pneumocystis.

PubMed

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.

Pilocarpine Seizures Cause Age-Dependent Impairment in Auditory Location Discrimination

ERIC Educational Resources Information Center

Neill, John C.; Liu, Zhao; Mikati, Mohammad; Holmes, Gregory L.

2005-01-01

Children who have status epilepticus have continuous or rapidly repeating seizures that may be life-threatening and may cause life-long changes in brain and behavior. The extent to which status epilepticus causes deficits in auditory discrimination is unknown. A naturalistic auditory location discrimination method was used to evaluate this…

Fire blight: applied genomic insights of the pathogen and host

USDA-ARS?s Scientific Manuscript database

The enterobacterial phytopathogen, Erwinia amylovora, causes fire blight, an invasive disease that threatens a wide range of commercial and ornamental Rosaceae host plants. The response elicited by E. amylovora in its host during disease development is similar to the hypersensitive reaction that ty...

Current advances on genetic resistance to rice blast disease

USDA-ARS?s Scientific Manuscript database

Rice blast disease caused by the fungal pathogen Magnaporthe oryzae is one of the most threatening fungal diseases resulting in significant annual crop losses worldwide. Blast disease has been effectively managed by a combination of resistant (R) gene deployment, application of fungicides, and suita...

[Chameleon spondylodiscitis : Challenge for geriatricians].

PubMed

Hofmann, Werner

2018-06-01

The incidence of spondylodiscitis is increasing and attributable to an aging population with multimorbidities. Spondylodiscitis represents a life-threatening disease. Typical clinical manifestations often involve nonspecific symptoms with back pain; however, due to the frequent absence of fever the disease is often overlooked. Pathogen detection and spinal imaging with magnetic resonance imaging (MRI) are essential for the diagnosis. Identification of the causative pathogen is particularly important for initiating targeted antibiotic treatment. Debridement and stabilization are the mainstays of surgical management, even though foreign material must be implanted into the focus of inflammation.

[Chameleon spondylodiscitis : Challenge for geriatricians].

PubMed

Hofmann, Werner

2017-10-01

The incidence of spondylodiscitis is increasing and attributable to an aging population with multimorbidities. Spondylodiscitis represents a life-threatening disease. Typical clinical manifestations often involve nonspecific symptoms with back pain; however, due to the frequent absence of fever the disease is often overlooked. Pathogen detection and spinal imaging with magnetic resonance imaging (MRI) are essential for the diagnosis. Identification of the causative pathogen is particularly important for initiating targeted antibiotic treatment. Debridement and stabilization are the mainstays of surgical management, even though foreign material must be implanted into the focus of inflammation.

Pathogenic Leptospira interrogans Exoproteins Are Primarily Involved in Heterotrophic Processes

PubMed Central

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

2015-01-01

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

Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation

PubMed Central

Nelson-Williams, Carol; Stiegler, Amy L; Loring, Erin; Choi, Murim; Overton, John; Meffre, Eric; Khokha, Mustafa K; Huttner, Anita J; West, Brian; Podoltsev, Nikolai A; Boggon, Titus J; Kazmierczak, Barbara I; Lifton, Richard P

2014-01-01

Upon detection of pathogen-associated molecular patterns, innate immune receptors initiate inflammatory responses. These receptors include cytoplasmic NOD-like receptors (NLRs), whose stimulation recruits and proteolytically activates caspase-1 within the inflammasome, a multi-protein complex. Caspase-1 mediates the production of interleukin-1 family cytokines (IL1FCs), leading to fever, and inflammatory cell death (pyroptosis)1,2. Mutations that constitutively activate these pathways underlie several autoinflammatory diseases with diverse clinical features3. We describe a family with a previously unreported syndrome featuring neonatal-onset enterocolitis, periodic fever, and fatal/near-fatal episodes of autoinflammation caused by a de novo gain-of-function mutation (p.V341A) in the HD1 domain of NLRC4 that co-segregates with disease. Mutant NLRC4 causes constitutive Interleukin-1 family cytokine production and macrophage cell death. Infected patient macrophages are polarized toward pyroptosis and exhibit abnormal staining for inflammasome components. These findings describe and reveal the cause of a life-threatening but treatable autoinflammatory disease that underscores the divergent roles of the NLRC4 inflammasome. PMID:25217960

The Autophagic Machinery in Enterovirus Infection

PubMed Central

Lai, Jeffrey K. F.; Sam, I-Ching; Chan, Yoke Fun

2016-01-01

The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome-mediated exit without lysis (AWOL). The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field. PMID:26828514

Vascular Pythiosis of the Lower Extremity in Northern Thailand: Ten Years' Experience.

PubMed

Reanpang, Termpong; Orrapin, Saritphat; Orrapin, Saranat; Arworn, Supapong; Kattipatanapong, Thanate; Srisuwan, Tanop; Vanittanakom, Nongnuch; Lekawanvijit, Suree P; Rerkasem, Kittipan

2015-09-01

Pythiosis is a disease caused by Pythium insidiosum, a fungus-like organism. P. insidiosum is pathogenic in mammals, particularly in horses, dogs, and humans. Human pythiosis can be classified into 4 types: (1) cutaneous/subcutaneous, (2) ocular, (3) vascular, and (4) disseminated pythiosis. Vascular pythiosis is a rare disease but a serious limb- and life-threatening infection. We reviewed 22 cases over a 10-year period in Maharaj Nakorn Chiang Mai/Chiang Mai University Hospital. The survival rate was around 63.6% during our follow-up period. The only effective treatment was complete excision of the infected tissue, which was done mainly by major amputation, such as above-knee amputation. This report raises awareness of this disease, which needs preemptive diagnosis and appropriate treatment. © The Author(s) 2015.

Rapid reversal of colonic pneumatosis with restoration of mesenteric arterial supply.

PubMed

Abidali, Hussein; Cole, Lauren; Seetharam, Anil Bellur

2018-06-07

Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cystic lesions within the wall of the large intestine and presents along a spectrum of clinical severity ranging from benign to life threatening. Etiopathogenesis is multifactorial and postulated to result from either mechanical or bacterial causes. In this report, we present a patient with chronic abdominal pain evaluated with colonoscopy revealing segmental PCI isolated to the distal colon. Further investigation revealed an abdominal aortic aneurysm (AAA) compromising the inferior mesenteric artery takeoff. Endovascular repair of the AAA resulted in clinical resolution of abdominal pain and endoscopic resolution of PCI. To our knowledge, this is the first report to document endoscopic resolution of PCI with restoration of mesenteric arterial supply, highlighting vascular insufficiency as a predisposing and reversible pathogenic mechanism.

The Autophagic Machinery in Enterovirus Infection.

PubMed

Lai, Jeffrey K F; Sam, I-Ching; Chan, Yoke Fun

2016-01-27

The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome-mediated exit without lysis (AWOL). The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field.

Patterns of decision making by wives of patients with life-threatening cardiac disease.

PubMed

Hall, Patricia; Sanford, Julie T; Demi, Alice S

2008-08-01

Implementation of the Patient Self-Determination Act (PSDA) in the United States has transferred decision making from the responsibility of health care professionals to the responsibility of family members. Dilemmas occurring as a result of this responsibility may cause stress and conflict among family members. The purpose of this study is to describe the patterns of decision making by family members of patients with life-threatening cardiac disease. Purposive sampling is used to select 10 wives of patients with life-threatening cardiovascular disease. Data are gathered through unstructured interviews and are analyzed using grounded theory and theory triangulation. Analysis of the data reveal three patterns of decision making: advocacy, acquiescence, and abdication.

Endovascular Management of Ureteroarterial Fistula: A Rare Potentially Life Threatening Cause of Hematuria

PubMed Central

Copelan, Alexander; Chehab, Monzer; Cash, Charles; Korman, Howard; Dixit, Purushottam

2014-01-01

Ureteroarterial fistula is a rare, potentially life-threatening cause of hematuria characterized by an abnormal channel between a ureter and artery. The rarity of this condition, complexity of predisposing risk factors and intermittence of symptoms may delay or obscure its diagnosis. With a high index of suspicion and careful angiographic evaluation, embarking on this condition is not only possible but sets the stage for curative intervention. We report a case of a ureteroarterial fistula presenting with intermittent hematuria, successfully diagnosed at angiography and managed with endovascular stent graft placement. PMID:25426238

Spatiotemporal patterns in the airborne dispersal of spinach downy mildew

USDA-ARS?s Scientific Manuscript database

Downy mildew, caused by the biotrophic oomycete pathogen, Peronospora effusa, is the most devastating disease of spinach that threatens sustainable production. The disease results in yellow lesions that render leaves unmarketable as the high value fresh produce. In this study, the levels of D...

Ancestral seed zones and genetic mixture of tanoak

Treesearch

Richard Dodd; Zara Rafii; Wasima Mayer

2010-01-01

Understanding the genetic structure of tanoak (Lithocarpus densiflorus) is necessary to pathologists seeking natural variation in resistance to Phytophthora ramorum, cause of sudden oak death (SOD), and to resource managers who need indications of conservation priorities for this species now threatened by this introduced pathogen. We investigated...

Candida, fluorescent stain (image)

MedlinePlus

... a fluorescent stain of Candida. Candida is a yeast (fungus) that causes mild disease, but in immunocompromised individuals it may cause life-threatening illness. (Image courtesy of the Centers for ...

Emerging fungal infections among children: A review on its clinical manifestations, diagnosis, and prevention

PubMed Central

Jain, Akansha; Jain, Shubham; Rawat, Swati

2010-01-01

The incidence of fungal infections is increasing at an alarming rate, presenting an enormous challenge to healthcare professionals. This increase is directly related to the growing population of immunocompromised individuals especially children resulting from changes in medical practice such as the use of intensive chemotherapy and immunosuppressive drugs. Although healthy children have strong natural immunity against fungal infections, then also fungal infection among children are increasing very fast. Virtually not all fungi are pathogenic and their infection is opportunistic. Fungi can occur in the form of yeast, mould, and dimorph. In children fungi can cause superficial infection, i.e., on skin, nails, and hair like oral thrush, candida diaper rash, tinea infections, etc., are various types of superficial fungal infections, subcutaneous fungal infection in tissues under the skin and lastly it causes systemic infection in deeper tissues. Most superficial and subcutaneous fungal infections are easily diagnosed and readily amenable to treatment. Opportunistic fungal infections are those that cause diseases exclusively in immunocompromised individuals, e.g., aspergillosis, zygomycosis, etc. Systemic infections can be life-threatening and are associated with high morbidity and mortality. Because diagnosis is difficult and the causative agent is often confirmed only at autopsy, the exact incidence of systemic infections is difficult to determine. The most frequently encountered pathogens are Candida albicans and Aspergillus spp. But other fungi such as non-albicans Candida spp. are increasingly important. PMID:21180463

Vertigo/dizziness in pediatric emergency department: Five years' experience.

PubMed

Raucci, Umberto; Vanacore, Nicola; Paolino, Maria Chiara; Silenzi, Romina; Mariani, Rosanna; Urbano, Antonella; Reale, Antonino; Villa, Maria Pia; Parisi, Pasquale

2016-05-01

Vertigo/Dizziness in childhood is not a rare cause of visits to the emergency department (ED). We analyzed a selected group with vertigo/dizziness to identify signs and symptoms that may help to guide the diagnostic approach and management. A total of 616 children admitted for vertigo to the ED over a five-year period were retrospectively reviewed. Their medical history, clinical characteristics, laboratory and neuroimaging tests, final diagnoses and management were analyzed. Migraine and syncope were the most frequent causes. Two patients were affected by life-threatening cardiac syncope, while structural life-threatening central nervous system diseases were found in 15 patients, none of whom presented with vertigo as an isolated clinical finding. Most cases of vertigo/dizziness in childhood that consist mainly of migraine and syncope are of benign origin. The prompt identification of neurological or cardiological signs or symptoms associated with vertigo in children is mandatory to rule out life-threatening conditions. © International Headache Society 2015.

The Medical NBC Battlebook

DTIC Science & Technology

2000-05-01

of fever and chills within the first day postexposure is associated with a severe and life-threatening radiation dose. Hyperthermia may occur in...required at 3-5 wks for 10-50% of personnel. Anticipated problems should include infection, bleeding, and fever . Wounding or burns will geometrically...weeks, 50-100% of personnel will develop pathogenic and opportunistic infections, bleeding, fever , loss of appetite, GI ulcerations, bloody diarrhea

The Human Polymeric Immunoglobulin Receptor Facilitates Invasion of Epithelial Cells by Streptococcus pneumoniae in a Strain-Specific and Cell Type-Specific Manner

PubMed Central

Brock, Sean C.; McGraw, Patricia A.; Wright, Peter F.; Crowe Jr., James E.

2002-01-01

Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes invasive life-threatening disease worldwide. This organism also commonly colonizes the upper respiratory epithelium in an asymptomatic fashion. To invade, this pathogen must traverse the respiratory epithelial barrier, allowing it to cause disease locally or disseminate hematogenously throughout the body. Previous work has demonstrated that S. pneumoniae choline-binding protein A, a pneumococcal surface protein, interacts specifically with the human polymeric immunoglobulin receptor, which is expressed by cells in the respiratory epithelium. Choline-binding protein A is required for efficient colonization of the nasopharynx in vivo. Additionally, a recent study showed that the R6x laboratory strain of S. pneumoniae invades a human pharyngeal cell line in a human polymeric immunoglobulin receptor-dependent manner. These findings raised the possibility that the interaction between choline-binding protein A and human polymeric immunoglobulin receptor may be a key determinant of S. pneumoniae pathogenesis. However, the strain used in prior invasion studies, R6x, is an unencapsulated, nonpathogenic strain. In the present study we determined the relative ability of strain R6x or pathogenic strains to invade a variety of human polymeric immunoglobulin receptor-expressing epithelial cell lines. The results of this work suggest that human polymeric immunoglobulin receptor-dependent enhanced invasion of epithelial cells by S. pneumoniae is a limited phenomenon that occurs in a strain-specific and cell type-specific manner. PMID:12183558

The epidemiology of life-threatening complications associated with reproductive process in public hospitals in Argentina.

PubMed

Karolinski, A; Mercer, R; Micone, P; Ocampo, C; Mazzoni, A; Fontana, O; Messina, A; Winograd, R; Frers, M C; Nassif, J C; Elordi, H C; Lapidus, A; Taddeo, C; Damiano, M; Lambruschini, R; Muzzio, C; Pecker, B; Natale, S; Nowacki, D; Betular, A; Breccia, G; Di Biase, L; Montes Varela, D; Dunaiewsky, A; Minsk, E; Fernández, D; Martire, L; Huespe, M; Laterra, C; Spagnuolo, R; Gregoris, C

2013-12-01

To analyse life-threatening obstetric complications that occurred in public hospitals in Argentina. Multicentre collaborative cross-sectional study. Twenty-five hospitals included in the Perinatal Network of Buenos Aires Metropolitan Area. Women giving birth in participating hospitals during a 1-year period. All cases of severe maternal morbidity (SMM) and maternal mortality (MM) during pregnancy (including miscarriage and induced abortion), labour and puerperium were included. Data were collected prospectively. Identification criteria, main causes and incidence of SMM; case-fatality rates, morbidity-mortality index and effective intervention's use rate. A total of 552 women with life-threatening conditions were identified: 518 with SMM, 34 with MM. Identification criteria for SMM were case-management (48.9%), organ dysfunction (15.2%) and mixed criteria (35.9%). Incidence of SMM was 0.8% (95% confidence interval [95% CI] 0.73-0.87%) and hospital maternal death ratio was 52.3 per 100 000 live births (95% CI 35.5-69.1). Main causes of MM were abortion complications and puerperal sepsis; main causes of SMM were postpartum haemorrhage and hypertension. Overall case-fatality rate was 6.2% (95% CI 4.4-8.6): the highest due to sepsis (14.8%) and abortion complications (13.3%). Morbidity-mortality index was 15:1 (95% CI 7.5-30.8). Use rate of known effective interventions to prevent or treat main causes of MM and SMM was 52.3% (95% CI 46.9-57.7). This study describes the importance of life-threatening obstetric complications that took place in public hospitals with comprehensive obstetric care and the low utilisation of known effective interventions that may decrease rates of SMM and MM. It also provides arguments that justify the need to develop a surveillance system for SMM. © 2013 RCOG.

Slowing spread of sudden oak death in Oregon forests, 2001–2015

Treesearch

Alan Kanaskie; Randy Wiese; Danny Norlander; Jon Laine; Sarah Navarro; Ellen Michaels Goheen; Ron Rhatigan; Everett Hansen; Wendy Sutton; Paul Reeser; Nik Grunwald; Zhian Kamvar; Nancy Osterbauer

2017-01-01

Sudden oak death, caused by Phytophthora ramorum, is lethal to tanoak (Notholithocarpus densiflorus) and threatens this species throughout its range in Oregon. The disease was first discovered in coastal southwest Oregon forests in July 2001. An interagency team attempted to eradicate the pathogen through a program of...

A holistic approach to genetic conservation of Pinus strobiformis

Treesearch

K.M. Waring; R. Sniezko; B.A. Goodrich; C. Wehenkel; J.J. Jacobs

2017-01-01

Pinus strobiformis (southwestern white pine) is threatened by both a rapidly changing climate and the tree disease white pine blister rust, caused by an introduced fungal pathogen, Cronartium ribicola. We began a proactive program in ~2009 to sustain P. strobiformis that includes genetic conservation, research, and management strategies. Research...

Role of alternate hosts in epidemiology and pathogen variation of cereal rusts

USDA-ARS?s Scientific Manuscript database

Cereal rusts, caused by obligate and biotrophic fungi in the genus Puccinia of basidiomycete are an important group of diseases threatening the world food security. With the recent discovery of alternate hosts for the stripe rust fungus (Puccinia striiformis), all cereal rust fungi are now known ...

Season-long dynamics of spinach downy mildew determined by spore trapping and disease

USDA-ARS?s Scientific Manuscript database

Peronospora effusa is an obligate oomycete pathogen, and the cause of downy mildew of spinach. Downy mildew threatens sustainable production of fresh market organic spinach in California, and routine fungicide sprays are often necessary for conventional production. In this study, airborne P. effus...

Livestock Drugs and Disease: The Fatal Combination behind Breeding Failure in Endangered Bearded Vultures

PubMed Central

Blanco, Guillermo; Lemus, Jesús A.

2010-01-01

There is increasing concern about the impact of veterinary drugs and livestock pathogens as factors damaging wildlife health, especially of threatened avian scavengers feeding upon medicated livestock carcasses. We conducted a comprehensive study of failed eggs and dead nestlings in bearded vultures (Gypaetus barbatus) to attempt to elucidate the proximate causes of breeding failure behind the recent decline in productivity in the Spanish Pyrenees. We found high concentrations of multiple veterinary drugs, primarily fluoroquinolones, in most failed eggs and nestlings, associated with multiple internal organ damage and livestock pathogens causing disease, especially septicaemia by swine pathogens and infectious bursal disease. The combined impact of drugs and disease as stochastic factors may result in potentially devastating effects exacerbating an already high risk of extinction and should be considered in current conservation programs for bearded vultures and other scavenger species, especially in regards to dangerous veterinary drugs and highly pathogenic poultry viruses. PMID:21152405

A rare case of acute pancreatitis and life-threatening hemolytic anemia associated with Epstein-Barr virus infection in a young healthy adult.

PubMed

Singh, Sukhchain; Khosla, Pam

2016-01-01

Epstein-Barr virus (EBV) is a common infection that affects 95% of adults worldwide at some point during life. It is usually asymptomatic or causes a self-limiting clinical syndrome known as infectious mononucleosis. It rarely causes complications. Here, we present a case of a healthy 21-year-old female college student who suffered from severe pancreatitis and life-threatening autoimmune hemolytic anemia in association with EBV infection, and we also discuss the common presentation of EBV infection and the diagnosis and treatment of simple and complicated EBV infection. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

PubMed Central

Swart, A. Leoni; Harrison, Christopher F.; Eichinger, Ludwig; Steinert, Michael; Hilbi, Hubert

2018-01-01

Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella-containing vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of “effector” proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit. The mechanism of LCV formation appears to be evolutionarily conserved, and therefore, amoebae are not only ecologically significant niches for Legionella spp., but also useful cellular models for eukaryotic phagocytes. In particular, Acanthamoeba castellanii and Dictyostelium discoideum emerged over the last years as versatile and powerful models. Using genetic, biochemical and cell biological approaches, molecular interactions between amoebae and Legionella pneumophila have recently been investigated in detail with a focus on the role of phosphoinositide lipids, small and large GTPases, autophagy components and the retromer complex, as well as on bacterial effectors targeting these host factors. PMID:29552544

In-Frame and Unmarked Gene Deletions in Burkholderia cenocepacia via an Allelic Exchange System Compatible with Gateway Technology.

PubMed

Fazli, Mustafa; Harrison, Joe J; Gambino, Michela; Givskov, Michael; Tolker-Nielsen, Tim

2015-06-01

Burkholderia cenocepacia is an emerging opportunistic pathogen causing life-threatening infections in immunocompromised individuals and in patients with cystic fibrosis, which are often difficult, if not impossible, to treat. Understanding the genetic basis of virulence in this emerging pathogen is important for the development of novel treatment regimes. Generation of deletion mutations in genes predicted to encode virulence determinants is fundamental to investigating the mechanisms of pathogenesis. However, there is a lack of appropriate selectable and counterselectable markers for use in B. cenocepacia, making its genetic manipulation problematic. Here we describe a Gateway-compatible allelic exchange system based on the counterselectable pheS gene and the I-SceI homing endonuclease. This system provides efficiency in cloning homology regions of target genes and allows the generation of precise and unmarked gene deletions in B. cenocepacia. As a proof of concept, we demonstrate its utility by deleting the Bcam1349 gene, encoding a cyclic di-GMP (c-di-GMP)-responsive regulator protein important for biofilm formation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

In-Frame and Unmarked Gene Deletions in Burkholderia cenocepacia via an Allelic Exchange System Compatible with Gateway Technology

PubMed Central

Fazli, Mustafa; Harrison, Joe J.; Gambino, Michela; Givskov, Michael

2015-01-01

Burkholderia cenocepacia is an emerging opportunistic pathogen causing life-threatening infections in immunocompromised individuals and in patients with cystic fibrosis, which are often difficult, if not impossible, to treat. Understanding the genetic basis of virulence in this emerging pathogen is important for the development of novel treatment regimes. Generation of deletion mutations in genes predicted to encode virulence determinants is fundamental to investigating the mechanisms of pathogenesis. However, there is a lack of appropriate selectable and counterselectable markers for use in B. cenocepacia, making its genetic manipulation problematic. Here we describe a Gateway-compatible allelic exchange system based on the counterselectable pheS gene and the I-SceI homing endonuclease. This system provides efficiency in cloning homology regions of target genes and allows the generation of precise and unmarked gene deletions in B. cenocepacia. As a proof of concept, we demonstrate its utility by deleting the Bcam1349 gene, encoding a cyclic di-GMP (c-di-GMP)-responsive regulator protein important for biofilm formation. PMID:25795676

Molecular diagnosis of chronic granulomatous disease.

PubMed

Roos, D; de Boer, M

2014-02-01

Patients with chronic granulomatous disease (CGD) suffer from recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, liver, brain and bones. Frequently found pathogens are Staphylococcus aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia and Salmonella species. CGD is a rare (∼1:250 000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. This enzyme generates superoxide and is essential for intracellular killing of pathogens by phagocytes. Molecular diagnosis of CGD involves measuring NADPH oxidase activity in phagocytes, measuring protein expression of NADPH oxidase components and mutation analysis of genes encoding these components. Residual oxidase activity is important to know for estimation of the clinical course and the chance of survival of the patient. Mutation analysis is mandatory for genetic counselling and prenatal diagnosis. This review summarizes the different assays available for the diagnosis of CGD, the precautions to be taken for correct measurements, the flow diagram to be followed, the assays for confirmation of the diagnosis and the determinations for carrier detection and prenatal diagnosis. © 2013 British Society for Immunology.

Dendritic cells coordinate innate immunity via MyD88 signaling to control Listeria monocytogenes infection.

PubMed

Arnold-Schrauf, Catharina; Dudek, Markus; Dielmann, Anastasia; Pace, Luigia; Swallow, Maxine; Kruse, Friederike; Kühl, Anja A; Holzmann, Bernhard; Berod, Luciana; Sparwasser, Tim

2014-02-27

Listeria monocytogenes (LM), a facultative intracellular Gram-positive pathogen, can cause life-threatening infections in humans. In mice, the signaling cascade downstream of the myeloid differentiation factor 88 (MyD88) is essential for proper innate immune activation against LM, as MyD88-deficient mice succumb early to infection. Here, we show that MyD88 signaling in dendritic cells (DCs) is sufficient to mediate the protective innate response, including the production of proinflammatory cytokines, neutrophil infiltration, bacterial clearance, and full protection from lethal infection. We also demonstrate that MyD88 signaling by DCs controls the infection rates of CD8α(+) cDCs and thus limits the spread of LM to the T cell areas. Furthermore, in mice expressing MyD88 in DCs, inflammatory monocytes, which are required for bacterial clearance, are activated independently of intrinsic MyD88 signaling. In conclusion, CD11c(+) conventional DCs critically integrate pathogen-derived signals via MyD88 signaling during early infection with LM in vivo. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Zebrafish and Streptococcal Infections.

PubMed

Saralahti, A; Rämet, M

2015-09-01

Streptococcal bacteria are a versatile group of gram-positive bacteria capable of infecting several host organisms, including humans and fish. Streptococcal species are common colonizers of the human respiratory and gastrointestinal tract, but they also cause some of the most common life-threatening, invasive infections in humans and aquaculture. With its unique characteristics and efficient tools for genetic and imaging applications, the zebrafish (Danio rerio) has emerged as a powerful vertebrate model for infectious diseases. Several zebrafish models introduced so far have shown that zebrafish are suitable models for both zoonotic and human-specific infections. Recently, several zebrafish models mimicking human streptococcal infections have also been developed. These models show great potential in providing novel information about the pathogenic mechanisms and host responses associated with human streptococcal infections. Here, we review the zebrafish infection models for the most relevant streptococcal species: the human-specific Streptococcus pneumoniae and Streptococcus pyogenes, and the zoonotic Streptococcus iniae and Streptococcus agalactiae. The recent success and the future potential of these models for the study of host-pathogen interactions in streptococcal infections are also discussed. © 2015 The Foundation for the Scandinavian Journal of Immunology.

Apigenin protects mice from pneumococcal pneumonia by inhibiting the cytolytic activity of pneumolysin.

PubMed

Song, Meng; Li, Li; Li, Meng; Cha, Yonghong; Deng, Xuming; Wang, Jianfeng

2016-12-01

Streptococcus pneumoniae is an important human pathogenic bacterium that can cause various life-threatening infections. Pneumolysin (PLY), the pore-forming toxin that forms large pores in the cell membrane, is a key virulence factor secreted by S. pneumoniae that penetrates the physical defenses of the host and plays an important role in the pathogenesis of pneumococcal diseases, such as pneumonia, meningitis, bacteremia and otitis media. This study showed that apigenin, one of the bioflavonoids widely found in herbs, inhibits PLY-induced hemolysis by inhibiting the oligomerization of PLY and has no anti-S. pneumoniae activity. In addition, when PLY was incubated with human alveolar epithelial (A549) cells, apigenin could effectively alleviate PLY-mediated cell injury. In vivo studies further demonstrated that apigenin could protect mice against S. pneumoniae pneumonia. These results imply that apigenin could directly interact with PLY to decrease the pathogenicity of S. pneumoniae and that novel therapeutics against S. pneumoniae PLY might provide greater effectiveness in combatting S. pneumoniae pneumonia. Copyright © 2016 Elsevier B.V. All rights reserved.

A Product of Heme Catabolism Modulates Bacterial Function and Survival

PubMed Central

Nobles, Christopher L.; Green, Sabrina I.; Maresso, Anthony W.

2013-01-01

Bilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI) tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis, we investigated the effect of bilirubin on two enteric pathogens; enterohemorrhagic E. coli (EHEC), a Gram-negative that causes life-threatening intestinal infections, and E. faecalis, a Gram-positive human commensal bacterium known to be an opportunistic pathogen with broad-spectrum antibiotic resistance. We demonstrate that bilirubin can protect EHEC from exogenous and host-generated reactive oxygen species (ROS) through the absorption of free radicals. In contrast, E. faecalis was highly susceptible to bilirubin, which causes significant membrane disruption and uncoupling of respiratory metabolism in this bacterium. Interestingly, similar results were observed for other Gram-positive bacteria, including B. cereus and S. aureus. A model is proposed whereby bilirubin places distinct selective pressure on enteric bacteria, with Gram-negative bacteria being protected from ROS (positive outcome) and Gram-positive bacteria being susceptible to membrane disruption (negative outcome). This work suggests bilirubin has differential but biologically relevant effects on bacteria and justifies additional efforts to determine the role of this neglected waste catabolite in disease processes, including animal models. PMID:23935485

Spontaneous splenic rupture in an active duty Marine upon return from Iraq: a case report

PubMed Central

2010-01-01

Introduction Atraumatic splenic rupture is a rare event that has been associated with several infectious disease processes. In the active duty military population, potential exposure to these pathogens is significant. Here we discuss the case of an active duty Marine with spontaneous splenic rupture upon return from a six-month deployment in Iraq. Case presentation A previously healthy 30-year-old Caucasian male active duty Marine presented with abdominal pain, fever and diarrhea after deployment to Iraq in support of Operation Iraqi Freedom. Based on clinical and radiographic evidence, a diagnosis of spontaneous splenic rupture was ultimately suspected. After exploratory laparotomy with confirmation of rupture, splenectomy was performed, and the patient made a full, uneventful recovery. Histopathologic examination revealed mild splenomegaly with a ruptured capsule of undetermined cause. Conclusion Spontaneous splenic rupture is a rare event that may lead to life-threatening hemorrhage if not diagnosed and treated quickly. Although the cause of this patient's case was unknown, atraumatic splenic rupture has been associated with a variety of infectious diseases and demonstrates some risks the active duty military population may face while on deployment. Having an awareness of these pathogens and their role in splenic rupture, clinicians caring for military personnel must be prepared to recognize and treat this potentially fatal complication. PMID:21054871

Microbiological Safety of Processed Meat Products Formulated with Low Nitrite Concentration: A Mini Review.

PubMed

Lee, Soomin; Lee, Heeyoung; Kim, Sejeong; Lee, Jeeyeon; Ha, Jimyeong; Choi, Yukyung; Oh, Hyemin; Choi, Kyoung-Hee; Yoon, Yohan

2018-03-13

Nitrite plays a major role in inhibiting the growth of foodborne pathogens, including Clostridium botulinum that causes botulism, a life-threatening disease. Nitrite serves as a color-fixing agent in processed meat products. However, N-nitroso compounds can be produced from nitrite. They are considered as carcinogens. Thus, consumers desire processed meat products that contain lower concentrations (below conventional concentrations of products) of nitrite or no nitrite at all, although the portion of nitrite intake by processed meat consumption in total nitrite intake is very low. However, lower nitrite levels might expose consumers to risk of botulism poisoning due to C. botulinum or illness caused by other foodborne pathogens. Hence, lower nitrite concentrations in combination with other factors such as low pH, high NaCl level, and others have been recommended to decrease the risk of food poisoning. In addition, natural compounds that can inhibit bacterial growth and function as color-fixing agents have been developed to replace nitrite in processed meat products. However, their antibotulinal effects have not been fully clarified. Therefore, to have processed meat products with lower nitrite concentrations, low pH, high NaCl concentration, and others should also be applied together. Before using natural compounds as replacement of nitrite, their antibotulinal activities should be examined.

Screening of In Vivo Activated Genes in Enterococcus faecalis during Insect and Mouse Infections and Growth in Urine

PubMed Central

Hanin, Aurelie; Sava, Irina; Bao, YinYin; Huebner, Johannes; Hartke, Axel; Auffray, Yanick; Sauvageot, Nicolas

2010-01-01

Enterococcus faecalis is part of the commensal microbiota of humans and its main habitat is the gastrointestinal tract. Although harmless in healthy individuals, E. faecalis has emerged as a major cause of nosocomial infections. In order to better understand the transformation of a harmless commensal into a life-threatening pathogen, we developed a Recombination-based In Vivo Expression Technology for E. faecalis. Two R-IVET systems with different levels of sensitivity have been constructed in a E. faecalis V583 derivative strain and tested in the insect model Galleria mellonella, during growth in urine, in a mouse bacteremia and in a mouse peritonitis model. Our combined results led to the identification of 81 in vivo activated genes. Among them, the ef_3196/7 operon was shown to be strongly induced in the insect host model. Deletion of this operonic structure demonstrated that this two-component system was essential to the E. faecalis pathogenic potential in Galleria. Gene ef_0377, induced in insect and mammalian models, has also been further analyzed and it has been demonstrated that this ankyrin-encoding gene was also involved in E. faecalis virulence. Thus these R-IVET screenings led to the identification of new E. faecalis factors implied in in vivo persistence and pathogenic potential of this opportunistic pathogen. PMID:20686694

A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.

PubMed

Yu, Qilin; Dong, Yijie; Xu, Ning; Qian, Kefan; Chen, Yulu; Zhang, Biao; Xing, Laijun; Li, Mingchun

2014-11-01

Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases. Iron acquisition is an important factor for pathogen-host interaction and also a significant element for the pathogenicity of this organism. Ferric reductases, which convert ferric iron into ferrous iron, are important components of the high-affinity iron uptake system. Sequence analyses have identified at least 17 putative ferric reductase genes in C. albicans genome. CFL1 was the first ferric reductase identified in C. albicans. However, little is known about its roles in C. albicans physiology and pathogenicity. In this study, we found that disruption of CFL1 led to hypersensitivity to chemical and physical cell wall stresses, activation of the cell wall integrity (CWI) pathway, abnormal cell wall composition, and enhanced secretion, indicating a defect in CWI in this mutant. Moreover, this mutant showed abnormal mitochondrial activity and morphology, suggesting a link between ferric reductases and mitochondrial function. In addition, this mutant displayed decreased ability of adhesion to both the polystyrene microplates and buccal epithelial cells and invasion of host epithelial cells. These findings revealed a novel role of C. albicans Cfl1 in maintenance of CWI, mitochondrial function, and interaction between this pathogen and the host. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

The in vitro fungicidal activity of human macrophages against Penicillium marneffei is suppressed by dexamethasone.

PubMed

Ma, Tuan; Chen, Renqiong; Li, Xiqing; Lu, Changming; Xi, Liyan

2015-09-01

Penicillium marneffei (P. marneffei) is a pathogenic fungus that can persist in macrophages and cause a life-threatening systemic mycosis in immunocompromised hosts. To elucidate the mechanisms underlying this opportunistic fungal infection, we established the co-culture system of P. marneffei conidia and human monocyte-derived macrophages (MDM) for investigating the interactions between them. And, we impaired the immune state of MDM by the addition of dexamethasone (DEX). Compared with immunocompetent MDM without DEX treatment in response to P. marneffei, DEX could damage MDM function in initiating the innate immune response through decreasing TNF-α production and the proportion of P. marneffei conidia in mature phagolysosomes, while the red pigment secretion by P. marneffei conidia was promoted by DEX following MDM lysis. Our data provide the evidence that DEX-treated MDM have a low fungicidal activity against P. marneffei that causes penicilliosis in immunocompromised hosts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reduced itraconazole concentration and durations are successful in treating Batrachochytrium dendrobatidis infection in amphibians.

PubMed

Brannelly, Laura A

2014-03-14

Amphibians are experiencing the greatest decline of any vertebrate class and a leading cause of these declines is a fungal pathogen, Batrachochytrium dendrobatidis (Bd), which causes the disease chytridiomycosis. Captive assurance colonies are important worldwide for threatened amphibian species and may be the only lifeline for those in critical threat of extinction. Maintaining disease free colonies is a priority of captive managers, yet safe and effective treatments for all species and across life stages have not been identified. The most widely used chemotherapeutic treatment is itraconazole, although the dosage commonly used can be harmful to some individuals and species. We performed a clinical treatment trial to assess whether a lower and safer but effective dose of itraconazole could be found to cure Bd infections. We found that by reducing the treatment concentration from 0.01-0.0025% and reducing the treatment duration from 11-6 days of 5 min baths, frogs could be cured of Bd infection with fewer side effects and less treatment-associated mortality.

Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

PubMed

Hannemann, Sebastian; Galán, Jorge E

2017-07-01

Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

Challenges in the management of massive intraorbital and hemifacial arteriovenous malformation as causing life-threatening epistaxis.

PubMed

Manuel, Anura Michelle; Kalimuthu, Santhi; Pathmanathan, Sitra Siri; Narayanan, Prepageran; Zainal Abidin, Zurina; Azmi, Khairul; Khalil, Alizan

2017-04-01

Arteriovenous malformations are congenital lesions that may evolve with time and manifest in a plethora of presentations. They can occur as torrential epistaxis when it extensively involves the facial region. Multi-imaging modalities are available to assist in characterizing the structure of the lesion as well as its location and extent. This complex disease requires a multidisciplinary team approach with preoperative embolization and surgery. We present a rare cause of life-threatening epistaxis in a gentleman with a longstanding orbital and hemifacial arteriovenous malformation and discuss the complexities involved in its management. Copyright © 2017. Published by Elsevier Taiwan.

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

PubMed Central

Sato, Hiromi

2017-01-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection. PMID:28750011

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells.

PubMed

Sato, Hiromi; Coburn, Jenifer

2017-07-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection.

Clinical Appearance of Oral Candida Infection and Therapeutic Strategies

PubMed Central

Patil, Shankargouda; Rao, Roopa S.; Majumdar, Barnali; Anil, Sukumaran

2015-01-01

Candida species present both as commensals and opportunistic pathogens of the oral cavity. For decades, it has enthralled the clinicians to investigate its pathogenicity and to improvise newer therapeutic regimens based on the updated molecular research. Candida is readily isolated from the oral cavity, but simple carriage does not predictably result in development of an infection. Whether it remains as a commensal, or transmutes into a pathogen, is usually determined by pre-existing or associated variations in the host immune system. The candida infections may range from non-life threatening superficial mucocutaneous disorders to invasive disseminated disease involving multiple organs. In fact, with the increase in number of AIDS cases, there is a resurgence of less common forms of oral candida infections. The treatment after confirmation of the diagnosis should include recognizing and eliminating the underlying causes such as ill-fitting oral appliances, history of medications (antibiotics, corticosteroids, etc.), immunological and endocrine disorders, nutritional deficiency states and prolonged hospitalization. Treatment with appropriate topical antifungal agents such as amphotericin, nystatin, or miconazole usually resolves the symptoms of superficial infection. Occasionally, administration of systemic antifungal agents may be necessary in immunocompromised patients, the selection of which should be based upon history of recent azole exposure, a history of intolerance to an antifungal agent, the dominant Candida species and current susceptibility data. PMID:26733948

Effects of nanosecond pulsed electric fields (nsPEFs) on the human fungal pathogen Candida albicans: an in vitro study

NASA Astrophysics Data System (ADS)

Guo, Jinsong; Dang, Jie; Wang, Kaile; Zhang, Jue; Fang, Jing

2018-05-01

Candida albicans is the leading human fungal pathogen that causes many life-threatening infections. Notably, the current clinical trial data indicate that Candida species shows the emerging resistance to anti-fungal drugs. The aim of this study was to evaluate the antifungal effects of nanosecond pulsed electric fields (nsPEFs) as a novel drug-free strategy in vitro. In this study, we investigated the inactivation and permeabilization effects of C. albicans under different nsPEFs exposure conditions (100 pulses, 100 ns in duration, intensities of 20, 40 kV cm‑1). Cell death was studied by annexin-V and propidium iodide staining. The changes of intracellular Ca2+ concentration after nsPEFs treatment were observed using Fluo-4 AM. Results show that C. albicans cells and biofilms were both obviously inhibited and destroyed after nsPEFs treatment. Furthermore, C. albicans cells were significantly permeabilized after nsPEFs treatment. Additionally, nsPEFs exposure led to a large amount of DNA and protein leakage. Importantly, nsPEFs induced a field strength-dependent apoptosis in C. albicans cells. Further experiments revealed that Ca2+ involved in nsPEFs induced C. albicans apoptosis. In conclusion, this proof-of-concept study provides a potential alternative drug-free strategy for killing pathogenic Candida species.

Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention.

PubMed

Mount, Hillary R; Boyle, Sean D

2017-09-01

The etiologies of meningitis range in severity from benign and self-limited to life-threatening with potentially severe morbidity. Bacterial meningitis is a medical emergency that requires prompt recognition and treatment. Mortality remains high despite the introduction of vaccinations for common pathogens that have reduced the incidence of meningitis worldwide. Aseptic meningitis is the most common form of meningitis with an annual incidence of 7.6 per 100,000 adults. Most cases of aseptic meningitis are viral and require supportive care. Viral meningitis is generally self-limited with a good prognosis. Examination maneuvers such as Kernig sign or Brudzinski sign may not be useful to differentiate bacterial from aseptic meningitis because of variable sensitivity and specificity. Because clinical findings are also unreliable, the diagnosis relies on the examination of cerebrospinal fluid obtained from lumbar puncture. Delayed initiation of antibiotics can worsen mortality. Treatment should be started promptly in cases where transfer, imaging, or lumbar puncture may slow a definitive diagnosis. Empiric antibiotics should be directed toward the most likely pathogens and should be adjusted by patient age and risk factors. Dexamethasone should be administered to children and adults with suspected bacterial meningitis before or at the time of initiation of antibiotics. Vaccination against the most common pathogens that cause bacterial meningitis is recommended. Chemoprophylaxis of close contacts is helpful in preventing additional infections.

Aspergillosis and stem cell transplantation: An overview of experimental pathogenesis studies.

PubMed

Al-Bader, Nadia; Sheppard, Donald C

2016-11-16

Invasive aspergillosis is a life-threatening infection caused by the opportunistic filamentous fungus Aspergillus fumigatus. Patients undergoing haematopoietic stem cell transplant (HSCT) for the treatment of hematological malignancy are at particularly high risk of developing this fatal infection. The susceptibility of HSCT patients to infection with A. fumigatus is a consequence of a complex interplay of both fungal and host factors. Here we review our understanding of the host-pathogen interactions underlying the susceptibility of the immunocompromised host to infection with A. fumigatus with a focus on the experimental validation of fungal and host factors relevant to HSCT patients. These include fungal factors such as secondary metabolites, cell wall constituents, and metabolic adaptations that facilitate immune evasion and survival within the host microenvironment, as well as the innate and adaptive immune responses involved in host defense against A. fumigatus.

Invasive pathogen threatens bird-pine mutualism: Implications for sustaining a high-elevation ecosystem

Treesearch

Shawn T. McKinney; Carl E. Fiedler; Diana F. Tomback

2009-01-01

Human-caused disruptions to seed-dispersal mutualisms increase the extinction risk for both plant and animal species. Large-seeded plants can be particularly vulnerable due to highly specialized dispersal systems and no compensatory regeneration mechanisms. Whitebark pine (Pinus albicaulis), a keystone subalpine species, obligately depends upon the Clark's...

Genetic evidence that butternut canker was recently introduced into North America

Treesearch

Glenn R. Furnier; Allison M. Stoiz; Raka M. Mustaphi; Michael E. Ostry

1999-01-01

Butternut (Juglans cinerea) is seriously threatened by a canker disease caused by Sirococens clavigignenti-juglandacearum, a fungus with no known sexual stage. This pathogen was first reported in 1967 and is now found throughout the native range of butternut, suggesting that it was introduced into North America. We used randomly...

A Novel Bacterium Associated with Lymphadenitis in a Patient with Chronic Granulomatous Disease

PubMed Central

Greenberg, David E; Ding, Li; Zelazny, Adrian M; Stock, Frida; Wong, Alexandra; Anderson, Victoria L; Miller, Georgina; Kleiner, David E; Tenorio, Allan R; Brinster, Lauren; Dorward, David W; Murray, Patrick R; Holland, Steven M

2006-01-01

Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system causing defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections. We identified a novel gram-negative rod in excised lymph nodes from a patient with CGD. Gram-negative rods grew on charcoal-yeast extract, but conventional tests could not identify it. The best 50 matches of the 16S rRNA (using BLAST) were all members of the family Acetobacteraceae, with the closest match being Gluconobacter sacchari. Patient serum showed specific band recognition in whole lysate immunoblot. We used mouse models of CGD to determine whether this organism was a genuine CGD pathogen. Intraperitoneal injection of gp91phox −/− (X-linked) and p47 phox −/− (autosomal recessive) mice with this bacterium led to larger burdens of organism recovered from knockout compared with wild-type mice. Knockout mouse lymph nodes had histopathology that was similar to that seen in our patient. We recovered organisms with 16S rRNA sequence identical to the patient's original isolate from the infected mice. We identified a novel gram-negative rod from a patient with CGD. To confirm its pathogenicity, we demonstrated specific immune reaction by high titer antibody, showed that it was able to cause similar disease when introduced into CGD, but not wild-type mice, and we recovered the same organism from pathologic lesions in these mice. Therefore, we have fulfilled Koch's postulates for a new pathogen. This is the first reported case of invasive human disease caused by any of the Acetobacteraceae. Polyphasic taxonomic analysis shows this organism to be a new genus and species for which we propose the name Granulobacter bethesdensis. PMID:16617373

Fungal model systems and the elucidation of pathogenicity determinants

PubMed Central

Perez-Nadales, Elena; Almeida Nogueira, Maria Filomena; Baldin, Clara; Castanheira, Sónia; El Ghalid, Mennat; Grund, Elisabeth; Lengeler, Klaus; Marchegiani, Elisabetta; Mehrotra, Pankaj Vinod; Moretti, Marino; Naik, Vikram; Oses-Ruiz, Miriam; Oskarsson, Therese; Schäfer, Katja; Wasserstrom, Lisa; Brakhage, Axel A.; Gow, Neil A.R.; Kahmann, Regine; Lebrun, Marc-Henri; Perez-Martin, José; Di Pietro, Antonio; Talbot, Nicholas J.; Toquin, Valerie; Walther, Andrea; Wendland, Jürgen

2014-01-01

Fungi have the capacity to cause devastating diseases of both plants and animals, causing significant harvest losses that threaten food security and human mycoses with high mortality rates. As a consequence, there is a critical need to promote development of new antifungal drugs, which requires a comprehensive molecular knowledge of fungal pathogenesis. In this review, we critically evaluate current knowledge of seven fungal organisms used as major research models for fungal pathogenesis. These include pathogens of both animals and plants; Ashbya gossypii, Aspergillus fumigatus, Candida albicans, Fusarium oxysporum, Magnaporthe oryzae, Ustilago maydis and Zymoseptoria tritici. We present key insights into the virulence mechanisms deployed by each species and a comparative overview of key insights obtained from genomic analysis. We then consider current trends and future challenges associated with the study of fungal pathogenicity. PMID:25011008

Determinants of severe dehydration from diarrheal disease at hospital presentation: Evidence from 22 years of admissions in Bangladesh

PubMed Central

Andrews, Jason R.; Leung, Daniel T.; Ahmed, Shahnawaz; Malek, Mohammed Abdul; Ahmed, Dilruba; Begum, Yasmin Ara; Qadri, Firdausi; Ahmed, Tahmeed; Faruque, Abu Syed Golam; Nelson, Eric J.

2017-01-01

Background To take advantage of emerging opportunities to reduce morbidity and mortality from diarrheal disease, we need to better understand the determinants of life-threatening severe dehydration (SD) in resource-poor settings. Methodology/findings We analyzed records of patients admitted with acute diarrheal disease over twenty-two years at the International Centre for Diarrhoeal Disease Research, Bangladesh (1993–2014). Patients presenting with and without SD were compared by multivariable logistic regression models, which included socio-demographic factors and pathogens isolated. Generalized additive models evaluated non-linearities between age or household income and SD. Among 55,956 admitted patients, 13,457 (24%) presented with SD. Vibrio cholerae was the most common pathogen isolated (12,405 patients; 22%), and had the strongest association with SD (AOR 4.77; 95% CI: 4.41–5.51); detection of multiple pathogens did not exacerbate SD risk. The highest proportion of severely dehydrated patients presented in a narrow window only 4–12 hours after symptom onset. Risk of presenting with SD increased sharply from zero to ten years of age and remained high throughout adolescence and adulthood. Adult women had a 38% increased odds (AOR 1.38; 95% CI: 1.30–1.46) of SD compared to adult men. The probability of SD increased sharply at low incomes. These findings were consistent across pathogens. Conclusions/significance There remain underappreciated populations vulnerable to life-threatening diarrheal disease that include adult women and the very poor. In addition to efforts that address diarrheal disease in young children, there is a need to develop interventions for these other high-risk populations that are accessible within 4 hours of symptom onset. PMID:28448489

Determinants of severe dehydration from diarrheal disease at hospital presentation: Evidence from 22 years of admissions in Bangladesh.

PubMed

Andrews, Jason R; Leung, Daniel T; Ahmed, Shahnawaz; Malek, Mohammed Abdul; Ahmed, Dilruba; Begum, Yasmin Ara; Qadri, Firdausi; Ahmed, Tahmeed; Faruque, Abu Syed Golam; Nelson, Eric J

2017-04-01

To take advantage of emerging opportunities to reduce morbidity and mortality from diarrheal disease, we need to better understand the determinants of life-threatening severe dehydration (SD) in resource-poor settings. We analyzed records of patients admitted with acute diarrheal disease over twenty-two years at the International Centre for Diarrhoeal Disease Research, Bangladesh (1993-2014). Patients presenting with and without SD were compared by multivariable logistic regression models, which included socio-demographic factors and pathogens isolated. Generalized additive models evaluated non-linearities between age or household income and SD. Among 55,956 admitted patients, 13,457 (24%) presented with SD. Vibrio cholerae was the most common pathogen isolated (12,405 patients; 22%), and had the strongest association with SD (AOR 4.77; 95% CI: 4.41-5.51); detection of multiple pathogens did not exacerbate SD risk. The highest proportion of severely dehydrated patients presented in a narrow window only 4-12 hours after symptom onset. Risk of presenting with SD increased sharply from zero to ten years of age and remained high throughout adolescence and adulthood. Adult women had a 38% increased odds (AOR 1.38; 95% CI: 1.30-1.46) of SD compared to adult men. The probability of SD increased sharply at low incomes. These findings were consistent across pathogens. There remain underappreciated populations vulnerable to life-threatening diarrheal disease that include adult women and the very poor. In addition to efforts that address diarrheal disease in young children, there is a need to develop interventions for these other high-risk populations that are accessible within 4 hours of symptom onset.

Allovahlkampfia spelaea Causing Keratitis in Humans

PubMed Central

Tolba, Mohammed Essa Marghany; Huseein, Enas Abdelhameed Mahmoud; Farrag, Haiam Mohamed Mahmoud; Mohamed, Hanan El Deek; Kobayashi, Seiki; Suzuki, Jun; Ali, Tarek Ahmed Mohamed; Sugano, Sumio

2016-01-01

Background Free-living amoebae are present worldwide. They can survive in different environment causing human diseases in some instances. Acanthamoeba sp. is known for causing sight-threatening keratitis in humans. Free-living amoeba keratitis is more common in developing countries. Amoebae of family Vahlkampfiidae are rarely reported to cause such affections. A new genus, Allovahlkampfia spelaea was recently identified from caves with no data about pathogenicity in humans. We tried to identify the causative free-living amoeba in a case of keratitis in an Egyptian patient using morphological and molecular techniques. Methods Pathogenic amoebae were culture using monoxenic culture system. Identification through morphological features and 18S ribosomal RNA subunit DNA amplification and sequencing was done. Pathogenicity to laboratory rabbits and ability to produce keratitis were assessed experimentally. Results Allovahlkampfia spelaea was identified as a cause of human keratitis. Whole sequence of 18S ribosomal subunit DNA was sequenced and assembled. The Egyptian strain was closely related to SK1 strain isolated in Slovenia. The ability to induce keratitis was confirmed using animal model. Conclusions This the first time to report Allovahlkampfia spelaea as a human pathogen. Combining both molecular and morphological identification is critical to correctly diagnose amoebae causing keratitis in humans. Use of different pairs of primers and sequencing amplified DNA is needed to prevent misdiagnosis. PMID:27415799

A Multicenter, Open-label Study of CMX001 Treatment of Serious Diseases or Conditions Caused by dsDNA Viruses

ClinicalTrials.gov

2013-08-28

Male or Female Patients With a Serious or Immediately Life-threatening; Disease or Condition Caused by CMV, ADV, HSV, VAVC, VARV or; Monkeypox Viruses(s) Who Have a Life Expectancy of ≥ 2 Weeks and for; Whom no Comparable or Satisfactory Alternative Therapy is Available

Susceptibility to disease varies with ontogeny and immunocompetence in a threatened amphibian.

PubMed

Abu Bakar, Amalina; Bower, Deborah S; Stockwell, Michelle P; Clulow, Simon; Clulow, John; Mahony, Michael J

2016-08-01

Ontogenetic changes in disease susceptibility have been demonstrated in many vertebrate taxa, as immature immune systems and limited prior exposure to pathogens can place less developed juveniles at a greater disease risk. By causing the disease chytridiomycosis, Batrachochytrium dendrobatidis (Bd) infection has led to the decline of many amphibian species. Despite increasing knowledge on how Bd varies in its effects among species, little is known on the interaction between susceptibility and development within host species. We compared the ontogenetic susceptibility of post-metamorphic green and golden bell frogs Litoria aurea to chytridiomycosis by simultaneously measuring three host-pathogen responses as indicators of the development of the fungus-infection load, survival rate, and host immunocompetence-following Bd exposure in three life stages (recently metamorphosed juveniles, subadults, adults) over 95 days. Frogs exposed to Bd as recently metamorphosed juveniles acquired higher infection loads and experienced lower immune function and lower survivorship than subadults and adults, indicating an ontogenetic decline in chytridiomycosis susceptibility. By corresponding with an intrinsic developmental maturation in immunocompetence seen in uninfected frogs, we suggest these developmental changes in host susceptibility in L. aurea may be immune mediated. Consequently, the physiological relationship between ontogeny and immunity may affect host population structure and demography through variation in life stage survival, and understanding this can shape management targets for effective amphibian conservation.

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion.

PubMed

Mailänder-Sánchez, Daniela; Braunsdorf, Christina; Grumaz, Christian; Müller, Christoph; Lorenz, Stefan; Stevens, Philip; Wagener, Jeanette; Hebecker, Betty; Hube, Bernhard; Bracher, Franz; Sohn, Kai; Schaller, Martin

2017-01-01

Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.

Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb® sorbent porous polymer beads

PubMed Central

Ruggeberg, Karl-Gustav; O’Sullivan, Pamela; Guliashvili, Tamaz; Scheirer, Andrew R.; Golobish, Thomas D.; Capponi, Vincent J.; Chan, Phillip P.

2018-01-01

Objective Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system. Measurements and main results Purified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead) device in vitro. Except for the TNF-α trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent. Conclusions This study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions. PMID:29370247

Telling Your Partner You Have an STD

MedlinePlus

... STD after a confirmed diagnosis may be a criminal offense in some states. Some STDs can affect fertility later in life if they're not treated early on. Some STDs can cause life-threatening infections, especially if they're not ...

Insights into virulence factors determining the pathogenicity of Cronobacter sakazakii.

PubMed

Singh, Niharika; Goel, Gunjan; Raghav, Mamta

2015-01-01

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

Insights into virulence factors determining the pathogenicity of Cronobacter sakazakii

PubMed Central

Singh, Niharika; Goel, Gunjan; Raghav, Mamta

2015-01-01

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

Biggest Threats

MedlinePlus

... Resistant Salmonella Serotype Typhi Salmonella serotype Typhi causes typhoid fever, a potentially life-threatening disease. People with typhoid fever usually have a high fever, abdominal pain, and ...

Severe sepsis facilitates intestinal colonization by extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and transfer of the SHV-18 resistance gene to Escherichia coli during antimicrobial treatment.

PubMed

Guan, Jun; Liu, Shaoze; Lin, Zhaofen; Li, Wenfang; Liu, Xuefeng; Chen, Dechang

2014-01-01

Infections caused by multidrug-resistant pathogens are frequent and life threatening in critically ill patients. To investigate whether severe sepsis affects gut colonization by resistant pathogens and genetic exchange between opportunistic pathogens, we tested the intestinal-colonization ability of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain carrying the SHV-18 resistance gene and the transfer ability of the resistance gene to endogenous Escherichia coli under ceftriaxone treatment in rats with burn injury only or severe sepsis induced by burns plus endotoxin exposure. Without ceftriaxone treatment, the K. pneumoniae strain colonized the intestine in both septic and burned rats for a short time, with clearance occurring earlier in burn-only rats but never in sham burn rats. In both burned and septic rats, the colonization level of the challenge strain dropped at the beginning and then later increased during ceftriaxone treatment, after which it declined gradually. This pattern coincided with the change in resistance of K. pneumoniae to ceftriaxone during and after ceftriaxone treatment. Compared with burn-only injury, severe sepsis had a more significant effect on the change in antimicrobial resistance to ceftriaxone. Only in septic rats was the resistance gene successfully transferred from the challenge strain to endogenous E. coli during ceftriaxone treatment; the gene persisted for at least 4 weeks after ceftriaxone treatment. We concluded that severe sepsis can facilitate intestinal colonization by an exogenous resistant pathogen and the transfer of the resistance gene to a potential endogenous pathogen during antimicrobial treatment.

Succinylome Analysis Reveals the Involvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis*

PubMed Central

Yang, Mingkun; Wang, Yan; Chen, Ying; Cheng, Zhongyi; Gu, Jing; Deng, Jiaoyu; Bi, Lijun; Chen, Chuangbin; Mo, Ran; Wang, Xude; Ge, Feng

2015-01-01

Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, remains one of the most prevalent human pathogens and a major cause of mortality worldwide. Metabolic network is a central mediator and defining feature of the pathogenicity of Mtb. Increasing evidence suggests that lysine succinylation dynamically regulates enzymes in carbon metabolism in both bacteria and human cells; however, its extent and function in Mtb remain unexplored. Here, we performed a global succinylome analysis of the virulent Mtb strain H37Rv by using high accuracy nano-LC-MS/MS in combination with the enrichment of succinylated peptides from digested cell lysates and subsequent peptide identification. In total, 1545 lysine succinylation sites on 626 proteins were identified in this pathogen. The identified succinylated proteins are involved in various biological processes and a large proportion of the succinylation sites are present on proteins in the central metabolism pathway. Site-specific mutations showed that succinylation is a negative regulatory modification on the enzymatic activity of acetyl-CoA synthetase. Molecular dynamics simulations demonstrated that succinylation affects the conformational stability of acetyl-CoA synthetase, which is critical for its enzymatic activity. Further functional studies showed that CobB, a sirtuin-like deacetylase in Mtb, functions as a desuccinylase of acetyl-CoA synthetase in in vitro assays. Together, our findings reveal widespread roles for lysine succinylation in regulating metabolism and diverse processes in Mtb. Our data provide a rich resource for functional analyses of lysine succinylation and facilitate the dissection of metabolic networks in this life-threatening pathogen. PMID:25605462

Integrated inference and evaluation of host–fungi interaction networks

PubMed Central

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

An HPLC-MS Characterization of the Changes in Sweet Orange Leaf Metabolite Profile following Infection by the Bacterial Pathogen Canditatus Liberibacter asiaticus

USDA-ARS?s Scientific Manuscript database

Huanglonbing1 (HLB) presumably caused by Canditatus Liberibacter asiaticus (Clas) threatens the commercial U.S. citrus crop of an annual value of $3 billion. The earliest significant differences between the metabolomes of leaves from greenhouse-grown sweet orange trees infected with Clas and of heal...

Genomic analysis of a novel gene conferring resistance to Ug99 stem rust in Triticum turgidum ssp. dicoccum

USDA-ARS?s Scientific Manuscript database

Wheat production is threatened by the disease stem rust, which is caused by the biotrophic fungal pathogen Puccinia graminis Pers.:Pers. f. sp. tritici (Pgt). Among all known Pgt races, TTKSK (Ug99) and TRTTF are significant threats to North American wheat production due to their virulence against f...

Phytosanitation Methods Influence Posttreatment Colonization of Juglans nigra Logs by Pityophthorus juglandis (Coleoptera: Curculionidae: Scolytinae)

Treesearch

J. Audley; A. E. Mayfield; S. W. Myers; A. Taylor; W. E. Klingeman

2015-01-01

Several North American walnut species (Juglans spp.) are threatened by thousand cankers disease which is caused by the walnut twig beetle (Pityophthorus juglandis Blackman) and its associated fungal plant pathogen, Geosmithia morbida M. Kolarý´k, E. Freeland, C. Utley and N. Tisserat sp. nov. Spread of this...

A bioclimatic approach to predict global regions with suitable climate space for Puccina psidii

Treesearch

J. W. Hanna; R. N. Graca; M. -S. Kim; A. L. Ross-Davis; R. D. Hauff; J. W. Uchida; C. Y. Kadooka; M. B. Rayamajhi; M. Arguedas Gamboa; D. J. Lodge; R. Medel Medel-Ortiz; A. Lopez Ramirez; P. G. Cannon; A. C. Alfenas; N. B. Klopfenstein

2012-01-01

Puccinia psidii, the cause of eucalypt-guava-'ohi'a-myrtle rust, can infect diverse plants within the Myrtaceae, and this rust pathogen has the potential to threaten numerous forest ecosystems worldwide. Known occurrence records from Brazil, Uruguay, Paraguay, Costa Rica, USA (Hawaii, Florida, and Puerto Rico), and Japan were used to develop bioclimatic...

Distinctive expansion of gene families associated with plant cell wall degradation, secondary metabolism, and nutrient uptake in the genomes of grapevine trunk pathogens

USDA-ARS?s Scientific Manuscript database

Trunk diseases threaten the longevity and productivity of grapevines in all viticulture production systems. They are caused by distantly-related fungi that form chronic wood infections, but variation in wood-decay abilities and production of phytotoxic compounds are thought to contribute to their un...

White pine blister rust resistance in limber pine: Evidence for a major gene

Treesearch

A. W. Schoettle; R. A. Sniezko; A. Kegley; K. S. Burns

2014-01-01

Limber pine (Pinus flexilis) is being threatened by the lethal disease white pine blister rust caused by the non-native pathogen Cronartium ribicola. The types and frequencies of genetic resistance to the rust will likely determine the potential success of restoration or proactive measures. These first extensive inoculation trials using individual tree seed collections...

Temporal association between land-based runoff events and California sea otter (Enhydra lutris nereis) protozoal mortalities.

PubMed

Shapiro, Karen; Miller, Melissa; Mazet, Jonna

2012-04-01

Toxoplasma gondii and Sarcocystis neurona have caused significant morbidity and mortality in threatened Southern sea otters (Enhydra lutris nereis) along the central California coast. Because only terrestrial animals are known to serve as definitive hosts for T. gondii and S. neurona, infections in otters suggest a land to sea flow of these protozoan pathogens. To better characterize the role of overland runoff in delivery of terrestrially derived fecal pathogens to the near shore, we assessed the temporal association between indicators of runoff and the timing of sea otter deaths due to T. gondii and S. neurona. Sea otter stranding records 1998-2004, from Monterey and Estero bays were reviewed and cases identified for which T. gondii or S. neurona were determined to be a primary or contributing cause of death. Precipitation and stream flow data from both study sites were used as indicators of land-based runoff. Logistic regression was applied to determine if a temporal association could be detected between protozoal mortalities and runoff indicators that occur in the 2 mo preceding mortality events. A significant association was found between S. neurona otter deaths at Estero Bay and increased stream flow that occurred 30-60 days prior to mortality events. At this site, the cause of otter mortality following increased river flows was 12 times more likely to be S. neurona infection compared with nonprotozoal causes of death. There were no significant associations between the timing of T. gondii otter deaths and indicators of overland runoff. Our results indicate that the association between overland runoff and otter mortalities is affected by geography as well as parasite type, and highlight the complex mechanisms that influence transmission of terrestrially derived pathogens to marine wildlife. Policy and management practices that aim to mitigate discharges of contaminated overland runoff can aid conservation efforts by reducing pathogen pollution of coastal waters, which impacts the health of threatened marine wildlife and humans.

A peptide resource for the analysis of Staphylococcus aureus in host pathogen interaction studies

PubMed Central

Depke, Maren; Michalik, Stephan; Rabe, Alexander; Surmann, Kristin; Brinkmann, Lars; Jehmlich, Nico; Bernhardt, Jörg; Hecker, Michael; Wollscheid, Bernd; Sun, Zhi; Moritz, Robert L.; Völker, Uwe; Schmidt, Frank

2016-01-01

Staphylococcus aureus is an opportunistic human pathogen, which can cause life-threatening disease. Proteome analyses of the bacterium can provide new insights into its pathophysiology and important facets of metabolic adaptation and, thus, aid the recognition of targets for intervention. However, the value of such proteome studies increases with their comprehensiveness. We present an MS–driven, proteome-wide characterization of the strain S. aureus HG001. Combining 144 high precision proteomic data sets, we identified 19 109 peptides from 2088 distinct S. aureus HG001 proteins, which account for 72% of the predicted ORFs. Peptides were further characterized concerning pI, GRAVY, and detectability scores in order to understand the low peptide coverage of 8.7% (19 109 out of 220 245 theoretical peptides). The high quality peptide-centric spectra have been organized into a comprehensive peptide fragmentation library (SpectraST) and used for identification of S. aureus-typic peptides in highly complex host–pathogen interaction experiments, which significantly improved the number of identified S. aureus proteins compared to a MASCOT search. This effort now allows the elucidation of crucial pathophysiological questions in S. aureus-specific host–pathogen interaction studies through comprehensive proteome analysis. The S. aureus-specific spectra resource developed here also represents an important spectral repository for SRM or for data-independent acquisition MS approaches. All MS data have been deposited in the ProteomeXchange with identifier PXD000702 (http://proteomecentral.proteomexchange.org/dataset/PXD000702). PMID:26224020

A peptide resource for the analysis of Staphylococcus aureus in host-pathogen interaction studies.

PubMed

Depke, Maren; Michalik, Stephan; Rabe, Alexander; Surmann, Kristin; Brinkmann, Lars; Jehmlich, Nico; Bernhardt, Jörg; Hecker, Michael; Wollscheid, Bernd; Sun, Zhi; Moritz, Robert L; Völker, Uwe; Schmidt, Frank

2015-11-01

Staphylococcus aureus is an opportunistic human pathogen, which can cause life-threatening disease. Proteome analyses of the bacterium can provide new insights into its pathophysiology and important facets of metabolic adaptation and, thus, aid the recognition of targets for intervention. However, the value of such proteome studies increases with their comprehensiveness. We present an MS-driven, proteome-wide characterization of the strain S. aureus HG001. Combining 144 high precision proteomic data sets, we identified 19 109 peptides from 2088 distinct S. aureus HG001 proteins, which account for 72% of the predicted ORFs. Peptides were further characterized concerning pI, GRAVY, and detectability scores in order to understand the low peptide coverage of 8.7% (19 109 out of 220 245 theoretical peptides). The high quality peptide-centric spectra have been organized into a comprehensive peptide fragmentation library (SpectraST) and used for identification of S. aureus-typic peptides in highly complex host-pathogen interaction experiments, which significantly improved the number of identified S. aureus proteins compared to a MASCOT search. This effort now allows the elucidation of crucial pathophysiological questions in S. aureus-specific host-pathogen interaction studies through comprehensive proteome analysis. The S. aureus-specific spectra resource developed here also represents an important spectral repository for SRM or for data-independent acquisition MS approaches. All MS data have been deposited in the ProteomeXchange with identifier PXD000702 (http://proteomecentral.proteomexchange.org/dataset/PXD000702). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solar irradiance limits the long-term survival of Listeria monocytogenes in seawater.

PubMed

NicAogáin, K; Magill, D; O'Donoghue, B; Conneely, A; Bennett, C; O'Byrne, C P

2018-03-01

Seafood has often been implicated in outbreaks of food-borne illness caused by Listeria monocytogenes but the source of contamination is usually not known. In this study we investigated the possibility that this pathogen could survive in seawater for an extended time period. Freshly collected seawater samples were inoculated with 1 × 10 8  CFU per ml of L. monocytogenes EGD-e and survival was monitored by plate counting for up to 25 days. When incubated in the dark, either at ambient temperatures (4-14°C) or at 16°C, >10 4  CFU per ml survivors were present after 25 days. However, when the seawater cell suspensions were exposed to ambient light (solar irradiation) and temperatures, L. monocytogenes lost viability rapidly and no survivors could be detected after the 80 h time point. Both UV-A and visible light in the blue region of the spectrum (470 nm) were found to contribute to this effect. The stress inducible sigma factor σ B was found to play a role in survival of L. monocytogenes in seawater. Together these data demonstrate that solar irradiation is a critical determinant of L. monocytogenes survival in marine environments. The data further suggest the possibility of controlling this food-borne pathogen in food-processing environments using visible light. Listeria monocytogenes is a food-borne bacterial pathogen capable of causing the life-threatening infection, listeriosis. In seafood the route of contamination from the environment is often not well understood as this pathogen is not generally thought to survive well in seawater. Here we provide evidence that L. monocytogenes is capable of surviving for long periods of time in seawater when light is excluded. Sunlight is demonstrated to have a significant effect on the survival of this pathogen in seawater, and both visible (470 nm) and UV-A light are shown to contribute to this effect. © 2017 The Society for Applied Microbiology.

Hypothyroidism

MedlinePlus

... thyroid causes high levels of “bad” (LDL) cholesterol. Mental health issues. Depression that occurs with hypothyroidism can worsen over time. Myxedema. A rare, life-threatening condition. Symptoms are ...

Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions.

PubMed

Kidane, Yared H; Lawrence, Christopher; Murali, T M

2013-10-07

Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host's tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host's tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants. In this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans. Our computational approaches and methodologies described here can now be applied to newly generated or expanded data sets for further elucidation of additional drug targets. Moreover, identified immunomodulators may be used to generate experimentally testable hypotheses that could help in the discovery of broad-spectrum immunotherapeutic interventions. All of our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc.

Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions

PubMed Central

2013-01-01

Background Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host’s tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host’s tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants. Results In this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans. Conclusions Our computational approaches and methodologies described here can now be applied to newly generated or expanded data sets for further elucidation of additional drug targets. Moreover, identified immunomodulators may be used to generate experimentally testable hypotheses that could help in the discovery of broad-spectrum immunotherapeutic interventions. All of our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc PMID:24099000

Genetic susceptibility to Candida infections

PubMed Central

Smeekens, Sanne P; van de Veerdonk, Frank L; Kullberg, Bart Jan; Netea, Mihai G

2013-01-01

Candida spp. are medically important fungi causing severe mucosal and life-threatening invasive infections, especially in immunocompromised hosts. However, not all individuals at risk develop Candida infections, and it is believed that genetic variation plays an important role in host susceptibility. On the one hand, severe fungal infections are associated with monogenic primary immunodeficiencies such as defects in STAT1, STAT3 or CARD9, recently discovered as novel clinical entities. On the other hand, more common polymorphisms in genes of the immune system have also been associated with fungal infections such as recurrent vulvovaginal candidiasis and candidemia. The discovery of the genetic susceptibility to Candida infections can lead to a better understanding of the pathogenesis of the disease, as well as to the design of novel immunotherapeutic strategies. This review is part of the review series on host-pathogen interactions. See more reviews from this series. PMID:23629947

Adaptive Immunity to Fungi

PubMed Central

Wüthrich, Marcel; Deepe, George S.; Klein, Bruce

2013-01-01

Only a handful of the more than 100,000 fungal species on our planet cause disease in humans, yet the number of life-threatening fungal infections in patients has recently skyrocketed as a result of advances in medical care that often suppress immunity intensely. This emerging crisis has created pressing needs to clarify immune defense mechanisms against fungi, with the ultimate goal of therapeutic applications. Herein, we describe recent insights in understanding the mammalian immune defenses deployed against pathogenic fungi. The review focuses on adaptive immune responses to the major medically important fungi and emphasizes how dendritic cells and subsets in various anatomic compartments respond to fungi, recognize their molecular patterns, and signal responses that nurture and shape the differentiation of T cell subsets and B cells. Also emphasized is how the latter deploy effector and regulatory mechanisms that eliminate these nasty invaders while also constraining collateral damage to vital tissue. PMID:22224780

Genome Analysis of Streptococcus pyogenes Associated with Pharyngitis and Skin Infections

PubMed Central

Ibrahim, Joe; Eisen, Jonathan A.; Jospin, Guillaume; Coil, David A.; Khazen, Georges

2016-01-01

Streptococcus pyogenes is a very important human pathogen, commonly associated with skin or throat infections but can also cause life-threatening situations including sepsis, streptococcal toxic shock syndrome, and necrotizing fasciitis. Various studies involving typing and molecular characterization of S. pyogenes have been published to date; however next-generation sequencing (NGS) studies provide a comprehensive collection of an organism’s genetic variation. In this study, the genomes of nine S. pyogenes isolates associated with pharyngitis and skin infection were sequenced and studied for the presence of virulence genes, resistance elements, prophages, genomic recombination, and other genomic features. Additionally, a comparative phylogenetic analysis of the isolates with global clones highlighted their possible evolutionary lineage and their site of infection. The genomes were found to also house a multitude of features including gene regulation systems, virulence factors and antimicrobial resistance mechanisms. PMID:27977735

Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae*

PubMed Central

Rego, Sara; Heal, Timothy J.; Pidwill, Grace R.; Till, Marisa; Robson, Alice; Lamont, Richard J.; Sessions, Richard B.; Jenkinson, Howard F.; Race, Paul R.; Nobbs, Angela H.

2016-01-01

Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans. Complementary crystallographic and biophysical characterization of BspA reveal a novel β-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections. PMID:27311712

Structure-Based Approach to the Development of Potent and Selective Inhibitors of Dihydrofolate Reductase from Cryptosporidium

PubMed Central

Bolstad, David B.; Bolstad, Erin S. D.; Frey, Kathleen M.; Wright, Dennis L.; Anderson, Amy C.

2008-01-01

Cryptosporidiosis is an emerging infectious disease that can be life-threatening in an immune-compromised individual and causes gastrointestinal distress lasting up to 2 weeks in an immune-competent individual. There are few therapeutics available for effectively treating this disease. We have been exploring dihydrofolate reductase (DHFR) as a potential target in Cryptosporidium. On the basis of the structure of the DHFR enzyme from C. hominis, we have developed a novel scaffold that led to the discovery of potent (38 nM) and efficient inhibitors of this enzyme. Recently, we have advanced these inhibitors to the next stage of development. Using the structures of both the protozoal and human enzymes, we have developed inhibitors with nanomolar potency (1.1 nM) against the pathogenic enzyme and high levels (1273-fold) of selectivity over the human enzyme. PMID:18834108

Rhodotorula fungemia of an intensive care unit patient and review of published cases.

PubMed

Spiliopoulou, Anastasia; Anastassiou, Evangelos D; Christofidou, Myrto

2012-10-01

Rhodotorula species are commensal yeasts that have emerged as a cause of life-threatening fungemia in severely immunocompromised patients. A case of Rhodotorula mucilaginosa fungemia in a 48-year-old woman that had undergone consecutive abdominal surgeries due to ovarian cancer and bowel necrosis while she was receiving fluconazole prophylaxis is presented. Several risk factors were identified such as presence of central venous catheters, solid organ neoplasm, abdominal surgery and administration of antibiotics. Identification was performed using commercial systems. The yeast was resistant to fluconazole, posaconazole and voriconazole and to echinocandins, whereas MIC to amphotericin B was 1.5 mg/L. Furthermore, published cases of Rhodotorula spp fungemia during the last decade are reviewed. In conclusion, Rhodotorula spp must be considered a potential pathogen in patients with immunosupression and central venous catheters. Correct identification is mandatory for appropriate management, as Rhodotorula spp are resistant to antifungal agents, such as fluconazole and echinocandins.

Synergistic Effects and Mechanisms of Budesonide in Combination with Fluconazole against Resistant Candida albicans.

PubMed

Li, Xiuyun; Yu, Cuixiang; Huang, Xin; Sun, Shujuan

2016-01-01

Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases in the clinic. The emergence of drug resistance in Candida albicans has become a noteworthy phenomenon due to the extensive use of antifungal agents and the development of biofilms. This study showed that budesonide potentiates the antifungal effect of fluconazole against fluconazole-resistant Candida albicans strains both in vitro and in vivo. In addition, our results demonstrated, for the first time, that the combination of fluconazole and budesonide can reverse the resistance of Candida albicans by inhibiting the function of drug transporters, reducing the formation of biofilms, promoting apoptosis and inhibiting the activity of extracellular phospholipases. This is the first study implicating the effects and mechanisms of budesonide against Candida albicans alone or in combination with fluconazole, which may ultimately lead to the identification of new potential antifungal targets.

Interference of Aspergillus fumigatus with the immune response.

PubMed

Heinekamp, Thorsten; Schmidt, Hella; Lapp, Katrin; Pähtz, Vera; Shopova, Iordana; Köster-Eiserfunke, Nora; Krüger, Thomas; Kniemeyer, Olaf; Brakhage, Axel A

2015-03-01

Aspergillus fumigatus is a saprotrophic filamentous fungus and also the most prevalent airborne fungal pathogen of humans. Depending on the host's immune status, the variety of diseases caused by A. fumigatus ranges from allergies in immunocompetent hosts to life-threatening invasive infections in patients with impaired immunity. In contrast to the majority of other Aspergillus species, which are in most cases nonpathogenic, A. fumigatus features an armory of virulence determinants to establish an infection. For example, A. fumigatus is able to evade the human complement system by binding or degrading complement regulators. Furthermore, the fungus interferes with lung epithelial cells, alveolar macrophages, and neutrophil granulocytes to prevent killing by these immune cells. This chapter summarizes the different strategies of A. fumigatus to manipulate the immune response. We also discuss the potential impact of recent advances in immunoproteomics to improve diagnosis and therapy of an A. fumigatus infection.

Early pneumopericardium after heart transplantation.

PubMed

Duero Posada, Juan G; Moayedi, Yasbanoo; Alhussein, Mosaad; Bunce, Paul E; Yau, Terrence M; Ross, Heather J

2018-02-01

A 60-year-old woman with a history of dilated cardiomyopathy underwent heart transplantation. One month post discharge, she presented to clinic with low-grade fever and productive cough. Her chest radiograph showed air-fluid levels in the pericardial silhouette. Transthoracic echocardiogram showed a large complex pericardial collection with no evidence of cardiac tamponade. The patient was urgently taken to the operating room for exploration. A large "egg-shaped" mass in the pericardium measuring 10 × 12 cm with gaseous material was aspirated. As the posterior wall of the mass was firmly adhered to the right atrium, the capsule was incompletely excised. We present the case of a potentially life-threatening complication post transplantation that required surgical debridement and life-long antibiotic suppressive therapy. To our knowledge, this is the first report of purulent pericardial collection caused by Enterobacter cancerogenous. Further research is required to better understand the biology of this microorganism and the role it may play as a pathogen in immunocompromised patients following solid organ transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Haemorrhagic septicaemia in a pig caused by extraintestinal pathogenic Escherichia coli (ExPEC) as a differential diagnosis in classical swine fever--case report and review of the literature].

PubMed

Reiner, Gerald; von Berg, Stephan; Hillen, Sonja; Clemens, Nina; Huisinger, Maike; Burkhardt, Eberhard; Weiss, Reinhardt; Reinacher, Manfred

2010-01-01

Domestic pig herds in some regions of Germany are permanently threatened by Classical Swine Fever. In the case of suspicion, a series of infectious and non infectious causes has to be excluded. The present paper describes a case of Escherichia coli septicaemia, with clinical and pathological symptoms that could not be differentiated from European or African Swine Fever. The E. coli strain could not be classified by standard serotyping. Virulence factors common for ETEC (enterotoxic E. coli) or EDEC (edema-disease E. coli) were not detected. Instead, we found P-fimbriae and aerobactin, thus characterising this strain as an extraintestinal pathogenic strain. Such strains have sporadicly been reported as the cause of septicaemia in piglets or weaners, but the present case is the first report of an E. coli-associated septicaemia in an adult pig. This case shows that extraintestinal pathogenic E. coli can be the cause of severe septicaemia and haemorrhagia. They thus have to be considered as a further differential diagnosis in swine fever.

Prey choice and habitat use drive sea otter pathogen exposure in a resource-limited coastal system

USGS Publications Warehouse

Johnson, Christine K.; Tinker, M. Tim; Estes, James A.; Conrad, Patricia A.; Staedler, Michelle M.; Miller, Melissa A.; Jessup, David A.; Mazet, Jonna A.K.

2014-01-01

The processes promoting disease in wild animal populations are highly complex, yet identifying these processes is critically important for conservation when disease is limiting a population. By combining field studies with epidemiologic tools, we evaluated the relationship between key factors impeding southern sea otter (Enhydra lutris nereis) population growth: disease and resource limitation. This threatened population has struggled to recover despite protection, so we followed radio-tagged sea otters and evaluated infection with 2 disease-causing protozoal pathogens, Toxoplasma gondii and Sarcocystis neurona, to reveal risks that increased the likelihood of pathogen exposure. We identified patterns of pathogen infection that are linked to individual animal behavior, prey choice, and habitat use. We detected a high-risk spatial cluster of S. neurona infections in otters with home ranges in southern Monterey Bay and a coastal segment near San Simeon and Cambria where otters had high levels of infection with T. gondii. We found that otters feeding on abalone, which is the preferred prey in a resource-abundant marine ecosystem, had a very low risk of infection with either pathogen, whereas otters consuming small marine snails were more likely to be infected with T. gondii. Individual dietary specialization in sea otters is an adaptive mechanism for coping with limited food resources along central coastal California. High levels of infection with protozoal pathogens may be an adverse consequence of dietary specialization in this threatened species, with both depleted resources and disease working synergistically to limit recovery.

Prey choice and habitat use drive sea otter pathogen exposure in a resource-limited coastal system

PubMed Central

Johnson, Christine K.; Tinker, Martin T.; Estes, James A.; Conrad, Patricia A.; Staedler, Michelle; Miller, Melissa A.; Jessup, David A.; Mazet, Jonna A. K.

2009-01-01

The processes promoting disease in wild animal populations are highly complex, yet identifying these processes is critically important for conservation when disease is limiting a population. By combining field studies with epidemiologic tools, we evaluated the relationship between key factors impeding southern sea otter (Enhydra lutris nereis) population growth: disease and resource limitation. This threatened population has struggled to recover despite protection, so we followed radio-tagged sea otters and evaluated infection with 2 disease-causing protozoal pathogens, Toxoplasma gondii and Sarcocystis neurona, to reveal risks that increased the likelihood of pathogen exposure. We identified patterns of pathogen infection that are linked to individual animal behavior, prey choice, and habitat use. We detected a high-risk spatial cluster of S. neurona infections in otters with home ranges in southern Monterey Bay and a coastal segment near San Simeon and Cambria where otters had high levels of infection with T. gondii. We found that otters feeding on abalone, which is the preferred prey in a resource-abundant marine ecosystem, had a very low risk of infection with either pathogen, whereas otters consuming small marine snails were more likely to be infected with T. gondii. Individual dietary specialization in sea otters is an adaptive mechanism for coping with limited food resources along central coastal California. High levels of infection with protozoal pathogens may be an adverse consequence of dietary specialization in this threatened species, with both depleted resources and disease working synergistically to limit recovery. PMID:19164513

CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro

PubMed Central

Ngo Ndjom, Colette G.; Kantor, Lindsay V.; Jones, Harlan P.

2017-01-01

Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28–50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH) in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH–pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP), sepsis and septic shock. PMID:28690980

A mouse model for the human pathogen Salmonella Typhi

PubMed Central

Song, Jeongmin; Willinger, Tim; Rongvaux, Anthony; Eynon, Elizabeth E.; Stevens, Sean; Manz, Markus G.; Flavell, Richard A.; Galán, Jorge E.

2010-01-01

SUMMARY Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, a life-threatening disease of humans. The lack of an animal model due to S. typhi's strict human host specificity has been a significant obstacle in the understanding of its pathogenesis and the development of a safe and effective vaccine against typhoid fever. We report here the development of a mouse model for S. Typhi infection. We showed that immunodeficient Rag2 -/- γc -/- mice engrafted with human fetal liver hematopoietic stem and progenitor cells were able to support S. Typhi replication and persistent infection. A S. Typhi strain carrying a mutation in a gene required for its virulence in humans was not able to replicate in these humanized mice. In contrast, another mutant strain unable to produce the recently identified typhoid toxin, exhibited increased replication suggesting a potential role for this toxin in the establishment of persistent infection. Furthermore, infected animals mounted a human innate and adaptive immune response to S. Typhi resulting in the production of cytokines and pathogen-specific antibodies. These results therefore indicate that this animal model can be used to study S. Typhi pathogenesis and to evaluate potential vaccine candidates against typhoid fever. PMID:20951970

A brief review of moxifloxacin in the treatment of elderly patients with community-acquired pneumonia (CAP)

PubMed Central

Ferrara, Anna M

2007-01-01

Community-acquired pneumonia (CAP) remains a common cause of morbidity and a potentially life-threatening illness throughout the world mainly in elderly patients. Initial antibacterial treatment, usually empirical, should be as effective as possible in order to assure rapid clinical resolution and reduce high rates of hospitalization and mortality especially affecting aged patients. New fluoroquinolones with potent activity against the most important respiratory pathogens including Streptococcus pneumoniae, a key pathogen mainly in old patients with CAP, have been recently suggested by several international guidelines as monotherapy for the treatment of most CAP patient categories. Among newer derivatives, moxifloxacin, an advanced generation 8-methoxy quinolone, has demonstrated good clinical and bacteriological efficacy in large, well designed clinical trials both in adults and old patients with CAP, achieving also in aged people efficacy comparable with that of standard treatments. Good pharmacokinetic characteristics such as excellent penetration into respiratory tract tissues and fluids, optimal bioavailability, simplicity of once-daily dosing, and good tolerability, represent potential advantages of moxifloxacin over other therapies. In addition, primarily due to a shorter length of hospital stay, moxifloxacin has been shown to save costs compared with standard therapy. PMID:18044134

BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.

PubMed

Taylor, Raymond; Kotian, Pravin; Warren, Travis; Panchal, Rekha; Bavari, Sina; Julander, Justin; Dobo, Sylvia; Rose, Angela; El-Kattan, Yahya; Taubenheim, Brian; Babu, Yarlagadda; Sheridan, William P

2016-01-01

The adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.

A novel small molecule methyltransferase is important for virulence in Candida albicans.

PubMed

Lissina, Elena; Weiss, David; Young, Brian; Rella, Antonella; Cheung-Ong, Kahlin; Del Poeta, Maurizio; Clarke, Steven G; Giaever, Guri; Nislow, Corey

2013-12-20

Candida albicans is an opportunistic pathogen capable of causing life-threatening infections in immunocompromised individuals. Despite its significant health impact, our understanding of C. albicans pathogenicity is limited, particularly at the molecular level. One of the largely understudied enzyme families in C. albicans are small molecule AdoMet-dependent methyltransferases (smMTases), which are important for maintenance of cellular homeostasis by clearing toxic chemicals, generating novel cellular intermediates, and regulating intra- and interspecies interactions. In this study, we demonstrated that C. albicans Crg1 (CaCrg1) is a bona fide smMTase that interacts with the toxin in vitro and in vivo. We report that CaCrg1 is important for virulence-related processes such as adhesion, hyphal elongation, and membrane trafficking. Biochemical and genetic analyses showed that CaCrg1 plays a role in the complex sphingolipid pathway: it binds to exogenous short-chain ceramides in vitro and interacts genetically with genes of glucosylceramide pathway, and the deletion of CaCRG1 leads to significant changes in the abundance of phytoceramides. Finally we found that this novel lipid-related smMTase is required for virulence in the waxmoth Galleria mellonella, a model of infection.

Suspension of oysters reduces the populations of Vibrio parahaemolyticus and Vibrio vulnificus.

PubMed

Cole, K M; Supan, J; Ramirez, A; Johnson, C N

2015-09-01

Vibrio parahaemolyticus (Vp) and Vibrio vulnificus (Vv) are associated with the consumption of raw oysters and cause illnesses ranging from simple gastroenteritis to life-threatening septicaemia. These halophilic bacteria are frequently found in marine and estuarine systems, accumulating within the tissues of a number of aquatic organisms and passing on to humans after consumption, through contaminated water, or via open wounds. As benthic organisms capable of filtering 40 gallons of water per hour, sediment is an important source of potentially pathogenic vibrios in oysters destined for raw consumption. This research used off-bottom oyster culture to reduce vibrio concentrations in oysters. Colony hybridization was used to enumerate Vp and Vv in bottom and suspended oysters. Vv and Vp concentrations were generally lower in oysters suspended off-bottom, and suspension decreased vibrio loads in oysters by an average of 13%. Suspension of oysters reduced vibrio concentrations. This study found that oyster suspension significantly reduced some populations of potentially pathogenic vibrios. These results indicate that oyster suspension could be a viable approach for preharvest treatment to reduce illness in consumers of raw oysters. © 2015 The Society for Applied Microbiology.

Interactions of Aspergillus fumigatus Conidia with Airway Epithelial Cells: A Critical Review

PubMed Central

Croft, Carys A.; Culibrk, Luka; Moore, Margo M.; Tebbutt, Scott J.

2016-01-01

Aspergillus fumigatus is an environmental filamentous fungus that also acts as an opportunistic pathogen able to cause a variety of symptoms, from an allergic response to a life-threatening disseminated fungal infection. The infectious agents are inhaled conidia whose first point of contact is most likely to be an airway epithelial cell (AEC). The interaction between epithelial cells and conidia is multifaceted and complex, and has implications for later steps in pathogenesis. Increasing evidence has demonstrated a key role for the airway epithelium in the response to respiratory pathogens, particularly at early stages of infection; therefore, elucidating the early stages of interaction of conidia with AECs is essential to understand the establishment of infection in cohorts of at-risk patients. Here, we present a comprehensive review of the early interactions between A. fumigatus and AECs, including bronchial and alveolar epithelial cells. We describe mechanisms of adhesion, internalization of conidia by AECs, the immune response of AECs, as well as the role of fungal virulence factors, and patterns of fungal gene expression characteristic of early infection. A clear understanding of the mechanisms involved in the early establishment of infection by A. fumigatus could point to novel targets for therapy and prophylaxis. PMID:27092126

Structures of Cryptococcus neoformans Protein Farnesyltransferase Reveal Strategies for Developing Inhibitors That Target Fungal Pathogens

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

Hast, Michael A.; Nichols, Connie B.; Armstrong, Stephanie M.

Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, including AIDS patients and transplant recipients. Few antifungals can treat C. neoformans infections, and drug resistance is increasing. Protein farnesyltransferase (FTase) catalyzes post-translational lipidation of key signal transduction proteins and is essential in C. neoformans. We present a multidisciplinary study validating C. neoformans FTase (CnFTase) as a drug target, showing that several anticancer FTase inhibitors with disparate scaffolds can inhibit C. neoformans and suggesting structure-based strategies for further optimization of these leads. Structural studies are an essential element for species-specific inhibitor development strategies by revealing similarities andmore » differences between pathogen and host orthologs that can be exploited. We, therefore, present eight crystal structures of CnFTase that define the enzymatic reaction cycle, basis of ligand selection, and structurally divergent regions of the active site. Crystal structures of clinically important anticancer FTase inhibitors in complex with CnFTase reveal opportunities for optimization of selectivity for the fungal enzyme by modifying functional groups that interact with structurally diverse regions. A substrate-induced conformational change in CnFTase is observed as part of the reaction cycle, a feature that is mechanistically distinct from human FTase. Our combined structural and functional studies provide a framework for developing FTase inhibitors to treat invasive fungal infections.« less

Infections in immunocompromised patients. II. Established therapy and its limitations.

PubMed

Periti, P; Mazzei, T

1985-01-01

Diseases affecting host defense mechanisms include neutropenia, aplastic anemia, leukemia, lymphocytopenia (B- and T-lymphocyte abnormalities), deficiencies of complement, splenectomy, diabetes mellitus, renal failure, and autoimmune diseases. Immunocompromised patients face frequent life-threatening complications of infections, particularly when they are hospitalized and receiving cytotoxic myelosuppressive drugs. Oral antimicrobial agents affect the flora of the host's alimentary tract, enhancing colonization by resistant, potentially pathogenic, strains and species, especially in a hospital environment. Nalidixic acid, oxolinic acid, pipemidic acid, polymyxins, co-trimoxazole, polyene antibiotics, and framycetin, which preserve anaerobic colon flora, do not affect the host's colonization resistance and can be given in oral doses high enough to suppress and clear susceptible potential pathogens from the intestinal tract. Such prophylactic treatment permits patients to stay hospitalized in ward conditions. In the compromised host who has fever and suspected septicemia, a decision concerning treatment should be made within an hour of notification of the patient's condition. In acute stages of life-threatening infection, the principal aim of antimicrobial chemotherapy is to provide the most potent treatment; at this stage, the accompanying side effects are less important. An essential component of therapy should be an aminoglycoside paired with a beta-lactam antibiotic. Because the incidence of staphylococcal resistance to antibiotics is high, preliminary sensitivity-testing is essential when staphylococcal sepsis threatens the life of a compromised host. Despite aggressive antibiotic therapy, more than half of immunocompromised patients and patients with severe underlying diseases die when gram-negative bacteria invade their blood. In these patients, medical or surgical removal of the septic focus is a major part of management, but plasma or plasma fractions should be given to correct hypovolemia, and an agent such as dopamine should be administered if volume replacement fails to restore adequate blood pressure. A high dose of corticosteroids should have a beneficial effect, and, for neutropenic patients with gram-negative bacteremia or fever, transfusion with functional neutrophils improves survival.

Gene conservation of Pinus aristata: a collection with ecological context for management today and resources for tomorrow

Treesearch

A.W. Schoettle

2017-01-01

Pinus aristata, Rocky Mountain bristlecone pine, has a narrow geographic and elevational distribution and is threatened by rapid climate change, the introduced pathogen Cronartium ribicola that causes white pine blister rust (WPBR), and bark beetles. The core distribution of P. aristata is near and at treeline in central and southern Colorado and...

Intestinal obstruction repair

MedlinePlus

... abdominal wall. This may be done using a colostomy , ileostomy , or mucous fistula. ... which may cause life-threatening problems Problems with colostomy or ileostomy Temporary paralysis (freezing up) of the ...

Differences in anxiety and depression between male and female caregivers of children with a disorder of sex development.

PubMed

Wolfe-Christensen, Cortney; Fedele, David A; Mullins, Larry L; Lakshmanan, Yegappan; Wisniewski, Amy B

2014-07-01

To examine whether male and female caregivers of children with a disorder of sex development (DSD) differ in levels of anxious and depressive symptoms. Participants included 80 caregivers (40 males, 40 females) of 40 children with a DSD. Children were categorized based on illness characteristics including ambiguous genitalia, life-threatening, and life-threatening with ambiguous genitalia. Caregivers completed measures of anxious and depressive symptoms. A significant caregiver × diagnosis interaction for anxious symptoms emerged, with male caregivers of children with both ambiguous genitalia and a life-threatening condition reporting significantly lower levels of anxious symptoms than female caregivers of the same children. The findings are surprising because of the low level of anxious symptoms reported by male caregivers of children with a complex DSD. It is possible that they have disengaged themselves from the child and/or diagnosis, causing their female counterparts to take on more responsibility.

Rash Decisions: An Approach to Dangerous Rashes Based on Morphology.

PubMed

Santistevan, Jamie; Long, Brit; Koyfman, Alex

2017-04-01

Rash is a common complaint in the emergency department. Many causes of rash are benign; however, some patients may have a life-threatening diagnosis. This review will present an algorithmic approach to rashes, focusing on life-threatening causes of rash in each category. Rash is common, with a wide range of etiologies. The differential is broad, consisting of many conditions that are self-resolving. However, several conditions associated with rash are life threatening. Several keys can be utilized to rapidly diagnose and manage these deadly rashes. Thorough history and physical examination, followed by consideration of red flags, are essential. This review focuses on four broad categories based on visual and tactile characteristic patterns of rashes: petechial/purpuric, erythematous, maculopapular, and vesiculobullous. Rashes in each morphologic group will be further categorized based on clinical features such as the presence or absence of fever and distribution of skin lesions. Rashes can be divided into petechial/purpuric, erythematous, maculopapular, and vesiculobullous. After this differentiation, the presence of fever and systemic signs of illness should be assessed. Through the breakdown of rashes into these classes, emergency providers can ensure deadly conditions are considered. Published by Elsevier Inc.

Comparing culture and molecular methods for the identification of microorganisms involved in necrotizing soft tissue infections.

PubMed

Rudkjøbing, Vibeke Børsholt; Thomsen, Trine Rolighed; Xu, Yijuan; Melton-Kreft, Rachael; Ahmed, Azad; Eickhardt, Steffen; Bjarnsholt, Thomas; Poulsen, Steen Seier; Nielsen, Per Halkjær; Earl, Joshua P; Ehrlich, Garth D; Moser, Claus

2016-11-08

Necrotizing soft tissue infections (NSTIs) are a group of infections affecting all soft tissues. NSTI involves necrosis of the afflicted tissue and is potentially life threatening due to major and rapid destruction of tissue, which often leads to septic shock and organ failure. The gold standard for identification of pathogens is culture; however molecular methods for identification of microorganisms may provide a more rapid result and may be able to identify additional microorganisms that are not detected by culture. In this study, tissue samples (n = 20) obtained after debridement of 10 patients with NSTI were analyzed by standard culture, fluorescence in situ hybridization (FISH) and multiple molecular methods. The molecular methods included analysis of microbial diversity by 1) direct 16S and D2LSU rRNA gene Microseq 2) construction of near full-length 16S rRNA gene clone libraries with subsequent Sanger sequencing for most samples, 3) the Ibis T5000 biosensor and 4) 454-based pyrosequencing. Furthermore, quantitative PCR (qPCR) was used to verify and determine the relative abundance of Streptococcus pyogenes in samples. For 70 % of the surgical samples it was possible to identify microorganisms by culture. Some samples did not result in growth (presumably due to administration of antimicrobial therapy prior to sampling). The molecular methods identified microorganisms in 90 % of the samples, and frequently detected additional microorganisms when compared to culture. Although the molecular methods generally gave concordant results, our results indicate that Microseq may misidentify or overlook microorganisms that can be detected by other molecular methods. Half of the patients were found to be infected with S. pyogenes, but several atypical findings were also made including infection by a) Acinetobacter baumannii, b) Streptococcus pneumoniae, and c) fungi, mycoplasma and Fusobacterium necrophorum. The study emphasizes that many pathogens can be involved in NSTIs, and that no specific "NSTI causing" combination of species exists. This means that clinicians should be prepared to diagnose and treat any combination of microbial pathogens. Some of the tested molecular methods offer a faster turnaround time combined with a high specificity, which makes supplemental use of such methods attractive for identification of microorganisms, especially for fulminant life-threatening infections such as NSTI.

Fatal BK virus pneumonia following stem cell transplantation.

PubMed

Akazawa, Y; Terada, Y; Yamane, T; Tanaka, S; Aimoto, M; Koh, H; Nakane, T; Koh, K-R; Nakamae, H; Ohsawa, M; Wakasa, K; Hino, M

2012-12-01

We report the case of a 39-year-old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV-associated late-onset hemorrhagic cystitis (HC) with long-term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late-onset HC, but BKV-associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients. © 2012 John Wiley & Sons A/S.

Chimpanzee adenoviral vectors as vaccines for outbreak pathogens

PubMed Central

2017-01-01

ABSTRACT The 2014–15 Ebola outbreak in West Africa highlighted the potential for large disease outbreaks caused by emerging pathogens and has generated considerable focus on preparedness for future epidemics. Here we discuss drivers, strategies and practical considerations for developing vaccines against outbreak pathogens. Chimpanzee adenoviral (ChAd) vectors have been developed as vaccine candidates for multiple infectious diseases and prostate cancer. ChAd vectors are safe and induce antigen-specific cellular and humoral immunity in all age groups, as well as circumventing the problem of pre-existing immunity encountered with human Ad vectors. For these reasons, such viral vectors provide an attractive platform for stockpiling vaccines for emergency deployment in response to a threatened outbreak of an emerging pathogen. Work is already underway to develop vaccines against a number of other outbreak pathogens and we will also review progress on these approaches here, particularly for Lassa fever, Nipah and MERS. PMID:29083948

Optical illusions and life-threatening traffic crashes: A perspective on aerial perspective.

PubMed

Redelmeier, Donald A; Raza, Sheharyar

2018-05-01

Aerial perspective illusion is a feature of visual perception where landscapes appear relatively close in clear light and distant in dim light. We hypothesized that bright sunlight might cause drivers to perceive distant terrain as relatively close and misinterpret the approach speed of surrounding landscape as unduly slow. This hypothesis would mean, in turn, that drivers in bright sunlight may underestimate their progress on the road, compensate by traveling at a faster baseline speed, and ultimately increase the prevailing risk of a life-threatening traffic crash. We conducted three pilot studies to illustrate how the illusion might contribute to a life- threatening traffic crash. The first illustration used a questionnaire to demonstrate that most respondents were mistaken when judging the distance between simple balls in different positions. The second illustration involved an experimental manipulation to assess whether aerial perspective influenced judgments about the relative positions of vehicles in traffic. The third illustration analyzed a segment of high-volume fast-speed traffic and found an increased frequency of speeding under bright sunlight. Together with past work based on the visual arts, these examples illustrate how an aerial perspective illusion can affect distance perception, may appear in realistic traffic situations, and could potentially contribute to the risk of a life-threatening traffic crash. An awareness of this hypothesis might lead to applications on how optical illusions could extend to everyday traffic and might potentially inform safety warnings to prevent life- threatening crashes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prevalence of epilepsy and seizure disorders as causes of apparent life- threatening event (ALTE) in children admitted to a tertiary hospital.

PubMed

Anjos, Alessandra Marques dos; Nunes, Magda Lahorgue

2009-09-01

To determine the prevalence and describe clinical characteristics of seizure disorders and epilepsy as causes of apparent life- threatening event (ALTE) in children admitted at the emergency and followed in a tertiary hospital. Cross-sectional study with prospective data collection using specific guidelines to determine the etiology of ALTE. During the study, 30 (4.2%) children admitted to the hospital had a diagnosis of ALTE. There was a predominance of males (73%) and term infants (70%). Neonatal neurological disorders and neuropsychomotor development delay were found respectively in 13.4% and 10% of the cases. Etiological investigation revealed that 50% of the cases were idiopathic, and 13.4% were caused by epilepsy or seizure disorders. Although all patients had recurrent ALTE events, epilepsy had not been previously suspected. Epilepsy should be included in the differential diagnosis of ALTE, particularly when events are recurrent.

Dengue fever (image)

MedlinePlus

Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

Quinine

MedlinePlus

... not been shown to be effective for this purpose, and may cause serious or life-threatening side ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

Fidaxomicin

MedlinePlus

... by Clostridium difficile (C. difficile; a type of bacteria that my cause severe or life-threatening diarrhea.) ... medications called macrolide antibiotics. It works by killing bacteria in the intestines.Fidaxomicin will not treat infections ...

Modulation of Pathogenic B Cells through Inhibition of Phosphatidylinositol 3-Kinases

DTIC Science & Technology

2015-10-01

SF298] Note: An abstract is required to be provided in Block 14 This proposal addresses the FY12 PRMRP topic area on lupus . Lupus is a life...threatening disease that primarily affects women. Lupus patients develop antibodies that recognize proteins made by the body. This leads to tissue damage and...susceptible to other types of infections. Lupus treatment could be improved by specifically targeting the B cells involved in making the “self” antibodies

Modulation of Pathogenic B Cells through Inhibition of Phosphatidylinositol 3-Kinases

DTIC Science & Technology

2014-10-01

SF298] Note: An abstract is required to be provided in Block 14 This proposal will address the FY12 PRMRP topic area on lupus . Lupus is a life...threatening disease that primarily affects women. Lupus patients develop antibodies that recognize proteins made by the body. This leads to tissue...susceptible to other types of infections. Lupus treatment could be improved by specifically targeting the B cells involved in making the “self

Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report

PubMed Central

2010-01-01

Introduction We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity. Case presentation As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region. Conclusion Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever. PMID:20525295

Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report.

PubMed

Ezzat, Rajan Fuad; Hussein, Hiwa A; Baban, Trifa Shawkat; Rashid, Abbas Tahir; Abdullah, Khaled Musttafa

2010-06-03

We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity. As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region. Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever.

Lactose Intolerance

MedlinePlus

... scientists identify cause, possible treatment for life-threatening gut condition Jun 29, 2017 An enzyme deficiency contributes ... Research & Funding Current Funding Opportunities Research Programs & Contacts Human Subjects Research Funding Process Research Training & Career Development ...

Barrett's Esophagus

MedlinePlus

... scientists identify cause, possible treatment for life-threatening gut condition Jun 29, 2017 An enzyme deficiency contributes ... Research & Funding Current Funding Opportunities Research Programs & Contacts Human Subjects Research Funding Process Research Training & Career Development ...

AIDS (image)

MedlinePlus

AIDS (acquired immune deficiency syndrome) is caused by HIV (human immunodeficiency virus), and is a syndrome that ... life-threatening illnesses. There is no cure for AIDS, but treatment with antiviral medicine can suppress symptoms. ...

Rupture of an ascending and descending thoracic aortic aneurysm causing tension hemothorax: a case report.

PubMed

Pizon, Anthony; Bissell, Brad J; Gilmore, Nathan

2012-10-01

A ruptured thoracic aortic aneurysm is a life-threatening condition and can lead to a tension hemothorax. To describe the presentation and management of a case of a tension hemothorax. An 84-year-old woman presented in respiratory distress and was found to have a tension hemothorax. The cause was the rupture of an ascending and descending thoracic aortic aneurysm. She was managed with intubation, mechanical ventilation, and chest tube placement with stabilization. Definitive operative repair was deferred due to the patient's comorbidities and wishes of the family. A tension hemothorax can result from an ascending and descending thoracic aneurysm, as this case describes. Emergent therapy is necessary as this is a life-threatening condition. Copyright © 2012 Elsevier Inc. All rights reserved.

Microsurgical scalp reconstruction after a mountain lion attack.

PubMed

Hazani, Ron; Buntic, Rudolf F; Brooks, Darrell

2008-09-01

Mountain lion attacks on humans are rare and potentially fatal. Although few victims experience minor injuries, permanent disfigurement and disability is common among survivors of these assaults. Since 1986, a steady number of mountain lion attacks have been noted in California. We report a recent attack of a cougar on a couple hiking in California's Prairie Creek Redwoods State Park. The victim sustained a significant scalp injury that led to a life-threatening soft-tissue infection. We present an analysis of the injury pattern as it relates to the bite marks, the resulting degloving injury, and the surgical reconstruction. We also offer a current survey of the pathogens often found in cats' and mountain lions' bite wounds and the appropriate antibiotic treatment. Given the infrequency at which clinicians encounter mountain lion injuries, we recommend that after initial management and exclusion of life threatening injuries patients be transferred to a tertiary care facility capable of managing the various reconstructive challenges such as the one presented in this case.

Life-threatening hypersplenism due to idiopathic portal hypertension in early childhood: case report and review of the literature

PubMed Central

2010-01-01

Background Idiopathic portal hypertension (IPH) is a disorder of unknown etiology and is characterized clinically by portal hypertension, splenomegaly, and hypersplenism accompanied by pancytopenia. This study evaluates the pathogenic concept of the disease by a systematic review of the literature and illustrates novel pathologic and laboratory findings. Case Presentation We report the first case of uncontrolled splenic hyperperfusion and enlargement with subsequent hypersplenism leading to life-threatening complications of IPH in infancy and emergent splenectomy. Conclusions Our results suggest that splenic NO and VCAM-1, rather than ET-1, have a significant impact on the development of IPH, even at a very early stage of disease. The success of surgical interventions targeting the splenic hyperperfusion suggests that the primary defect in the regulation of splenic blood flow seems to be crucial for the development of IPH. Thus, beside other treatment options splenectomy needs to be considered as a prime therapeutic option for IPH. PMID:20961440

Prevention and control of enterohaemorrhagic Escherichia coli (EHEC) infections: memorandum from a WHO meeting. WHO Consultation on Prevention and Control of Enterohaemorrhagic Escherichia coli (EHEC) Infections.

PubMed Central

Reilly, A.

1998-01-01

Escherichia coli is a commonly occurring inhabitant of the intestine of humans and other animals, but there are several pathogenic types of E. coli which cause a variety of human diseases. One of these pathogenic types, E. coli O157:H7, belongs to the group of enterohaemorrhagic E. coli (EHEC) which produce potent toxins and cause a particularly severe form of disease, haemorrhagic colitis (HC). About 10% of patients with HC can go on to develop haemolytic uraemic syndrome (HUS), a life-threatening complication of E. coli O157:H7 infection that is characterized by acute renal failure, haemolytic anaemia, and thrombocytopenia. These sequelae are particularly serious in young children and older people. On average, 2-7% of patients with HUS die, but in some outbreaks among the elderly the mortality rate has been as high as 50%. This Memorandum reviews the growing importance of E. coli O157:H7 as a foodborne pathogen and reports on the issues of surveillance, outbreak investigation, and control strategies with respect to EHEC infections that were discussed at the WHO Consultation on Prevention and Control of EHEC Infections, held in Geneva on 28 April to 1 May 1997. Recommended measures for prevention and control include the following: use of potable water in food production; presentation of clean animals at slaughter; improved hygiene throughout the slaughter process; appropriate use of food processing measures; thorough cooking of foods; and the education of food handlers, abattoir workers, and farm workers on the principles and application of food hygiene. PMID:9744244

Interferon-γ promotes phagocytosis of Cryptococcus neoformans but not Cryptococcus gattii by murine macrophages.

PubMed

Ikeda-Dantsuji, Yurika; Ohno, Hideaki; Tanabe, Koichi; Umeyama, Takashi; Ueno, Keigo; Nagi, Minoru; Yamagoe, Satoshi; Kinjo, Yuki; Miyazaki, Yoshitsugu

2015-12-01

Among invasive fungal infections, cryptococcosis caused by inhalation of Cryptococcus neoformans or Cryptococcus gattii is particularly dangerous because it can disseminate to the central nervous system and cause life-threatening meningitis or meningoencephalitis. Previous reports described significant differences in the histopathological features of C. neoformans and C. gattii infection, such as greater pathogen proliferation and a limited macrophage response in mouse lung infected by C. gattii. To elucidate the difference in pathogenicity of these two Cryptococcus species, we investigated the interaction of C. neoformans and C. gattii with murine macrophages, the first line of host defense, by confocal laser microscopy. Only thin-capsulated, and not thick-capsulated C. neoformans and C. gattii were phagocytosed by macrophages. Preactivation with interferon-γ increased the phagocytic rate of thin-capsulated C. neoformans up to two-fold, but did not promote phagocytosis of thin-capsulated C. gattii. Lipopolysaccharide preactivation or Aspergillus fumigatus conidia co-incubation had no effect on internalization of thin-capsulated C. neoformans or C. gattii by macrophages. Phagocytosis of live thin-capsulated C. neoformans, but not that of live thin-capsulated C. gattii, induced interleukin-12 release from macrophages. However, phagocytosis of heat-killed or paraformaldehyde-fixed thin-capsulated C. neoformans did not increase IL-12 release, showing that the internalization of live yeast is important for initiating the immune response during C. neoformans-macrophage interactions. Our data suggest that macrophage response to C. gattii is limited compared with that to C. neoformans and that these results may partially explain the limited immune response and the greater pathogenicity of C. gattii. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Deaths from Necrotizing Fasciitis in the United States, 2003–2013

PubMed Central

Arif, N.; Yousfi, S.; Vinnard, C.

2017-01-01

SUMMARY Necrotizing fasciitis is a life-threatening infection requiring urgent surgical and medical therapy. Our objective was to estimate the mortality burden of necrotizing fasciitis in the United States, and to identify time trends in the incidence rate of necrotizing fasciitis-related mortality. We obtained data from the National Center for Health Statistics, which receives information from death certificates from all states, including demographic information and cause of death. The U.S. Multiple Cause of Death Files were searched from 2003 through 2013 for a listing of NF (ICD10 code M72.6) as either the underlying or contributing cause of death. We identified a total of 9,871 necrotizing fasciitis-related deaths in the U.S. between 2003 and 2013 (Figure 1), corresponding to a crude mortality rate of 4.8 deaths per 1,000,000 person-years, without a significant time trend. Compared to white individuals, the incidence rate of necrotizing fasciitis-associated death was greater among black, Hispanic, and American Indian individuals, and lower among Asian individuals. Streptococcal infection was most commonly identified in cases where a pathogen was reported. Diabetes mellitus and obesity were more commonly observed among necrotizing fasciitis-related deaths compared with deaths due to other causes. Racial differences in the incidence of necrotizing fasciitis-related deaths merits further investigation. PMID:26548496

Deaths from necrotizing fasciitis in the United States, 2003-2013.

PubMed

Arif, N; Yousfi, S; Vinnard, C

2016-04-01

Necrotizing fasciitis (NF) is a life-threatening infection requiring urgent surgical and medical therapy. Our objective was to estimate the mortality burden of NF in the United States, and to identify time trends in the incidence rate of NF-related mortality. We obtained data from the National Center for Health Statistics, which receives information from death certificates from all states, including demographic information and cause of death. The U.S. Multiple Cause of Death Files were searched from 2003 to 2013 for a listing of NF (ICD-10 code M72.6) as either the underlying or contributing cause of death. We identified a total of 9871 NF-related deaths in the United States between 2003 and 2013, corresponding to a crude mortality rate of 4·8 deaths/1,000,000 person-years, without a significant time trend. Compared to white individuals, the incidence rate of NF-associated death was greater in black, Hispanic, and American Indian individuals, and lower in Asian individuals. Streptococcal infection was most commonly identified in cases where a pathogen was reported. Diabetes mellitus and obesity were more commonly observed in NF-related deaths compared to deaths due to other causes. Racial differences in the incidence of NF-related deaths merits further investigation.

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

PubMed Central

Braunsdorf, Christina; Grumaz, Christian; Müller, Christoph; Lorenz, Stefan; Stevens, Philip; Wagener, Jeanette; Hebecker, Betty; Hube, Bernhard; Bracher, Franz; Sohn, Kai; Schaller, Martin

2017-01-01

Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG. PMID:29023454

Preparing the landscape for invasion - Early intervention approaches for threatened high elevation white pine ecosystems

Treesearch

Anna W. Schoettle; Richard A. Sniezko; Kelly S. Burns; Freeman Floyd

2007-01-01

White pine blister rust is now a permanent resident of North America. The disease continued to cause tree mortality and impact ecosystems in many areas. However, not all high elevation white pine ecosystems have been invaded; the pathogen is still spreading within the distributions of the whitebark, limber, foxtail, Rocky Mountain bristlecone pine and has yet to infect...

Agrochemicals against malaria, sleeping sickness, leishmaniasis and Chagas disease.

PubMed

Witschel, Matthias; Rottmann, Matthias; Kaiser, Marcel; Brun, Reto

2012-01-01

In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively.

Agrochemicals against Malaria, Sleeping Sickness, Leishmaniasis and Chagas Disease

PubMed Central

Witschel, Matthias; Rottmann, Matthias; Kaiser, Marcel; Brun, Reto

2012-01-01

In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively. PMID:23145187

Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management.

PubMed

Yazdanbakhsh, Karina; Ware, Russell E; Noizat-Pirenne, France

2012-07-19

Red blood cell transfusions have reduced morbidity and mortality for patients with sickle cell disease. Transfusions can lead to erythrocyte alloimmunization, however, with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and difficulty in finding compatible units, which can cause transfusion delays. In this review, we discuss the risk factors associated with alloimmunization with emphasis on possible mechanisms that can trigger delayed hemolytic transfusion reactions in sickle cell disease, and we describe the challenges in transfusion management of these patients, including opportunities and emerging approaches for minimizing this life-threatening complication.

Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut.

PubMed

Porse, Andreas; Gumpert, Heidi; Kubicek-Sutherland, Jessica Z; Karami, Nahid; Adlerberth, Ingegerd; Wold, Agnes E; Andersson, Dan I; Sommer, Morten O A

2017-01-01

Elucidating the adaptive strategies and plasticity of bacterial genomes in situ is crucial for understanding the epidemiology and evolution of pathogens threatening human health. While much is known about the evolution of Escherichia coli in controlled laboratory environments, less effort has been made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut during the first year of life. One E. coli lineage causes a urinary tract infection (UTI) and experiences several alterations of its genomic content during subsequent antibiotic treatment. Interestingly, all isolates of this uropathogenic E. coli strain carried a highly stable plasmid implicated in virulence of diverse pathogenic strains from all over the world. While virulence elements are certainly beneficial during infection scenarios, their role in gut colonization and pathogen persistence is poorly understood. We performed in vivo competitive fitness experiments to assess the role of this highly disseminated virulence plasmid in gut colonization, but found no evidence for a direct benefit of plasmid carriage. Through plasmid stability assays, we demonstrate that this plasmid is maintained in a parasitic manner, by strong first-line inheritance mechanisms, acting on the single-cell level, rather than providing a direct survival advantage in the gut. Investigating the ecology of endemic accessory genetic elements, in their pathogenic hosts and native environment, is of vital importance if we want to understand the evolution and persistence of highly virulent and drug resistant bacterial isolates.

Impedance based detection of pathogenic E. coli O157:H7 using a ferrocene-antimicrobial peptide modified biosensor.

PubMed

Li, Yongxin; Afrasiabi, Rouzbeh; Fathi, Farkhondeh; Wang, Nan; Xiang, Cuili; Love, Ryan; She, Zhe; Kraatz, Heinz-Bernhard

2014-08-15

Escherichia coli O157:H7 can cause life-threatening gastrointestinal diseases and has been a severe public health problem worldwide in recent years. A novel biosensor for the detection of E. coli O157:H7 is described here using a film composed of ferrocene-peptide conjugates, in which the antimicrobial peptide magainin I has been incorporated as the biorecognition element. Electrochemical impedance spectroscopy was employed to investigate the surface characteristics of the newly developed biosensor and to monitor the interactions between the peptide film and the pathogenic bacteria. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were employed to confirm the immobilization of ferrocene-conjugate onto the gold surface. Non-pathogenic E. coli K12, Staphylococcus epidermidis and Bacillus subtilis were used in this study to evaluate the selectivity of the proposed biosensor. The results have shown the order of the preferential selectivity of the method is E. coli O157:H7>non-pathogenic E. coli>gram positive species. The detection of E. coli O157:H7 with a sensitivity of 10(3)cfu/mL is enabled by the biosensor. The experimental conditions have been optimized and the plot of changes of charge transfer resistance (ΔRCT) and the logarithm of the cell concentration of E. coli O157:H7 shows a linear correlation in the range of 10(3)-10(7)cfu/mL with a correlation coefficient of 0.983. Copyright © 2014 Elsevier B.V. All rights reserved.

Naloxone Nasal Spray

MedlinePlus

... emergency medical treatment to reverse the life-threatening effects of a known or suspected opiate (narcotic) overdose. ... called opiate antagonists. It works by blocking the effects of opiates to relieve dangerous symptoms caused by ...

Gemtuzumab Ozogamicin Injection

MedlinePlus

... cause serious or life-threatening reactions during an infusion and for up to a day afterwards. You ... watch you closely while you are receiving the infusion and shortly after the infusion to be sure ...

[Dignity of human life: euthanasia and suicide].

PubMed

Niebrój, Lesław

2005-07-01

Euthanasia is commonly considered as a form of suicide. The study aims to explore if such a presumption could be justified. Philosophical analysis of concepts of "human being", "human person", "biological life" and "life of human person", undertaken in this article, proved that the effective cause of suicide is obviously different from such a cause of euthanasia. Suicide aims to destruct life of a human person which is considered deprived of its dignity. Euthanasia's effective cause is to protect the dignity of such a life which is threatened by low quality of biological life caused both by the disease as well as by the applied treatment even if palliative only. On the basis of these considerations the main conclusion is drawn: suicide and euthanasia having different moral (material) subjects should be also ethically evaluated in a different way.

DNA aptamers as a novel approach to neutralize Staphylococcus aureus α-toxin.

PubMed

Vivekananda, Jeevalatha; Salgado, Christi; Millenbaugh, Nancy J

2014-02-14

Staphylococcus aureus is a versatile pathogen capable of causing a broad spectrum of diseases ranging from superficial skin infections to life threatening conditions such as endocarditis, septicemia, pneumonia and toxic shock syndrome. In vitro and in vivo studies identified an exotoxin, α-toxin, as a major cause of S. aureus toxicity. Because S. aureus has rapidly evolved resistance to a number of antibiotics, including methicillin, it is important to identify new therapeutic strategies, other than antibiotics, for inhibiting the harmful effects of this pathogen. Aptamers are single-stranded DNA or RNA oligonucleotides with three-dimensional folded conformations that bind with high affinity and selectivity to targets and modulate their biological functions. The goal of this study was to isolate DNA aptamers that specifically inhibit the cytotoxic activity of α-toxin. After 10 rounds of Systematic Evolution of Ligands by EXponential Enrichment (SELEX), 49 potential anti-α-toxin aptamers were identified. In vitro neutralization assays demonstrated that 4 of these 49 aptamers, AT-27, AT-33, AT-36, and AT-49, significantly inhibited α-toxin-mediated cell death in Jurkat T cells. Furthermore, RT-PCR analysis revealed that α-toxin increased the transcription of the inflammatory cytokines TNF-α and IL-17 and that anti-α-toxin aptamers AT-33 and AT-36 inhibited the upregulation of these genes. Collectively, the data suggest the feasibility of generating functionally effective aptamers against α-toxin for treatment of S. aureus infections. Published by Elsevier Inc.

Actinomyces in Chronic Granulomatous Disease: An Emerging and Unanticipated Pathogen

PubMed Central

Reichenbach, Janine; Lopatin, Uri; Mahlaoui, Nizar; Beovic, Bojana; Siler, Ulrich; Zbinden, Reinhard; Seger, Reinhard A.; Galmiche, Louise; Brousse, Nicole; Kayal, Samer; Güngör, Tayfun; Blanche, Stéphane; Holland, Steven M.

2014-01-01

Background Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections, mostly by catalase-producing organisms. We report for the first time, to our knowledge, chronic infections with Actinomyces species in 10 patients with CGD. Actinomycosis is a chronic granulomatous condition that commonly manifests as cervicofacial, pulmonary, or abdominal disease, caused by slowly progressive infection with oral and gastrointestinal commensal Actinomyces species. Treatment of actinomycosis is usually simple in immunocompetent individuals, requiring long-term, high-dose intravenous penicillin, but is more complicated in those with CGD because of delayed diagnosis and an increased risk of chronic invasive or debilitating disease. Methods Actinomyces was identified by culture, staining, 16S ribosomal DNA polymerase chain reaction, and/ or a complement fixation test in 10 patients with CGD. Results All 10 patients presented with a history of fever and elevated inflammatory signs without evident focus. Diagnosis was delayed and clinical course severe and protracted despite high-dose intravenous antibiotic therapy and/or surgery. These results suggest an unrecognized and unanticipated susceptibility to weakly pathogenic Actinomyces species in patients with CGD because these are catalase-negative organisms previously thought to be nonpathogenic in CGD. Conclusions Actinomycosis should be vigorously sought and promptly treated in patients with CGD presenting with uncommon and prolonged clinical signs of infection. Actinomycosis is a catalase-negative infection important to consider in CGD. PMID:19874205

Lysozyme activates Enterococcus faecium to induce necrotic cell death in macrophages.

PubMed

Gröbner, Sabine; Fritz, Evelyn; Schoch, Friederike; Schaller, Martin; Berger, Alexander C; Bitzer, Michael; Autenrieth, Ingo B

2010-10-01

Enterococci are commensal organisms in the alimentary tract. However, they can cause a variety of life-threatening infections, especially in nosocomial settings. We hypothesized that induction of cell death might enable these facultative pathogenic bacteria to evade the innate immune response and to cause infections of their host. We demonstrate that E. faecium when exposed to lysozyme induces cell death in macrophages in vitro and in vivo. Flow cytometric analyses of J774A.1 macrophages infected with E. faecium revealed loss of cell membrane integrity indicated by uptake of propidium iodide and decrease of the inner mitochondrial transmembrane potential DeltaPsi(m). Inhibition of caspases, treatment of macrophages with cytochalasin D, or rifampicin did not prevent cells from dying, suggesting cell death mechanisms that are independent of caspase activation, bacterial uptake, and intracellular bacterial replication. Characteristics of necrotic cell death were demonstrated by both lack of procaspase 3 activation and cell shrinkage, electron microscopy, and release of lactate dehydrogenase. Pretreatment of E. faecium with lysozyme and subsequently with broad spectrum protease considerably reduced cell death, suggesting that a bacterial surface protein is causative for cell death induction. Moreover, in a mouse peritonitis model we demonstrated that E. faecium induces cell death of peritoneal macrophages in vivo. Altogether, our results show that enterococci, under specific conditions such as exposure to lysozyme, induce necrotic cell death in macrophages, which might contribute to disseminated infections by these facultative pathogenic bacteria.

Jaundice in infants and children: causes, diagnosis and management.

PubMed

Chee, Y Y; Chung, P H; Wong, R M; Wong, K K

2018-05-21

Jaundice is caused by an accumulation of bilirubin in the blood. The presentation in infants and children can be indicative of a wide range of conditions, with some self-limiting and others potentially life-threatening. This article aims to provide a concise review of the common medical and surgical causes in children and discuss their diagnosis and management.

Who Gets Fungal Infections?

MedlinePlus

... can also happen in people without weak immune systems Fungal infections that are not life-threatening, such ... to cause an infection. People with weak immune systems Infections that happen because a person’s immune system ...

Genetics Home Reference: hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis

MedlinePlus

... which scar tissue forms in the lungs . Pulmonary fibrosis eventually causes difficulty breathing and can be life-threatening within ... Keavney B, Bézieau S, Mayosi BM. Mutations in FAM111B cause hereditary fibrosing ... myopathy, and pulmonary fibrosis. Am J Hum Genet. 2013 Dec 5;93( ...

77 FR 55091 - National Childhood Cancer Awareness Month, 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... Proclamation Every year, thousands of children across America are diagnosed with cancer--an often life-threatening illness that remains the leading cause of death by disease for children under the age of 15. The causes of pediatric cancer are still largely unknown, and though new discoveries are resulting in new...

The threat of emerging infections.

PubMed

1996-11-01

A variety of newly discovered pathogens and new forms of older infectious agents threaten to reemerge. Typical symptoms of acute infection are fever, headache, malaise, vomiting, and diarrhea. Some of the better-known emerging viral infections include dengue, filoviruses (Ebola, Marburg), hantaviruses, hepatitis B, hepatitis C, HIV, influenza, lassa fever, measles, rift valley fever, rotavirus, and yellow fever. Emerging bacterial infections include cholera, Escherichia coli 0157:H7, legionnaires disease (Legionella), lyme disease, streptococcus infections (group A), tuberculosis, and typhoid. Emerging parasitic infections include cryptosporidium and other waterborne pathogens and malaria. The causes of many diseases are still shrouded in mystery; thus, treatments and cures for them are as yet unknown.

Urinary tract infections: epidemiology, mechanisms of infection and treatment options

PubMed Central

Flores-Mireles, Ana L.; Walker, Jennifer N.; Caparon, Michael; Hultgren, Scott J.

2015-01-01

Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host–pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs. PMID:25853778

Acid Reflux (GER and GERD) in Adults

MedlinePlus

... scientists identify cause, possible treatment for life-threatening gut condition Jun 29, 2017 An enzyme deficiency contributes ... Research & Funding Current Funding Opportunities Research Programs & Contacts Human Subjects Research Funding Process Research Training & Career Development ...

Acid Reflux (GER & GERD) in Children & Teens

MedlinePlus

... scientists identify cause, possible treatment for life-threatening gut condition Jun 29, 2017 An enzyme deficiency contributes ... Research & Funding Current Funding Opportunities Research Programs & Contacts Human Subjects Research Funding Process Research Training & Career Development ...

Take a Bite Out of Mosquito Stings

MedlinePlus

... a mosquito bite can cause anaphylaxis (an-a-fi-LAK-sis), a potentially life-threatening condition characterized ... Immunology 555 East Wells Street Suite 1100, Milwaukee , WI 53202-3823 (414) 272-6071 Additional Contact Information ...

Bacterial RNA induces myocyte cellular dysfunction through the activation of PKR

PubMed Central

Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V.; Tai, TC; Saleh, Mazen; Parrillo, Joseph E.; Kumar, Anand

2012-01-01

Severe sepsis and the ensuing septic shock are serious life threatening conditions. These diseases are triggered by the host's over exuberant systemic response to the infecting pathogen. Several surveillance mechanisms have evolved to discriminate self from foreign RNA and accordingly trigger effective cellular responses to target the pathogenic threats. The RNA-dependent protein kinase (PKR) is a key component of the cytoplasmic RNA sensors involved in the recognition of viral double-stranded RNA (dsRNA). Here, we identify bacterial RNA as a distinct pathogenic pattern recognized by PKR. Our results indicate that natural RNA derived from bacteria directly binds to and activates PKR. We further show that bacterial RNA induces human cardiac myocyte apoptosis and identify the requirement for PKR in mediating this response. In addition to bacterial immunity, the results presented here may also have implications in cardiac pathophysiology. PMID:22833816

Classification of human pathogen bacteria for early screening using electronic nose

NASA Astrophysics Data System (ADS)

Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan

2017-10-01

This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.

Life-threatening macroglossia after posterior fossa surgery: a surgical positioning problem?

PubMed

Vermeersch, G; Menovsky, T; De Ridder, D; De Bodt, M; Saldien, V; Van de Heyning, P

2014-01-01

A 55-year-old woman was operated in the lateral park bench position with significant neck flexion and oral packing. Macroglossia was noticed immediately postoperatively after endotracheal extubation. The patient was reintubated for 13 days and subsequently required a tracheostoma. After the placement of the tracheostoma and the removal of the endotracheal tube, the congestion of the tongue decreased markedly within 24 hours. Macroglossia is a rare complication following posterior fossa procedures with few cases reported so far. It can cause airway obstruction, which could be a life-threatening complication, and it therefore requires prompt treatment. The aetiology of postoperative macroglossia remains uncertain and has been attributed to arterial, venous and lymphatic compression, mechanical compression, or neurogenic causes. This article describes new insights into aetiology and also describes preventive measures and possible treatment.

Characterizing Pneumocystis in the Lungs of Bats: Understanding Pneumocystis Evolution and the Spread of Pneumocystis Organisms in Mammal Populations

PubMed Central

Akbar, Haroon; Pinçon, Claire; Aliouat-Denis, Cecile-Marie; Derouiche, Sandra; Taylor, Maria-Lucia; Pottier, Muriel; Carreto-Binaghi, Laura-Helena; González-González, Antonio E.; Courpon, Aurore; Barriel, Véronique; Guillot, Jacques; Chabé, Magali; Suarez-Alvarez, Roberto O.; Aliouat, El Moukhtar; Dei-Cas, Eduardo

2012-01-01

Bats belong to a wide variety of species and occupy diversified habitats, from cities to the countryside. Their different diets (i.e., nectarivore, frugivore, insectivore, hematophage) lead Chiroptera to colonize a range of ecological niches. These flying mammals exert an undisputable impact on both ecosystems and circulation of pathogens that they harbor. Pneumocystis species are recognized as major opportunistic fungal pathogens which cause life-threatening pneumonia in severely immunocompromised or weakened mammals. Pneumocystis consists of a heterogeneous group of highly adapted host-specific fungal parasites that colonize a wide range of mammalian hosts. In the present study, 216 lungs of 19 bat species, sampled from diverse biotopes in the New and Old Worlds, were examined. Each bat species may be harboring a specific Pneumocystis species. We report 32.9% of Pneumocystis carriage in wild bats (41.9% in Microchiroptera). Ecological and behavioral factors (elevation, crowding, migration) seemed to influence the Pneumocystis carriage. This study suggests that Pneumocystis-host association may yield much information on Pneumocystis transmission, phylogeny, and biology in mammals. Moreover, the link between genetic variability of Pneumocystis isolated from populations of the same bat species and their geographic area could be exploited in terms of phylogeography. PMID:23001662

Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling.

PubMed

Graham, Morag R; Smoot, Laura M; Migliaccio, Cristi A Lux; Virtaneva, Kimmo; Sturdevant, Daniel E; Porcella, Stephen F; Federle, Michael J; Adams, Gerald J; Scott, June R; Musser, James M

2002-10-15

Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease.

Evaluation of the protective efficacy of four novel identified membrane associated proteins of Streptococcus suis serotype 2.

PubMed

Zhou, Yang; Wang, Yan; Deng, Limei; Zheng, Chengkun; Yuan, Fangyan; Chen, Huanchun; Bei, Weicheng; Li, Jinquan

2015-05-05

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that can also cause epidemics of life-threatening infections in humans. Surface proteins of pathogens play a critical role in the interaction with host system or environment, as they take part in processes like virulence, cytotoxicity, adhesion, signaling or transport, etc. Thus, surface proteins identified by the screening of immunoproteomic techniques are promising vaccine candidates or diagnostic markers. In this study, four membrane associated proteins (MAP) identified by immunoproteomic method were cloned and expressed as recombinant proteins with his-tag. Screening for vaccine candidates were firstly performed by protection assay in vivo and immunization with Sbp markedly protected mice against systemic S. suis 2 infection. The immune responses and protective of Sbp were further evaluated. The results showed that Sbp could elicit a strong humoral antibody response and protect mice from lethal challenge with S. suis 2. The antiserum against Sbp could efficiently impede survival of bacterial in whole blood killing assay and conferred significant protection against S. suis 2 infection in passive immunization assays. The findings indicate that Sbp may serve as an important factor in the pathogenesis of S. suis 2 and would be a promising subunit vaccine candidate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design and synthesis of a biotinylated chemical probe for detecting the molecular targets of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin.

PubMed

Baker, Ysobel R; Galloway, Warren R J D; Hodgkinson, James T; Spring, David R

2013-09-25

Pseudomonas aeruginosa is a human pathogen associated with a variety of life-threatening nosocomial infections. This organism produces a range of virulence factors which actively cause damage to host tissues. One such virulence factor is pyocyanin, known to play a crucial role in the pathogenesis of P. aeruginosa infections. Previous studies had identified a novel compound capable of strongly inhibiting the production of pyocyanin. It was postulated that this inhibition results from modulation of an intercellular communication system termed quorum sensing, via direct binding of the compound with the LasR protein receptor. This raised the possibility that the compound could be an antagonist of quorum sensing in P. aeruginosa, which could have important implications as this intercellular signaling mechanism is known to regulate many additional facets of P. aeruginosa pathogenicity. However, there was no direct evidence for the binding of the active compound to LasR (or any other targets). Herein we describe the design and synthesis of a biotin-tagged version of the active compound. This could potentially be used as an affinity-based chemical probe to ascertain, in a direct fashion, the active compound's macromolecular biological targets, and thus better delineate the mechanism by which it reduces the level of pyocyanin production.

The germline variants in DNA repair genes in pediatric medulloblastoma: a challenge for current therapeutic strategies.

PubMed

Trubicka, Joanna; Żemojtel, Tomasz; Hecht, Jochen; Falana, Katarzyna; Piekutowska-Abramczuk, Dorota; Płoski, Rafał; Perek-Polnik, Marta; Drogosiewicz, Monika; Grajkowska, Wiesława; Ciara, Elżbieta; Moszczyńska, Elżbieta; Dembowska-Bagińska, Bożenna; Perek, Danuta; Chrzanowska, Krystyna H; Krajewska-Walasek, Małgorzata; Łastowska, Maria

2017-04-04

The defects in DNA repair genes are potentially linked to development and response to therapy in medulloblastoma. Therefore the purpose of this study was to establish the spectrum and frequency of germline variants in selected DNA repair genes and their impact on response to chemotherapy in medulloblastoma patients. The following genes were investigated in 102 paediatric patients: MSH2 and RAD50 using targeted gene panel sequencing and NBN variants (p.I171V and p.K219fs*19) by Sanger sequencing. In three patients with presence of rare life-threatening adverse events (AE) and no detected variants in the analyzed genes, whole exome sequencing was performed. Based on combination of molecular and immunohistochemical evaluations tumors were divided into molecular subgroups. Presence of variants was tested for potential association with the occurrence of rare life-threatening AE and other clinical features. We have identified altogether six new potentially pathogenic variants in MSH2 (p.A733T and p.V606I), RAD50 (p.R1093*), FANCM (p.L694*), ERCC2 (p.R695C) and EXO1 (p.V738L), in addition to two known NBN variants. Five out of twelve patients with defects in either of MSH2, RAD50 and NBN genes suffered from rare life-threatening AE, more frequently than in control group (p = 0.0005). When all detected variants were taken into account, the majority of patients (8 out of 15) suffered from life-threatening toxicity during chemotherapy. Our results, based on the largest systematic study performed in a clinical setting, provide preliminary evidence for a link between defects in DNA repair genes and treatment related toxicity in children with medulloblastoma. The data suggest that patients with DNA repair gene variants could need special vigilance during and after courses of chemotherapy.

Hyperkalemia.

PubMed

Hollander-Rodriguez, Joyce C; Calvert, James F

2006-01-15

Hyperkalemia is a potentially life-threatening metabolic problem caused by inability of the kidneys to excrete potassium, impairment of the mechanisms that move potassium from the circulation into the cells, or a combination of these factors. Acute episodes of hyperkalemia commonly are triggered by the introduction of a medication affecting potassium homeostasis; illness or dehydration also can be triggers. In patients with diabetic nephropathy, hyperkalemia may be caused by the syndrome of hyporeninemic hypoaldosteronism. The presence of typical electrocardiographic changes or a rapid rise in serum potassium indicates that hyperkalemia is potentially life threatening. Urine potassium, creatinine, and osmolarity should be obtained as a first step in determining the cause of hyperkalemia, which directs long-term treatment. Intravenous calcium is effective in reversing electrocardiographic changes and reducing the risk of arrhythmias but does not lower serum potassium. Serum potassium levels can be lowered acutely by using intravenous insulin and glucose, nebulized beta2 agonists, or both. Sodium polystyrene therapy, sometimes with intravenous furosemide and saline, is then initiated to lower total body potassium levels.

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

PubMed

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

2015-07-01

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

Plants’ Natural Products as Alternative Promising Anti-Candida Drugs

PubMed Central

Soliman, Sameh; Alnajdy, Dina; El-Keblawy, Ali A.; Mosa, Kareem A.; Khoder, Ghalia; Noreddin, Ayman M.

2017-01-01

Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. PMID:28989245

Dirofilaria immitis and Angiostrongylus vasorum: The current situation of two major canine heartworms in Portugal.

PubMed

Alho, Ana Margarida; Meireles, José; Schnyder, Manuela; Cardoso, Luís; Belo, Silvana; Deplazes, Peter; de Carvalho, Luís Madeira

2018-03-15

Cardiopulmonary nematodes are life-threatening pet parasites increasingly reported throughout Europe, with overlapping endemic areas. Dirofilaria immitis is a mosquito-borne whilst Angiostrongylus vasorum is a snail-borne pathogen. Both adult nematodes reside in the pulmonary arteries and right cardiac ventricle of domestic and wild canids, causing a wide spectrum of clinical presentations ranging from cough, dyspnoea and exercise intolerance to severe vascular and pulmonary disease with hearth failure that may lead to death. Information about the prevalence and distribution of cardiopulmonary parasites is essential for the control of animal diseases and, in the case of D. immitis, for the control of potentially associated illnesses in humans. However, in Portugal, heartworm studies are limited to few surveys and case reports, possibly underestimating the relevance of these nematodes. The present work reviews the data on cardiopulmonary dirofilariosis and angiostrongylosis in dogs in Portugal, providing a comprehensive update of the epidemiological situation during the past 20 years. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Listeria monocytogenes sequence type 1 is predominant in ruminant rhombencephalitis

PubMed Central

Dreyer, Margaux; Aguilar-Bultet, Lisandra; Rupp, Sebastian; Guldimann, Claudia; Stephan, Roger; Schock, Alexandra; Otter, Arthur; Schüpbach, Gertraud; Brisse, Sylvain; Lecuit, Marc; Frey, Joachim; Oevermann, Anna

2016-01-01

Listeria (L.) monocytogenes is an opportunistic pathogen causing life-threatening infections in diverse mammalian species including humans and ruminants. As little is known on the link between strains and clinicopathological phenotypes, we studied potential strain-associated virulence and organ tropism in L. monocytogenes isolates from well-defined ruminant cases of clinical infections and the farm environment. The phylogeny of isolates and their virulence-associated genes were analyzed by multilocus sequence typing (MLST) and sequence analysis of virulence-associated genes. Additionally, a panel of representative isolates was subjected to in vitro infection assays. Our data suggest the environmental exposure of ruminants to a broad range of strains and yet the strong association of sequence type (ST) 1 from clonal complex (CC) 1 with rhombencephalitis, suggesting increased neurotropism of ST1 in ruminants, which is possibly related to its hypervirulence. This study emphasizes the importance of considering clonal background of L. monocytogenes isolates in surveillance, epidemiological investigation and disease control. PMID:27848981

Laboratory Approach to the Diagnosis of Culture-Negative Infective Endocarditis.

PubMed

Subedi, S; Jennings, Z; Chen, S C-A

2017-08-01

Blood-culture negative endocarditis (BCNE) accounts for up to 35% of all cases of infective endocarditis (IE) and is a serious life-threatening condition with considerable morbidity and mortality. Rapid detection and identification of the causative pathogen is essential for timely, directed therapy. Blood-culture negative endocarditis presents a diagnostic and therapeutic challenge. Causes of BCNE are varied including: treatment with antibiotic agents prior to blood culture collection; sub-optimal specimen collection; and/or infection due to fastidious (eg. nutritionally variant streptococci), intracellular (eg. Coxiella burnetii, Bartonella species) or non-culturable or difficult to culture organisms (eg. Mycobacteria, Tropheryma whipplei and fungi); as well as non-infective aetiologies. Here, we review aetiological and diagnostic approaches to BCNE including newer molecular based techniques, with a brief summary of imaging investigation and treatment principles. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Emerging intracellular receptors for hemorrhagic fever viruses.

PubMed

Jae, Lucas T; Brummelkamp, Thijn R

2015-07-01

Ebola virus and Lassa virus belong to different virus families that can cause viral hemorrhagic fever, a life-threatening disease in humans with limited treatment options. To infect a target cell, Ebola and Lassa viruses engage receptors at the cell surface and are subsequently shuttled into the endosomal compartment. Upon arrival in late endosomes/lysosomes, the viruses trigger membrane fusion to release their genome into the cytoplasm. Although contact sites at the cell surface were recognized for Ebola virus and Lassa virus, it was postulated that Ebola virus requires a critical receptor inside the cell. Recent screens for host factors identified such internal receptors for both viruses: Niemann-Pick disease type C1 protein (NPC1) for Ebola virus and lysosome-associated membrane protein 1 (LAMP1) for Lassa virus. A cellular trigger is needed to permit binding of the viral envelope protein to these intracellular receptors. This 'receptor switch' represents a previously unnoticed step in virus entry with implications for host-pathogen interactions and viral tropism. Copyright © 2015 Elsevier Ltd. All rights reserved.

The roles of biofilm matrix polysaccharide Psl in mucoid Pseudomonas aeruginosa biofilms.

PubMed

Ma, Luyan; Wang, Shiwei; Wang, Di; Parsek, Matthew R; Wozniak, Daniel J

2012-07-01

The opportunistic pathogen Pseudomonas aeruginosa causes life-threatening, persistent infections in patients with cystic fibrosis (CF). Persistence is attributed to the ability of these bacteria to form structured communities (biofilms). Biofilms rely on an extracellular polymeric substances matrix to maintain structure. Psl exopolysaccharide is a key matrix component of nonmucoid biofilms, yet the role of Psl in mucoid biofilms is unknown. In this report, using a variety of mutants in a mucoid P. aeruginosa background, we found that deletion of Psl-encoding genes dramatically decreased their biofilm formation ability, indicating that Psl is also a critical matrix component of mucoid biofilms. Our data also suggest that the overproduction of alginate leads to mucoid biofilms, which occupy more space, whereas Psl-dependent biofilms are densely packed. These data suggest that Psl polysaccharide may have significant contributions in biofilm persistence in patients with CF and may be helpful for designing therapies for P. aeruginosa CF infection. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Cryptococcus and Phagocytes: Complex Interactions that Influence Disease Outcome

PubMed Central

Leopold Wager, Chrissy M.; Hole, Camaron R.; Wozniak, Karen L.; Wormley, Floyd L.

2016-01-01

Cryptococcus neoformans and C. gattii are fungal pathogens that cause life-threatening disease. These fungi commonly enter their host via inhalation into the lungs where they encounter resident phagocytes, including macrophages and dendritic cells, whose response has a pronounced impact on the outcome of disease. Cryptococcus has complex interactions with the resident and infiltrating innate immune cells that, ideally, result in destruction of the yeast. These phagocytic cells have pattern recognition receptors that allow recognition of specific cryptococcal cell wall and capsule components. However, Cryptococcus possesses several virulence factors including a polysaccharide capsule, melanin production and secretion of various enzymes that aid in evasion of the immune system or enhance its ability to thrive within the phagocyte. This review focuses on the intricate interactions between the cryptococci and innate phagocytic cells including discussion of manipulation and evasion strategies used by Cryptococcus, anti-cryptococcal responses by the phagocytes and approaches for targeting phagocytes for the development of novel immunotherapeutics. PMID:26903984

Molecular characterization of Acanthamoeba strains isolated from the oral cavity of hemodialysis patients in Iran.

PubMed

Niyyati, Maryam; Arab-Mazar, Zahra; Lasjerdi, Zohreh; Lorenzo-Morales, Jacob; Espotin, Adel; Yadegarynia, Davood; Gachkar, Latif; Rahmati Roodsari, Sara

2017-11-01

Free-living amoebae (FLA) of the genus Acanthamoeba are opportunistic pathogenic agents able to cause life-threatening infections in immunosuppressed patients. Chronic kidney disease impairs adaptive and innate immunity. Thus, patients with chronic kidney disease are prone to opportunistic infections by potentially pathogenic FLA. Therefore, in the present study, the investigation of Acanthamoeba genotypes isolated from the oral cavity of hemodialysis patients of reference hospitals in Iran was aimed, using both morphology and molecular (sequence-based analysis) tools. Furthermore, classification of the strains at the genotype level was performed on the basis of differences in the diagnostic fraction 3 (DF3) region of the 18S rRNA gene. The pathogenic potential of the isolated amoebae was also determined using thermotolerance and osmotolerance assays. Out of the 187 oral cavity samples investigated, nine (4.8%) were positive for FLA. DNA sequencing of the ASA.A1 region of the 18S rRNA gene revealed that the isolated strains belonged to the Acanthamoeba T1 and T4 genotypes. Genotype T1 was isolated for the first time from a patient in Iran. Interestingly, the T1 strain (AN2 strain) exhibits a high pathogenic potential in tolerance assays. The pathogenicity assay revealed that five strains were able to grow at high temperatures (37-40 °C) and high osmolarity (0.5 and 1 M D-mannitol) conditions; thus, they were considered as potentially pathogenic strains. Moreover, two of the patients were positive for Vermamoeba genus. The present study is the first report of genotype T1 isolation in Iran and the first to identify the occurrence of Acanthamoeba and Vermamoeba genera in patients undergoing hemodialysis worldwide. Monitoring hemodialysis and renal failure patients should be a priority for possible control of Acanthamoeba and other FLA-related diseases.

Landscape epidemiology and control of pathogens with cryptic and long-distance dispersal: sudden oak death in northern Californian forests.

PubMed

Filipe, João A N; Cobb, Richard C; Meentemeyer, Ross K; Lee, Christopher A; Valachovic, Yana S; Cook, Alex R; Rizzo, David M; Gilligan, Christopher A

2012-01-01

Exotic pathogens and pests threaten ecosystem service, biodiversity, and crop security globally. If an invasive agent can disperse asymptomatically over long distances, multiple spatial and temporal scales interplay, making identification of effective strategies to regulate, monitor, and control disease extremely difficult. The management of outbreaks is also challenged by limited data on the actual area infested and the dynamics of spatial spread, due to financial, technological, or social constraints. We examine principles of landscape epidemiology important in designing policy to prevent or slow invasion by such organisms, and use Phytophthora ramorum, the cause of sudden oak death, to illustrate how shortfalls in their understanding can render management applications inappropriate. This pathogen has invaded forests in coastal California, USA, and an isolated but fast-growing epidemic focus in northern California (Humboldt County) has the potential for extensive spread. The risk of spread is enhanced by the pathogen's generalist nature and survival. Additionally, the extent of cryptic infection is unknown due to limited surveying resources and access to private land. Here, we use an epidemiological model for transmission in heterogeneous landscapes and Bayesian Markov-chain-Monte-Carlo inference to estimate dispersal and life-cycle parameters of P. ramorum and forecast the distribution of infection and speed of the epidemic front in Humboldt County. We assess the viability of management options for containing the pathogen's northern spread and local impacts. Implementing a stand-alone host-free "barrier" had limited efficacy due to long-distance dispersal, but combining curative with preventive treatments ahead of the front reduced local damage and contained spread. While the large size of this focus makes effective control expensive, early synchronous treatment in newly-identified disease foci should be more cost-effective. We show how the successful management of forest ecosystems depends on estimating the spatial scales of invasion and treatment of pathogens and pests with cryptic long-distance dispersal. © 2012 Filipe et al.

A case of fetal intestinal volvulus without malrotation causing severe anemia.

PubMed

Nakagawa, Tomoko; Tachibana, Daisuke; Kitada, Kohei; Kurihara, Yasushi; Terada, Hiroyuki; Koyama, Masayasu; Sakae, Yukari; Morotomi, Yoshiki; Nomura, Shiho; Saito, Mika

2015-01-01

Fetal intestinal volvulus without malrotation is a rare, life-threatening disease. Left untreated, hemorrhage from necrotic bowel tissue will lead to severe fetal anemia and even intrauterine death. We encountered a case of fetal intestinal volvulus causing severe anemia, which was diagnosed postnatally and successfully treated with surgical intervention.

A Case of Fetal Intestinal Volvulus Without Malrotation Causing Severe Anemia

PubMed Central

Nakagawa, Tomoko; Tachibana, Daisuke; Kitada, Kohei; Kurihara, Yasushi; Terada, Hiroyuki; Koyama, Masayasu; Sakae, Yukari; Morotomi, Yoshiki; Nomura, Shiho; Saito, Mika

2015-01-01

Fetal intestinal volvulus without malrotation is a rare, life-threatening disease. Left untreated, hemorrhage from necrotic bowel tissue will lead to severe fetal anemia and even intrauterine death. We encountered a case of fetal intestinal volvulus causing severe anemia, which was diagnosed postnatally and successfully treated with surgical intervention. PMID:25628516

Statins and Voriconazole Induce Programmed Cell Death in Acanthamoeba castellanii

PubMed Central

López-Arencibia, Atteneri; Sifaoui, Ines; Reyes-Batlle, María; Valladares, Basilio; Martínez-Carretero, Enrique; Piñero, José E.; Maciver, Sutherland K.; Lorenzo-Morales, Jacob

2015-01-01

Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a life-threatening encephalitis. In order to treat those infections properly, it is necessary to target the treatment not only to the trophozoite but also to the cyst. Furthermore, it may be advantageous to avoid parasite killing by necrosis, which may induce local inflammation. We must also avoid toxicity of host tissue. Many drugs which target eukaryotes are known to induce programmed cell death (PCD), but this process is poorly characterized in Acanthamoeba. Here, we study the processes of programmed cell death in Acanthamoeba, induced by several drugs, such as statins and voriconazole. We tested atorvastatin, fluvastatin, simvastatin, and voriconazole at the 50% inhibitory concentrations (IC50s) and IC90s that we have previously established. In order to evaluate this phenomenon, we investigated the DNA fragmentation, one of the main characteristics of PCD, with quantitative and qualitative techniques. Also, the changes related to phosphatidylserine exposure on the external cell membrane and cell permeability were studied. Finally, because caspases are key to PCD pathways, caspase activity was evaluated in Acanthamoeba. All the drugs assayed in this study induced PCD in Acanthamoeba. To the best of our knowledge, this is the first study where PCD induced by drugs is described quantitatively and qualitatively in Acanthamoeba. PMID:25733513

Potential of protein kinase inhibitors for treating herpesvirus associated disease

PubMed Central

Li, Renfeng; Hayward, S. Diane

2013-01-01

Herpesviruses are ubiquitous human pathogens that establish life-long persistent infections. Clinical manifestations range from mild self-limiting outbreaks such as childhood rashes and cold sores to the more severe and life threatening outcomes of disseminated infection, encephalitis and cancer. Nucleoside analog drugs that target viral DNA replication provide the primary means of treatment. However, extended use of these drugs can result in selection for drug resistant strains, particularly in immunocompromised patients. In this review, we will present recent observations about the participation of cellular protein kinases in herpesvirus biology and discuss the potential for targeting these protein kinases as well as the herpesvirus encoded protein kinases as an anti-herpesvirus therapeutic strategy. PMID:23608036

Rescue patient from tracheal obstruction by dislocated bronchial stent during tracheostomy surgery with readily available tools: A case report.

PubMed

Chang, Hung-Yu; Man, Kee-Ming; Liao, Kate Hsiurong; Chiang, Yi-Ying; Chen, Kuen-Bao

2017-09-01

Airway stenting is a well-established method that relieves symptoms and maintains airway patency in patients with airway obstruction. Serious complications caused by airway stents such as stent dislocation and airway obstruction during surgery are life-threatening. An 80-year-old man was treated with bronchial stent for left bronchus obstruction caused by metastatic esophageal cancer. During tracheostomy surgery, he suffered from acute tracheal obstruction caused by dislocated bronchial stent. Esophageal cancer, left bronchus obstruction, respiratory failure, tracheal obstruction. Threading a 5.0-sized endotracheal tube combined with an Eschmann tracheal tube introducer to prop up the collapsed stent. The bronchial stent was re-expanded and threaded into right main bronchus and ventilation restored. Patient with airway stent undergoing surgery with airway involved should be performed under the support of a backup physician and equipment that are capable of handling potentially life-threatening complications of airway stent. If not, in the emergent situation of tracheal obstruction due to tracheal/bronchial stent, protruding through the stent with a suitable, small-sized endotracheal tube with Eschmann tracheal tube introducer may be an alternative skill for saving life weighted with possible complications.

Assessing the potential for maladaptation during active management of limber pine populations: A common garden study detects genetic differentiation in response to soil moisture in the Southern Rocky Mountains

Treesearch

Erin M. Borgman; Anna W. Schoettle; Amy L. Angert

2015-01-01

Active management is needed to sustain healthy limber pine (Pinus flexilis E. James) forests in the Southern Rocky Mountains (henceforth, Southern Rockies), as they are threatened by the interaction of the mountain pine beetle (Dendroctonus ponderosae Hopkins) epidemic, climate change, and the spread of the non-native pathogen that causes white pine blister...

Obstetrical referrals by traditional birth attendants.

PubMed

Mustafa, Rozina; Hashmi, Haleema; Mustafa, Rubina

2012-01-01

In Pakistan 90% of births are conducted by TBA's. In most cases, TBA's are unable to diagnose the complications and are often unable to take decisions on timely referral. The objective of this study was to determine the prevalence, nature and outcome of life threatening obstetrical conditions in referrals by Traditional Birth Attendants (TBAs). This Observational, Descriptive study was conducted from January to December 2007, in the obstetrical unit of Fatima Hospital, Baqai Medical University, a tertiary care community based hospital. The study included patients referred by TBA's who developed life threatening obstetric conditions (LTOCs). Total 64 patients were referred by TBA's. The prevalence was 7.8%. Out of them, 53 (82.8%) patients admitted with life threatening obstetric conditions. The near-miss morbidities and mortalities were 45 (84.9%) and 8 (15%) respectively. Maternal mortality to Near-miss morbidity ratio was 1:6. Obstructed labour caused near-miss morbidity in 32 (60.3%) patients with no mortality. Postpartum haemorrhage as life threatening condition developed in 16 (30.1%) patients with 10 (18.8%) near-miss morbidities and 6 (11.3%) mortalities. Puerperal sepsis accounted for 1 (1.88%) near-miss morbidity and 2 (3.76%) mortalities. The mortality index for puerperal sepsis is (66.6%) almost double of postpartum haemorrhage (37.5%). Mortality to near miss morbidity ratio is high. Misidentification and late referrals of complicated cases by TBA's were responsible for near-miss morbidities and mortalities.

Laboratory-associated infections and biosafety.

PubMed Central

Sewell, D L

1995-01-01

An estimated 500,000 laboratory workers in the United States are at risk of exposure to infectious agents that cause disease ranging from inapparent to life-threatening infections, but the precise risk to a given worker unknown. The emergence of human immunodeficiency virus and hantavirus, the continuing problem of hepatitis B virus, and the reemergence of Mycobacterium tuberculosis have renewed interest in biosafety for the employees of laboratories and health care facilities. This review examines the history, the causes, and the methods for prevention of laboratory-associated infections. The initial step in a biosafety program is the assessment of risk to the employee. Risk assessment guidelines include the pathogenicity of the infectious agent, the method of transmission, worker-related risk factors, the source and route of infection, and the design of the laboratory facility. Strategies for the prevention and management of laboratory-associated infections are based on the containment of the infectious agent by physical separation from the laboratory worker and the environment, employee education about the occupational risks, and availability of an employee health program. Adherence to the biosafety guidelines mandated or proposed by various governmental and accrediting agencies reduces the risk of an occupational exposure to infectious agents handled in the workplace. PMID:7553572

Removal of bacteria Legionella pneumophila, Escherichia coli, and Bacillus subtilis by (super)cavitation.

PubMed

Šarc, Andrej; Kosel, Janez; Stopar, David; Oder, Martina; Dular, Matevž

2018-04-01

In sufficient concentrations, the pathogenic bacteria L. pneumophila can cause a respiratory illness that is known as the "Legionnaires" disease. Moreover, toxic Shiga strains of bacteria E. coli can cause life-threatening hemolytic-uremic syndrome. Because of the recent restrictions imposed on the usage of chlorine, outbreaks of these two bacterial species have become more common. In this study we have developed a novel rotation generator and its effectiveness against bacteria Legionella pneumophila and Escherichia coli was tested for various types of hydrodynamic cavitation (attached steady cavitation, developed unsteady cavitation and supercavitation). The results show that the supercavitation was the only effective form of cavitation. It enabled more than 3 logs reductions for both bacterial species and was also effective against a more persistent Gram positive bacteria, B. subtilis. The deactivation mechanism is at present unknown. It is proposed that when bacterial cells enter a supercavitation cavity, an immediate pressure drop occurs and this results in bursting of the cellular membrane. The new rotation generator that induced supercavitation proved to be economically and microbiologically far more effective than the classical Venturi section (super)cavitation. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibiofilm effect of Nocardiopsis sp. GRG 1 (KT235640) compound against biofilm forming Gram negative bacteria on UTIs.

PubMed

Rajivgandhi, Govindan; Vijayan, Ramachandran; Maruthupandy, Muthuchamy; Vaseeharan, Baskaralingam; Manoharan, Natesan

2018-05-01

Urinary tract infections (UTIs) are diverse public health complication and caused by range of pathogens, however mostly Gram negative bacteria cause significant life threatening risks to different populations. The prevalence rate and antimicrobial resistance among the Gram negative uropathogens alarmed significantly heighten the economic burden of these infections. In this study, we investigated the antibiofilm efficiency of Pyrrolo [1,2-a] pyrazine-1,4-dione,hexahydro-3-(2-methylpropyl) extracted from endophytic actinomycetes Nocardiopsis sp. GRG 1 (KT235640) against P. mirabilis and E. coli. The extracted compound was characterized through TLC, HPLC, GC-MS, LC-MS and confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM). The compound, Pyrrolo [1,2-a] pyrazine-1, 4-dione, hexahydro-3-(2-methylpropyl) inhibits both bacterial biofilm formation as well as reduces the viability of preformed biofilms. Furthermore, CLSM image shows cell shrinkage, disorganized cell membrane and loss of viability. The SEM result also confirms the cell wall degradation in treated cells of the bacteria. Hence, the Pyrrolo [1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) is active against P. mirabilis and E. coli. Copyright © 2018 Elsevier Ltd. All rights reserved.

Association of a Bacteriophage with Meningococcal Disease in Young Adults

PubMed Central

Gray, Stephen J.; Kaczmarski, Edward B.; McCarthy, Noel D.; Nassif, Xavier; Maiden, Martin C. J.; Tinsley, Colin R.

2008-01-01

Despite being the agent of life-threatening meningitis, Neisseria meningitidis is usually carried asymptomatically in the nasopharynx of humans and only occasionally causes disease. The genetic bases for virulence have not been entirely elucidated and the search for new virulence factors in this species is hampered by the lack of an animal model representative of the human disease. As an alternative strategy we employ a molecular epidemiological approach to establish a statistical association of a candidate virulence gene with disease in the human population. We examine the distribution of a previously-identified genetic element, a temperate bacteriophage, in 1288 meningococci isolated from cases of disease and asymptomatic carriage. The phage was over-represented in disease isolates from young adults indicating that it may contribute to invasive disease in this age group. Further statistical analysis indicated that between 20% and 45% of the pathogenic potential of the five most common disease-causing meningococcal groups was linked to the presence of the phage. In the absence of an animal model of human disease, this molecular epidemiological approach permitted the estimation of the influence of the candidate virulence factor. Such an approach is particularly valuable in the investigation of exclusively human diseases. PMID:19065260

Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial Pathogen Streptococcus pyogenes.

PubMed

Blom, Anna M; Magda, Michal; Kohl, Lisa; Shaughnessy, Jutamas; Lambris, John D; Ram, Sanjay; Ermert, David

2017-12-01

Bacteria can cause life-threatening infections, such as pneumonia, meningitis, or sepsis. Antibiotic therapy is a mainstay of treatment, although antimicrobial resistance has drastically increased over the years. Unfortunately, safe and effective vaccines against most pathogens have not yet been approved, and thus developing alternative treatments is important. We analyzed the efficiency of factor H (FH)6-7/Fc, a novel antibacterial immunotherapeutic protein against the Gram-positive bacterium Streptococcus pyogenes This protein is composed of two domains of complement inhibitor human FH (FH complement control protein modules 6 and 7) that bind to S. pyogenes , linked to the Fc region of IgG (FH6-7/Fc). FH6-7/Fc has previously been shown to enhance complement-dependent killing of, and facilitate bacterial clearance in, animal models of the Gram-negative pathogens Haemophilus influenzae and Neisseria meningitidis We hypothesized that activation of complement by FH6-7/Fc on the surface of Gram-positive bacteria such as S. pyogenes will enable professional phagocytes to eliminate the pathogen. We found that FH6-7/Fc alleviated S. pyogenes- induced sepsis in a transgenic mouse model expressing human FH ( S. pyogenes binds FH in a human-specific manner). Furthermore, FH6-7/Fc, which binds to protein H and selected M proteins, displaced FH from the bacterial surface, enhanced alternative pathway activation, and reduced bacterial blood burden by opsonophagocytosis in a C3-dependent manner in an ex vivo human whole-blood model. In conclusion, FH-Fc chimeric proteins could serve as adjunctive treatments against multidrug-resistant bacterial infections. Copyright © 2017 by The American Association of Immunologists, Inc.

African trypanosomiasis with special reference to Egyptian Trypanosoma evansi: is it a neglected zoonosis?

PubMed

El-Bahnasawy, Mamdouh M M; Khater, Mai Kh A; Morsy, Tosson A

2014-12-01

Trypanosomes (including humans) are blood and sometimes tissue parasites of the order Kinetoplastida, family Trypanosomatidae, genus Trypanosoma, principally transmitted by biting insects where most of them undergo a biological cycle. They are divided into Stercoraria with the posterior station inoculation, including T. cruzi, both an extra- and intracellular parasite that causes Chagas disease, a major human disease affecting 15 million people and threatening 100 million people in Latin America, and the Salivaria with the anterior station inoculation, mainly African livestock pathogenic trypanosomes, including the agents of sleeping sickness, a major human disease affecting around half a million people and threatening 60 million people in Africa. Now, T. evansi was reported in man is it required to investigate its zoonotic potential?

Necrotizing fasciitis due to Serratia marcescens: case report and review of the literature.

PubMed

Majumdar, Rohit; Crum-Cianflone, Nancy F

2016-06-01

Necrotizing fasciitis is a severe, life-threatening infection.  Serratia marcescens, a Gram-negative bacterium, is an extremely rare cause of necrotizing fasciitis. A case of S. marcescens necrotizing fasciitis is described, and a comprehensive review of the literature (1966-2015) of monomicrobial cases due to this organism performed. We report the first case of S. marcescens necrotizing fasciitis in the setting of calciphylaxis associated with end-stage renal disease.  A comprehensive review of the literature of S. marcescens necrotizing fasciitis is provided to enhance the awareness of this increasingly recognized infection, and to provide a concise summary of risk factors, treatment, and outcome. Our case and review highlight the potential risk factors for S. marcescens necrotizing fasciitis, including underlying renal disease and open wounds, and demonstrate the emergence of this organism as a cause of severe, life-threatening soft tissue infections.

Development and transmission of antimicrobial resistance among Gram-negative bacteria in animals and their public health impact.

PubMed

Mukerji, Shewli; O'Dea, Mark; Barton, Mary; Kirkwood, Roy; Lee, Terence; Abraham, Sam

2017-02-28

Gram-negative bacteria are known to cause severe infections in both humans and animals. Antimicrobial resistance (AMR) in Gram-negative bacteria is a major challenge in the treatment of clinical infections globally due to the propensity of these organisms to rapidly develop resistance against antimicrobials in use. In addition, Gram-negative bacteria possess highly efficient mechanisms through which the AMR can be disseminated between pathogenic and commensal bacteria of the same or different species. These unique traits of Gram-negative bacteria have resulted in evolution of Gram-negative bacterial strains demonstrating resistance to multiple classes of antimicrobials. The evergrowing resistance issue has not only resulted in limitation of treatment options but also led to increased treatment costs and mortality rates in humans and animals. With few or no new antimicrobials in production to combat severe life-threatening infections, AMR has been described as the one of the most severe, long-term threats to human health. Aside from overuse and misuse of antimicrobials in humans, another factor that has exacerbated the emergence of AMR in Gram-negative bacteria is the veterinary use of antimicrobials that belong to the same classes considered to be critically important for treating serious life-threatening infections in humans. Despite the fact that development of AMR dates back to before the introduction of antimicrobials, the recent surge in the resistance towards all available critically important antimicrobials has emerged as a major public health issue. This review thus focuses on discussing the development, transmission and public health impact of AMR in Gram-negative bacteria in animals. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

[Streptococcal mediastinitis after thyroidectomy. A literature review].

PubMed

Bures, C; Zielinski, V; Klatte, T; Swietek, N; Kober, F; Tatzgern, E; Bobak-Wieser, R; Gschwandtner, E; Gilhofer, M; Wechsler-Fördös, A; Hermann, M

2015-12-01

Surgical site infections after thyroid surgery are mostly superficial and can be well treated. Streptococcal mediastinitis in contrast is a rare but life-threatening complication. A 57-year-old female patient experienced septic fever, increase of inflammation parameters and erythema 2 days after thyroid surgery for Graves' disease. This process was triggered by a three-compartment infection by group A Streptococcus (GAS) with involvement of the mediastinum. Therapy over 6 weeks including seven wound revisions with the patient under general anesthesia, pathogen-adapted antibiotic treatment and cervical negative pressure treatment managed to control the infection. A total of 21 cases have been published on this phenomenon, 11 of which had a fatal outcome. High fever and surgical site erythema in the early postoperative period after thyroid surgery can be signs of a GAS infection, which might lead to necrotizing, descending, life-threatening mediastinitis. Early diagnosis with support of computed tomography (CT) scans, immediate therapy including wound opening, lavage, intravenous antibiotic treatment with penicillin and clindamycin are vital. If treatment resistance occurs, cervical negative pressure treatment should be considered.

Monomicrobial necrotizing fasciitis in a single center: the emergence of Gram-negative bacteria as a common pathogen.

PubMed

Yahav, D; Duskin-Bitan, H; Eliakim-Raz, N; Ben-Zvi, H; Shaked, H; Goldberg, E; Bishara, J

2014-11-01

Necrotizing fasciitis (NF) is a life-threatening soft tissue infection. It is usually caused by Streptococcus pyogenes and other Gram-positive bacteria. Several reports, however, emphasize the importance of Gram-negative rods in this infection. We retrospectively studied all cases of monomicrobial necrotizing fasciitis hospitalized in our center during the years 2002-2012. We compared clinical characteristics and outcomes of patients with Gram-negative versus Gram-positive infection. Forty-five cases were reviewed, 19 caused by Gram-negative organisms, 10 of them Escherichia coli, and 26 caused by Gram-positive organisms, 10 of them S. pyogenes. Compared to Gram-positive infections, patients with Gram-negative infections were more likely to have a baseline malignancy (9/19, 47.4%) or to have undergone recent surgery (4/19, 42.3%). The 30-day mortality was higher among Gram-negative infected patients (8/19, 42.1% vs. 8/26, 30.8%). Creatine phosphokinase (CPK) was elevated in a minority of patients with Gram-negative necrotizing fasciitis, and its absolute value was lower than in Gram-positive necrotizing fasciitis. In our center, 42% of monomicrobial necrotizing fasciitis cases were found to be caused by Gram-negative organisms, mostly E. coli. These infections usually appeared in immunocompromised or postoperative patients, often presented with normal CPK levels, and were associated with high mortality rates.

Parallels in amphibian and bat declines from pathogenic fungi.

PubMed

Eskew, Evan A; Todd, Brian D

2013-03-01

Pathogenic fungi have substantial effects on global biodiversity, and 2 emerging pathogenic species-the chytridiomycete Batrachochytrium dendrobatidis, which causes chytridiomycosis in amphibians, and the ascomycete Geomyces destructans, which causes white-nose syndrome in hibernating bats-are implicated in the widespread decline of their vertebrate hosts. We synthesized current knowledge for chytridiomycosis and white-nose syndrome regarding disease emergence, environmental reservoirs, life history characteristics of the host, and host-pathogen interactions. We found striking similarities between these aspects of chytridiomycosis and white-nose syndrome, and the research that we review and propose should help guide management of future emerging fungal diseases.

Host cell interactions of outer membrane vesicle-associated virulence factors of Enterohemorrhagic Escherichia coli O157: intracellular delivery, trafficking and mechanisms of cell injury

USDA-ARS?s Scientific Manuscript database

Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, confocal laser...

Arboviruses associated with human disease in Australia.

PubMed

Russell, R C; Dwyer, D E

2000-11-01

Mosquito-borne arboviruses are an important public health issue in Australia. The alphaviruses Ross River and Barmah Forest virus are widespread and active annually, and cause debilitating polyarthritis. The flaviviruses Murray Valley encephalitis, Kunjin and Japanese encephalitis virus are restricted in distribution and activity but may cause life-threatening illness, and dengue viruses are active in some areas.

Isolation and purification of antigenic components of Cryptococcus.

PubMed

Wozniak, Karen L; Levitz, Stuart M

2009-01-01

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

Leaning in to the power of the possible: the crucial role of women scientists on preventing Haemophilus influenzae type b disease.

PubMed

O'Brien, Katherine L; Anderson, Porter W

2014-03-01

Beginning in an era when female scientists were a lonely minority, women have made major contributions to our understanding of Haemophilus influenzae type b (Hib) as a pathogen, its treatment and its prevention. The individual scientific and public health contributions, and their collective impact, are reviewed in the context of the development and successful implementation of highly efficacious Hib vaccines that are now being deployed to nearly every country worldwide for the prevention of life-threatening pediatric Hib disease.

Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing

PubMed Central

Martin, MA; Klein, TE; Dong, BJ; Pirmohamed, M; Haas, DW; Kroetz, DL

2012-01-01

Human leukocyte antigen B (HLA-B) is responsible for presenting peptides to immune cells and plays a critical role in normal immune recognition of pathogens. A variant allele, HLA-B★57:01, is associated with increased risk of a hypersensitivity reaction to the anti-HIV drug abacavir. In the absence of genetic prescreening, hypersensitivity affects ∼6% of patients and can be life-threatening with repeated dosing. We provide recommendations (updated periodically at http://www.pharmkgb.org) for the use of abacavir based on HLA-B genotype. PMID:22378157

Hacker within! Ehrlichia chaffeensis Effector Driven Phagocyte Reprogramming Strategy

PubMed Central

Lina, Taslima T.; Farris, Tierra; Luo, Tian; Mitra, Shubhajit; Zhu, Bing; McBride, Jere W.

2016-01-01

Ehrlichia chaffeensis is a small, gram negative, obligately intracellular bacterium that preferentially infects mononuclear phagocytes. It is the etiologic agent of human monocytotropic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms that underlie Ehrlichia host cellular reprogramming strategies that enable intracellular survival. PMID:27303657

Life-Threatening Atypical Case of Acute Generalized Exanthematous Pustulosis.

PubMed

Tajmir-Riahi, Azadeh; Wörl, Petra; Harrer, Thomas; Schliep, Stefan; Schuler, Gerold; Simon, Miklos

2017-01-01

Antibiotics are known to cause severe cutaneous adverse reactions, such as the rare acute generalized exanthematous pustulosis (AGEP). Unlike Stevens-Johnson syndrome or toxic epidermal necrolysis, AGEP is rarely life-threatening. Systemic involvement is not typical, and if present usually coincides with a mild elevation of the hepatic enzymes and a decrease in renal function. Hence, AGEP is known to have a good prognosis and to be life-threatening only in elderly patients or patients with chronic diseases. Herein, we report a case of AGEP in a young healthy male leading to systemic inflammatory response syndrome and to treatment in an intensive care unit after being treated with 5 different antibiotics. Initial symptoms were not indicative for AGEP and the patient's course of disease led promptly to critical cardiorespiratory symptoms and systemic inflammatory response syndrome. We assume that the administration of the 5 different antibiotics resulted in type IV allergy as well as secondary infection with Enterococcus faecium and Staphylococcus aureus, while the underlying periodontitis also contributed to the severity of this case. © 2017 S. Karger AG, Basel.

Inhibitory effect of streptococci on the growth of M. catarrhalis strains and the diversity of putative bacteriocin-like gene loci in the genomes of S. pneumoniae and its relatives.

PubMed

Ikryannikova, L N; Malakhova, M V; Lominadze, G G; Karpova, I Yu; Kostryukova, E S; Mayansky, N A; Kruglov, A N; Klimova, E A; Lisitsina, E S; Ilina, E N; Govorun, V M

2017-12-13

S. pneumoniae is a facultative human pathogen causing a wide range of infections including the life-threatening pneumoniae or meningitis. It colonizes nasopharynx as well as its closest phylogenetic relatives S. pseudopneumoniae and S. mitis. Both the latter, despite the considerable morphological and phenotypic similarity with the pneumococcus, are considerably less pathogenic for humans and cause infections mainly in the immunocompromized hosts. In this work, we compared the inhibitory effect of S. pneumoniae and its relatives on the growth of Moraxella catarrhalis strains using the culture-based antagonistic test. We observed that the inhibitory effect of S. mitis strains is kept when a hydrogen peroxide produced by cells is inactivated by catalase, and even when the live cells are killed in chloroform vapors, in contrast to the pneumococcus whose inhibiting ability disappeared when the cells die. It was suggested that this effect may be due to the production of bacterial antimicrobial peptides by S. mitis, so we examined the genomes of our strains for the presence of bacteriocin-like peptides encoding genes. We observed that a set of bacteriocin-like genes in the genome of S. mitis is greatly poorer in comparison with S. pneumoniae one; moreover, in one S. mitis strain we found no bacteriocin-like genes. It could mean that there are probably some additional opportunities of S. mitis to inhibit the growth of competing neighbors which are still have to be discovered.

Life After the Event: A Review of Basic Life Support Training for Parents Following Apparent Life-Threatening Events and Their Experience and Practices Following Discharge.

PubMed

Macken, W L; Clarke, N; Nadeem, M; Coghlan, D

2017-05-10

Apparent Life-Threatening Events (ALTEs) are a common presentation to paediatric hospitals and represent a significant cause of parental anxiety. Basic Life Support (BLS) training is recommended for all caregivers following ALTEs. This study aimed to assess the rate of caregiver BLS training and reviewed parents experience following discharge. Parents were interviewed by phone following discharge. Over the study period 25 children attended the Emergency Department with ALTE, 17/25 (68%) were trained and 13/17 (76%) were contactable for interview. All parents found training decreased their anxiety level and were interested in attending for re-training. BLS resuscitation was subsequently required by 2/13 (15%) of children. Non-medical grade monitors were in use by 10/13 (77%) of caregivers following discharge. Caregivers are eager to engage in BLS training and it effectively reduces their caregiver anxiety. We recommend an increase in instructor staff and use of group re-training post discharge.

Integrated genomics of Mucorales reveals novel therapeutic targets

USDA-ARS?s Scientific Manuscript database

Mucormycosis is a life-threatening infection caused by Mucorales fungi. We sequenced 30 fungal genomes and performed transcriptomics with three representative Rhizopus and Mucor strains with human airway epithelial cells during fungal invasion to reveal key host and fungal determinants contributing ...

Synthesis of natural acylphloroglucinol-based antifungal compounds against Cryptococcus species

USDA-ARS?s Scientific Manuscript database

Thirty-five analogs of naturally occurring acylphloroglucinols were designed and synthesized to identify antifungal compounds against Cryptococcus spp. that causes the life-threatening disseminated cryptococcosis. In vitro antifungal testing showed that 17 compounds were active against C. neoformans...

21 CFR 310.546 - Drug products containing active ingredients offered over-the-counter (OTC) for the treatment and...

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Quinine sulfate may cause unpredictable serious and life-threatening hypersensitivity reactions requiring... commerce that is not in compliance with this section is subject to regulatory action. [59 FR 43252, Aug. 22...

A novel approach of virulome based reverse vaccinology for exploring and validating peptide-based vaccine candidates against the most troublesome nosocomial pathogen: Acinetobacter baumannii.

PubMed

Ahmad, Sajjad; Azam, Syed Sikander

2018-05-05

Acinetobacter baumannii is one of the major cause of nosocomial infections around the globe. The emergence of hyper-virulent strains of the pathogen greatly narrows down therapeutic options for patients infected with this red alert superbug. Development of a peptide-based vaccine can offers an alternative, attractive, and cost-effective remedy for multidrug-resistant A. baumannii associated complications. Herein, we introduced a novel virulome based Reverse Vaccinology for screening peptide based vaccine candidates against A. baumannii and its validation using a negative control. The pipeline screened "FYLNDQPVS" of polysaccharide export outer membrane protein (EpsA) and "LQNNTRRMK" of chaperone-usher pathway protein B (CsuB) as broad-spectrum peptides for induction of targeted immune responses. The 9-mer epitope of both proteins was rendered virulent, antigenic, non-allergen, and highly conserved among thirty-four completely annotated strains. Interactome examination unravels peptides protein direct and indirect interactions with biological significant pathways, essential for A. baumannii pathogenesis and survival. Protein-peptide docking aids in addition by unveiling deep binding of the epitopes in the active site of the most prevalent binding allele in the human population-the DRB1*0101. Both the proteins till to date are not characterized for immunoprotective efficacy and desirable to be deciphered experimentally. The designed series of in silico filters rejected few recently reported peptide and non-peptide vaccine targets and has delivered outcomes, which we believe will enrich the existing knowledge of vaccinology against this life-threatening human pathogen. Copyright © 2018 Elsevier Inc. All rights reserved.

Candida albicans-Induced Epithelial Damage Mediates Translocation through Intestinal Barriers

PubMed Central

2018-01-01

ABSTRACT Life-threatening systemic infections often occur due to the translocation of pathogens across the gut barrier and into the bloodstream. While the microbial and host mechanisms permitting bacterial gut translocation are well characterized, these mechanisms are still unclear for fungal pathogens such as Candida albicans, a leading cause of nosocomial fungal bloodstream infections. In this study, we dissected the cellular mechanisms of translocation of C. albicans across intestinal epithelia in vitro and identified fungal genes associated with this process. We show that fungal translocation is a dynamic process initiated by invasion and followed by cellular damage and loss of epithelial integrity. A screen of >2,000 C. albicans deletion mutants identified genes required for cellular damage of and translocation across enterocytes. Correlation analysis suggests that hypha formation, barrier damage above a minimum threshold level, and a decreased epithelial integrity are required for efficient fungal translocation. Translocation occurs predominantly via a transcellular route, which is associated with fungus-induced necrotic epithelial damage, but not apoptotic cell death. The cytolytic peptide toxin of C. albicans, candidalysin, was found to be essential for damage of enterocytes and was a key factor in subsequent fungal translocation, suggesting that transcellular translocation of C. albicans through intestinal layers is mediated by candidalysin. However, fungal invasion and low-level translocation can also occur via non-transcellular routes in a candidalysin-independent manner. This is the first study showing translocation of a human-pathogenic fungus across the intestinal barrier being mediated by a peptide toxin. PMID:29871918

Septic Pulmonary Embolism Requiring Critical Care: Clinicoradiological Spectrum, Causative Pathogens and Outcomes

PubMed Central

Chou, Deng-Wei; Wu, Shu-Ling; Chung, Kuo-Mou; Han, Shu-Chen; Cheung, Bruno Man-Hon

2016-01-01

OBJECTIVES: Septic pulmonary embolism is an uncommon but life-threatening disorder. However, data on patients with septic pulmonary embolism who require critical care have not been well reported. This study elucidated the clinicoradiological spectrum, causative pathogens and outcomes of septic pulmonary embolism in patients requiring critical care. METHODS: The electronic medical records of 20 patients with septic pulmonary embolism who required intensive care unit admission between January 2005 and December 2013 were reviewed. RESULTS: Multiple organ dysfunction syndrome developed in 85% of the patients, and acute respiratory failure was the most common organ failure (75%). The most common computed tomographic findings included a feeding vessel sign (90%), peripheral nodules without cavities (80%) or with cavities (65%), and peripheral wedge-shaped opacities (75%). The most common primary source of infection was liver abscess (40%), followed by pneumonia (25%). The two most frequent causative pathogens were Klebsiella pneumoniae (50%) and Staphylococcus aureus (35%). Compared with survivors, nonsurvivors had significantly higher serum creatinine, arterial partial pressure of carbon dioxide, and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, and they were significantly more likely to have acute kidney injury, disseminated intravascular coagulation and lung abscesses. The in-hospital mortality rate was 30%. Pneumonia was the most common cause of death, followed by liver abscess. CONCLUSIONS: Patients with septic pulmonary embolism who require critical care, especially those with pneumonia and liver abscess, are associated with high mortality. Early diagnosis, appropriate antibiotic therapy, surgical intervention and respiratory support are essential. PMID:27759843

Shared influence of pathogen and host genetics on a trade-off between latent period and spore production capacity in the wheat pathogen, Puccinia triticina.

PubMed

Pariaud, Bénédicte; Berg, Femke; Bosch, Frank; Powers, Stephen J; Kaltz, Oliver; Lannou, Christian

2013-02-01

Crop pathogens are notorious for their rapid adaptation to their host. We still know little about the evolution of their life cycles and whether there might be trade-offs between fitness components, limiting the evolutionary potential of these pathogens. In this study, we explored a trade-off between spore production capacity and latent period in Puccinia triticina, a fungal pathogen causing leaf rust on wheat. Using a simple multivariate (manova) technique, we showed that the covariance between the two traits is under shared control of host and pathogen, with contributions from host genotype (57%), pathogen genotype (18.4%) and genotype × genotype interactions (12.5%). We also found variation in sign and strength of genetic correlations for the pathogen, when measured on different host varieties. Our results suggest that these important pathogen life-history traits do not freely respond to directional selection and that precise evolutionary trajectories are contingent on the genetic identity of the interacting host and pathogen.

TD/GC-MS analysis of volatile markers emitted from mono- and co-cultures of Enterobacter cloacae and Pseudomonas aeruginosa in artificial sputum.

PubMed

Lawal, Oluwasola; Knobel, Hugo; Weda, Hans; Nijsen, Tamara M E; Goodacre, Royston; Fowler, Stephen J

2018-01-01

Infections such as ventilator-associated pneumonia (VAP) can be caused by one or more pathogens. Current methods for identifying these pathogenic microbes often require invasive sampling, and can be time consuming, due to the requirement for prolonged cultural enrichment along with selective and differential plating steps. This results in delays in diagnosis which in such critically ill patients can have potentially life-threatening consequences. Therefore, a non-invasive and timely diagnostic method is required. Detection of microbial volatile organic compounds (VOCs) in exhaled breath is proposed as an alternative method for identifying these pathogens and may distinguish between mono- and poly-microbial infections. To investigate volatile metabolites that discriminate between bacterial mono- and co-cultures. VAP-associated pathogens Enterobacter cloacae and Pseudomonas aeruginosa were cultured individually and together in artificial sputum medium for 24 h and their headspace was analysed for potential discriminatory VOCs by thermal desorption gas chromatography-mass spectrometry. Of the 70 VOCs putatively identified, 23 were found to significantly increase during bacterial culture (i.e. likely to be released during metabolism) and 13 decreased (i.e. likely consumed during metabolism). The other VOCs showed no transformation (similar concentrations observed as in the medium). Bacteria-specific VOCs including 2-methyl-1-propanol, 2-phenylethanol, and 3-methyl-1-butanol were observed in the headspace of axenic cultures of E. cloacae , and methyl 2-ethylhexanoate in the headspace of P. aeruginosa cultures which is novel to this investigation. Previously reported VOCs 1-undecene and pyrrole were also detected. The metabolites 2-methylbutyl acetate and methyl 2-methylbutyrate, which are reported to exhibit antimicrobial activity, were elevated in co-culture only. The observed VOCs were able to differentiate axenic and co-cultures. Validation of these markers in exhaled breath specimens could prove useful for timely pathogen identification and infection type diagnosis.

The Candida albicans Hwp2p can complement the lack of filamentation of a Saccharomyces cerevisiae flo11 null strain.

PubMed

Younes, Samer S; Khalaf, Roy A

2013-06-01

The opportunistic fungal pathogen Candida albicans is one of the leading agents of life-threatening infections affecting immunocompromised individuals. Many factors make C. albicans a successful pathogen. These include the ability to switch between yeast and invasive hyphal morphologies in addition to an arsenal of cell wall virulence factors such as lipases, proteases, dismutases and adhesins that promote the attachment to the host, a prerequisite for invasive growth. We have previously characterized Hwp2, a C. albicans cell wall protein which we found necessary for proper oxidative stress, biofilm formation and adhesion to host cells. Baker's yeast Saccharomyces cerevisiae also possesses adhesins that promote aggregation and flocculence. Flo11 is one such adhesin that has sequence similarity to Hwp2. Here we determined that transforming an HWP2 cassette can complement the lack of filamentation of an S. cerevisiae flo11 null strain and impart on S. cerevisiae adhesive properties similar to those of a pathogen.

Socio-Cultural Matrix of Raising a Child with Food Allergies: Experiences of a Migrant Mother

ERIC Educational Resources Information Center

Sanagavarapu, Prathyusha

2004-01-01

Children with life-threatening food allergies are increasing in number in Australia. A variety of foods such as dairy milk, peanut and tree nuts, fish and egg can cause severe allergic reactions in some children. The foods that cause allergies could trigger severe breathing difficulties (anaphylaxis) for these children and, if not treated…

Ecological investigations to select mitigation options to reduce vehicle-caused mortality of a threatened butterfly

Treesearch

Sara B. Zielin; Jalene Littlejohn; Catherine E. de Rivera; Winston P. Smith; Sandra L. Jacobson

2016-01-01

Whereas roads that bisect habitat are known to decrease population size through animal-vehicle collisions or interruption of key life history events, it is not always obvious how to reduce such impacts, especially for flying organisms. We needed a quick, cost-efficient and effective way to determine how best to decrease vehicle-caused mortality while maintaining...

Recombinant Expression of a Genome-encoded N-acetylmuramoyl-L-alanine Amidase that Synergistically Lyses Listeria monocytogenes Biofilms with a Protease

USDA-ARS?s Scientific Manuscript database

Listeria monocytogenes plays a significant role in human food-borne disease caused by eating food contaminated with the bacterium and although incidence is low it is a leading cause of life-threatening, bacterial food-borne disease in humans. L. monocytogenes serotypes 1/2a and 4b can form mixed-cu...

Embolization of a Hemorrhoid Following 18 Hours of Life-Threatening Bleeding

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

Berczi, Viktor, E-mail: berczi@hotmail.com; Gopalan, Deepa; Cleveland, Trevor J

2008-01-15

Hemorrhoids usually do not pose diagnostic difficulties and they rarely cause massive bleeding. We report a case of massive rectal bleeding over 18 h needing 22 U blood transfusion treated by superselective transcatheter coil embolization 12 h following operative treatment performed in a different hospital. Diagnostic angiography with a view to superselective embolization, following failure of sigmoidoscopy to localize and treat the cause of hemorrhage, might act as a life-saving treatment in massive rectal bleeding, obviating the need for repeated endoscopy or emergency surgery.

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2013 CFR

2013-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2012 CFR

2012-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

Host-like carbohydrates promote bloodstream survival of Vibrio vulnificus in vivo.

PubMed

Lubin, Jean-Bernard; Lewis, Warren G; Gilbert, Nicole M; Weimer, Cory M; Almagro-Moreno, Salvador; Boyd, E Fidelma; Lewis, Amanda L

2015-08-01

Sialic acids are found on all vertebrate cell surfaces and are part of a larger class of molecules known as nonulosonic acids. Many bacterial pathogens synthesize related nine-carbon backbone sugars; however, the role(s) of these non-sialic acid molecules in host-pathogen interactions is poorly understood. Vibrio vulnificus is the leading cause of seafood-related death in the United States due to its ability to quickly access the host bloodstream, which it can accomplish through gastrointestinal or wound infection. However, little is known about how this organism persists systemically. Here we demonstrate that sialic acid-like molecules are present on the lipopolysaccharide of V. vulnificus, are required for full motility and biofilm formation, and also contribute to the organism's natural resistance to polymyxin B. Further experiments in a murine model of intravenous V. vulnificus infection demonstrated that expression of nonulosonic acids had a striking benefit for bacterial survival during bloodstream infection and dissemination to other tissues in vivo. In fact, levels of bacterial persistence in the blood corresponded to the overall levels of these molecules expressed by V. vulnificus isolates. Taken together, these results suggest that molecules similar to sialic acids evolved to facilitate the aquatic lifestyle of V. vulnificus but that their emergence also resulted in a gain of function with life-threatening potential in the human host. Copyright © 2015, Lubin et al.

Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay.

PubMed

Heintz-Buschart, Anna; Eickhoff, Holger; Hohn, Erwin; Bilitewski, Ursula

2013-03-10

Candida albicans is one of the most common opportunistic fungal pathogens, causing life-threatening disease in immunocompromised patients. As it is not primarily a pathogen, but can exist in a commensal state, we aimed at the identification of new anti-infective compounds which do not eradicate the fungus, but primarily disable a virulence determinant. The yeast–hyphae-dimorphism of C. albicans is considered a major contributor to fungal disease, as mutants locked into either yeast or hyphal state have been shown to be less virulent in the mouse-model. We devised a high-throughput screening procedure which allows us to find inhibitors of the induction of hyphae. Hyphae-formation was induced by nitrogen starvation at 37 °C and neutral pH in a reporter strain, which couples promoter activity of the hyphae-specific HWP1 to β-galactosidase expression. In a pilot screening of 720 novel synthetic compounds, we identified substances which inhibited the outgrowth of germ tubes. They belonged to chemical classes not yet known for antimycotic properties, namely methyl aryl-oxazoline carboxylates, dihydrobenzo[d]isoxazolones and thiazolo[4,5-e]benzoisoxazoles. In conclusion we developed a novel screening assay, which addresses the morphological switch from the yeast form of C. albicans to its hyphal form and identified novel chemical structures with activity against C. albicans. Copyright © 2012 Elsevier B.V. All rights reserved.

The water channel protein aquaporin 1 regulates cellular metabolism and competitive fitness in a global fungal pathogen Cryptococcus neoformans.

PubMed

Meyers, Gena Lee; Jung, Kwang-Woo; Bang, Soohyun; Kim, Jungyeon; Kim, Sooah; Hong, Joohyeon; Cheong, Eunji; Kim, Kyoung Heon; Bahn, Yong-Sun

2017-06-01

In this study, an aquaporin protein, Aqp1, in Cryptococcus neoformans, which can lead either saprobic or parasitic lifestyles and causes life-threatening fungal meningitis was identified and characterized. AQP1 expression was rapidly induced (via the HOG pathway) by osmotic or oxidative stress. In spite of such transcriptional regulation, Aqp1 was found to be largely unnecessary for adaptation to diverse environmental stressors, regardless of the presence of the polysaccharide capsule. The latter is shown here to be a key environmental-stress protectant for C. neoformans. Furthermore, Aqp1 was not required for the development and virulence of C. neoformans. Deletion of AQP1 increased hydrophobicity of the cell surface. The comparative metabolic profiling analysis of the aqp1Δ mutant and AQP1-overexpressing strains revealed that deletion of AQP1 significantly increased cellular accumulation of primary and secondary metabolites, whereas overexpression of AQP1 depleted such metabolites, suggesting that this water channel protein performs a critical function in metabolic homeostasis. In line with this result, it was found that the aqp1Δ mutant (which is enriched with diverse metabolites) survived better than the wild type and a complemented strain, indicating that Aqp1 is likely to be involved in competitive fitness of this fungal pathogen. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Protective mucosal Th2 immune response against Toxoplasma gondii by murine mesenteric lymph node dendritic cells.

PubMed

Dimier-Poisson, Isabelle; Aline, Fleur; Mévélec, Marie-Noëlle; Beauvillain, Céline; Buzoni-Gatel, Dominique; Bout, Daniel

2003-09-01

Toxoplasma gondii, an obligate intracellular parasite pathogen which initially invades the intestinal epithelium before disseminating throughout the body, may cause severe sequelae in fetuses and life-threatening neuropathy in immunocompromised patients. Immune protection is usually thought to be performed through a systemic Th1 response; considering the route of parasite entry it is important to study and characterize the local mucosal immune response to T. gondii. Despite considerable effort, Toxoplasma-targeted vaccines have proven to be elusive using conventional strategies. We report the use of mesenteric lymph node dendritic cells (MLNDCs) pulsed ex vivo with T. gondii antigens (TAg) as a novel investigation approach to vaccination against T. gondii-driven pathogenic processes. Using a murine model, we demonstrate in two genetically distinct mouse strains (C57BL/6 and CBA/J) that adoptively transferred TAg-pulsed MLNDCs elicit a mucosal Toxoplasma-specific Th2-biased immune response in vivo and confer strong protection against infection. We also observe that MLNDCs mostly traffic to the intestine where they enhance resistance by reduction in the mortality and in the number of brain cysts. Thus, ex vivo TAg-pulsed MLNDCs represent a powerful tool for the study of protective immunity to T. gondii, delivered through its natural route of entry. These findings might impact the design of vaccine strategies against other invasive microorganisms known to be delivered through digestive tract.

Glucosylceramide Administration as a Vaccination Strategy in Mouse Models of Cryptococcosis.

PubMed

Mor, Visesato; Farnoud, Amir M; Singh, Ashutosh; Rella, Antonella; Tanno, Hiromasa; Ishii, Keiko; Kawakami, Kazuyoshi; Sato, Toshiya; Del Poeta, Maurizio

2016-01-01

Cryptococcus neoformans is an opportunistic fungal pathogen and the causative agent of the disease cryptococcosis. Cryptococcosis is initiated as a pulmonary infection and in conditions of immune deficiency disseminates to the blood stream and central nervous system, resulting in life-threatening meningoencephalitis. A number of studies have focused on the development of a vaccine against Cryptococcus, primarily utilizing protein-conjugated components of the Cryptococcus polysaccharide capsule as antigen. However, there is currently no vaccine against Cryptococcus in the clinic. Previous studies have shown that the glycosphingolipid, glucosylceramide (GlcCer), is a virulence factor in C. neoformans and antibodies against this lipid inhibit fungal growth and cell division. In the present study, we have investigated the possibility of using GlcCer as a therapeutic agent against C. neoformans infections in mouse models of cryptococcosis. GlcCer purified from a non-pathogenic fungus, Candida utilis, was administered intraperitoneally, prior to infecting mice with a lethal dose of C. neoformans. GlcCer administration prevented the dissemination of C. neoformans from the lungs to the brain and led to 60% mouse survival. GlcCer administration did not cause hepatic injury and elicited an anti-GlcCer antibody response, which was observed independent of the route of administration and the strains of mouse. Taken together, our results suggest that fungal GlcCer can protect mice against lethal doses of C. neoformans infection and can provide a viable vaccination strategy against Cryptococcus.

Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

PubMed Central

2014-01-01

SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology practice. However, identification of some strains will still be problematic, necessitating DNA sequencing of multiple housekeeping gene fragments or full-length 16S rRNA genes. PMID:24696434

Life history trade-offs and relaxed selection can decrease bacterial virulence in environmental reservoirs.

PubMed

Mikonranta, Lauri; Friman, Ville-Petri; Laakso, Jouni

2012-01-01

Pathogen virulence is usually thought to evolve in reciprocal selection with the host. While this might be true for obligate pathogens, the life histories of opportunistic pathogens typically alternate between within-host and outside-host environments during the infection-transmission cycle. As a result, opportunistic pathogens are likely to experience conflicting selection pressures across different environments, and this could affect their virulence through life-history trait correlations. We studied these correlations experimentally by exposing an opportunistic bacterial pathogen Serratia marcescens to its natural protist predator Tetrahymena thermophila for 13 weeks, after which we measured changes in bacterial traits related to both anti-predator defence and virulence. We found that anti-predator adaptation (producing predator-resistant biofilm) caused a correlative attenuation in virulence. Even though the direct mechanism was not found, reduction in virulence was most clearly connected to a predator-driven loss of a red bacterial pigment, prodigiosin. Moreover, life-history trait evolution was more divergent among replicate populations in the absence of predation, leading also to lowered virulence in some of the 'predator absent' selection lines. Together these findings suggest that the virulence of non-obligatory, opportunistic bacterial pathogens can decrease in environmental reservoirs through life history trade-offs, or random accumulation of mutations that impair virulence traits under relaxed selection.

Aerobic vaginal pathogens and their sensitivity pattern.

PubMed

Mumtaz, Shamim; Ahmad, Mumtaz; Aftab, Irum; Akhtar, Naeem; ul Hassan, Masood; Hamid, Abdul

2008-01-01

The vaginal flora is a complicated environment, containing dozens of microbiological species in variable quantities and relative proportions. The frequent cause of vaginal discharge is an infection or colonization with different microorganisms. Some pathologic conditions causing vaginitis are well defined yet, 7-72% of women with vaginitis may remain undiagnosed and such forms of abnormal vaginal flora neither considered as normal, nor can be called bacterial vaginosis have been termed as 'intermediate flora' and its management probably differ from that of bacterial vaginosis. It is of crucial importance in pregnant females at risk of preterm delivery. The present study has been conducted especially to elucidate this type of aerobic vaginal isolates and their culture and sensitivity towards currently used antibiotics. This study was conducted at the Microbiology Department of Fauji Foundation Hospital, Rawalpindi over a period of two years (April 2004-March 2006). One thousand, nine hundred and twenty three high vaginal swabs, both from indoor and outdoor patients were collected, cultured and their susceptibility to various antibiotics was determined. Significant growth was obtained in 731 samples. The highest frequency of infection (39.5%) was observed at 31-40 years followed by 41-50 years (35.8%). About 76% were from outdoor and 24% were from indoor patients. Staphylococcus aureus was the most prevalent vaginal pathogen at 11-60 yrs & with highest prevalence at 31-40 years followed by 41-50 years. It was a predominant pathogen in both indoor (35%) as well as outdoor (41.6%) patients, followed by enteric gram-negative bacilli and other gram-positive cocci. There were very few antibiotics among the conventionally available aminoglycosides, third generation cephalosporins, penicillin, quinolones, sulfonamides and tetracyclines possessing good sensitivity (> 80%) against any one the common aerobic vaginal pathogens. The effective chemotherapeutics agents belong to the groups of carbapenems and beta-lactams beta-lactamase inhibitor combinations. The high prevalence of gynaecological infections demands that the patients with gynaecological symptoms be investigated thoroughly. Culture must invariably be done. Currently the antibiotics showing good sensitivity are very expensive. So there is a need for an effective antimicrobial policy. Effective drug should be reserved for the treatment of serious life threatening situations only.

Life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite in the construction sites.

PubMed

Sohn, C H; Seo, D W; Ryoo, S M; Lee, J H; Kim, W Y; Lim, K S; Oh, B J

2014-01-01

Construction workers are exposed to a wide variety of health hazards such as poisoning at the construction sites. Various forms of poisoning incidents in construction workers have been reported. However, studies on methemoglobinemia caused by unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites have not been reported yet. The aim of this study was to evaluate life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites and describe similar incidents involving ingestion of antifreeze admixtures in Korea. Retrospective observational case series study on patients with methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite admitted to the emergency department (ED) from January 1, 2010 to December 31, 2012 and cases reported to the Korea Occupational Safety and Health Agency (KOSHA) was performed. Results. Six victims were admitted to our ED. They had methemoglobin levels ranging from 32.4% to 71.5% and all of them recovered after receiving one (2 mg/kg) or two doses infusion of methylene blue. From the data of the KOSHA, six incidents that caused 27 victims were identified. Of 27 victims, five were included in the ED cases. For all incidents, antifreeze admixtures were not contained in their original containers and all new containers did not have a new label. All workers mistook antifreeze admixtures for water. Among the 28 victims included in this study, four died. Unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites can cause life-threatening methemoglobinemia. There is a need to store and label potentially hazardous materials properly to avoid unintentional ingestion at the construction sites.

Respiratory Diseases among U.S. Military Personnel: Countering Emerging Threats

PubMed Central

Callahan, Johnny D.; Hawksworth, Anthony W.; Fisher, Carol A.; Gaydos, Joel C.

1999-01-01

Emerging respiratory disease agents, increased antibiotic resistance, and the loss of effective vaccines threaten to increase the incidence of respiratory disease in military personnel. We examine six respiratory pathogens (adenoviruses, influenza viruses, Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma pneumoniae, and Bordetella pertussis) and review the impact of the diseases they cause, past efforts to control these diseases in U.S. military personnel, as well as current treatment and surveillance strategies, limitations in diagnostic testing, and vaccine needs. PMID:10341174

Photodynamic therapy in peri-implantitis

NASA Astrophysics Data System (ADS)

Leretter, Marius; Cândea, Adrian; Topala, Florin

2014-01-01

Peri-implantitis is like Damocles sword, threatening over our final results as is the most common cause of implant failure. It is, was and will be one of the most challenging tasks for the practitioner to deal with. The rough implant surface offers the ideal conditions for the pathogenic bacteria to stick and multiply. Even more, the growing mature biofilm is harder to eliminate. Mechanical cleaning and rinsing is not capable to destroy it entirely. Most treatment protocols include strong antibiotics, disregarding their side effects and interactions with other medications.

[Jellyfish and poison-producing animals that endanger swimmers].

PubMed

Litschauer-Poursadrollah, M; Mayer, D E; Hemmer, W; Jarisch, R

2010-05-01

Exposure to fresh water as well as to sea water can cause unpleasant consequences. The water of lakes or biotopes may be the reason for severe itching reactions on exposed skin, caused by cercariae. Exposure to seawater may lead to skin affections including itching or burning urticarial lesions as well as life threatening reactions. The causes for these reactions are especially species of jellyfish. (c) Georg Thieme Verlag KG Stuttgart. New York.

The Pathogen-Host Interactions database (PHI-base): additions and future developments

PubMed Central

Urban, Martin; Pant, Rashmi; Raghunath, Arathi; Irvine, Alistair G.; Pedro, Helder; Hammond-Kosack, Kim E.

2015-01-01

Rapidly evolving pathogens cause a diverse array of diseases and epidemics that threaten crop yield, food security as well as human, animal and ecosystem health. To combat infection greater comparative knowledge is required on the pathogenic process in multiple species. The Pathogen-Host Interactions database (PHI-base) catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and protist pathogens. Mutant phenotypes are associated with gene information. The included pathogens infect a wide range of hosts including humans, animals, plants, insects, fish and other fungi. The current version, PHI-base 3.6, available at http://www.phi-base.org, stores information on 2875 genes, 4102 interactions, 110 host species, 160 pathogenic species (103 plant, 3 fungal and 54 animal infecting species) and 181 diseases drawn from 1243 references. Phenotypic and gene function information has been obtained by manual curation of the peer-reviewed literature. A controlled vocabulary consisting of nine high-level phenotype terms permits comparisons and data analysis across the taxonomic space. PHI-base phenotypes were mapped via their associated gene information to reference genomes available in Ensembl Genomes. Virulence genes and hotspots can be visualized directly in genome browsers. Future plans for PHI-base include development of tools facilitating community-led curation and inclusion of the corresponding host target(s). PMID:25414340

Molecular Mechanisms of Bacterial Pathogenicity

NASA Astrophysics Data System (ADS)

Fuchs, Thilo Martin

Cautious optimism has arisen over recent decades with respect to the long struggle against bacteria, viruses, and parasites. This has been offset, however, by a fatal complacency stemming from previous successes such as the development of antimicrobial drugs, the eradication of smallpox, and global immunization programs. Infectious diseases nevertheless remain the world's leading cause of death, killing at least 17 million persons annually [61]. Diarrheal diseases caused by Vibrio cholerae or Shigella dysenteriae kill about 3 million persons every year, most of them young children: Another 4 million die of tuberculosis or tetanus. Outbreaks of diphtheria in Eastern Europe threatens the population with a disease that had previously seemed to be overcome. Efforts to control infectious diseases more comprehensively are undermined not only by socioeconomic conditions but also by the nature of the pathogenic organisms itself; some isolates of Staphylococcus aureus and Enterobacter have become so resistant to drugs by horizontal gene transfer that they are almost untreatable. In addition, the mechanism of genetic variability helps pathogens to evade the human immune system, thus compromising the development of powerful vaccines. Therefore detailed knowledge of the molecular mechanisms of microbial pathogenicity is absolutely necessary to develop new strategies against infectious diseases and thus to lower their impact on human health and social development.

Wildlife trade and global disease emergence.

PubMed

Karesh, William B; Cook, Robert A; Bennett, Elizabeth L; Newcomb, James

2005-07-01

The global trade in wildlife provides disease transmission mechanisms that not only cause human disease outbreaks but also threaten livestock, international trade, rural livelihoods, native wildlife populations, and the health of ecosystems. Outbreaks resulting from wildlife trade have caused hundreds of billions of dollars of economic damage globally. Rather than attempting to eradicate pathogens or the wild species that may harbor them, a practical approach would include decreasing the contact rate among species, including humans, at the interface created by the wildlife trade. Since wildlife marketing functions as a system of scale-free networks with major hubs, these points provide control opportunities to maximize the effects of regulatory efforts.

Does decisional conflict differ across race and ethnicity groups? A study of parents whose children have a life-threatening illness.

PubMed

Knapp, Caprice; Sberna-Hinojosa, Melanie; Baron-Lee, Jacqueline; Curtis, Charlotte; Huang, I-Chan

2014-05-01

Children with life-threatening illnesses and their families may face a myriad of medical decisions in their lifetimes. Oftentimes these complicated medical decisions cause disagreements among patients, families, and providers about what is the best course of action. Although no evidence exists, it is possible that conflict may affect subgroups of the population differently. This study aims to investigate how decisional conflict varies among racial and ethnic subgroups. Two hundred sixty-six surveys were completed with parents whose children have a life-threatening illness. All children lived in Florida and were enrolled in the Medicaid program. The Decisional Conflict Scale, overall and broken down into its five distinct subscales, was used to assess parental decision-making. Descriptive, bivariate, and multivariate analyses were conducted. Subgroup analyses were conducted on Latino respondents. Our bivariate results suggest that minority parents report less Effective Decision Making (p<0.05) and report less Support in Decision Making (p<0.05) compared to white, non-Hispanic parents. For the subgroup analysis, we found that those who identify as Mexican American and Central/South American report having greater Uncertainty in Choosing Options (p<0.05) and less Values Clarity (p<0.05) as compared to Puerto Rican or Cuban Americans. Results from the multivariate analyses suggest that those whose primary language is not English are associated with greater Uncertainty in Choosing Options (p<0.05). Values Clarity was lower for children who were diagnosed with their life-threatening condition at birth (p<0.05) as compared to children diagnosed at a later time. Our study is the first to describe racial and ethnic differences in decisional conflict of parents of children with life-threatening illnesses. Significant differences exist by race, ethnicity, language spoken, and diagnosis time across several subdomains of decisional conflict. These differences are important to address when creating clinical care plans, engaging in shared decision-making, and creating interventions to alleviate decisional conflict.

Challenges in predicting climate and environmental effects on vector-borne disease episystems in a changing world.

PubMed

Tabachnick, W J

2010-03-15

Vector-borne pathogens cause enormous suffering to humans and animals. Many are expanding their range into new areas. Dengue, West Nile and Chikungunya have recently caused substantial human epidemics. Arthropod-borne animal diseases like Bluetongue, Rift Valley fever and African horse sickness pose substantial threats to livestock economies around the world. Climate change can impact the vector-borne disease epidemiology. Changes in climate will influence arthropod vectors, their life cycles and life histories, resulting in changes in both vector and pathogen distribution and changes in the ability of arthropods to transmit pathogens. Climate can affect the way pathogens interact with both the arthropod vector and the human or animal host. Predicting and mitigating the effects of future changes in the environment like climate change on the complex arthropod-pathogen-host epidemiological cycle requires understanding of a variety of complex mechanisms from the molecular to the population level. Although there has been substantial progress on many fronts the challenges to effectively understand and mitigate the impact of potential changes in the environment on vector-borne pathogens are formidable and at an early stage of development. The challenges will be explored using several arthropod-borne pathogen systems as illustration, and potential avenues to meet the challenges will be presented.

The impact of Staphylococcus aureus-associated molecular patterns on staphylococcal superantigen-induced toxic shock syndrome and pneumonia.

PubMed

Tilahun, Ashenafi Y; Karau, Melissa; Ballard, Alessandro; Gunaratna, Miluka P; Thapa, Anusa; David, Chella S; Patel, Robin; Rajagopalan, Govindarajan

2014-01-01

Staphylococcus aureus is capable of causing a spectrum of human illnesses. During serious S. aureus infections, the staphylococcal pathogen-associated molecular patterns (PAMPs) such as peptidoglycan, lipoteichoic acid, and lipoproteins and even intact S. aureus, are believed to act in conjunction with the staphylococcal superantigens (SSAg) to activate the innate and adaptive immune system, respectively, and cause immunopathology. However, recent studies have shown that staphylococcal PAMPs could suppress inflammation by several mechanisms and protect from staphylococcal toxic shock syndrome, a life-threatening systemic disease caused by toxigenic S. aureus. Given the contradictory pro- and anti-inflammatory roles of staphylococcal PAMPs, we examined the effects of S. aureus-derived molecular patterns on immune responses driven by SSAg in vivo using HLA-DR3 and HLA-DQ8 transgenic mice. Our study showed that neither S. aureus-derived peptidoglycans (PGN), lipoteichoic acid (LTA), nor heat-killed Staphylococcus aureus (HKSA) inhibited SSAg-induced T cell proliferation in vitro. They failed to antagonize the immunostimulatory effects of SSAg in vivo as determined by their inability to attenuate systemic cytokine/chemokine response and reduce SSAg-induced T cell expansion. These staphylococcal PAMPs also failed to protect HLA-DR3 as well as HLA-DQ8 transgenic mice from either SSAg-induced toxic shock or pneumonia induced by a SSAg-producing strain of S. aureus.

Point-of-care G6PD diagnostics for Plasmodium vivax malaria is a clinical and public health urgency.

PubMed

Baird, J Kevin

2015-12-14

Malaria caused by Plasmodium vivax threatens over 2 billion people globally and sickens tens of millions annually. Recent clinical evidence discredits the long-held notion of this infection as intrinsically benign revealing an often threatening course associated with mortality. Most acute attacks by this species derive from latent forms in the human liver called hypnozoites. Radical cure for P. vivax malaria includes therapy aimed both at the acute attack (blood schizontocidal) and against future attacks (hypnozoitocidal). The only hypnozoitocide available is primaquine, a drug causing life-threatening acute hemolytic anemia in patients with the inherited blood disorder glucose-6-phosphate dehydrogenase (G6PD) deficiency. This disorder affects 400 million people worldwide, at an average prevalence of 8 % in malaria-endemic nations. In the absence of certain knowledge regarding the G6PD status of patients infected by P. vivax, providers must choose between the risk of harm caused by primaquine and that caused by the parasite by withholding therapy. Resolving this dilemma requires the availability of point-of-care G6PD diagnostics practical for use in the impoverished rural tropics where the vast majority of malaria patients seek care.

Effects of Enterococcus faecalis CECT 7121 on Cryptosporidium parvum infection in mice

USDA-ARS?s Scientific Manuscript database

Cryptosporidium is an opportunistic protozoan parasite of humans and animals worldwide, causes diarrheal disease that is typically self-limiting in immunocompetent hosts but often life-threatening to immunocompromised individuals. However, there is a lack of completely efficient therapy available. P...

Warfarin-induced toxic epidermal necrolysis in combination therapy of Henoch-Schönlein purpura nephritis: a case report.

PubMed

Kasahara, Katsuaki; Gotoh, Yoshimitsu; Kuroyanagi, Yoshiyuki; Nagano, China

2017-07-14

Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN. We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch-Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications. To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.

Perception of the etiology of illness: causal attributions in a heart patient population.

PubMed

Koslowsky, M; Croog, S H; La Voie, L

1978-10-01

This study examined perceived causes of myocardial infarction in a patient population of 345 men previously free from significant medical problems. Investigation of their perceptions following the life-threatening illness crisis indicated that stress and tension factors were the causes most commonly cited. Possible social and psychological correlates are analyzed using an attribution theory framework, and their implications are discussed.

Isolation and Purification of Antigenic Components of Cryptococcus

PubMed Central

Wozniak, Karen L.; Levitz, Stuart M.

2012-01-01

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

Diagnosis, Treatment, and Prevention of Hemodialysis Emergencies.

PubMed

Saha, Manish; Allon, Michael

2017-02-07

Given the high comorbidity in patients on hemodialysis and the complexity of the dialysis treatment, it is remarkable how rarely a life-threatening complication occurs during dialysis. The low rate of dialysis emergencies can be attributed to numerous safety features in modern dialysis machines; meticulous treatment and testing of the dialysate solution to prevent exposure to trace elements, toxins, and pathogens; adherence to detailed treatment protocols; and extensive training of dialysis staff to handle medical emergencies. Most hemodialysis emergencies can be attributed to human error. A smaller number are due to rare idiosyncratic reactions. In this review, we highlight major emergencies that may occur during hemodialysis treatments, describe their pathogenesis, offer measures to minimize them, and provide specific interventions to prevent catastrophic consequences on the rare occasions when such emergencies arise. These emergencies include dialysis disequilibrium syndrome, venous air embolism, hemolysis, venous needle dislodgement, vascular access hemorrhage, major allergic reactions to the dialyzer or treatment medications, and disruption or contamination of the dialysis water system. Finally, we describe root cause analysis after a dialysis emergency has occurred to prevent a future recurrence. Copyright © 2017 by the American Society of Nephrology.

Fighting microbial infections: A lesson from amphibian skin-derived esculentin-1 peptides.

PubMed

Mangoni, Maria Luisa; Luca, Vincenzo; McDermott, Alison M

2015-09-01

Due to the growing emergence of resistance to commercially available antibiotics/antimycotics in virtually all clinical microbial pathogens, the discovery of alternative anti-infective agents, is greatly needed. Gene-encoded antimicrobial peptides (AMPs) hold promise as novel therapeutics. In particular, amphibian skin is one of the richest storehouses of AMPs, especially that of the genus Rana, with esculentins-1 being among the longest (46 amino acids) AMPs found in nature to date. Here, we report on the recently discovered in vitro and in vivo activities and mechanism of action of two derivatives of the N-terminal part of esculentin-1a and -1b peptides, primarily against two relevant opportunistic microorganisms causing a large number of life-threatening infections worldwide; i.e. the Gram-negative bacterium Pseudomonas aeruginosa and the yeast Candida albicans. Because of distinct advantages compared to several mammalian AMPs, the two selected frog skin AMP-derivatives represent attractive candidates for the development of new antimicrobial compounds with expanded properties, for both human and veterinary medicine. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnosis, Treatment, and Prevention of Hemodialysis Emergencies

PubMed Central

Saha, Manish

2017-01-01

Given the high comorbidity in patients on hemodialysis and the complexity of the dialysis treatment, it is remarkable how rarely a life-threatening complication occurs during dialysis. The low rate of dialysis emergencies can be attributed to numerous safety features in modern dialysis machines; meticulous treatment and testing of the dialysate solution to prevent exposure to trace elements, toxins, and pathogens; adherence to detailed treatment protocols; and extensive training of dialysis staff to handle medical emergencies. Most hemodialysis emergencies can be attributed to human error. A smaller number are due to rare idiosyncratic reactions. In this review, we highlight major emergencies that may occur during hemodialysis treatments, describe their pathogenesis, offer measures to minimize them, and provide specific interventions to prevent catastrophic consequences on the rare occasions when such emergencies arise. These emergencies include dialysis disequilibrium syndrome, venous air embolism, hemolysis, venous needle dislodgement, vascular access hemorrhage, major allergic reactions to the dialyzer or treatment medications, and disruption or contamination of the dialysis water system. Finally, we describe root cause analysis after a dialysis emergency has occurred to prevent a future recurrence. PMID:27831511

Management of chronic osteomyelitis of the tibia with life-threatening complications under negative pressure wound therapy and isolation of Helcococcus kunzii.

PubMed

Stanger, Katrin M; Albert, Frauke; Kneser, Ulrich; Bogdan, Christian; Horch, Raymund E

2015-08-01

We report the case of an 86-year-old man with severe wound infection originating from a chronic crural ulcer of the lower limb, which under negative pressure wound therapy led to excessive tissue necrosis and perforation of the anterior tibial artery. A swab taken 10 and 7 days preoperatively was positive for Helcococcus kunzii. H. kunzii has been described as a potentially pathogenic organism. The questions whether the negative pressure wound therapy itself caused the bleeding or the negative pressure wound therapy, which generates an anaerobic atmosphere, has triggered the growth and invasion of the facultative anaerobic bacterium H. kunzii and owing to the infection the artery perforated or whether the bacteria has no influence at all remain currently unanswered. After surgical debridement the signs of infection were completely eliminated, and a free musculocutaneous flap led to rapid healing of the wound. Following which H. kunzii was no longer detectable. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Differences in Rhodococcus equi Infections Based on Immune Status and Antibiotic Susceptibility of Clinical Isolates in a Case Series of 12 Patients and Cases in the Literature

PubMed Central

Suzuki, Yasuhiro; Ribes, Julie A.; Thornton, Alice

2016-01-01

Rhodococcus equi is an unusual zoonotic pathogen that can cause life-threatening diseases in susceptible hosts. Twelve patients with R. equi infection in Kentucky were compared to 137 cases reported in the literature. Although lungs were the primary sites of infection in immunocompromised patients, extrapulmonary involvement only was more common in immunocompetent patients (P < 0.0001). Mortality in R. equi-infected HIV patients was lower in the HAART era (8%) than in pre-HAART era (56%) (P < 0.0001), suggesting that HAART improves prognosis in these patients. Most (85–100%) of clinical isolates were susceptible to vancomycin, clarithromycin, rifampin, aminoglycosides, ciprofloxacin, and imipenem. Interestingly, there was a marked difference in susceptibility of the isolates to cotrimoxazole between Europe (35/76) and the US (15/15) (P < 0.0001). Empiric treatment of R. equi infection should include a combination of two antibiotics, preferably selected from vancomycin, imipenem, clarithromycin/azithromycin, ciprofloxacin, rifampin, or cotrimoxazole. Local antibiograms should be checked prior to using cotrimoxazole due to developing resistance. PMID:27631004

Proteomics analysis of BHK-21 cells infected with a fixed strain of rabies virus.

PubMed

Zandi, Fatemeh; Eslami, Naser; Soheili, Masoomeh; Fayaz, Ahmad; Gholami, Alireza; Vaziri, Behrouz

2009-05-01

Rabies is a neurotropic virus that causes a life threatening acute viral encephalitis. The complex relationship of rabies virus (RV) with the host leads to its replication and spreading toward the neural network, where viral pathogenic effects appeared as neuronal dysfunction. In order to better understand the molecular basis of this relationship, a proteomics study on baby hamster kidney cells infected with challenge virus standard strain of RV was performed. This cell line is an in vitro model for rabies infection and is commonly used for viral seed preparation. The direct effect of the virus on cellular protein machinery was investigated by 2-DE proteome mapping of infected versus control cells followed by LC-MS/MS identification. This analysis revealed significant changes in expression of 14 proteins, seven of these proteins were viral and the remaining were host proteins with different known functions: cytoskeletal (capping protein, vimentin), anti-oxidative stress (superoxide dismutase), regulatory (Stathmin), and protein synthesis (P0). Despite of limited changes appeared upon rabies infection, they present a set of interesting biochemical pathways for further investigation on viral-host interaction.

Development of a multiplex PCR assay for the detection and differentiation of Burkholderia pseudomallei, Burkholderia mallei, Burkholderia thailandensis, and Burkholderia cepacia complex.

PubMed

Zakharova, Irina; Teteryatnikova, Natalya; Toporkov, Andrey; Viktorov, Dmitry

2017-10-01

Two species of Burkholderia pseudomallei complex (Bpc), B. pseudomallei and B. mallei, can cause severe life-threatening infections. Rapidly discerning individual species within the group and separating them from other opportunistic pathogens of the Burkholderia cepacia complex (Bcc) is essential to establish a correct diagnosis and for epidemiological surveillance. In this study, a multiplex PCR assay based on the detection of an individual set of chromosomal beta-lactamase genes for single-step identification and differentiation of B. pseudomallei, B. mallei, B. thailandensis, and Bcc was developed. Two pairs of primers specific to a distinct class of B metallo-beta-lactamase genes and a pair of primers specific to the oxacillin-hydrolyzing class D beta-lactamase gene were demonstrated to successfully discriminate species within Bpc and from Bcc. The assay sensitivity was 9561 genomic equivalents (GE) for B. pseudomallei, 7827 GE for B. mallei, 8749 GE for B. thailandensis and 6023 GE for B. cepacia. Copyright © 2017 Elsevier B.V. All rights reserved.

Antifungal potential of marine natural products.

PubMed

El-Hossary, Ebaa M; Cheng, Cheng; Hamed, Mostafa M; El-Sayed Hamed, Ashraf Nageeb; Ohlsen, Knut; Hentschel, Ute; Abdelmohsen, Usama Ramadan

2017-01-27

Fungal diseases represent an increasing threat to human health worldwide which in some cases might be associated with substantial morbidity and mortality. However, only few antifungal drugs are currently available for the treatment of life-threatening fungal infections. Furthermore, plant diseases caused by fungal pathogens represent a worldwide economic problem for the agriculture industry. The marine environment continues to provide structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. Among these secondary metabolites, several compounds with noteworthy antifungal activities have been isolated from marine microorganisms, invertebrates, and algae. During the last fifteen years, around 65% of marine natural products possessing antifungal activities have been isolated from sponges and bacteria. This review gives an overview of natural products from diverse marine organisms that have shown in vitro and/or in vivo potential as antifungal agents, with their mechanism of action whenever applicable. The natural products literature is covered from January 2000 until June 2015, and we are reporting the chemical structures together with their biological activities, as well as the isolation source. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Structural Insights into Inhibition of Sterol 14[alpha]-Demethylase in the Human Pathogen Trypanosoma cruzi

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

Lepesheva, Galina I.; Hargrove, Tatiana Y.; Anderson, Spencer

2010-09-02

Trypanosoma cruzi causes Chagas disease (American trypanosomiasis), which threatens the lives of millions of people and remains incurable in its chronic stage. The antifungal drug posaconazole that blocks sterol biosynthesis in the parasite is the only compound entering clinical trials for the chronic form of this infection. Crystal structures of the drug target enzyme, Trypanosoma cruzi sterol 14{alpha}-demethylase (CYP51), complexed with posaconazole, another antifungal agent fluconazole and an experimental inhibitor, (R)-4{prime}-chloro-N-(1-(2,4-dichlorophenyl)-2-(1H-imid-azol-1-yl)ethyl)biphenyl-4-carboxamide (VNF), allow prediction of important chemical features that enhance the drug potencies. Combined with comparative analysis of inhibitor binding parameters, influence on the catalytic activity of the trypanosomal enzymemore » and its human counterpart, and their cellular effects at different stages of the Trypanosoma cruzi life cycle, the structural data provide a molecular background to CYP51 inhibition and azole resistance and enlighten the path for directed design of new, more potent and selective drugs to develop an efficient treatment for Chagas disease.« less

Translational metagenomics and the human resistome: confronting the menace of the new millennium.

PubMed

Willmann, Matthias; Peter, Silke

2017-01-01

The increasing threat of antimicrobial resistance poses one of the greatest challenges to modern medicine. The collection of all antimicrobial resistance genes carried by various microorganisms in the human body is called the human resistome and represents the source of resistance in pathogens that can eventually cause life-threatening and untreatable infections. A deep understanding of the human resistome and its multilateral interaction with various environments is necessary for developing proper measures that can efficiently reduce the spread of resistance. However, the human resistome and its evolution still remain, for the most part, a mystery to researchers. Metagenomics, particularly in combination with next-generation-sequencing technology, provides a powerful methodological approach for studying the human microbiome as well as the pathogenome, the virolume and especially the resistome. We summarize below current knowledge on how the human resistome is shaped and discuss how metagenomics can be employed to improve our understanding of these complex processes, particularly as regards a rapid translation of new findings into clinical diagnostics, infection control and public health.

Human Pathogen Shown to Cause Disease in the Threatened Eklhorn Coral Acropora palmata

PubMed Central

Sutherland, Kathryn Patterson; Shaban, Sameera; Joyner, Jessica L.; Porter, James W.; Lipp, Erin K.

2011-01-01

Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS), a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine “reverse zoonosis” involving the transmission of a human pathogen (S. marcescens) to a marine invertebrate (A. palmata). These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival. PMID:21858132

The role of vaccines in fighting antimicrobial resistance (AMR).

PubMed

Jansen, Kathrin U; Anderson, Annaliesa S

2018-05-22

The problem of antimicrobial resistance (AMR) and the associated morbidity and mortality due to antibiotic resistant bacterial pathogens is not new. However, AMR has been increasing at an alarming rate with appearances of diseases caused by bacteria exhibiting resistance to not just one but multiple classes of antibiotics. The World Health Organization (WHO) supported by governments, health ministries and health agencies has formulated global action plans to combat the rise in AMR, supporting a number of proven initiatives such as antimicrobial stewardship, investments in development of new classes of antibiotics, and educational programs designed to eliminate inappropriate antibiotic use. Vaccines as tools to reduce AMR have historically been under-recognized, yet the positive effect in reducing AMR has been well established. For example Haemophilus influenzae type B (Hib) as well as Streptococcus pneumoniae (pneumococcal) conjugate vaccines have impressive track records in not only preventing life threatening diseases caused by these bacteria, but also reducing antibiotic use and AMR. This paper will describe the drivers of antibiotic use and subsequent development of AMR; it will make the case how existing vaccines are already participating in combatting AMR, describe future prospects for the role of new vaccines in development to reduce AMR, and highlight challenges associated with future vaccine development to combat AMR.

Putative type II toxin-antitoxin systems in Listeria monocytogenes isolated from clinical, food, and animal samples in Iran.

PubMed

Kalani, Behrooz Sadeghi; Irajian, Gholamreza; Lotfollahi, Lida; Abdollahzadeh, Esmail; Razavi, Shabnam

2018-06-04

Listeria monocytogenes is known as a major food-borne pathogen causing a severe life-threatening disease, listeriosis, in susceptible patients. This bacterium has special features that facilitate its survival in different conditions and cause resistance to antibacterial agents and biocides. Toxin-antitoxin (TA) system has a potential to be introduced as an antibacterial target because of its participation in cell physiology, including stress response, antiphage activity, biofilm formation, and resistance to antibiotics. In this study, after the identification of 6 genes of 3 TA pairs (lM/E-lM/F, lM/S-lM/B and ydc/D-ydc/E) via existing databases, the presence and expression level of these genes were investigated by PCR and q-PCR techniques, respectively. The result of RT-qPCR revealed that identified genes were expressed in different strains and ydc (maz) increased under thermal stress. It seems that the products of these genes play an important role in the physiology and survival of the bacterium especially in heat stress. Presence of 6 detected TA genes in all of the tested isolates demonstrated that TA system could be an antibacterial target in L. monocytogenes; however, more research is needed to explain the actual role of these genes. Copyright © 2018. Published by Elsevier Ltd.

Urinary tract infections in pregnancy.

PubMed

Ovalle, A; Levancini, M

2001-01-01

Urinary tract infections are very common during pregnancy. Escherichia coli is the most common pathogen isolated from pregnant women. Ampicillin should not be used because of its high resistance to Escherichia coli. Pyelonephritis can cause morbidity and can be life-threatening to both mother and fetus. Second and third-generation cephalosporins are recommended for treatment, administered initially intravenously during hospitalization. Cultures and the study of virulence factors of uropathogenic Escherichia coli are recommended for the adequate management of pyelonephritis. The lower genital tract infection associated with pyelonephritis is responsible for the failure of antibiotic treatment. Asymptomatic bacteriuria can evolve into cystitis or pyelonephritis. All pregnant women should be routinely screened for bacteriuria using urine culture, and should be treated with nitrofurantoin, sulfixosazole or first-generation cephalosporins. Recurrent urinary infection should be treated with prophylactic antibiotics. Pregnant women who develop urinary tract infections with group B streptococcal infection should be treated with prophylactic antibiotics during labour to prevent neonatal sepsis. Preterm delivery is frequent. Evidence suggests that infection plays a role in the pathogenesis of preterm labour. Experimental models in pregnant mice support the theory that Escherichia coli propagated by the transplacental route, involving bacterial adhesins, induces preterm delivery, but this has not been demonstrated in humans. Ascending lower genital tract infections are the most probable cause of preterm delivery, but this remains to be proved.

Drinking water source and human Toxoplasma gondii infection in the United States: A cross-sectional analysis of NHANES data

EPA Science Inventory

Toxoplasma gondii imparts a considerable burden to public health. Human toxoplasmosis can be life-threatening in immunocompromised individuals, has been associated with psychiatric disorders, and can cause severe congenital pathologies, spontaneous abortion, or stillbirth. Enviro...

Growth kinetics and model comparison of cronobacter sakazakii in reconstituted powdered infant formula

USDA-ARS?s Scientific Manuscript database

Cronobacter sakazakii is a life-threatening bacterium, primarily implicated in illnesses associated with the consumption of powdered infant formula (PIF). It can cause rare but invasive infections, leading to sepsis, meningitis, or necrotizing enterocolitis in infants fed with contaminated PIF. Th...

Pythium invasion of plant-based life support systems: biological control and sources

NASA Technical Reports Server (NTRS)

Jenkins, D. G.; Cook, K. L.; Garland, J. L.; Board, K. F.; Sager, J. C. (Principal Investigator)

2000-01-01

Invasion of plant-based life support systems by plant pathogens could cause plant disease and disruption of life support capability. Root rot caused by the fungus, Pythium, was observed during tests of prototype plant growth systems containing wheat at the Kennedy Space Center (KSC). We conducted experiments to determine if the presence of complex microbial communities in the plant root zone (rhizosphere) resisted invasion by the Pythium species isolated from the wheat root. Rhizosphere inocula of different complexity (as assayed by community-level physiological profile: CLPP) were developed using a dilution/extinction approach, followed by growth in hydroponic rhizosphere. Pythium growth on wheat roots and concomitant decreases in plant growth were inversely related to the complexity of the inocula during 20-day experiments in static hydroponic systems. Pythium was found on the seeds of several different wheat cultivars used in controlled environmental studies, but it is unclear if the seed-borne fungal strain(s) were identical to the pathogenic strain recovered from the KSC studies. Attempts to control pathogens and their effects in hydroponic life support systems should include early inoculation with complex microbial communities, which is consistent with ecological theory.

Mountain biking injuries in rural England.

PubMed

Jeys, L M; Cribb, G; Toms, A D; Hay, S M

2001-06-01

Off road mountain biking is now an extremely popular recreation and a potent cause of serious injury. To establish the morbidity associated with this sport. Data were collected prospectively over one year on all patients presenting with an injury caused by either recreational or competitive off road mountain biking. Eighty four patients were identified, 70 males and 14 females, with a mean age of 22.5 years (range 8-71). Most accidents occurred during the summer months, most commonly in August. Each patient had an average of 1.6 injuries (n = 133) and these were divided into 15 categories, ranging from minor soft tissue to potentially life threatening. Operative intervention was indicated for 19 patients (23%) and several required multiple procedures. The commonest injuries were clavicle fractures (13%), shoulder injuries (12%), and distal radial fractures (11%). However, of a more sinister nature, one patient had a C2/3 dislocation requiring urgent stabilisation, one required a chest drain for a haemopneumothorax, and another required an emergency and life saving nephrectomy. This sport has recently experienced an explosion in popularity, and, as it carries a significant risk of potentially life threatening injury across all levels of participation, the use of protective equipment to reduce this significant morbidity may be advisable.

Improving disease resistance of butternut (Juglans cinerea), a threatened fine hardwood: a case for single-tree selection through genetic improvement and deployment.

PubMed

Michler, Charles H; Pijut, Paula M; Jacobs, Douglass F; Meilan, Richard; Woeste, Keith E; Ostry, Michael E

2006-01-01

Approaches for the development of disease-resistant butternut (Juglans cinerea L.) are reviewed. Butternut is a threatened fine hardwood throughout its natural range in eastern North America because of the invasion of the exotic fungus, Sirococcus clavigignenti-juglandacearum Nair, Kostichka and Kuntz, which causes butternut canker. Early efforts were made to identify and collect putatively resistant germ plasm, identify vectors and to characterize the disease. More recently, molecular techniques have been employed to genetically characterize both the pathogen and the resistant germ plasm. Much of the host resistance may originate from hybridization with a close Asian relative, Japanese walnut (Juglans ailanthifolia Carr.), and from a few natural phenotypic variants. Further genetic characterization is needed before classical breeding or genetic modification can be used to produce canker-resistant trees.

20 CFR 416.1248 - Exclusion of gifts to children with life-threatening conditions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Exclusion of gifts to children with life... gifts to children with life-threatening conditions. In determining the resources of an individual who has not attained 18 years of age and who has a life-threatening condition, we will exclude any gifts...

Candida albicans Hap43 Is a Repressor Induced under Low-Iron Conditions and Is Essential for Iron-Responsive Transcriptional Regulation and Virulence ▿

PubMed Central

Hsu, Po-Chen; Yang, Cheng-Yao; Lan, Chung-Yu

2011-01-01

Candida albicans is an opportunistic fungal pathogen that exists as normal flora in healthy human bodies but causes life-threatening infections in immunocompromised patients. In addition to innate and adaptive immunities, hosts also resist microbial infections by developing a mechanism of “natural resistance” that maintains a low level of free iron to restrict the growth of invading pathogens. C. albicans must overcome this iron-deprived environment to cause infections. There are three types of iron-responsive transcriptional regulators in fungi; Aft1/Aft2 activators in yeast, GATA-type repressors in many fungi, and HapX/Php4 in Schizosaccharomyces pombe and Aspergillus species. In this study, we characterized the iron-responsive regulator Hap43, which is the C. albicans homolog of HapX/Php4 and is repressed by the GATA-type repressor Sfu1 under iron-sufficient conditions. We provide evidence that Hap43 is essential for the growth of C. albicans under low-iron conditions and for C. albicans virulence in a mouse model of infection. Hap43 was not required for iron acquisition under low-iron conditions. Instead, it was responsible for repression of genes that encode iron-dependent proteins involved in mitochondrial respiration and iron-sulfur cluster assembly. We also demonstrated that Hap43 executes its function by becoming a transcriptional repressor and accumulating in the nucleus in response to iron deprivation. Finally, we found a connection between Hap43 and the global corepressor Tup1 in low-iron-induced flavinogenesis. Taken together, our data suggest a complex interplay among Hap43, Sfu1, and Tup1 to coordinately regulate iron acquisition, iron utilization, and other iron-responsive metabolic activities. PMID:21131439

Non-traumatic right hepatic artery pseudoaneurysm: an unusual cause of hemobilia and obstructive jaundice.

PubMed

Alvi, Abdul Rehman; Bibi, Shahida; Zia-ur-Rehman; Khan, Salma

2009-12-01

Most hepatic artery pseudoaneurysms (HAPA) are post traumatic, and non-traumatic pseudoaneurysm is rarely reported. It is a potentially life threatening vascular disorder and difficult to diagnose before rupture. Early diagnosis and prompt nonoperative intervention of this lesion could be life saving. The authors report the case of a patient with hemobilia caused by ruptured right hepatic artery pseudoaneurysm and subsequently developed right hepatic duct stricture, which has not been reported previously. This patient was successfully treated with endovascular stent graft of pseudoaneurysm and endoscopic stenting of right hepatic duct stricture.

Scedosporium prolificans fungaemia in a patient with acute lymphoblastic leukaemia.

PubMed

Kubisiak-Rzepczyk, H; Gil, L; Zawirska, A; Kubisiak-Michalska, A; Mol, A; Reich, A; Komarnicki, M; Adamski, Z

2013-12-01

Aggressive chemotherapy and immunosuppressive treatment may prolong patients' life, but influence the risk of severe, life-threatening infections. Here, we report the case of a 21-year-old caucasian female who developed a disseminated infection of Scedosporium prolificans after allogenic stem cell transplantation performed for treatment of relapsed acute lymphoblastic leukaemia. The pathogen was isolated from the blood and identified on the basis of its macroscopic and microscopic morphological features. The empirical treatment with amphotericin B provided no improvement. However, introduction of intravenous voriconazole resulted in amelioration of fever. Unfortunately, the patient died due to progression of underlying disease and multiorgan failure. However, this case report indicates a possible relevance of voriconazole-based treatment regimens in invasive S. prolificans infections. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The top 10 oomycete pathogens in molecular plant pathology

USDA-ARS?s Scientific Manuscript database

Oomycetes form a deep lineage of eukaryotic organisms that includes a large number of plant pathogens that threaten natural and managed ecosystems. We undertook a survey to query the community for their ranking of plant pathogenic oomycete taxa based on scientific and economic importance. In total, ...

Disruption of the GABA shunt affects mitochondrial respiration and virulence in the cereal pathogen Fusarium graminearum.

PubMed

Bönnighausen, Jakob; Gebhard, Daniel; Kröger, Cathrin; Hadeler, Birgit; Tumforde, Thomas; Lieberei, Reinhard; Bergemann, Jörg; Schäfer, Wilhelm; Bormann, Jörg

2015-12-01

The cereal pathogen Fusarium graminearum threatens food and feed production worldwide. It reduces the yield and poisons the remaining kernels with mycotoxins, notably deoxynivalenol (DON). We analyzed the importance of gamma-aminobutanoic acid (GABA) metabolism for the life cycle of this fungal pathogen. GABA metabolism in F. graminearum is partially regulated by the global nitrogen regulator AreA. Genetic disruption of the GABA shunt by deletion of two GABA transaminases renders the pathogen unable to utilize the plant stress metabolites GABA and putrescine. The mutants showed increased sensitivity against oxidative stress, GABA accumulation in the mycelium, downregulation of two key enzymes of the TCA cycle, disturbed potential gradient in the mitochondrial membrane and lower mitochondrial oxygen consumption. In contrast, addition of GABA to the wild type resulted in its rapid turnover and increased mitochondrial steady state oxygen consumption. GABA concentrations are highly upregulated in infected wheat tissues. We conclude that GABA is metabolized by the pathogen during infection increasing its energy production, whereas the mutants accumulate GABA intracellularly resulting in decreased energy production. Consequently, the GABA mutants are strongly reduced in virulence but, because of their DON production, are able to cross the rachis node. © 2015 John Wiley & Sons Ltd.

Treatment of cashew extracts with Aspergillopepsin reduces IgE binding to cashew allergens

USDA-ARS?s Scientific Manuscript database

Cashew nuts can cause serious and sometimes life threatening reactions in people that suffer from food allergies. These reactions are mediated by immunoglobulin E binding (IgE) to allergenic cashew proteins. Enzymes from Aspergillus fungal species are used in many industrial and pharmaceutical appli...

Drinking water source associated with Toxoplasma gondii and Helicobacter pylori infections in the United States: A cross-sectional analysis of NHANES data

EPA Science Inventory

Toxoplasma gondii and Helicobacter pylori impart considerable burdens to public health. Toxoplasmosis can be life threatening in immunocompromised individuals, has been associated with psychiatric disorders, and can cause severe congenital pathologies. Infections with H. pylori a...

A Repeated Observation Approach for Estimating the Street Homeless Population

ERIC Educational Resources Information Center

Berry, Brent

2007-01-01

Risks of life on the street caused by inclement weather, harassment, and assault threaten the unsheltered homeless population. We address some challenges of enumerating the street homeless population by testing a novel capture-recapture (CR) estimation approach that models individuals' intermittent daytime visibility. We tested walking and…

Pica in Persons with Developmental Disabilities: Characteristics, Diagnosis, and Assessment

ERIC Educational Resources Information Center

Matson, Johnny L.; Belva, Brian; Hattier, Megan A.; Matson, Michael L.

2011-01-01

Pica is a very serious and often life threatening problem which occurs largely in persons with developmental disabilities. The topic has received sporadic attention from researchers for several decades. This paper reviews definitions, diagnostic implications, causes, prevalence, and assessment methods that have been described in the research…

Increasing CO2 threatens human nutrition

USDA-ARS?s Scientific Manuscript database

Dietary deficiencies of zinc and iron are a major global public health problem. An estimated two billion people suffer these deficiencies causing a loss of 63 million life years annually. Most of these people depend upon grains and legumes as their primary dietary source of zinc and iron. This manu...

A Case of Congenital Folliculitis Caused by Pseudomonas aeruginosa in a Preterm Neonate.

PubMed

Matsui, Koichiro; Okazaki, Kaoru; Horikoshi, Yuho; Kakinuma, Ryota; Kondo, Masatoshi

2017-07-24

Intrauterine infections are associated with life-threatening neonatal conditions such as sepsis, intracranial hemorrhage, and chronic lung disease. Herein we present a case of generalized congenital folliculitis caused by Pseudomonas aeruginosa in a preterm neonate of 27 weeks gestational age successfully treated with antibiotics. Folliculitis is an important manifestation of intrauterine P. aeruginosa infection, and prompt, effective treatment is crucial to ensuring a good prognosis.

Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus

PubMed Central

Eyal, Zohar; Matzov, Donna; Krupkin, Miri; Wekselman, Itai; Paukner, Susanne; Zimmerman, Ella; Rozenberg, Haim; Bashan, Anat; Yonath, Ada

2015-01-01

The emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with the known antibiotics linezolid and telithromycin, as well as with a new, highly potent pleuromutilin derivative, BC-3205. These crystal structures shed light on specific structural motifs of the S. aureus ribosome and the binding modes of the aforementioned antibiotics. Moreover, by analyzing the ribosome structure and comparing it with those of nonpathogenic bacterial models, we identified some unique internal and peripheral structural motifs that may be potential candidates for improving known antibiotics and for use in the design of selective antibiotic drugs against S. aureus. PMID:26464510

Silage review: Foodborne pathogens in silage and their mitigation by silage additives.

PubMed

Queiroz, O C M; Ogunade, I M; Weinberg, Z; Adesogan, A T

2018-05-01

Silage is one of the main ingredients in dairy cattle diets and it is an important source of nutrients, particularly energy and digestible fiber. Unlike properly made and managed silage, poorly made or contaminated silage can also be a source of pathogenic bacteria that may decrease dairy cow performance, reduce the safety and quality dairy products, and compromise animal and human health. Some of the pathogenic bacteria that are frequently or occasionally associated with silage are enterobacteria, Listeria, Bacillus spp., Clostridium spp., and Salmonella. The symptoms caused by these bacteria in dairy cows vary from mild diarrhea and reduced feed intake by Clostridium spp. to death and abortion by Listeria. Contamination of food products with pathogenic bacteria can cause losses of millions of dollars due to recalls of unsafe foods and decreases in the shelf life of dairy products. The presence of pathogenic bacteria in silage is usually due to contamination or poor management during the fermentation, aerobic exposure, or feed-out stages. Silage additives and inoculants can improve the safety of silage as well as the fermentation, nutrient recovery, quality, and shelf life. This review summarizes the literature on the main foodborne pathogens that occasionally infest silage and how additives can improve silage safety. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Structural basis of mammalian glycan targeting by Vibrio cholerae cytolysin and biofilm proteins

PubMed Central

De, Swastik; Kaus, Katherine; Sinclair, Shada

2018-01-01

Vibrio cholerae is an aquatic gram-negative microbe responsible for cholera, a pandemic disease causing life-threatening diarrheal outbreaks in populations with limited access to health care. Like most pathogenic bacteria, V. cholerae secretes virulence factors to assist colonization of human hosts, several of which bind carbohydrate receptors found on cell-surfaces. Understanding how pathogenic virulence proteins specifically target host cells is important for the development of treatment strategies to fight bacterial infections. Vibrio cholerae cytolysin (VCC) is a secreted pore-forming toxin with a carboxy-terminal β-prism domain that targets complex N-glycans found on mammalian cell-surface proteins. To investigate glycan selectivity, we studied the VCC β-prism domain and two additional β-prism domains found within the V. cholerae biofilm matrix protein RbmC. We show that the two RbmC β-prism domains target a similar repertoire of complex N-glycan receptors as VCC and find through binding and modeling studies that a branched pentasaccharide core (GlcNAc2-Man3) represents the likely footprint interacting with these domains. To understand the structural basis of V. cholerae β-prism selectivity, we solved high-resolution crystal structures of fragments of the pentasaccharide core bound to one RbmC β-prism domain and conducted mutagenesis experiments on the VCC toxin. Our results highlight a common strategy for cell-targeting utilized by both toxin and biofilm matrix proteins in Vibrio cholerae and provide a structural framework for understanding the specificity for individual receptors. Our results suggest that a common strategy for disrupting carbohydrate interactions could affect multiple virulence factors produced by V. cholerae, as well as similar β-prism domains found in other vibrio pathogens. PMID:29432487

Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions

PubMed Central

MacCallum, Donna M.; Brown, Gordon D.

2017-01-01

ABSTRACT   The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host’s arginase activity to prevent the conversion of l-arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans-induced arginase activity with the arginase-specific substrate inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l-arginine metabolism in macrophages during an infection, potentiating its own survival. PMID:28119468

Minority Elderly Adaptation to Life-Threatening Events: An Overview with Methodological Consideration.

ERIC Educational Resources Information Center

Trimble, Joseph E.; And Others

A review of pertinent research on the adaptation of ethnic minority elderly to life-threatening events (personal, man-made, or natural) exposes voids in the research, presents methodological considerations, and indicates that ethnic minority elderly are disproportionately victimized by life-threatening events. Unusually high numbers of…

Conservation implications of physiological carry-over effects in bats recovering from white-nose syndrome.

PubMed

Davy, Christina M; Mastromonaco, Gabriela F; Riley, Julia L; Baxter-Gilbert, James H; Mayberry, Heather; Willis, Craig K R

2017-06-01

Although it is well documented that infectious diseases can pose threats to biodiversity, the potential long-term consequences of pathogen exposure on individual fitness and its effects on population viability have rarely been studied. We tested the hypothesis that pathogen exposure causes physiological carry-over effects with a pathogen that is uniquely suited to this question because the infection period is specific and time limited. The fungus Pseudogymnoascus destructans causes white-nose syndrome (WNS) in hibernating bats, which either die due to the infection while hibernating or recover following emergence from hibernation. The fungus infects all exposed individuals in an overwintering site simultaneously, and bats that survive infection during hibernation clear the pathogen within a few weeks following emergence. We quantified chronic stress during the active season, when bats are not infected, by measuring cortisol in bat claws. Free-ranging Myotis lucifugus who survived previous exposure to P. destructans had significantly higher levels of claw cortisol than naïve individuals. Thus, cryptic physiological carry-over effects of pathogen exposure may persist in asymptomatic, recovered individuals. If these effects result in reduced survival or reproductive success, they could also affect population viability and even act as a third stream in the extinction vortex. For example, significant increases in chronic stress, such as those indicated here, are correlated with reduced reproductive success in a number of species. Future research should directly explore the link between pathogen exposure and the viability of apparently recovered populations to improve understanding of the true impacts of infectious diseases on threatened populations. © 2016 Society for Conservation Biology.

Bartonella entry mechanisms into mammalian host cells.

PubMed

Eicher, Simone C; Dehio, Christoph

2012-08-01

The Gram-negative genus Bartonella comprises arthropod-borne pathogens that typically infect mammals in a host-specific manner. Bartonella bacilliformis and Bartonella quintana are human-specific pathogens, while several zoonotic bartonellae specific for diverse animal hosts infect humans as an incidental host. Clinical manifestations of Bartonella infections range from mild symptoms to life-threatening disease. Following transmission by blood-sucking arthropods or traumatic contact with infected animals, bartonellae display sequential tropisms towards endothelial and possibly other nucleated cells and erythrocytes, the latter in a host-specific manner. Attachment to the extracellular matrix (ECM) and to nucleated cells is mediated by surface-exposed bacterial adhesins, in particular trimeric autotransporter adhesins (TAAs). The subsequent engulfment of the pathogen into a vacuolar structure follows a unique series of events whereby the pathogen avoids the endolysosomal compartments. For Bartonella henselae and assumingly most other species, the infection process is aided at different steps by Bartonella effector proteins (Beps). They are injected into host cells through the type IV secretion system (T4SS) VirB/D4 and subvert host cellular functions to favour pathogen uptake. Bacterial binding to erythrocytes is mediated by Trw, another T4SS, in a strictly host-specific manner, followed by pathogen-forced uptake involving the IalB invasin and subsequent replication and persistence within a membrane-bound intra-erythrocytic compartment. © 2012 Blackwell Publishing Ltd.

In vitro lysis and acute transfusion reactions with hemolysis caused by inappropriate storage of canine red blood cell products.

PubMed

Patterson, J; Rousseau, A; Kessler, R J; Giger, U

2011-01-01

Transfusion of red blood cell (RBC) products carries considerable risk for adverse reactions, including life-threatening hemolytic reactions. To report the occurrence and investigation of life-threatening acute transfusion reactions with hemolysis in dogs likely related to inappropriate blood product storage. Four dogs with acute transfusion reactions and other recipients of blood products. Medical records were reviewed from 4 dogs with suspected acute hemolytic transfusion reactions after receiving RBC products at a veterinary clinic over a 1-month period. Medical records of other animals receiving blood products in the same time period also were reviewed. Blood compatibility and product quality were assessed, subsequent transfusions were closely monitored, and products were diligently audited. During or immediately after RBC product transfusion, 4 dogs developed hemolysis, hemoglobinuria, or both. Two dogs died and 1 was euthanized because of progressive clinical signs compatible with an acute hemolytic transfusion reaction. Blood type and blood compatibility were confirmed. RBC units from 2 blood banks were found to be hemolyzed after storage in the clinic's refrigerator; no bacterial contamination was identified. After obtaining a new refrigerator dedicated to blood product storage, the problem of hemolyzed units and acute transfusion reactions with hemolysis completely resolved. Acute life-threatening transfusion reactions can be caused by inappropriate storage of RBC products. In addition to infectious disease screening and ensuring blood-type compatibility, quality assessment of blood products, appropriate collection, processing, and storage techniques as well as recipient monitoring are critical to provide safe, effective transfusions. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Calmodulin Mutations Associated with Recurrent Cardiac Arrest in Infants

PubMed Central

Crotti, Lia; Johnson, Christopher N.; Graf, Elisabeth; De Ferrari, Gaetano M.; Cuneo, Bettina F.; Ovadia, Marc; Papagiannis, John; Feldkamp, Michael D.; Rathi, Subodh G.; Kunic, Jennifer D.; Pedrazzini, Matteo; Wieland, Thomas; Lichtner, Peter; Beckmann, Britt-Maria; Clark, Travis; Shaffer, Christian; Benson, D. Woodrow; Kääb, Stefan; Meitinger, Thomas; Strom, Tim M.; Chazin, Walter J.; Schwartz, Peter J.; George, Alfred L.

2013-01-01

Background Life-threatening disorders of heart rhythm may arise during infancy and can result in the sudden and tragic death of a child. We performed exome sequencing on two unrelated infants presenting with recurrent cardiac arrest to discover a genetic cause. Methods and Results We ascertained two unrelated infants (probands) with recurrent cardiac arrest and dramatically prolonged QTc interval who were both born to healthy parents. The two parent-child trios were investigated using exome sequencing to search for de novo genetic variants. We then performed follow-up candidate gene screening on an independent cohort of 82 subjects with congenital long-QT syndrome without an identified genetic cause. Biochemical studies were performed to determine the functional consequences of mutations discovered in two genes encoding calmodulin. We discovered three heterozygous de novo mutations in either CALM1 or CALM2, two of the three human genes encoding calmodulin, in the two probands and in two additional subjects with recurrent cardiac arrest. All mutation carriers were infants who exhibited life-threatening ventricular arrhythmias combined variably with epilepsy and delayed neurodevelopment. Mutations altered residues in or adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain. Recombinant mutant calmodulins exhibited several fold reductions in calcium binding affinity. Conclusions Human calmodulin mutations disrupt calcium ion binding to the protein and are associated with a life-threatening condition in early infancy. Defects in calmodulin function will disrupt important calcium signaling events in heart affecting membrane ion channels, a plausible molecular mechanism for potentially deadly disturbances in heart rhythm during infancy. PMID:23388215

Stent-Graft Repair of a Large Cervical Internal Carotid Artery Pseudoaneurysm Causing Dysphagia

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

Gupta, Vivek, E-mail: drvivekgupta.pgi@gmail.com; Niranjan, Khandelwal; Rawat, Lokesh

2009-05-15

Pseudoaneurysms of the cervical internal carotid artery (ICA) are rare and most frequently result from trauma, infection, or sometimes spontaneously. They have the potential to cause life-threatening hemorrhage; thus, their immediate management is necessary. Endovascular treatment by stent graft placement in the affected artery appears to be a safe and effective treatment option. We present a case of a child who presented with neck swelling and dysphagia caused by a ruptured cervical ICA pseudoaneurysm which was managed by stent graft placement.

The Pathogen-Host Interactions database (PHI-base): additions and future developments.

PubMed

Urban, Martin; Pant, Rashmi; Raghunath, Arathi; Irvine, Alistair G; Pedro, Helder; Hammond-Kosack, Kim E

2015-01-01

Rapidly evolving pathogens cause a diverse array of diseases and epidemics that threaten crop yield, food security as well as human, animal and ecosystem health. To combat infection greater comparative knowledge is required on the pathogenic process in multiple species. The Pathogen-Host Interactions database (PHI-base) catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and protist pathogens. Mutant phenotypes are associated with gene information. The included pathogens infect a wide range of hosts including humans, animals, plants, insects, fish and other fungi. The current version, PHI-base 3.6, available at http://www.phi-base.org, stores information on 2875 genes, 4102 interactions, 110 host species, 160 pathogenic species (103 plant, 3 fungal and 54 animal infecting species) and 181 diseases drawn from 1243 references. Phenotypic and gene function information has been obtained by manual curation of the peer-reviewed literature. A controlled vocabulary consisting of nine high-level phenotype terms permits comparisons and data analysis across the taxonomic space. PHI-base phenotypes were mapped via their associated gene information to reference genomes available in Ensembl Genomes. Virulence genes and hotspots can be visualized directly in genome browsers. Future plans for PHI-base include development of tools facilitating community-led curation and inclusion of the corresponding host target(s). © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Viable-but-Nonculturable Listeria monocytogenes and Salmonella enterica Serovar Thompson Induced by Chlorine Stress Remain Infectious.

PubMed

Highmore, Callum J; Warner, Jennifer C; Rothwell, Steve D; Wilks, Sandra A; Keevil, C William

2018-04-17

The microbiological safety of fresh produce is monitored almost exclusively by culture-based detection methods. However, bacterial food-borne pathogens are known to enter a viable-but-nonculturable (VBNC) state in response to environmental stresses such as chlorine, which is commonly used for fresh produce decontamination. Here, complete VBNC induction of green fluorescent protein-tagged Listeria monocytogenes and Salmonella enterica serovar Thompson was achieved by exposure to 12 and 3 ppm chlorine, respectively. The pathogens were subjected to chlorine washing following incubation on spinach leaves. Culture data revealed that total viable L. monocytogenes and Salmonella Thompson populations became VBNC by 50 and 100 ppm chlorine, respectively, while enumeration by direct viable counting found that chlorine caused a <1-log reduction in viability. The pathogenicity of chlorine-induced VBNC L. monocytogenes and Salmonella Thompson was assessed by using Caenorhabditis elegans Ingestion of VBNC pathogens by C. elegans resulted in a significant life span reduction ( P = 0.0064 and P < 0.0001), and no significant difference between the life span reductions caused by the VBNC and culturable L. monocytogenes treatments was observed. L. monocytogenes was visualized beyond the nematode intestinal lumen, indicating resuscitation and cell invasion. These data emphasize the risk that VBNC food-borne pathogens could pose to public health should they continue to go undetected. IMPORTANCE Many bacteria are known to enter a viable-but-nonculturable (VBNC) state in response to environmental stresses. VBNC cells cannot be detected by standard laboratory culture techniques, presenting a problem for the food industry, which uses these techniques to detect pathogen contaminants. This study found that chlorine, a sanitizer commonly used for fresh produce, induces a VBNC state in the food-borne pathogens Listeria monocytogenes and Salmonella enterica It was also found that chlorine is ineffective at killing total populations of the pathogens. A life span reduction was observed in Caenorhabditis elegans that ingested these VBNC pathogens, with VBNC L. monocytogenes as infectious as its culturable counterpart. These data show that VBNC food-borne pathogens can both be generated and avoid detection by industrial practices while potentially retaining the ability to cause disease. Copyright © 2018 Highmore et al.

Isolation of Fungal Pathogens to an Edible Mushroom, Pleurotus eryngii, and Development of Specific ITS Primers

PubMed Central

Kim, Sang-Woo; Kim, Sinil; Lee, Hyun-Jun; Park, Ju-Wan

2013-01-01

Fungal pathogens have caused severe damage to the commercial production of Pleurotus eryngii, the king oyster mushroom, by reducing production yield, causing deterioration of commercial value, and shortening shelf-life. Four strains of pathogenic fungi, including Trichoderma koningiopsis DC3, Phomopsis sp. MP4, Mucor circinelloides MP5, and Cladosporium bruhnei MP6, were isolated from the bottle culture of diseased P. eryngii. A species-specific primer set was designed for each fungus from the ITS1-5.8S rDNA-ITS2 sequences. PCR using the ITS primer set yielded a unique DNA band for each fungus without any cross-reaction, proving the validity of our method in detection of mushroom fungal pathogens. PMID:24493949

A comparison of "life threatening injury" concept in the Turkish Penal Code and trauma scoring systems.

PubMed

Fedakar, Recep; Aydiner, Ahmet Hüsamettin; Ercan, Ilker

2007-07-01

To compare accuracy and to check the suitability of the Glasgow Coma Scale (GCS), the Revised Trauma Score (RTS), the Injury Severity Score (ISS), the New Injury Severity Score (NISS) and the Trauma and Injury Severity Score (TRISS), the scoring systems widely used in international trauma studies, in the evaluation of the "life threatening injury" concept established by the Turkish Penal Code. The age, sex, type of trauma, type and localizations of wounds, GCS, RTS, ISS, NISS and TRISS values, the decision of life threatening injury of 627 trauma patients admitted to Emergency Department of the Uludag University Medical School Hospital in year 2003 were examined. A life-threatening injury was present in 35.2% of the cases examined. GCS, RTS, ISS, NISS and TRISS confirmed the decision of life threatening injury with percentages of 74.8%, 76.9%, 88.7%, 86.6% and 68.6%, respectively. The best cut-off point 14 was determined in the ISS system with 79.6% sensitivity and 93.6% specificity. All of the cases with sole linear skull fracture officially decided as life threatening injury had an ISS of 5, a NISS of 6 and the best scores of GCS (15), RTS (7.8408) and TRISS (100%). ISS and NISS appeared to be the best trauma scoring systems that can be used for the decision of life threatening injury, compared with GCS, RTS and TRISS. Thus, ISS and NISS can be acceptable for using the evaluation of the life threatening injury concept established by the Turkish Penal Code.

Life-threatening cryoglobulinemia: clinical and immunological characterization of 29 cases.

PubMed

Ramos-Casals, Manuel; Robles, Angel; Brito-Zerón, Pilar; Nardi, Norma; Nicolás, José M; Forns, Xavier; Plaza, Joan; Yagüe, Jordi; Sánchez-Tapias, Jose M; Font, Josep

2006-12-01

To analyze the etiology, clinical presentation, and outcomes of patients with life-threatening cryoglobulinemic vasculitis. We studied 209 consecutive patients with cryoglobulinemic vasculitis. A potentially life-threatening cryoglobulinemia was considered as the development of renal failure, vasculitic abdominal involvement, pulmonary hemorrhage, or central nervous system involvement. Twenty-nine (14%) patients had life-threatening cryoglobulinemic vasculitis. There were 17 women and 12 men, with a mean age of 57 years. In 17 (59%) patients, life-threatening cryoglobulinemia was the initial clinical feature of the disease. The 29 patients had a total of 33 life-threatening episodes, which included renal failure due to cryoglobulinemic glomerulonephritis (n = 18), intestinal vasculitis (n = 8), pulmonary hemorrhage (n = 4), and central nervous system involvement (n = 3). In comparison with a control group of age-sex-matched patients with milder cryoglobulinemic vasculitis, those with severe cryoglobulinemic vasculitis had a higher frequency of fever (28% versus 7%, P = 0.017), type II cryoglobulins (100% versus 59%, P = 0.008), low C3 levels (55% versus 20%, P = 0.001), and a higher mean value of cryocrit (11.4% versus 3.3%, P = 0.004). Nineteen (66%) of the 29 patients with life-threatening involvement died, with the mortality rate reaching 100% in patients with intestinal ischemia and pulmonary hemorrhage. Life-threatening cryoglobulinemic vasculitis was observed in 14% of our patients, with almost two-thirds of episodes occurring at the onset of the disease. Fever, high cryocrit levels, and low C3 levels were associated with this severe presentation. Two-thirds of the patients died, with mortality for pulmonary hemorrhage and intestinal ischemia reaching 100%.

Growth rate, transmission mode and virulence in human pathogens.

PubMed

Leggett, Helen C; Cornwallis, Charlie K; Buckling, Angus; West, Stuart A

2017-05-05

The harm that pathogens cause to hosts during infection, termed virulence, varies across species from negligible to a high likelihood of rapid death. Classic theory for the evolution of virulence is based on a trade-off between pathogen growth, transmission and host survival, which predicts that higher within-host growth causes increased transmission and higher virulence. However, using data from 61 human pathogens, we found the opposite correlation to the expected positive correlation between pathogen growth rate and virulence. We found that (i) slower growing pathogens are significantly more virulent than faster growing pathogens, (ii) inhaled pathogens and pathogens that infect via skin wounds are significantly more virulent than pathogens that are ingested, but (iii) there is no correlation between symptoms of infection that aid transmission (such as diarrhoea and coughing) and virulence. Overall, our results emphasize how virulence can be influenced by mechanistic life-history details, especially transmission mode, that determine how parasites infect and exploit their hosts.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'. © 2017 The Authors.

Kisameet Clay Exhibits Potent Antibacterial Activity against the ESKAPE Pathogens.

PubMed

Behroozian, Shekooh; Svensson, Sarah L; Davies, Julian

2016-01-26

The ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens cause an increasing number of nosocomial infections worldwide since they escape the inhibitory effect of the available antibiotics and the immune response. Here, we report the broad-spectrum and potent antibacterial activity of Kisameet clay, a natural clay mineral from British Columbia, Canada, against a group of multidrug-resistant ESKAPE strains. The results suggest that this natural clay might be developed as a therapeutic option for the treatment of serious infections caused by these important pathogens. More than 50 years of misuse and overuse of antibiotics has led to a plague of antibiotic resistance that threatens to reduce the efficacy of antimicrobial agents available for the treatment of infections due to resistant organisms. The main threat is nosocomial infections in which certain pathogens, notably the ESKAPE organisms, are essentially untreatable and contribute to increasing mortality and morbidity in surgical wards. The pipeline of novel antimicrobials in the pharmaceutical industry is essentially empty. Thus, there is a great need to seek for new sources for the treatment of recalcitrant infectious diseases. We describe experiments that demonstrate the efficacy of a "natural" medicine, Kisameet clay, against all of the ESKAPE strains. We suggest that this material is worthy of clinical investigation for the treatment of infections due to multidrug-resistant organisms. Copyright © 2016 Behroozian et al.

Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

PubMed Central

2011-01-01

Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness. PMID:21284886

Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity.

PubMed

Boyce, Walter M; Weisenberger, Mara E; Penedo, M Cecilia T; Johnson, Christine K

2011-02-01

A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.

Incidence and management of life-threatening adverse events during cardiac catheterization for congenital heart disease.

PubMed

Lin, C Huie; Hegde, Sanjeet; Marshall, Audrey C; Porras, Diego; Gauvreau, Kimberlee; Balzer, David T; Beekman, Robert H; Torres, Alejandro; Vincent, Julie A; Moore, John W; Holzer, Ralf; Armsby, Laurie; Bergersen, Lisa

2014-01-01

Continued advancements in congenital cardiac catheterization and interventions have resulted in increased patient and procedural complexity. Anticipation of life-threatening events and required rescue measures is a critical component to preprocedural preparation. We sought to determine the incidence and nature of life-threatening adverse events in congenital and pediatric cardiac catheterization, risk factors, and resources necessary to anticipate and manage events. Data from 8905 cases performed at the 8 participating institutions of the Congenital Cardiac Catheterization Project on Outcomes were captured between 2007 and 2010 [median 1,095/site (range 133-3,802)]. The incidence of all life-threatening events was 2.1 % [95 % confidence interval (CI) 1.8-2.4 %], whereas mortality was 0.28 % (95 % CI 0.18-0.41 %). Fifty-seven life-threatening events required cardiopulmonary resuscitation, whereas 9 % required extracorporeal membrane oxygenation. Use of a risk adjustment model showed that age <1 year [odd ratio (OR) 1.9, 95 % CI 1.4-2.7, p < 0.001], hemodynamic vulnerability (OR 1.6, 95 % CI 1.1-2.3, p < 0.01), and procedure risk (category 3: OR 2.3, 95 % CI 1.3-4.1; category 4: OR 4.2, 95 % CI 2.4-7.4) were predictors of life-threatening events. Using this model, standardized life-threatening event ratios were calculated, thus showing that one institution had a life-threatening event rate greater than expected. Congenital cardiac catheterization and intervention can be performed safely with a low rate of life-threatening events and mortality; preprocedural evaluation of risk may optimize preparation of emergency rescue and bailout procedures. Risk predictors (age < 1, hemodynamic vulnerability, and procedure risk category) can enhance preprocedural patient risk stratification and planning.

Protozoal agents: what are the dangers for the public water supply?

PubMed

Steiner, T S; Thielman, N M; Guerrant, R L

1997-01-01

Safe and efficient treatment of drinking water has been one of the major public health advances of the twentieth century. People in developed countries generally take for granted that their water is safe to drink, a luxury the majority of the world's population does not have. The leading cause of infant mortality in the developing world is infectious diarrhea, and the prevalence of diarrheal pathogens is largely influenced by the quality and quantity of clean water available for drinking and washing. Until recently, modern water treatment had all but eliminated these concerns in developed nations. Over the past two decades, however, the safety of our water supply has been threatened by the emergence of Cryptosporidium parvum, a protozoal pathogen. The hearty oocysts of this organism survive chlorination and filtration to cause a diarrheal illness that, while unpleasant enough in healthy people, is devastating in immunocompromised individuals. The 1993 Milwaukee outbreak, in which 403,000 people developed diarrhea from drinking water that met all the updated federal safety standards, demonstrated the tremendous public health importance of this organism. While earlier attention had focused on Giardia and amebic infections, the other "emerging" protozoan besides Cryptosporidium is Cyclospora. This review discusses the protozoal pathogens, including Cryptosporidium parvum, Giardia lamblia, Entamoeba histolytica, and Cyclospora cayetanensis, that cause waterborne diarrheal outbreaks and the threats they pose to the public.

Are disease reservoirs special? Taxonomic and life history characteristics

PubMed Central

Burgess, Tristan L.; Eskew, Evan A.; Roth, Tara M.; Stephenson, Nicole; Foley, Janet E.

2017-01-01

Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases. PMID:28704402

Experimental and natural infections in MyD88- and IRAK-4-deficient mice and humans

PubMed Central

von Bernuth, Horst; Picard, Capucine; Puel, Anne; Casanova, Jean-Laurent

2013-01-01

Most Toll-like-receptors (TLRs) and interleukin-1 receptors (IL-1Rs) signal via myeloid differentiation primary response 88 (MyD88) and interleukin-1 receptor-associated kinase 4 (IRAK-4). The combined roles of these two receptor families in the course of experimental infections have been assessed in MyD88- and IRAK-4-deficient mice for almost fifteen years. These animals have been shown to be susceptible to 46 pathogens: 27 bacteria, 8 viruses, 7 parasites, and 4 fungi. Humans with inborn MyD88 or IRAK-4 deficiency were first identified in 2003. They suffer from naturally occurring life-threatening infections caused by a small number of bacterial species, although the incidence and severity of these infections decrease with age. Mouse TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be vital to combat a wide array of experimentally administered pathogens at most ages. By contrast, human TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be effective in the natural setting against only a few bacteria and is most important in infancy and early childhood. The roles of TLRs and IL-1Rs in protective immunity deduced from studies in mutant mice subjected to experimental infections should therefore be reconsidered in the light of findings for natural infections in humans carrying mutations as discussed in this review. PMID:23255009

Characterization of the type 2 NADH:menaquinone oxidoreductases from Staphylococcus aureus and the bactericidal action of phenothiazines.

PubMed

Schurig-Briccio, Lici A; Yano, Takahiro; Rubin, Harvey; Gennis, Robert B

2014-07-01

Methicillin-resistant Staphylococcus aureus (MRSA) is currently one of the principal multiple drug resistant bacterial pathogens causing serious infections, many of which are life-threatening. Consequently, new therapeutic targets are required to combat such infections. In the current work, we explore the type 2 Nicotinamide adenine dinucleotide reduced form (NADH) dehydrogenases (NDH-2s) as possible drug targets and look at the effects of phenothiazines, known to inhibit NDH-2 from Mycobacterium tuberculosis. NDH-2s are monotopic membrane proteins that catalyze the transfer of electrons from NADH via flavin adenine dinucleotide (FAD) to the quinone pool. They are required for maintaining the NADH/Nicotinamide adenine dinucleotide (NAD(+)) redox balance and contribute indirectly to the generation of proton motive force. NDH-2s are not present in mammals, but are the only form of respiratory NADH dehydrogenase in several pathogens, including S. aureus. In this work, the two putative ndh genes present in the S. aureus genome were identified, cloned and expressed, and the proteins were purified and characterized. Phenothiazines were shown to inhibit both of the S. aureus NDH-2s with half maximal inhibitory concentration (IC50) values as low as 8μM. However, evaluating the effects of phenothiazines on whole cells of S. aureus was complicated by the fact that they are also acting as uncouplers of oxidative phosphorylation. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. Copyright © 2014 Elsevier B.V. All rights reserved.

Glucosylceramide Administration as a Vaccination Strategy in Mouse Models of Cryptococcosis

PubMed Central

Mor, Visesato; Farnoud, Amir M.; Singh, Ashutosh; Rella, Antonella; Tanno, Hiromasa; Ishii, Keiko; Kawakami, Kazuyoshi; Sato, Toshiya; Del Poeta, Maurizio

2016-01-01

Cryptococcus neoformans is an opportunistic fungal pathogen and the causative agent of the disease cryptococcosis. Cryptococcosis is initiated as a pulmonary infection and in conditions of immune deficiency disseminates to the blood stream and central nervous system, resulting in life-threatening meningoencephalitis. A number of studies have focused on the development of a vaccine against Cryptococcus, primarily utilizing protein-conjugated components of the Cryptococcus polysaccharide capsule as antigen. However, there is currently no vaccine against Cryptococcus in the clinic. Previous studies have shown that the glycosphingolipid, glucosylceramide (GlcCer), is a virulence factor in C. neoformans and antibodies against this lipid inhibit fungal growth and cell division. In the present study, we have investigated the possibility of using GlcCer as a therapeutic agent against C. neoformans infections in mouse models of cryptococcosis. GlcCer purified from a non-pathogenic fungus, Candida utilis, was administered intraperitoneally, prior to infecting mice with a lethal dose of C. neoformans. GlcCer administration prevented the dissemination of C. neoformans from the lungs to the brain and led to 60% mouse survival. GlcCer administration did not cause hepatic injury and elicited an anti-GlcCer antibody response, which was observed independent of the route of administration and the strains of mouse. Taken together, our results suggest that fungal GlcCer can protect mice against lethal doses of C. neoformans infection and can provide a viable vaccination strategy against Cryptococcus. PMID:27082428

Complete structural characterization of the lipid A fraction of a clinical strain of B. cepacia genomovar I lipopolysaccharide.

PubMed

Silipo, Alba; Molinaro, Antonio; Cescutti, Paola; Bedini, Emiliano; Rizzo, Roberto; Parrilli, Michelangelo; Lanzetta, Rosa

2005-05-01

Burkholderia cepacia, a Gram-negative bacterium ubiquitous in the environment, is a plant pathogen causing soft rot of onions. This microorganism has recently emerged as a life-threatening multiresistant pathogen in cystic fibrosis patients. An important virulence factor of B. cepacia is the lipopolysaccharide (LPS) fraction. Clinical isolates and environmental strains possess LPS of high inflammatory nature, which induces a high level production of cytokines. For the first time, the complete structure of the lipid A components isolated from the lipopolysaccharide fraction of a clinical strain of B. cepacia is described. The structural studies carried out by selective chemical degradations, MS, and NMR spectroscopy revealed multiple species differing in the acylation and in the phosphorylation patterns. The highest mass species was identified as a penta-acylated tetrasaccharide backbone containing two phosphoryl-arabinosamine residues in addition to the archetypal glucosamine disaccharide [Arap4N-l-beta-1-P-4-beta-D-GlcpN-(1-6)-alpha-D-GlcpN-1-P-1-beta-L-Arap4N]. Lipid A fatty acids substitution was also deduced, with two 3-hydroxytetradecanoic acids 14:0 (3-OH) in ester linkage, and two 3-hydroxyhexadecanoic acids 16:0 (3-OH) in amide linkage, one of which was substituted by a secondary 14:0 residue at its C-3. Other lipid A species present in the mixture and exhibiting lower molecular weight lacked one or both beta-L-Arap4N residues.

Spirituality in the context of life-threatening illness and life-transforming change.

PubMed

Young, William C; Nadarajah, Sheeba R; Skeath, Perry R; Berger, Ann M

2015-06-01

Individuals with life-threatening illness often engage in some form of spirituality to meet increased needs for meaning and purpose. This study aimed to identify the role of spirituality in persons who had reported positive, life-transforming change in relation to life-threatening cancer or cardiac events, and to connect these roles to palliative and supportive care. A purposive sample of 10 cardiac survivors and 9 cancer survivors was recruited. Once the participants had given informed consent and passed screening in relation to life-transforming change and distress, they engaged in a semistructured one-hour qualitative interview on the theme of how their life-transforming change occurred in the context of their life-threatening illness. In the present article, our phenomenological analysis focuses on participants' references to purpose and meaning in their lives, with particular attention to the role and context of participants' spirituality. Participants mentioned spirituality, meaning, and purpose in many contexts, including connecting with family and friends, nature, art, music, and sometimes creating a relationship with God. Participants often accessed spirituality by enhancing connections in their own lives: with a higher power, people, their work, or themselves. These enhanced connections gave participants greater meaning and purpose in their lives, and substantially helped participants to adjust to their life-threatening illnesses. Understanding the roles and contexts of spirituality among patients with a life-threatening illness allows us to develop better palliative and supportive care plans. Spiritually oriented supportive care may include support groups, yoga, meditation, nature, music, prayer, or referral to spiritual or religious counselors. A quantitative scale is needed to help healthcare clinicians assess the spiritual and coping needs of individuals with life-threatening illness.

Ciguatera fish poisoning.

PubMed

Armstrong, Patrick; Murray, Peter; Nesdale, Annette; Peckler, Brad

2016-10-28

Ciguatera fish poisoning (CFP) is the most common cause of seafood-toxin poisoning in the world and is most prevalent in tropical and subtropical areas. It causes gastroenteritis but also myriad neurological and cardiovascular symptoms. We present a cluster of CFP that occurred in Wellington Hospital, New Zealand. It resulted in three patients with life threatening cardiotoxicity and a fourth case with severe gastro-intestinal symptoms. The epidemiology, clinical manifestations, diagnosis, treatment and public health issues are discussed.

Permanent Quadriplegia Following Replacement of Voice Prosthesis.

PubMed

Ozturk, Kayhan; Erdur, Omer; Kibar, Ertugrul

2016-11-01

The authors presented a patient with quadriplegia caused by cervical spine abscess following voice prosthesis replacement. The authors present the first reported permanent quadriplegia patient caused by voice prosthesis replacement. The authors wanted to emphasize that life-threatening complications may be faced during the replacement of voice prosthesis. Care should be taken during the replacement of voice prosthesis and if some problems have been faced during the procedure patients must be followed closely.

Complicated hypertension related to the abuse of ephedrine and caffeine alkaloids.

PubMed

Berman, Jeffrey A; Setty, Arathi; Steiner, Matthew J; Kaufman, Kenneth R; Skotzko, Christine

2006-01-01

Ephedra containing products (ECPs), which most often contain additional sources of caffeine alkaloids, may be an under-recognized cause of hypertension. ECPs, especially when used in combination or at higher than recommended doses, can cause life-threatening cardiovascular and neurological complications. We present a case of hypertensive encephalopathy with new onset generalized tonic-clonic seizure secondary to concomitant use of two OTC supplements containing a mixture of ephedrine and caffeine alkaloids.

The causes and frequency of acute hospitalization of patients with dementia in a long-term care facility.

PubMed Central

Zarian, D. A.; Peter, S. A.; Lee, S.; Kleinfeld, M.

1989-01-01

A retrospective study of 81 patients with dementia in a long-term care facility was conducted to determine the causes and frequency of acute hospitalization and the cause of death in the patients who succumbed during the acute hospital admission. Pneumonia and urinary tract infections were the most frequent causes of acute hospitalization; septicemia and respiratory failure were the most frequent causes of death. These results suggest that patients with dementia are prone to acquire life-threatening infections. Preventive measures to decrease the incidence of these complications are discussed. PMID:2500533

Berkeley Lab - Materials Sciences Division

Science.gov Websites

-486-6999 Urgent Radiation Protection Group Assistance Non-Life Threatening Event 24/7 Lab Phone: x7277 : 911 (no extentions required now) Non-Emergency Reporting (Fire and Police) Non-Life Threatening Event Spill Non-Life Threatening Event 24/7 Lab Phone: x6999 Cell Phone: 510-486-6999 Off Site Locations: 510

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2013 CFR

2013-04-01

... applications for drugs to treat life-threatening and severely-debilitating illnesses. 312.84 Section 312.84... Severely-debilitating Illnesses § 312.84 Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and severely-debilitating illnesses. (a) FDA's application of the...

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2014 CFR

2014-04-01

... applications for drugs to treat life-threatening and severely-debilitating illnesses. 312.84 Section 312.84... Severely-debilitating Illnesses § 312.84 Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and severely-debilitating illnesses. (a) FDA's application of the...

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2011 CFR

2011-04-01

... applications for drugs to treat life-threatening and severely-debilitating illnesses. 312.84 Section 312.84... Severely-debilitating Illnesses § 312.84 Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and severely-debilitating illnesses. (a) FDA's application of the...

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2012 CFR

2012-04-01

... applications for drugs to treat life-threatening and severely-debilitating illnesses. 312.84 Section 312.84... Severely-debilitating Illnesses § 312.84 Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and severely-debilitating illnesses. (a) FDA's application of the...

Life-threatening NLRC4-associated hyperinflammation successfully treated with Interleukin-18 inhibition

PubMed Central

Canna, Scott W.; Girard, Charlotte; Malle, Louise; de Jesus, Adriana; Romberg, Neil; Kelsen, Judith; Surrey, Lea F.; Russo, Pierre; Sleight, Andrew; Schiffrin, Eduardo; Gabay, Cem; Goldbach-Mansky, Raphaela; Behrens, Edward M.

2017-01-01

Capsule Summary NLRC4-inflammasome hyperactivity causes infantile-onset Macrophage Activation Syndrome and enterocolitis with extraordinary serum IL-18 elevation (NLRC4-MAS). Herein, we report a critically ill infant with severe, refractory NLRC4-MAS who showed sustained response to treatment with experimental IL-18 inhibition. PMID:27876626

Death Concerns among Individuals Newly Diagnosed with Lung Cancer

ERIC Educational Resources Information Center

Lehto, Rebecca; Therrien, Barbara

2010-01-01

Confronting the reality of death is an important challenge for individuals facing life-threatening illness such as lung cancer, the leading cause of cancer death. Few studies, however, document the nature of death-related concerns in individuals newly diagnosed with lung cancer. The aims of this exploratory study were to examine unsolicited…

30 CFR 551.6 - Obligations and rights under a permit or a Notice.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., coastal, or human environment; (3) Cause harm or damage to any mineral resource (in areas leased or not... environmental hazards which imminently threaten life and property; or (3) Adversely affect the environment... of the area for navigation and safety purposes. (d) Any persons conducting shallow test drilling or...

30 CFR 551.6 - Obligations and rights under a permit or a Notice.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., coastal, or human environment; (3) Cause harm or damage to any mineral resource (in areas leased or not... environmental hazards which imminently threaten life and property; or (3) Adversely affect the environment... of the area for navigation and safety purposes. (d) Any persons conducting shallow test drilling or...

30 CFR 551.6 - Obligations and rights under a permit or a Notice.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., coastal, or human environment; (3) Cause harm or damage to any mineral resource (in areas leased or not... environmental hazards which imminently threaten life and property; or (3) Adversely affect the environment... of the area for navigation and safety purposes. (d) Any persons conducting shallow test drilling or...

Strategies for Playground Injury Prevention: An Overview of a Playground Project

ERIC Educational Resources Information Center

Olsen, Heather; Hudson, Susan D.; Thompson, Donna

2010-01-01

Preventing injuries to children, especially debilitating and life threatening, requires an awareness of where these types of injuries occur during the school days. This review examines falls from playground equipment, events that have been identified as the leading causes of nonfatal unintentional injuries for children. Thus, the issue of…

The alpha-tocopherol form of vitamin E boosts elastase activity of human PMNs and their ability to kill Streptococcus pneumoniae

USDA-ARS?s Scientific Manuscript database

Despite the availability of vaccines, Streptococcus pneumoniae remains a leading cause of life-threatening infections such as pneumonia, bacteremia and meningitis. Polymorphonuclear leukocytes (PMNs) are a key determinant of disease course, because optimal host defense requires an initial robust pul...

The Experiences and Recommendations of Families with Children Who Have Congenital Toxoplasmosis

ERIC Educational Resources Information Center

Roberts, Jillian; Mortimer, Tamara; Mish, Sandra; Kerns, Kimberly; Jagdis, Frank; MacMath, Sheryl

2005-01-01

Toxoplasmosis infections are usually asymptomatic in health hosts, but can cause serious, sometimes life threatening, sequelae in infants when the mother acquires an acute infection during pregnancy and the parasite is transmitted via the placenta to the developing fetus. This article is part of a comprehensive research project investigating the…

3 CFR 8851 - Proclamation 8851 of August 31, 2012. National Childhood Cancer Awareness Month, 2012

Code of Federal Regulations, 2013 CFR

2013-01-01

... Childhood Cancer Awareness Month, 2012 8851 Proclamation 8851 Presidential Documents Proclamations Proclamation 8851 of August 31, 2012 Proc. 8851 National Childhood Cancer Awareness Month, 2012By the President... diagnosed with cancer—an often life-threatening illness that remains the leading cause of death by disease...

Gene Therapy Vector for the Treatment of Glycogen Storage Disease Type Ia (GSD-Ia) | NCI Technology Transfer Center | TTC

Cancer.gov

GSD-Ia is an inherited disorder of metabolism associated with life-threatening hypoglycemia, hepatic malignancy, and renal failure caused by the deficiency of glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC). NICHD seeks parties to license this invention towards commercialization.

Responses to Childhood Trauma: An International Perspective

ERIC Educational Resources Information Center

Little, Steven G.; Akin-Little, Angeleque

2011-01-01

Children throughout the world are exposed to traumatic events such as sexual or physical abuse, severe accidents, cancer or other life threatening illness, natural or man-made disasters, war, terrorism, the sudden death of a parent or close friend or relative, among other things. Recently, natural disasters have caused property damage and loss of…

The consequences of human-driven ocean acidification for marine life.

PubMed

Doney, Scott

2009-05-08

Rising atmospheric carbon dioxide is causing a wholesale shift in surface seawater chemistry, potentially threatening many marine organisms that form shells and skeletons from calcium carbonate. Recent papers suggest that the biological consequences of ocean acidification already may be underway and may be more complex, nuanced and widespread than previously thought.

Life-Threatening Hypokalemic Paralysis in a Young Bodybuilder

PubMed Central

Cheung, Kitty K. T.; So, Wing-Yee; Kong, Alice P. S.; Ma, Ronald C. W.; Chow, Francis C. C.

2014-01-01

We report a case of life-threatening hypokalemia in a 28-year-old bodybuilder who presented with sudden onset bilateral lower limbs paralysis few days after his bodybuilding competition. His electrocardiogram (ECG) showed typical u-waves due to severe hypokalemia (serum potassium 1.6 mmol/L, reference range (RR) 3.5–5.0 mmol/L). He was admitted to the intensive care unit (ICU) and was treated with potassium replacement. The patient later admitted that he had exposed himself to weight loss agents of unknown nature, purchased online, and large carbohydrate loads in preparation for the competition. He made a full recovery after a few days and discharged himself from the hospital against medical advice. The severe hypokalemia was thought to be caused by several mechanisms to be discussed in this report. With the ever rising number of new fitness centers recently, the ease of online purchasing of almost any drug, and the increasing numbers of youngsters getting into the bodybuilding arena, clinicians should be able to recognize the possible causes of sudden severe hypokalemia in these patients in order to revert the pathophysiology. PMID:24660073

Life-threatening hypokalemic paralysis in a young bodybuilder.

PubMed

Cheung, Kitty K T; So, Wing-Yee; Kong, Alice P S; Ma, Ronald C W; Chow, Francis C C

2014-01-01

We report a case of life-threatening hypokalemia in a 28-year-old bodybuilder who presented with sudden onset bilateral lower limbs paralysis few days after his bodybuilding competition. His electrocardiogram (ECG) showed typical u-waves due to severe hypokalemia (serum potassium 1.6 mmol/L, reference range (RR) 3.5-5.0 mmol/L). He was admitted to the intensive care unit (ICU) and was treated with potassium replacement. The patient later admitted that he had exposed himself to weight loss agents of unknown nature, purchased online, and large carbohydrate loads in preparation for the competition. He made a full recovery after a few days and discharged himself from the hospital against medical advice. The severe hypokalemia was thought to be caused by several mechanisms to be discussed in this report. With the ever rising number of new fitness centers recently, the ease of online purchasing of almost any drug, and the increasing numbers of youngsters getting into the bodybuilding arena, clinicians should be able to recognize the possible causes of sudden severe hypokalemia in these patients in order to revert the pathophysiology.

Approach to the patient with neutropenia in childhood

PubMed Central

Celkan, Tiraje; Koç, Begüm Şirin

2015-01-01

Neutrophils have an important role in host defense and acute inflammation. It is well known that susceptibility to infection increases when the neutrophil count is low. Neutropenia were classified as mild, moderate and severe according to the neutrophil counts, or acute and chronic depending on the duration of neutropenia, or congenital and acquired according to the mechanism. The patients with neutropenia are clinically different due to underlying mechanism, they have life- threatening infections or no infection may be observed. The most common cause of acquired neutropenia is viral infection, followed by drugs and autoimmune neutropenia. Congenital neutropenia are usually diagnosed by acute and life- threatening invasive bacterial and fungal infections. Immune system disorders and other systemic abnormalities may be accompanied or not. Recent years, novel single gen defects causing congenital neutropenia were defined through advanced genetic techniques. Molecular diagnosis is useful for risk stratification, choice of therapy and prognosis on follow- up. This review was prepared for pediatricians as a guide focused on approach neutropenia, which tests should be performed and when should be referred to a specialist. PMID:26568688

Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam.

PubMed

Barnes, Melissa D; Bethel, Christopher R; Alsop, Jim; Becka, Scott A; Rutter, Joseph D; Papp-Wallace, Krisztina M; Bonomo, Robert A

2018-05-01

Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen. Pseudomonas -derived cephlosporinase (PDC) is the major inducible cephalosporinase in P. aeruginosa In this investigation, we show that relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates PDC-3, with a k 2 / K of 41,400 M -1 s -1 and a k off of 0.00095 s -1 Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone. Relebactam promises to increase the efficacy of imipenem-cilastatin against P. aeruginosa . Copyright © 2018 American Society for Microbiology.

Prophylactic Measures During Induction for Acute Myeloid Leukemia.

PubMed

McCarthy, Matthew W; Walsh, Thomas J

2017-03-01

Improved management of infectious complications of acute myeloid leukemia (AML) has contributed substantially to the success of care over the past half century. An important approach to reducing infectious complications during the induction period of chemotherapy involves the use of prophylactic antibacterial, antiviral, and antifungal agents targeting likely pathogens. There is not a one-size-fits-all approach to prophylaxis; every patient undergoing induction therapy should be evaluated individually and within the context of local microbiologic epidemiology and host risk factors. Pharmacologic and non-pharmacologic interventions as well as novel diagnostic platforms can help mitigate the risk of life-threatening infection in patients with AML who undergo induction chemotherapy.

A case report of life-threatening acute dysphagia in dermatomyositis: Challenges in diagnosis and treatment.

PubMed

Kwon, Kyoung Min; Lee, Jung Soo; Kim, Yeo Hyung

2018-04-01

Although dysphagia is a known complication of dermatomyositis, sudden onset of dysphagia without the notable aggravation of other symptoms can make the diagnosis and treatment challenging. A 53-year-old male diagnosed as dermatomyositis 1 month ago came to our emergency department complaining of a sudden inability to swallow solid foods and liquids. The patient showed generalized edema, but the muscle power was not different compared with 1 month ago. Serum creatine kinase level was lower than that measured 2 weeks ago. Computed tomography scan of the larynx, chest, abdomen, and pelvis, an esophagogastroduodenoscopy, and brain magnetic resonance imaging were unremarkable. A videofluoroscopic swallowing study revealed inadequate pharyngeal contraction and slightly decreased upper esophageal sphincter opening with silent aspiration. Treatment with oral prednisolone, intravenous methylprednisolone, azathioprine, and intravenous immunoglobulins was applied. During the course of medical treatment for life-threatening dysphagia, he continued with rehabilitative therapy. He could swallow saliva at 2 months and showed normal swallowing function at 3 months from the onset of dysphagia. Dysphagia has not recurred for 3 years after recovery. A multidisciplinary approach is necessary to diagnose severe acute dysphagia due to exacerbation of underlying dermatomyositis rather than other structural or neurological causes. Appropriate supportive care is important because dysphagia can be life-threatening and last for a long time.

[Injuries to blood vessels near the heart caused by central venous catheters].

PubMed

Abram, J; Klocker, J; Innerhofer-Pompernigg, N; Mittermayr, M; Freund, M C; Gravenstein, N; Wenzel, V

2016-11-01

Injuries to blood vessels near the heart can quickly become life-threatening and include arterial injuries during central venous puncture, which can lead to hemorrhagic shock. We report 6 patients in whom injury to the subclavian artery and vein led to life-threatening complications. Central venous catheters are associated with a multitude of risks, such as venous thrombosis, air embolism, systemic or local infections, paresthesia, hemothorax, pneumothorax, and cervical hematoma, which are not always immediately discernible. The subclavian catheter is at a somewhat lower risk of catheter-associated sepsis and symptomatic venous thrombosis than approaches via the internal jugular and femoral veins. Indeed, access via the subclavian vein carries a substantial risk of pneumo- and hemothorax. Damage to the subclavian vein or artery can also occur during deliberate and inadvertent punctures and result in life-threatening complications. Therefore, careful consideration of the access route is required in relation to the patient and the clinical situation, to keep the incidence of complications as low as possible. For catheterization of the subclavian vein, puncture of the axillary vein in the infraclavicular fossa is a good alternative, because ultrasound imaging of the target vessel is easier than in the subclavian vein and the puncture can be performed much further from the lung.

Life-threatening bleeding in a case of autoantibody-induced factor VII deficiency.

PubMed

Okajima, K; Ishii, M

1999-02-01

A male patient presented with life-threatening bleeding induced by autoantibody-induced factor VII (F.VII) deficiency. This patient had macroscopic hematuria, skin ecchymosis, gastrointestinal bleeding, and a neck hematoma that was causing disturbed respiration. He developed acute renal failure and acute hepatic failure, probably due to obstruction of the ureters and the biliary tract, respectively. Although activated partial thromboplastin time was normal, prothrombin time (PT) was remarkably prolonged at 71.8 seconds compared to 14.0 seconds in a normal control. Both the immunoreactive level of F.VII antigen and the F.VII activity of the patient's plasma samples were < 1.0% of normal. Although an equal part of normal plasma was added to the patient's plasma, PT was not corrected. The patient's plasma inhibited F.VII activity. These findings suggested the presence of a plasma inhibitor for F.VII. After administration of large doses of methylprednisolone, PT was gradually shortened and plasma levels of F.VII increased over time. Bleeding, acute renal failure, and acute hepatic failure improved markedly following the steroid treatment. These observations suggest that life-threatening bleeding can be induced by autoantibody-induced F.VII deficiency and that immunosuppressive therapy using large doses of steroid can be successful in inhibiting the production of the autoantibody.

Treating foodborne illness.

PubMed

Steiner, Theodore

2013-09-01

In healthy adults and children in developed countries, most foodborne and water-borne infections are short-lived and resolve without specific treatment. In developing areas, these infections may produce acute mortality and chronic morbidity caused by developmental impairment. Immune-compromised hosts are at increased risk of life-threatening complications. This article reviews recommendations for the treatment of the most common and important foodborne illnesses, focusing on those caused by infections or toxins of microbial origin. The cornerstone of life-saving treatment remains oral rehydration therapy, although the use of other supportive measures as well as antibiotics for certain infections is also recommended. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of the Holocaust on coping with cancer.

PubMed

Baider, L; Peretz, T; Kaplan De-Nour, A

1992-01-01

The aim of the study was to investigate whether surviving stressful life threatening situations influences coping with new stressful life threatening situations. The study group, therefore, was composed of 53 cancer patients (present life threatening situation) who had survived the Holocaust (past life threatening situation). They were compared to 53 cancer patients who had not gone through the Holocaust, matched for sociodemographic and medical background. The Holocaust survivors were unable to mobilize partial denial (had significantly higher scores on the Impact of Events Scale) and their psychological distress was much higher (significantly higher scores on the Brief Symptom Inventory). Their functioning however (as reported along the Psychosocial Adjustment to Physical Illness Scale) did not significantly differ from that of the comparison group. The possible mechanisms for these long term effects of past trauma are discussed as well as the need to regard traumatized persons as 'high risk' psychologically when they have to cope with new life threatening situations.

Mountain biking injuries in rural England

PubMed Central

Jeys, L; Cribb, G; Toms, A; Hay, S

2001-01-01

Background—Off road mountain biking is now an extremely popular recreation and a potent cause of serious injury. Aim—To establish the morbidity associated with this sport. Methods—Data were collected prospectively over one year on all patients presenting with an injury caused by either recreational or competitive off road mountain biking. Results—Eighty four patients were identified, 70 males and 14 females, with a mean age of 22.5 years (range 8–71). Most accidents occurred during the summer months, most commonly in August. Each patient had an average of 1.6 injuries (n = 133) and these were divided into 15 categories, ranging from minor soft tissue to potentially life threatening. Operative intervention was indicated for 19 patients (23%) and several required multiple procedures. The commonest injuries were clavicle fractures (13%), shoulder injuries (12%), and distal radial fractures (11%). However, of a more sinister nature, one patient had a C2/3 dislocation requiring urgent stabilisation, one required a chest drain for a haemopneumothorax, and another required an emergency and life saving nephrectomy. Conclusion—This sport has recently experienced an explosion in popularity, and, as it carries a significant risk of potentially life threatening injury across all levels of participation, the use of protective equipment to reduce this significant morbidity may be advisable. Key Words: mountain biking; injury PMID:11375881

Diseases Transmitted by Man's Best Friend: The Dog.

PubMed

Jacob, Jerry; Lorber, Bennett

2015-08-01

The relationship between dogs and humans is ancient and mutually beneficial. Dogs have served people well as companions, workmates, guides, and protectors. However, on occasion, dogs may injure humans through biting or may transmit pathogens resulting in a large number of problems ranging from a trivial rash to life-threatening bacteremia. Given that there are more than 80 million pet dogs in the United States, it is worth knowing the potential problems that can result from canine exposure. Annually, almost 5 million people in the United States suffer a dog bite. Dog bite wounds become infected up to 15% of the time. In those who have had a splenectomy, a dog bite may transmit the bacterium Capnocytophaga canimorsus, leading to life-threatening bacteremia. Other illnesses that humans can acquire from dog contact include ringworm, diarrheal disease (salmonellosis, campylobacteriosis, and intestinal parasites), leptospirosis, brucellosis, Q fever, visceral larva migrans, and echinococcosis. Evidence exists that the family dog may serve as a reservoir for uropathogenic Escherichia coli that can lead to urinary tract infections among human household contacts. In this article we discuss dog-related infectious diseases as well as measures to minimize dog-associated illness (e.g., do not disturb sleeping dogs; HIV-infected persons who wish to acquire a puppy should have the dog's stool checked for Cryptosporidium).

Successful silicon stent for life-threatening tracheal wall laceration.

PubMed

Yamamoto, Shinichi; Endo, Shunsuke; Endo, Tetsuya; Mitsuda, Sayaka

2013-01-01

We report an 86-year-old woman with a large tracheal laceration caused by tracheal intubation at cardiopulmonary arrest who underwent a successful stent procedure. Tracheal laceration developed in the membranous portion longitudinally 6 cm in length to 2 cm above the carina. Following 9 days' tracheal intubation, a Y-shaped silicon stent was inserted over the lacerated trachea. Four months after the stenting procedure, we removed the Y-shaped silicon stent from the healed membranous wall. The patient returned to daily life without requiring thoracotomy.

Fracture and distant migration of the Bard Recovery filter: a retrospective review of 363 implantations for potentially life-threatening complications.

PubMed

Tam, Matthew D; Spain, James; Lieber, Michael; Geisinger, Michael; Sands, Mark J; Wang, Weiping

2012-02-01

To report the occurrence of fracture of the Recovery filter and incidence of potentially life-threatening complications associated with fractured fragment migration. A retrospective study of images obtained after placement of Recovery inferior vena cava (IVC) filters from 2003 to 2006 was conducted at a single tertiary-care center. Images were reevaluated for fracture and migration; complications related to filter fracture were investigated. Kaplan-Meier survival analysis was performed to investigate the relationship between time in situ and fracture. A total of 363 Recovery filters were placed; 97 were retrieved, leaving 266 filters in situ (135 patients subsequently died of other causes). The following images were evaluated: 130 chest computed tomography (CT) scans, 153 abdominal CT scans, 254 chest radiographs, 148 radiographs of the abdomen/pelvis, and 106 cavagrams. Mean imaging follow-up interval was 18.4 months (maximum, 81.3 mo). No en bloc migration occurred outside the IVC. Twenty-six limb fractures (all short limbs) were identified in 20 patients; the earliest occurred at 4.1 months. Eight fragment migrations occurred into pulmonary arteries, seven into iliac/femoral veins, one into the right ventricle, and one into the renal vein. Seven fragments were intracaval near the filter, one was extracaval, and one could not be located. Kaplan-Meier survival estimates predicted a fracture rate of 40% at 5.5 years. Of the 20 patients with filter fractures, three died of unrelated causes and 17 remain asymptomatic. Recovery filter fractures occurred at the short limb only, with a suggested 5.5-year fracture risk of 40%. No life-threatening events occurred in patients with filter fracture. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Prevalence and potential pathogenicity of Vibrio parahaemolyticus in Chinese mitten crabs (Eriocheir sinensis) harvested from the River Thames estuary, England.

PubMed

Wagley, Sariqa; Koofhethile, Kegakilwe; Rangdale, Rachel

2009-01-01

Chinese mitten crabs (Eriocheir sinensis) have been described as an alien invasive species in the River Thames, United Kingdom, and elsewhere in Europe. The crabs can cause considerable physical damage to the riverbeds and threaten native ecosystems. Trapping has been considered an option, but such attempts to control mitten crab populations in Germany in the 1930s failed. In the United Kingdom, it has been suggested that commercial exploitation of the species could be employed as a control option. This study was conducted as part of a larger program to assess the suitability of a commercial Chinese mitten crab fishery in the River Thames. Crabs and water samples from the River Thames between 2003 and 2006 were examined for the human pathogenic bacterium Vibrio parahaemolyticus. All samples throughout this testing period were positive for V. parahaemolyticus. The putative pathogenicity markers, thermostable direct hemolysin and thermostable direct-related hemolysin, were detected in one sample, indicating that the crabs possessed the potential to cause V. parahaemolyticus-associated illness if consumed without further processing. Levels of V. parahaemolyticus were higher during the summer than in the winter. This is the first study of V. parahaemolyticus prevalence in European-adapted Chinese mitten crabs.

Pill in the blister pack: a rare cause of dysphagia in an elderly adult

PubMed Central

Laeeq, Syed Mudassir; Rai, Ayesha Aslam; Tasneem, Abbas Ali; Luck, Nasir Hassan; Majid, Zain

2015-01-01

Foreign body impaction in the esophagus amongst adults is not a common cause of dysphagia. Fish bone, food bolus, dentures may cause symptoms of dysphagia, odynophagia, chest pain or respiratory distress. It needs prompt evaluation along with removal of the substance either surgically or endoscopically to avoid the development of life threatening complications. Here we are reporting a case of an elderly male, who presented to us with a history of absolute dysphagia for one week, as a consequence of ingestion of a pill in blister pack. PMID:26918072

Recognizing Life-threatening Features of Dengue in Children and Health Seeking Behavior in Dengue Emergency Amongst Parents and Carers: A Cross-sectional study in Gombak District, Malaysia.

PubMed

Ariffin, F; Ramli, A S; Naim, N; Selamat, M I; Syed-Jamal, S J

2014-10-01

Dengue is life-threatening and the paediatric population is highly susceptible to complications. Deterioration can occur rapidly and ability to recognise early warning signs is crucial. This study aims to determine the knowledge and awareness of parents and carers and to predict their ability in recognising life-threatening symptoms and signs of dengue in children and to assess their health-seeking behaviour in dengue emergency. Methods This is a crosssectional study involving parents and carers of children ≤ 12 years old in schools and kindergartens in the Gombak district. Demographic details, knowledge on life-threatening symptoms and signs of dengue and health-seeking behaviour were collected using a self-administered questionnaire and knowledge scoring was done. The questionnaire was pilot tested with a Cronbach alpha of 0.82. The results were analysed using SPSS version 20.0. Results Total respondents were 866 with 44.8% men and 55.2% women. The mean age was 40.3 years (SD ± 5.7). Knowledge score of dengue life threatening features among respondents were good (30.0%) to average (56.8%). Respondents were able to recognise fever (98.5%), petechial rash (97.1%) and bleeding (65.2%) but were less able to recognise abdominal pain (22.3%) and passing less urine (28.2%) as life threatening dengue features. However, the ability to recognise fever is a poor predictor in recognising life threatening dengue in children compared to all other symptoms which were good predictors. A respondent that recognise stomach pain or neck stiffness were five times more likely to recognise life-threatening dengue. Respondents preferred to bring their children to the clinic (50.8%) or hospital (37.8%) themselves Instead of calling for ambulance. Worryingly, some would give antipyretics (3.6%) or wait for improvements (7.8%). Conclusion Concerted efforts by the schools, healthcare professionals and health authorities are required to educate parents and carers to identify life-threatening features of dengue and to improve their health seeking-behaviour.

Growth of Candida albicans hyphae.

PubMed

Sudbery, Peter E

2011-08-16

The fungus Candida albicans is often a benign member of the mucosal flora; however, it commonly causes mucosal disease with substantial morbidity and in vulnerable patients it causes life-threatening bloodstream infections. A striking feature of its biology is its ability to grow in yeast, pseudohyphal and hyphal forms. The hyphal form has an important role in causing disease by invading epithelial cells and causing tissue damage. This Review describes our current understanding of the network of signal transduction pathways that monitors environmental cues to activate a programme of hypha-specific gene transcription, and the molecular processes that drive the highly polarized growth of hyphae.

Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira.

PubMed

Adhikarla, Haritha; Wunder, Elsio A; Mechaly, Ariel E; Mehta, Sameet; Wang, Zheng; Santos, Luciane; Bisht, Vimla; Diggle, Peter; Murray, Gerald; Adler, Ben; Lopez, Francesc; Townsend, Jeffrey P; Groisman, Eduardo; Picardeau, Mathieu; Buschiazzo, Alejandro; Ko, Albert I

2018-01-01

Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira . In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator ) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one ( lvrB ) or both genes ( lvrA/B ) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium.

Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira

PubMed Central

Adhikarla, Haritha; Wunder, Elsio A.; Mechaly, Ariel E.; Mehta, Sameet; Wang, Zheng; Santos, Luciane; Bisht, Vimla; Diggle, Peter; Murray, Gerald; Adler, Ben; Lopez, Francesc; Townsend, Jeffrey P.; Groisman, Eduardo; Picardeau, Mathieu; Buschiazzo, Alejandro; Ko, Albert I.

2018-01-01

Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium. PMID:29600195

Animal venoms as antimicrobial agents.

PubMed

Perumal Samy, Ramar; Stiles, Bradley G; Franco, Octavio L; Sethi, Gautam; Lim, Lina H K

2017-06-15

Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens. Copyright © 2017 Elsevier Inc. All rights reserved.

Redefining disease emergence to improve prioritization and macro-ecological analyses.

PubMed

Rosenthal, Samantha R; Ostfeld, Richard S; McGarvey, Stephen T; Lurie, Mark N; Smith, Katherine F

2015-12-01

Microbial infections are as old as the hosts they sicken, but interest in the emergence of pathogens and the diseases they cause has been accelerating rapidly. The term 'emerging infectious disease' was coined in the mid-1900s to describe changes in disease dynamics in the modern era. Both the term and the phenomena it is meant to characterize have evolved and diversified over time, leading to inconsistencies and confusion. Here, we review the evolution of the term 'emerging infectious disease' (EID) in the literature as applied to human hosts. We examine the pathways (e.g., speciation or strain differentiation in the causative agent vs. rapid geographic expansion of an existing pathogen) by which diseases emerge. We propose a new framework for disease and pathogen emergence to improve prioritization. And we illustrate how the operational definition of an EID affects conclusions concerning the pathways by which diseases emerge and the ecological and socioeconomic drivers that elicit emergence. As EIDs appear to be increasing globally, and resources for science level off or decline, the research community is pushed to prioritize its focus on the most threatening diseases, riskiest potential pathogens, and the places they occur. The working definition of emerging infectious diseases and pathogens plays a crucial role in prioritization, but we argue that the current definitions may be impeding these efforts. We propose a new framework for classifying pathogens and diseases as "emerging" that distinguishes EIDs from emerging pathogens and novel potential pathogens. We suggest prioritization of: 1) EIDs for adaptation and mitigation, 2) emerging pathogens for preventive measures, and 3) novel potential pathogens for intensive surveillance.

Concurrent micro-RNA mediated silencing of tick-borne flavivirus replication in tick vector and in the brain of vertebrate host.

PubMed

Tsetsarkin, Konstantin A; Liu, Guangping; Kenney, Heather; Hermance, Meghan; Thangamani, Saravanan; Pletnev, Alexander G

2016-09-13

Tick-borne viruses include medically important zoonotic pathogens that can cause life-threatening diseases. Unlike mosquito-borne viruses, whose impact can be restrained via mosquito population control programs, for tick-borne viruses only vaccination remains the reliable means of disease prevention. For live vaccine viruses a concern exists, that spillovers from viremic vaccinees could result in introduction of genetically modified viruses into sustainable tick-vertebrate host transmission cycle in nature. To restrict tick-borne flavivirus (Langat virus, LGTV) vector tropism, we inserted target sequences for tick-specific microRNAs (mir-1, mir-275 and mir-279) individually or in combination into several distant regions of LGTV genome. This caused selective attenuation of viral replication in tick-derived cells. LGTV expressing combinations of target sequences for tick- and vertebrate CNS-specific miRNAs were developed. The resulting viruses replicated efficiently and remained stable in simian Vero cells, which do not express these miRNAs, however were severely restricted to replicate in tick-derived cells. In addition, simultaneous dual miRNA targeting led to silencing of virus replication in live Ixodes ricinus ticks and abolished virus neurotropism in highly permissive newborn mice. The concurrent restriction of adverse replication events in vertebrate and invertebrate hosts will, therefore, ensure the environmental safety of live tick-borne virus vaccine candidates.

Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States

PubMed Central

Ma, Hansong; Voelz, Kerstin; Ren, Ping; Carter, Dee A.; Chaturvedi, Vishnu; Bildfell, Robert J.; May, Robin C.; Heitman, Joseph

2010-01-01

Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts and to a lesser extent in immunocompromised hosts. The highest incidence for this disease is on Vancouver Island, Canada, where an outbreak is expanding into neighboring regions including mainland British Columbia and the United States. This outbreak is caused predominantly by C. gattii molecular type VGII, specifically VGIIa/major. In addition, a novel genotype, VGIIc, has emerged in Oregon and is now a major source of illness in the region. Through molecular epidemiology and population analysis of MLST and VNTR markers, we show that the VGIIc group is clonal and hypothesize it arose recently. The VGIIa/IIc outbreak lineages are sexually fertile and studies support ongoing recombination in the global VGII population. This illustrates two hallmarks of emerging outbreaks: high clonality and the emergence of novel genotypes via recombination. In macrophage and murine infections, the novel VGIIc genotype and VGIIa/major isolates from the United States are highly virulent compared to similar non-outbreak VGIIa/major-related isolates. Combined MLST-VNTR analysis distinguishes clonal expansion of the VGIIa/major outbreak genotype from related but distinguishable less-virulent genotypes isolated from other geographic regions. Our evidence documents emerging hypervirulent genotypes in the United States that may expand further and provides insight into the possible molecular and geographic origins of the outbreak. PMID:20421942

The Resources that Matter: Fundamental Social Causes of Health Disparities and the Challenge of Intelligence

ERIC Educational Resources Information Center

Link, Bruce G.; Phelan, Jo C.; Miech, Richard; Leckman-Westin, Emily

2008-01-01

A robust and very persistent association between indicators of socioeconomic status (SES) and the onset of life-threatening disease is a prominent concern of medical sociology. The persistence of the association over time and its generality across very different places suggests that no fixed set of intervening risk and protective factors can…

Research to Practice: Developing an Integrated Anaphylaxis Education Curriculum for School Nurses

ERIC Educational Resources Information Center

Cavanaugh, Rebecca; Strickland, C. June

2011-01-01

The numbers of school-aged children with life-threatening allergies that cause anaphylaxis continues to increase. Many states, including Washington, have responded to this by developing specific guidelines for school districts to follow in order to provide a safe learning environment for children with medical conditions that put them at risk for…

A rare cause of respiratory distress and edema in neonate: Panhypopituitarism.

PubMed

Dursun, Fatma; Kirmizibekmez, Heves; Metin, Fazilet

2017-01-01

Clinical presentation of hypopituitarism may be variable in the neonate. Symptoms are generally nonspecific, ranging from absent to severe, and even life-threatening, due to adrenocorticotrophic hormone deficiency. Presently described is a case of unexplained respiratory distress and edema in a neonate. Initial screening revealed panhypopituitarism. Respiratory distress improved after replacement treatment with hydrocortisone and thyroxine.

Late Effects of Treatment for Childhood Cancer (PDQ®)—Health Professional Version

Cancer.gov

Late effects of cancer treatment can cause serious, disabling, and life-threatening chronic health conditions that adversely affect the health of aging childhood cancer survivors. Learn about subsequent neoplasms and the cardiovascular, cognitive, psychosocial, digestive, endocrine, immune, musculoskeletal, reproductive, and urinary late effects of pediatric cancer treatment in this expert-reviewed summary.

Posttraumatic Stress Disorder in Children: What Elementary Teachers Should Know

ERIC Educational Resources Information Center

Ray, Jan

2014-01-01

Posttraumatic stress disorder (PTSD) is not limited to the men and women who have been exposed to the horrors of war through military service. Children who are exposed to traumatic and life-threatening events, such as school shootings, physical and sexual abuse, and community violence, also can suffer from PTSD. This article explores the causes,…

Adolescents' Self-Reported Suicide Attempts, Self-Harm Thoughts and Their Correlates across 17 European Countries

ERIC Educational Resources Information Center

Kokkevi, A.; Rotsika, V.; Arapaki, A.; Richardson, C.

2012-01-01

Background: Suicide is a leading cause of death among adolescents in Europe. Self-harm thoughts and behaviours are documented precursors of completed suicide. It is therefore of great importance to investigate the prevalence of suicide thoughts and attempts and their correlates, with the aim of preventing this major life-threatening public health…

Understanding, Predicting, and Preventing Life Changing and Life Threatening Health Changes among Aging Veterans and Civilians with Spinal Cord Injury

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0629 TITLE: Understanding, Predicting, and Preventing Life-Changing and Life-Threatening Health Changes among Aging...Threatening Health Changes among Aging Veterans and Civilians with Spinal Cord Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0629 5c. PROGRAM... health conditions, such as pressure ulcers and infections, that occur either in isolation or in combination. Our purpose is to identify how multiple

Prevalence and Genomic Characterization of Escherichia coli O157:H7 in Cow-Calf Herds throughout California.

PubMed

Worley, Jay N; Flores, Kristopher A; Yang, Xun; Chase, Jennifer A; Cao, Guojie; Tang, Shuai; Meng, Jianghong; Atwill, Edward R

2017-08-15

Escherichia coli serotype O157:H7 is a zoonotic food- and waterborne bacterial pathogen that causes a high hospitalization rate and can cause life-threatening complications. Increasingly, E. coli O157:H7 infections appear to originate from fresh produce. Ruminants, such as cattle, are a prominent reservoir of E. coli O157:H7 in the United States. California is one of the most agriculturally productive regions in the world for fresh produce, beef, and milk. The close proximity of fresh produce and cattle presents food safety challenges on a uniquely large scale. We performed a survey of E. coli O157:H7 on 20 farms in California to observe the regional diversity and prevalence of E. coli O157:H7. Isolates were obtained from enrichment cultures of cow feces. Some farms were sampled on two dates. Genomes from isolates were sequenced to determine their relatedness and pathogenic potential. E. coli O157:H7 was isolated from approximately half of the farms. The point prevalence of E. coli O157:H7 on farms was highly variable, ranging from zero to nearly 90%. Within farms, generally one or a few lineages were found, even when the rate of isolation was high. On farms with high isolation rates, a single clonal lineage accounted for most of the isolates. Farms that were visited months after the first visit might have had the same lineages of E. coli O157:H7. Strains of E. coli O157:H7 may be persistent for months on farms. IMPORTANCE This survey of 20 cow-calf operations from different regions of California provides an in depth look at resident Escherichia coli O157:H7 populations at the molecular level. E. coli O157:H7 is found to have a highly variable prevalence, and with whole-genome sequencing, high prevalences in herds were found to be due to a single lineage shed from multiple cows. Few repeat lineages were found between farms in this area; therefore, we predict that E. coli O157:H7 has significant diversity in this area beyond what is detected in this survey. All isolates from this study were found to have pathogenic potential based on the presence of key virulence gene sequences. This represents a novel insight into pathogen diversity within a single subtype and will inform future attempts to survey regional pathogen populations. Copyright © 2017 American Society for Microbiology.

Prevalence and Genomic Characterization of Escherichia coli O157:H7 in Cow-Calf Herds throughout California

PubMed Central

Worley, Jay N.; Flores, Kristopher A.; Yang, Xun; Chase, Jennifer A.; Cao, Guojie; Tang, Shuai; Meng, Jianghong

2017-01-01

ABSTRACT Escherichia coli serotype O157:H7 is a zoonotic food- and waterborne bacterial pathogen that causes a high hospitalization rate and can cause life-threatening complications. Increasingly, E. coli O157:H7 infections appear to originate from fresh produce. Ruminants, such as cattle, are a prominent reservoir of E. coli O157:H7 in the United States. California is one of the most agriculturally productive regions in the world for fresh produce, beef, and milk. The close proximity of fresh produce and cattle presents food safety challenges on a uniquely large scale. We performed a survey of E. coli O157:H7 on 20 farms in California to observe the regional diversity and prevalence of E. coli O157:H7. Isolates were obtained from enrichment cultures of cow feces. Some farms were sampled on two dates. Genomes from isolates were sequenced to determine their relatedness and pathogenic potential. E. coli O157:H7 was isolated from approximately half of the farms. The point prevalence of E. coli O157:H7 on farms was highly variable, ranging from zero to nearly 90%. Within farms, generally one or a few lineages were found, even when the rate of isolation was high. On farms with high isolation rates, a single clonal lineage accounted for most of the isolates. Farms that were visited months after the first visit might have had the same lineages of E. coli O157:H7. Strains of E. coli O157:H7 may be persistent for months on farms. IMPORTANCE This survey of 20 cow-calf operations from different regions of California provides an in depth look at resident Escherichia coli O157:H7 populations at the molecular level. E. coli O157:H7 is found to have a highly variable prevalence, and with whole-genome sequencing, high prevalences in herds were found to be due to a single lineage shed from multiple cows. Few repeat lineages were found between farms in this area; therefore, we predict that E. coli O157:H7 has significant diversity in this area beyond what is detected in this survey. All isolates from this study were found to have pathogenic potential based on the presence of key virulence gene sequences. This represents a novel insight into pathogen diversity within a single subtype and will inform future attempts to survey regional pathogen populations. PMID:28550057

[Implantable ECG recorder revealed the diagnosis in a baby with apparent life-threatening events].

PubMed

Hoorntje, T M; Langerak, W; Blokland-Loggers, H E; Sreeram, N

1999-09-25

A 14-month-old boy went through episodes of cyanosis and brief loss of consciousness. Extensive investigations failed to lead to a diagnosis, until an implanted ECG recorder revealed ECG abnormalities suggestive of strangulation. Interviews with the father and mother showed that this was indeed the case. The diagnosis of 'Münchhausen by proxy' was made. Psychiatric assistance and home help were called in. The child recovered well. If there is a suspicion of arrhythmia as the cause of apparent life-threatening events, prolonged ECG recordings are necessary. In a clinical environment it is possible to make continuous ECG recordings during a limited period. An insertable recorder allows continuous ECG recordings during a syncopal event and can be used for prolonged monitoring. The patient presented is the youngest infant in the world in whom such a device has been implanted.

Life- threatening hemothorax due to the inferior pulmonary ligament injury without obvious organ injuries: a case report.

PubMed

Kim, Jae Jun; Kim, Yong Hwan; Choi, Si Young; Jeong, Seong Cheol; Moon, Seok Whan

2015-03-21

Traumatic hemothorax is usually associated with obvious organ injuries, such as rib fractures, pulmonary injuries, and other mediastinal injuries. We present a rare case in which a 42-year- old Korean man who fell off of a roof, approximately 3 meters in height, resulting in a life-threatening hemothorax without obvious injuries to the thoracic organs. Chest CT showed a large amount of hemothorax in the right side of the thoracic cavity, and an active bleeding, presumably from the posterior intercostal or the phrenic artery, with a focal aneurysmal change. The emergency thoracotomy was performed to bring the active bleeding under control. The operative findings showed there were only the inferior pulmonary ligament tears, and the active bleeding from it. The postoperative course was uneventful and the patient was discharged without any complications. We should consider the inferior pulmonary ligamental injury as one of causes for traumatic hemothorax.

Research to practice: developing an integrated anaphylaxis education curriculum for school nurses.

PubMed

Cavanaugh, Rebecca; Strickland, C June

2011-06-01

The numbers of school-aged children with life-threatening allergies that cause anaphylaxis continues to increase. Many states, including Washington, have responded to this by developing specific guidelines for school districts to follow in order to provide a safe learning environment for children with medical conditions that put them at risk for anaphylaxis. School nurses require resources to assist them in providing health training for school staff on how to manage potentially life-threatening health conditions for children in their school, however, resources to address this training are limited. A search for and content analysis of currently available literature and resources about anaphylaxis and anaphylaxis training curricula revealed a lack of an integrated curriculum to train school staff. This article presents a discussion of the development of a train-the-trainer anaphylaxis education program providing school nurses with curriculum, lesson plans, teaching-learning activities, and resources for anaphylaxis education of all school staff.

Pediatric herpes simplex virus infections: an evidence-based approach to treatment.

PubMed

Sanders, Jennifer E; Garcia, Sylvia E

2014-01-01

Herpes simplex virus is a common virus that causes a variety of clinical presentations ranging from mild to life-threatening. Orolabial and genital herpes are common disorders that can often be managed in an outpatient setting; however, some patients do present to the emergency department with those conditions, and emergency clinicians should be aware of possible complications in the pediatric population. Neonatal herpes is a rare disorder, but prompt recognition and initiation of antiviral therapy is imperative, as the morbidity and mortality of the disease is high. Herpes encephalitis is an emergency that also requires a high index of suspicion to diagnose. Herpes simplex virus is also responsible for a variety of other clinical presentations, including herpes gladiatorum, herpetic whitlow, eczema herpeticum, and ocular herpes. This issue reviews the common clinical presentations of the herpes simplex virus, the life-threatening infections that require expedient identification and management, and recommended treatment regimens.

Protein A sepharose immunoadsorption: immunological and haemostatic effects in two cases of acquired haemophilia.

PubMed

Guillet, B; Kriaa, F; Huysse, M G; Proulle, V; George, C; Tchernia, G; D'Oiron, R; Laurian, Y; Charpentier, B; Lambert, T; Dreyfus, M

2001-09-01

Acquired haemophilia is a life-threatening disorder caused by circulating auto-antibodies that inhibit factor VIII coagulant activity (FBIII:C). Immunoadsorption on protein A sepharose (IA-PA) was performed in two bleeding patients with acquired haemophilia: we observed a dramatic and quick decrease in the anti-FVIII:C inhibitor titre leading to a normal, albeit transient, haemostatic status. In one case, IA-PA was the only procedure which succeeded in stopping massive haemorrhage. In the second case, IA-PA reinforced the haemostatic effect of recombinant activated factor VII by increasing the endogenous plasma factor VIII level. The efficacy of IA-PA was sustained with immunosuppressive treatment introduced, respectively, 10 and 15 d before the IA-PA procedures. Our experience with IA-PA suggests that this extracorporeal anti-FVIII:C removal procedure is a valuable therapeutic tool for acquired haemophilia and can alleviate life-threatening haemorrhages.

Understanding growers' decisions to manage invasive pathogens at the farm level.

PubMed

Breukers, Annemarie; van Asseldonk, Marcel; Bremmer, Johan; Beekman, Volkert

2012-06-01

Globalization causes plant production systems to be increasingly threatened by invasive pests and pathogens. Much research is devoted to support management of these risks. Yet, the role of growers' perceptions and behavior in risk management has remained insufficiently analyzed. This article aims to fill this gap by addressing risk management of invasive pathogens from a sociopsychological perspective. An analytical framework based on the Theory of Planned Behavior was used to explain growers' decisions on voluntary risk management measures. Survey information from 303 Dutch horticultural growers was statistically analyzed, including regression and cluster analysis. It appeared that growers were generally willing to apply risk management measures, and that poor risk management was mainly due to perceived barriers, such as high costs and doubts regarding efficacy of management measures. The management measures applied varied considerably among growers, depending on production sector and farm-specific circumstances. Growers' risk perception was found to play a role in their risk management, although the causal relation remained unclear. These results underscore the need to apply a holistic perspective to farm level management of invasive pathogen risk, considering the entire package of management measures and accounting for sector- and farm-specific circumstances. Moreover, they demonstrate that invasive pathogen risk management can benefit from a multidisciplinary approach that incorporates growers' perceptions and behavior.

Onychomycosis: Pathogenesis, Diagnosis, and Management

PubMed Central

Elewski, Boni E.

1998-01-01

Although not life-threatening, onychomycosis (a fungal infection of the nail, usually caused by a dermatophyte) constitutes an important public health problem because of its high prevalence (about 10% of the U.S. population) and associated morbidity. The disease can have certain negative consequences for patients, such as pain, and can potentially undermine work and social lives. This review discusses the etiology, classification, diagnosis, and treatment of onychomycosis. Four types of onychomycosis are recognized based on the site and pattern of fungal invasion. Dermatophyte fungi are the predominant pathogens, but yeasts (especially Candida albicans) and nondermatophyte molds may also be implicated. Accurate diagnosis requires direct microscopy and fungal culture. The differential diagnosis includes psoriasis, lichen planus, onychogryphosis, and nail trauma. Onychomycosis is more difficult to treat than most dermatophytoses because of the inherent slow growth of the nail. Older antifungal agents (ketoconazole and griseofulvin) are unsuitable for onychomycosis because of their relatively poor efficacy and potential adverse effects. Three recently developed antimycotic agents (fluconazole, itraconazole, and terbinafine) offer high cure rates and good safety profiles. In addition, the short treatment times (<3 months) and intermittent dosing schedules are likely to enhance compliance and reduce the costs of therapy. PMID:9665975

In vitro inhibitory activities of magnolol against Candida spp.

PubMed

Zhou, Peiru; Fu, Jingya; Hua, Hong; Liu, Xiaosong

2017-01-01

Candida spp. cause various infections involving the skin, mucosa, deep tissues, and even life-threatening candidemia. They are regarded as an important pathogen of nosocomial bloodstream infection, with a high mortality rate. As a result of prolonged exposure to azoles, the therapeutic failure associated with azoles resistance has become a serious challenge in clinical situations. Therefore, novel, alternative antifungals are required urgently. In the present study, the CLSI M-27A broth microdilution method and the 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay were used to evaluate the antifungal effects of magnolol against various standard Candida strains in planktonic mode and biofilm formation, respectively. The antifungal activity of magnolol was demonstrated in planktonic C. albicans and non-albicans Candida species, especially fluconazole-resistant Candida krusei , with the minimum inhibitory concentrations ranging from 10 to 40 μg/mL. The BMIC 90 (minimum concentration with 90% Candida biofilm inhibited) values of magnolol ranged from 20 to 160 μg/mL, whereas the BMIC 90 values of fluconazole were more than 128 μg/mL. As an alternative and broad-spectrum antifungal agent, magnolol might be of benefit to the treatment of refractory Candida infection.

Toxoplasma gondii Antigen-Pulsed-Dendritic Cell-Derived Exosomes Induce a Protective Immune Response against T. gondii Infection

PubMed Central

Aline, Fleur; Bout, Daniel; Amigorena, Sébastian; Roingeard, Philippe; Dimier-Poisson, Isabelle

2004-01-01

It was previously demonstrated that immunizing mice with spleen dendritic cells (DCs) that had been pulsed ex vivo with Toxoplasma gondii antigens triggers a systemic Th1-biased specific immune response and induces protection against infection. T. gondii can cause severe sequelae in the fetuses of mothers who acquire the infection during pregnancy, as well as life-threatening neuropathy in immunocompromised patients, in particular those with AIDS. Here, we investigate the efficacy of a novel cell-free vaccine composed of DC exosomes, which are secreted antigen-presenting vesicles that express functional major histocompatibility complex class I and II and T-cell-costimulatory molecules. They have already been shown to induce potent antitumor immune responses. We investigated the potential of DC2.4 cell line-derived exosomes to induce protective immunity against toxoplasmosis. Our data show that most adoptively transferred T. gondii-pulsed DC-derived exosomes were transferred to the spleen, elicited a strong systemic Th1-modulated Toxoplasma-specific immune response in vivo, and conferred good protection against infection. These findings support the possibility that DC-derived exosomes can be used for T. gondii immunoprophylaxis and for immunoprophylaxis against many other pathogens. PMID:15213158

Interplay between reactive oxygen species and hormones in the control of plant development and stress tolerance.

PubMed

Xia, Xiao-Jian; Zhou, Yan-Hong; Shi, Kai; Zhou, Jie; Foyer, Christine H; Yu, Jing-Quan

2015-05-01

As a consequence of a sessile lifestyle, plants are continuously exposed to changing environmental conditions and often life-threatening stresses caused by exposure to excessive light, extremes of temperature, limiting nutrient or water availability, and pathogen/insect attack. The flexible coordination of plant growth and development is necessary to optimize vigour and fitness in a changing environment through rapid and appropriate responses to such stresses. The concept that reactive oxygen species (ROS) are versatile signalling molecules in plants that contribute to stress acclimation is well established. This review provides an overview of our current knowledge of how ROS production and signalling are integrated with the action of auxin, brassinosteroids, gibberellins, abscisic acid, ethylene, strigolactones, salicylic acid, and jasmonic acid in the coordinate regulation of plant growth and stress tolerance. We consider the local and systemic crosstalk between ROS and hormonal signalling pathways and identify multiple points of reciprocal control, as well as providing insights into the integration nodes that involve Ca(2+)-dependent processes and mitogen-activated protein kinase phosphorylation cascades. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

GMP Synthase Is Required for Virulence Factor Production and Infection by Cryptococcus neoformans*

PubMed Central

Chitty, Jessica L.; Tatzenko, Tayla L.; Williams, Simon J.; Koh, Y. Q. Andre E.; Corfield, Elizabeth C.; Butler, Mark S.; Robertson, Avril A. B.; Cooper, Matthew A.; Kappler, Ulrike; Kobe, Bostjan; Fraser, James A.

2017-01-01

Over the last four decades the HIV pandemic and advances in medical treatments that also cause immunosuppression have produced an ever-growing cohort of individuals susceptible to opportunistic pathogens. Of these, AIDS patients are particularly vulnerable to infection by the encapsulated yeast Cryptococcus neoformans. Most commonly found in the environment in purine-rich bird guano, C. neoformans experiences a drastic change in nutrient availability during host infection, ultimately disseminating to colonize the purine-poor central nervous system. Investigating the consequences of this challenge, we have characterized C. neoformans GMP synthase, the second enzyme in the guanylate branch of de novo purine biosynthesis. We show that in the absence of GMP synthase, C. neoformans becomes a guanine auxotroph, the production of key virulence factors is compromised, and the ability to infect nematodes and mice is abolished. Activity assays performed using recombinant protein unveiled differences in substrate binding between the C. neoformans and human enzymes, with structural insights into these kinetic differences acquired via homology modeling. Collectively, these data highlight the potential of GMP synthase to be exploited in the development of new therapeutic agents for the treatment of disseminated, life-threatening fungal infections. PMID:28062578

High diversity of airborne fungi in the hospital environment as revealed by meta-sequencing-based microbiome analysis

PubMed Central

Tong, Xunliang; Xu, Hongtao; Zou, Lihui; Cai, Meng; Xu, Xuefeng; Zhao, Zuotao; Xiao, Fei; Li, Yanming

2017-01-01

Invasive fungal infections acquired in the hospital have progressively emerged as an important cause of life-threatening infection. In particular, airborne fungi in hospitals are considered critical pathogens of hospital-associated infections. To identify the causative airborne microorganisms, high-volume air samplers were utilized for collection, and species identification was performed using a culture-based method and DNA sequencing analysis with the Illumina MiSeq and HiSeq 2000 sequencing systems. Few bacteria were grown after cultivation in blood agar. However, using microbiome sequencing, the relative abundance of fungi, Archaea species, bacteria and viruses was determined. The distribution characteristics of fungi were investigated using heat map analysis of four departments, including the Respiratory Intensive Care Unit, Intensive Care Unit, Emergency Room and Outpatient Department. The prevalence of Aspergillus among fungi was the highest at the species level, approximately 17% to 61%, and the prevalence of Aspergillus fumigatus among Aspergillus species was from 34% to 50% in the four departments. Draft genomes of microorganisms isolated from the hospital environment were obtained by sequence analysis, indicating that investigation into the diversity of airborne fungi may provide reliable results for hospital infection control and surveillance. PMID:28045065

Different Reactive Oxygen Species Scavenging Properties of Flavonoids Determine Their Abilities to Extend the Shelf Life of Tomato.

PubMed

Zhang, Yang; De Stefano, Rosalba; Robine, Marie; Butelli, Eugenio; Bulling, Katharina; Hill, Lionel; Rejzek, Martin; Martin, Cathie; Schoonbeek, Henk-jan

2015-11-01

The shelf life of tomato (Solanum lycopersicum) fruit is determined by the processes of overripening and susceptibility to pathogens. Postharvest shelf life is one of the most important traits for commercially grown tomatoes. We compared the shelf life of tomato fruit that accumulate different flavonoids and found that delayed overripening is associated with increased total antioxidant capacity caused by the accumulation of flavonoids in the fruit. However, reduced susceptibility to Botrytis cinerea, a major postharvest fungal pathogen of tomato, is conferred by specific flavonoids only. We demonstrate an association between flavonoid structure, selective scavenging ability for different free radicals, and reduced susceptibility to B. cinerea. Our study provides mechanistic insight into how flavonoids influence the shelf life, information that could be used to improve the shelf life of tomato and, potentially, other soft fruit. © 2015 American Society of Plant Biologists. All Rights Reserved.

Different Reactive Oxygen Species Scavenging Properties of Flavonoids Determine Their Abilities to Extend the Shelf Life of Tomato1[OPEN

PubMed Central

Zhang, Yang; De Stefano, Rosalba; Robine, Marie; Butelli, Eugenio; Bulling, Katharina; Hill, Lionel; Rejzek, Martin; Martin, Cathie; Schoonbeek, Henk-jan

2015-01-01

The shelf life of tomato (Solanum lycopersicum) fruit is determined by the processes of overripening and susceptibility to pathogens. Postharvest shelf life is one of the most important traits for commercially grown tomatoes. We compared the shelf life of tomato fruit that accumulate different flavonoids and found that delayed overripening is associated with increased total antioxidant capacity caused by the accumulation of flavonoids in the fruit. However, reduced susceptibility to Botrytis cinerea, a major postharvest fungal pathogen of tomato, is conferred by specific flavonoids only. We demonstrate an association between flavonoid structure, selective scavenging ability for different free radicals, and reduced susceptibility to B. cinerea. Our study provides mechanistic insight into how flavonoids influence the shelf life, information that could be used to improve the shelf life of tomato and, potentially, other soft fruit. PMID:26082399

Pivoting the Plant Immune System from Dissection to Deployment

PubMed Central

Dangl, Jeffery L.; Horvath, Diana M.; Staskawicz, Brian J.

2013-01-01

Diverse and rapidly evolving pathogens cause plant diseases and epidemics that threaten crop yield and food security around the world. Research over the last 25 years has led to an increasingly clear conceptual understanding of the molecular components of the plant immune system. Combined with ever-cheaper DNA-sequencing technology and the rich diversity of germ plasm manipulated for over a century by plant breeders, we now have the means to begin development of durable (long-lasting) disease resistance beyond the limits imposed by conventional breeding and in a manner that will replace costly and unsustainable chemical controls. PMID:23950531

Diaphorina citri (Hemiptera: Liviidae) Vector Competence for the Citrus Greening Pathogen 'Candidatus Liberibacter Asiaticus'.

PubMed

Tabachnick, Walter J

2015-06-01

Characterizing the vector competence of Diaphorina citri Kuwayama for 'Candidatus Liberibacter asiaticus,' the pathogen causing citrus greening, is essential for understanding the epidemiology of this disease that is threatening the U.S. citrus industry. Vector competence studies have been difficult because of the biology of D. citri, the inability to culture the pathogen, and the available diagnostic methods used to detect the bacteria in plant and insect tissues. The methods employed in many studies of D. citri vector competence may have overestimated amounts of live 'Ca. L. asiaticus' in both plant and insect tissues, and it is possible that the amounts of phloem ingested by psyllids may not contain sufficient detectable pathogen using current diagnostic methods. As a result of the difficulty in characterizing D. citri vector competence, the several daunting challenges for providing D. citri that are unable to inoculate 'Ca. L. asiaticus', as a novel method to control greening are discussed. Suggestions to overcome some of these challenges are provided. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A De Novo-Assembly Based Data Analysis Pipeline for Plant Obligate Parasite Metatranscriptomic Studies.

PubMed

Guo, Li; Allen, Kelly S; Deiulio, Greg; Zhang, Yong; Madeiras, Angela M; Wick, Robert L; Ma, Li-Jun

2016-01-01

Current and emerging plant diseases caused by obligate parasitic microbes such as rusts, downy mildews, and powdery mildews threaten worldwide crop production and food safety. These obligate parasites are typically unculturable in the laboratory, posing technical challenges to characterize them at the genetic and genomic level. Here we have developed a data analysis pipeline integrating several bioinformatic software programs. This pipeline facilitates rapid gene discovery and expression analysis of a plant host and its obligate parasite simultaneously by next generation sequencing of mixed host and pathogen RNA (i.e., metatranscriptomics). We applied this pipeline to metatranscriptomic sequencing data of sweet basil (Ocimum basilicum) and its obligate downy mildew parasite Peronospora belbahrii, both lacking a sequenced genome. Even with a single data point, we were able to identify both candidate host defense genes and pathogen virulence genes that are highly expressed during infection. This demonstrates the power of this pipeline for identifying genes important in host-pathogen interactions without prior genomic information for either the plant host or the obligate biotrophic pathogen. The simplicity of this pipeline makes it accessible to researchers with limited computational skills and applicable to metatranscriptomic data analysis in a wide range of plant-obligate-parasite systems.

Landscape predictors of pathogen prevalence and range contractions in US bumblebees.

PubMed

McArt, Scott H; Urbanowicz, Christine; McCoshum, Shaun; Irwin, Rebecca E; Adler, Lynn S

2017-11-29

Several species of bumblebees have recently experienced range contractions and possible extinctions. While threats to bees are numerous, few analyses have attempted to understand the relative importance of multiple stressors. Such analyses are critical for prioritizing conservation strategies. Here, we describe a landscape analysis of factors predicted to cause bumblebee declines in the USA. We quantified 24 habitat, land-use and pesticide usage variables across 284 sampling locations, assessing which variables predicted pathogen prevalence and range contractions via machine learning model selection techniques. We found that greater usage of the fungicide chlorothalonil was the best predictor of pathogen ( Nosema bombi ) prevalence in four declining species of bumblebees. Nosema bombi has previously been found in greater prevalence in some declining US bumblebee species compared to stable species. Greater usage of total fungicides was the strongest predictor of range contractions in declining species, with bumblebees in the northern USA experiencing greater likelihood of loss from previously occupied areas. These results extend several recent laboratory and semi-field studies that have found surprising links between fungicide exposure and bee health. Specifically, our data suggest landscape-scale connections between fungicide usage, pathogen prevalence and declines of threatened and endangered bumblebees. © 2017 The Author(s).

Tachycardia may prognosticate life- or organ-threatening diseases in children with abdominal pain.

PubMed

Hayakawa, Itaru; Sakakibara, Hiroshi; Atsumi, Yukari; Hataya, Hiroshi; Terakawa, Toshiro

2017-06-01

Abdominal pain is common in children, but expeditious diagnosis of life- or organ-threatening diseases can be challenging. An evidence-based definition of tachycardia in children was established recently, but its diagnostic utility has not yet been studied. To test the hypothesis that abdominal pain with tachycardia may pose a higher likelihood of life- or organ-threatening diseases in children. A nested case-control study was conducted in a pediatric emergency department in 2013. Tachycardia was defined as a resting heart rate of more than 3 standard deviations above the average for that age. Life- or organ-threatening diseases were defined as "disorders that might result in permanent morbidity or mortality without appropriate intervention." A triage team recorded vital signs before emergency physicians attended patients. Patients with tachycardia (cases) and without tachycardia (controls) were systematically matched for age, sex, and month of visit. The groups were compared for the presence of life- or organ-threatening diseases. There were 1683 visits for abdominal pain, 1512 of which had vital signs measured at rest. Eighty-three patients experienced tachycardia, while 1429 did not. Fifty-eight cases and 58 controls were matched. Life- or organ-threatening diseases were more common in the case group (19%) than the control group (5%, p=0.043). The relative risk of tachycardia to the presence of the diseases was 3.7 (95% confidence interval 1.2-12.0). Tachycardia significantly increased the likelihood of life- or organ-threatening diseases. Tachycardia in children with abdominal pain should alert emergency physicians to the possibility of serious illness. Copyright © 2017 Elsevier Inc. All rights reserved.

Aspergillus sydowii and Other Potential Fungal Pathogens in Gorgonian Octocorals of the Ecuadorian Pacific.

PubMed

Soler-Hurtado, M Mar; Sandoval-Sierra, José Vladimir; Machordom, Annie; Diéguez-Uribeondo, Javier

2016-01-01

Emerging fungal diseases are threatening ecosystems and have increased in recent decades. In corals, the prevalence and consequences of these infections have also increased in frequency and severity. Coral reefs are affected by an emerging fungal disease named aspergillosis, caused by Aspergillus sydowii. This disease and its pathogen have been reported along the Caribbean and Pacific coasts of Colombia. Despite this, an important number of coral reefs worldwide have not been investigated for the presence of this pathogen. In this work, we carried out the surveillance of the main coral reef of the Ecuadorian Pacific with a focus on the two most abundant and cosmopolitan species of this ecosystem, Leptogorgia sp. and Leptogorgia obscura. We collected 59 isolates and obtained the corresponding sequences of the Internal Transcribed Spacers (ITS) of the ribosomal DNA. These were phylogenetically analyzed using MrBayes, which indicated the presence of two isolates of the coral reef pathogen A. sydowii, as well as 16 additional species that are potentially pathogenic to corals. Although the analyzed gorgonian specimens appeared healthy, the presence of these pathogens, especially of A. sydowii, alert us to the potential risk to the health and future survival of the Pacific Ecuadorian coral ecosystem under the current scenario of increasing threats and stressors to coral reefs, such as habitat alterations by humans and global climate change.

Apple anthracnose canker life cycle and disease cycle

USDA-ARS?s Scientific Manuscript database

Apple anthracnose [caused by Neofabraea malicorticis (H.S. Jacks) anamorph Cryptosporiopsis curvispora (Peck)] is a fungal disease that impacts apple production. The pathogen produces cankers on trees as well as a rot on the fruit known as ‘Bull’s-eye rot’. The cankers cause severe damage to trees...

[Thyrotoxic storm and myxedema coma].

PubMed

Takasu, N

1999-08-01

Thyrotoxic or hyperthyroid storm is a grave, life-threatening, but relatively infrequent medical emergency. Immediate causes of death in this emergency are severe hyperpyrexia and pulmonary edema associated with arrhythmias, shock, and coma. This emergency is found in Graves' patients most frequently. Myxedema coma is an emergency clinical state caused by severe deficiency of thyroid hormones. This crisis represents the extreme expression of hypothyroidism. While it is quite useful to elicit a history of previous hypothyroidism, thyroid surgery, or radioactive iodine treatment, it is not obtainable.

Odorous vaginal discharge - a case study for thorough investigation.

PubMed

Cernat, Geta; Leung, Lawrence

2011-08-01

Odorous vaginal discharge is a common presentation to general practitioners, and a frequent presentation for bacterial infections and sexually transmissible diseases. Busy GPs may be tempted to make a diagnosis from the clinical history and symptoms, and prescribe antibiotics as a first line treatment. This case highlights an unusual cause of persistent odorous vaginal discharge. If a thorough examination had not been conducted, the cause would have been overlooked, first line antibiotics would most likely have been ineffective, and potentially life threatening consequences may have occurred.

Increasing strawberry shelf-life with carvacrol and methyl cinnamate antimicrobial vapors released from edible films (abstract)

USDA-ARS?s Scientific Manuscript database

Shelf life of strawberries (Fragaria x ananassa) is limited by decay caused by microbial growth that negatively impacts their color, texture and weight. Plant natural volatile compounds, such as terpenoids and esters, have been reported to be effective against microbial pathogen growth. The advantag...

Diversifying selection in the wheat stem rust fungus acts predominantly on pathogen-associated gene families and reveals candidate effectors

PubMed Central

Sperschneider, Jana; Ying, Hua; Dodds, Peter N.; Gardiner, Donald M.; Upadhyaya, Narayana M.; Singh, Karam B.; Manners, John M.; Taylor, Jennifer M.

2014-01-01

Plant pathogens cause severe losses to crop plants and threaten global food production. One striking example is the wheat stem rust fungus, Puccinia graminis f. sp. tritici, which can rapidly evolve new virulent pathotypes in response to resistant host lines. Like several other filamentous fungal and oomycete plant pathogens, its genome features expanded gene families that have been implicated in host-pathogen interactions, possibly encoding effector proteins that interact directly with target host defense proteins. Previous efforts to understand virulence largely relied on the prediction of secreted, small and cysteine-rich proteins as candidate effectors and thus delivered an overwhelming number of candidates. Here, we implement an alternative analysis strategy that uses the signal of adaptive evolution as a line of evidence for effector function, combined with comparative information and expression data. We demonstrate that in planta up-regulated genes that are rapidly evolving are found almost exclusively in pathogen-associated gene families, affirming the impact of host-pathogen co-evolution on genome structure and the adaptive diversification of specialized gene families. In particular, we predict 42 effector candidates that are conserved only across pathogens, induced during infection and rapidly evolving. One of our top candidates has recently been shown to induce genotype-specific hypersensitive cell death in wheat. This shows that comparative genomics incorporating the evolutionary signal of adaptation is powerful for predicting effector candidates for laboratory verification. Our system can be applied to a wide range of pathogens and will give insight into host-pathogen dynamics, ultimately leading to progress in strategies for disease control. PMID:25225496

The common cold: potential for future prevention or cure.

PubMed

Passioti, Maria; Maggina, Paraskevi; Megremis, Spyridon; Papadopoulos, Nikolaos G

2014-02-01

The common cold is the most frequent, although generally mild, human disease. Human Rhinoviruses are the prevalent causative agents, but other viruses are also implicated. Being so common, viral colds, have significant implications on public health and quality of life, but may also be life-threatening for vulnerable groups of patients. Specific diagnosis and treatment of the common cold still remain unmet needs. Molecular diagnostic techniques allow specific detection of known pathogens as well as the identification of newly emerging viruses. Although a number of medications or natural treatments have been shown to have some effect, either on the number or on the severity of common colds, no single agent is considerably effective. Virus-specific management remains in most cases a challenging potential as many factors have to be taken into account, including the diversity of the viral genomes, the heterogeneity of affected individuals, as well as the complexity of this long standing host-virus relationship.

Special feature: alien pests threatening biodiversity of forest ecosystems. Editorial.

Treesearch

Naoto Kamata; Kurt W. Gottschalk

2007-01-01

Throughout the world, biological invasions have become one of the most important factors threatening biodiversity. Many species are introduced into "a new world" accidentally or intentionally. Most fail to become established, but some become established, colonize, and start to increase and expand their ranges. Some invasive pathogens damage and kill host...

Applying evolutionary biology to address global challenges

PubMed Central

Carroll, Scott P.; Jørgensen, Peter Søgaard; Kinnison, Michael T.; Bergstrom, Carl T.; Denison, R. Ford; Gluckman, Peter; Smith, Thomas B.; Strauss, Sharon Y.; Tabashnik, Bruce E.

2014-01-01

Two categories of evolutionary challenges result from escalating human impacts on the planet. The first arises from cancers, pathogens and pests that evolve too quickly, and the second from the inability of many valued species to adapt quickly enough. Applied evolutionary biology provides a suite of strategies to address these global challenges that threaten human health, food security, and biodiversity. This review highlights both progress and gaps in genetic, developmental and environmental manipulations across the life sciences that either target the rate and direction of evolution, or reduce the mismatch between organisms and human-altered environments. Increased development and application of these underused tools will be vital in meeting current and future targets for sustainable development. PMID:25213376

Yeast killer systems.

PubMed Central

Magliani, W; Conti, S; Gerloni, M; Bertolotti, D; Polonelli, L

1997-01-01

The killer phenomenon in yeasts has been revealed to be a multicentric model for molecular biologists, virologists, phytopathologists, epidemiologists, industrial and medical microbiologists, mycologists, and pharmacologists. The surprisingly widespread occurrence of the killer phenomenon among taxonomically unrelated microorganisms, including prokaryotic and eukaryotic pathogens, has engendered a new interest in its biological significance as well as its theoretical and practical applications. The search for therapeutic opportunities by using yeast killer systems has conceptually opened new avenues for the prevention and control of life-threatening fungal diseases through the idiotypic network that is apparently exploited by the immune system in the course of natural infections. In this review, the biology, ecology, epidemiology, therapeutics, serology, and idiotypy of yeast killer systems are discussed. PMID:9227858

Reprint of: B cell elimination in systemic lupus erythematosus. Clin. Immunol. 146(2) 90-103.

PubMed

Furtado, João; Isenberg, David A

2013-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Action and function of Chromobacterium violaceum in health and disease: Violacein as a promising metabolite to counteract gastroenterological diseases.

PubMed

Justo, Giselle Zenker; Durán, Nelson

2017-12-01

Chromobacterium violaceum is a Gram negative, β-proteobacterium found in the microbiota of tropical and subtropical environments. Although considered an opportunistic pathogen, infection rapidly progress to fatal sepsis, with metastatic abscesses. It is noteworthy the multidrug resistant phenotype of C. violaceum and the possibility of relapse. Recently, an influence of global climate in the incidence of cases beyond the previous areas has been observed. Furthermore, chronic granulomatous disease has been considered a risk factor to infection. Despite the increase in C. violaceum infection incidence and high mortality, most clinicians are not familiar with it. This review pointed out important features of this life threatening microorganism, including its pathogenicity, mechanistic aspects, genetic and drug resistance associated factors, and the clinical association with chronic granulomatous disease. In addition, its main metabolite violacein may be a promising agent to counteract gastroenterological diseases, such as colorectal cancer and inflammatory gastric lesions. Copyright © 2017 Elsevier Ltd. All rights reserved.

IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

PubMed Central

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

IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis.

PubMed

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.

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

PubMed

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

2016-10-01

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

Experimental infection of snakes with Ophidiomyces ophiodiicola causes pathological changes that typify snake fungal disease

USGS Publications Warehouse

Lorch, Jeffrey M.; Lankton, Julia S.; Werner, Katrien; Falendysz, Elizabeth A.; McCurley, Kevin; Blehert, David S.

2015-01-01

IMPORTANCE Skin infections in snakes, referred to as snake fungal disease (SFD), have been reported with increasing frequency in wild snakes in the eastern United States. While most of these infections are associated with the fungusOphidiomyces ophiodiicola, there has been no conclusive evidence to implicate this fungus as a primary pathogen. Furthermore, it is not understood why the infections affect different host populations differently. Our experiment demonstrates that O. ophiodiicola is the causative agent of SFD and can elicit pathological changes that likely impact fitness of wild snakes. This information, and the laboratory model we describe, will be essential in addressing unresolved questions regarding disease ecology and outcomes of O. ophiodiicola infection and helping to conserve snake populations threatened by the disease. The SFD model of infection also offers utility for exploring larger concepts related to comparative fungal virulence, host response, and host-pathogen evolution.

Future potential distribution of the emerging amphibian chytrid fungus under anthropogenic climate change.

PubMed

Rödder, Dennis; Kielgast, Jos; Lötters, Stefan

2010-11-01

Anthropogenic climate change poses a major threat to global biodiversity with a potential to alter biological interactions at all spatial scales. Amphibians are the most threatened vertebrates and have been subject to increasing conservation attention over the past decade. A particular concern is the pandemic emergence of the parasitic chytrid fungus Batrachochytrium dendrobatidis, which has been identified as the cause of extremely rapid large-scale declines and species extinctions. Experimental and observational studies have demonstrated that the host-pathogen system is strongly influenced by climatic parameters and thereby potentially affected by climate change. Herein we project a species distribution model of the pathogen onto future climatic scenarios generated by the IPCC to examine their potential implications on the pandemic. Results suggest that predicted anthropogenic climate change may reduce the geographic range of B. dendrobatidis and its potential influence on amphibian biodiversity.

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

PubMed

Neelam, Sudha; Niederkorn, Jerry Y

2017-06-01

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

Global Distribution of Two Fungal Pathogens Threatening Endangered Sea Turtles

PubMed Central

Sarmiento-Ramírez, Jullie M.; Abella-Pérez, Elena; Phillott, Andrea D.; Sim, Jolene; van West, Pieter; Martín, María P.; Marco, Adolfo; Diéguez-Uribeondo, Javier

2014-01-01

Nascent fungal infections are currently considered as one of the main threats for biodiversity and ecosystem health, and have driven several animal species into critical risk of extinction. Sea turtles are one of the most endangered groups of animals and only seven species have survived to date. Here, we described two pathogenic species, i.e., Fusarium falciforme and Fusarium keratoplasticum, that are globally distributed in major turtle nesting areas for six sea turtle species and that are implicated in low hatch success. These two fungi possess key biological features that are similar to emerging pathogens leading to host extinction, e.g., high virulence, and a broad host range style of life. Their optimal growth temperature overlap with the optimal incubation temperature for eggs, and they are able to kill up to 90% of the embryos. Environmental forcing, e.g., tidal inundation and clay/silt content of nests, were correlated to disease development. Thus, these Fusarium species constitute a major threat to sea turtle nests, especially to those experiencing environmental stressors. These findings have serious implications for the survival of endangered sea turtle populations and the success of conservation programs worldwide. PMID:24465748

Global distribution of two fungal pathogens threatening endangered sea turtles.

PubMed

Sarmiento-Ramírez, Jullie M; Abella-Pérez, Elena; Phillott, Andrea D; Sim, Jolene; van West, Pieter; Martín, María P; Marco, Adolfo; Diéguez-Uribeondo, Javier

2014-01-01

Nascent fungal infections are currently considered as one of the main threats for biodiversity and ecosystem health, and have driven several animal species into critical risk of extinction. Sea turtles are one of the most endangered groups of animals and only seven species have survived to date. Here, we described two pathogenic species, i.e., Fusarium falciforme and Fusarium keratoplasticum, that are globally distributed in major turtle nesting areas for six sea turtle species and that are implicated in low hatch success. These two fungi possess key biological features that are similar to emerging pathogens leading to host extinction, e.g., high virulence, and a broad host range style of life. Their optimal growth temperature overlap with the optimal incubation temperature for eggs, and they are able to kill up to 90% of the embryos. Environmental forcing, e.g., tidal inundation and clay/silt content of nests, were correlated to disease development. Thus, these Fusarium species constitute a major threat to sea turtle nests, especially to those experiencing environmental stressors. These findings have serious implications for the survival of endangered sea turtle populations and the success of conservation programs worldwide.

[Hemolysis and metastatic cancer in an elderly man].

PubMed

Remes, Kari; Raade, Merja; Karhumäki, Lauri; Timonen, Tuomo; Välimäki, Matti J

2015-01-01

Sometimes correct diagnoses is reached after many years and even after decades. Our patient had for decades suffered from a hemolytic disease, life-threatening, metastatic cancer at the age of almost 90 years was also suspected. The patient was finally diagnosed as having mild hereditary spherocytosis and the associated paraspinal extramedullar hematopoiesis as well as an osteoporotic vertebral fracture caused by osteoporosis.

Assessment of Genetic Screening in the Military

DTIC Science & Technology

against the likelihood of saving lives of military recruits with undetected, potentially life- threatening genetic conditions. Largegenomic databases...The goal of this project was to undertake a cost-benefit analysis of genetic testing in military populations . We weighed the costs of genetictesting...of asymptomatic populations were used to analyze the effect that genetic screening for hypertrophic cardiomyopathy(HCM, the most common cause of sudden

A rare cause of respiratory distress and edema in neonate: Panhypopituitarism

PubMed Central

Dursun, Fatma; Kirmizibekmez, Heves; Metin, Fazilet

2017-01-01

Clinical presentation of hypopituitarism may be variable in the neonate. Symptoms are generally nonspecific, ranging from absent to severe, and even life-threatening, due to adrenocorticotrophic hormone deficiency. Presently described is a case of unexplained respiratory distress and edema in a neonate. Initial screening revealed panhypopituitarism. Respiratory distress improved after replacement treatment with hydrocortisone and thyroxine. PMID:28971179

Discharge diagnoses in infants with apparent life-threatening event.

PubMed

Okada, Kazuko; Miyako, Motoko; Honma, Satoshi; Wakabayashi, Yasuko; Sugihara, Shigetaka; Osawa, Makiko

2003-10-01

There are various identifiable diseases or conditions that can be associated with an apparent life-threatening event (ALTE) in infancy. The present study was carried out to investigate the etiology of ALTE based on the discharge diagnoses. A protocol for the complete work-up used to examine the cause of ALTE was designed, and was carried out for 69 infants with ALTE. Gastroesophageal reflux disease (GERD) was demonstrated in 38 cases, and chronic gastric volvulus (CGV) was diagnosed in 21 (associated with GERD in 13 infants). Four cases of pertussis and two cases each of sepsis, laryngomalacia, respiratory immaturity, and premature ventricular contractions were found. Others cases presented with pneumonia, meningitis, intussuception, food allergy, epilepsy, and adenoid vegetations. In 12 of the 69 infants with ALTE, no abnormalities were found in any of the studies performed, including two patients with breath-holding spells. In 17 cases, two or more possibly contributing findings were diagnosed. It is important to recognize that gastroesophageal impairments such as GERD or CGV could be responsible for many incidences of ALTE in infancy. The authors recommend a trial be established to investigate the causes of ALTE, including gastroesophageal evaluations in all infants with ALTE.

Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

PubMed Central

Barber, Amelia E.; Norton, J. Paul; Wiles, Travis J.

2016-01-01

SUMMARY Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic Escherichia coli (UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host. PMID:26935136

A Class 1 Histone Deacetylase with Potential as an Antifungal Target

PubMed Central

Bauer, Ingo; Varadarajan, Divyavaradhi; Pidroni, Angelo; Gross, Silke; Vergeiner, Stefan; Faber, Birgit; Hermann, Martin; Tribus, Martin; Brosch, Gerald

2016-01-01

ABSTRACT Histone deacetylases (HDACs) remove acetyl moieties from lysine residues at histone tails and nuclear regulatory proteins and thus significantly impact chromatin remodeling and transcriptional regulation in eukaryotes. In recent years, HDACs of filamentous fungi were found to be decisive regulators of genes involved in pathogenicity and the production of important fungal metabolites such as antibiotics and toxins. Here we present proof that one of these enzymes, the class 1 type HDAC RpdA, is of vital importance for the opportunistic human pathogen Aspergillus fumigatus. Recombinant expression of inactivated RpdA shows that loss of catalytic activity is responsible for the lethal phenotype of Aspergillus RpdA null mutants. Furthermore, we demonstrate that a fungus-specific C-terminal region of only a few acidic amino acids is required for both the nuclear localization and catalytic activity of the enzyme in the model organism Aspergillus nidulans. Since strains with single or multiple deletions of other classical HDACs revealed no or only moderate growth deficiencies, it is highly probable that the significant delay of germination and the growth defects observed in strains growing under the HDAC inhibitor trichostatin A are caused primarily by inhibition of catalytic RpdA activity. Indeed, even at low nanomolar concentrations of the inhibitor, the catalytic activity of purified RpdA is considerably diminished. Considering these results, RpdA with its fungus-specific motif represents a promising target for novel HDAC inhibitors that, in addition to their increasing impact as anticancer drugs, might gain in importance as antifungals against life-threatening invasive infections, apart from or in combination with classical antifungal therapy regimes. PMID:27803184

Broad-range lytic bacteriophages that kill Staphylococcus aureus local field strains

PubMed Central

Boncompain, Carina A.; Amadio, Ariel A.; Carrasco, Soledad; Suárez, Cristian A.

2017-01-01

Staphylococcus aureus is a very successful opportunistic pathogen capable of causing a variety of diseases ranging from mild skin infections to life-threatening sepsis, meningitis and pneumonia. Its ability to display numerous virulence mechanisms matches its skill to display resistance to several antibiotics, including β-lactams, underscoring the fact that new anti-S. aureus drugs are urgently required. In this scenario, the utilization of lytic bacteriophages that kill bacteria in a genus -or even species- specific way, has become an attractive field of study. In this report, we describe the isolation, characterization and sequencing of phages capable of killing S. aureus including methicillin resistant (MRSA) and multi-drug resistant S. aureus local strains from environmental, animal and human origin. Genome sequencing and bio-informatics analysis showed the absence of genes encoding virulence factors, toxins or antibiotic resistance determinants. Of note, there was a high similarity between our set of phages to others described in the literature such as phage K. Considering that reported phages were obtained in different continents, it seems plausible that there is a commonality of genetic features that are needed for optimum, broad host range anti-staphylococcal activity of these related phages. Importantly, the high activity and broad host range of one of our phages underscores its promising value to control the presence of S. aureus in fomites, industry and hospital environments and eventually on animal and human skin. The development of a cocktail of the reported lytic phages active against S. aureus–currently under way- is thus, a sensible strategy against this pathogen. PMID:28742812

Broad-range lytic bacteriophages that kill Staphylococcus aureus local field strains.

PubMed

Abatángelo, Virginia; Peressutti Bacci, Natalia; Boncompain, Carina A; Amadio, Ariel F; Carrasco, Soledad; Suárez, Cristian A; Morbidoni, Héctor R

2017-01-01

Staphylococcus aureus is a very successful opportunistic pathogen capable of causing a variety of diseases ranging from mild skin infections to life-threatening sepsis, meningitis and pneumonia. Its ability to display numerous virulence mechanisms matches its skill to display resistance to several antibiotics, including β-lactams, underscoring the fact that new anti-S. aureus drugs are urgently required. In this scenario, the utilization of lytic bacteriophages that kill bacteria in a genus -or even species- specific way, has become an attractive field of study. In this report, we describe the isolation, characterization and sequencing of phages capable of killing S. aureus including methicillin resistant (MRSA) and multi-drug resistant S. aureus local strains from environmental, animal and human origin. Genome sequencing and bio-informatics analysis showed the absence of genes encoding virulence factors, toxins or antibiotic resistance determinants. Of note, there was a high similarity between our set of phages to others described in the literature such as phage K. Considering that reported phages were obtained in different continents, it seems plausible that there is a commonality of genetic features that are needed for optimum, broad host range anti-staphylococcal activity of these related phages. Importantly, the high activity and broad host range of one of our phages underscores its promising value to control the presence of S. aureus in fomites, industry and hospital environments and eventually on animal and human skin. The development of a cocktail of the reported lytic phages active against S. aureus-currently under way- is thus, a sensible strategy against this pathogen.

Long-read whole genome sequencing and comparative analysis of six strains of the human pathogen Orientia tsutsugamushi.

PubMed

Batty, Elizabeth M; Chaemchuen, Suwittra; Blacksell, Stuart; Richards, Allen L; Paris, Daniel; Bowden, Rory; Chan, Caroline; Lachumanan, Ramkumar; Day, Nicholas; Donnelly, Peter; Chen, Swaine; Salje, Jeanne

2018-06-01

Orientia tsutsugamushi is a clinically important but neglected obligate intracellular bacterial pathogen of the Rickettsiaceae family that causes the potentially life-threatening human disease scrub typhus. In contrast to the genome reduction seen in many obligate intracellular bacteria, early genetic studies of Orientia have revealed one of the most repetitive bacterial genomes sequenced to date. The dramatic expansion of mobile elements has hampered efforts to generate complete genome sequences using short read sequencing methodologies, and consequently there have been few studies of the comparative genomics of this neglected species. We report new high-quality genomes of O. tsutsugamushi, generated using PacBio single molecule long read sequencing, for six strains: Karp, Kato, Gilliam, TA686, UT76 and UT176. In comparative genomics analyses of these strains together with existing reference genomes from Ikeda and Boryong strains, we identify a relatively small core genome of 657 genes, grouped into core gene islands and separated by repeat regions, and use the core genes to infer the first whole-genome phylogeny of Orientia. Complete assemblies of multiple Orientia genomes verify initial suggestions that these are remarkable organisms. They have larger genomes compared with most other Rickettsiaceae, with widespread amplification of repeat elements and massive chromosomal rearrangements between strains. At the gene level, Orientia has a relatively small set of universally conserved genes, similar to other obligate intracellular bacteria, and the relative expansion in genome size can be accounted for by gene duplication and repeat amplification. Our study demonstrates the utility of long read sequencing to investigate complex bacterial genomes and characterise genomic variation.