Sample records for high consequence pathogens

  1. Adaptation of mammalian host-pathogen interactions in a changing arctic environment

    PubMed Central

    2011-01-01

    Many arctic mammals are adapted to live year-round in extreme environments with low winter temperatures and great seasonal variations in key variables (e.g. sunlight, food, temperature, moisture). The interaction between hosts and pathogens in high northern latitudes is not very well understood with respect to intra-annual cycles (seasons). The annual cycles of interacting pathogen and host biology is regulated in part by highly synchronized temperature and photoperiod changes during seasonal transitions (e.g., freezeup and breakup). With a warming climate, only one of these key biological cues will undergo drastic changes, while the other will remain fixed. This uncoupling can theoretically have drastic consequences on host-pathogen interactions. These poorly understood cues together with a changing climate by itself will challenge host populations that are adapted to pathogens under the historic and current climate regime. We will review adaptations of both host and pathogens to the extreme conditions at high latitudes and explore some potential consequences of rapid changes in the Arctic. PMID:21392401

  2. Adaptation of mammalian host-pathogen interactions in a changing arctic environment.

    PubMed

    Hueffer, Karsten; O'Hara, Todd M; Follmann, Erich H

    2011-03-11

    Many arctic mammals are adapted to live year-round in extreme environments with low winter temperatures and great seasonal variations in key variables (e.g. sunlight, food, temperature, moisture). The interaction between hosts and pathogens in high northern latitudes is not very well understood with respect to intra-annual cycles (seasons). The annual cycles of interacting pathogen and host biology is regulated in part by highly synchronized temperature and photoperiod changes during seasonal transitions (e.g., freezeup and breakup). With a warming climate, only one of these key biological cues will undergo drastic changes, while the other will remain fixed. This uncoupling can theoretically have drastic consequences on host-pathogen interactions. These poorly understood cues together with a changing climate by itself will challenge host populations that are adapted to pathogens under the historic and current climate regime. We will review adaptations of both host and pathogens to the extreme conditions at high latitudes and explore some potential consequences of rapid changes in the Arctic.

  3. Spatial variation in risk and consequence of Batrachochytrium salamandrivorans introduction in the USA

    USGS Publications Warehouse

    Richgels, Katherine L. D.; Russell, Robin E.; Adams, Michael J.; White, C. LeAnn; Campbell Grant, Evan H.

    2016-01-01

    A newly identified fungal pathogen, Batrachochytrium salamandrivorans (Bsal), is responsible for mass mortality events and severe population declines in European salamanders. The eastern USA has the highest diversity of salamanders in the world and the introduction of this pathogen is likely to be devastating. Although data are inevitably limited for new pathogens, disease-risk assessments use best available data to inform management decisions. Using characteristics of Bsal ecology, spatial data on imports and pet trade establishments, and salamander species diversity, we identify high-risk areas with both a high likelihood of introduction and severe consequences for local salamanders. We predict that the Pacific coast, southern Appalachian Mountains and mid-Atlantic regions will have the highest relative risk from Bsal. Management of invasive pathogens becomes difficult once they are established in wildlife populations; therefore, import restrictions to limit pathogen introduction and early detection through surveillance of high-risk areas are priorities for preventing the next crisis for North American salamanders.

  4. Benefits of a European project on diagnostics of highly pathogenic agents and assessment of potential "dual use" issues.

    PubMed

    Grunow, Roland; Ippolito, G; Jacob, D; Sauer, U; Rohleder, A; Di Caro, A; Iacovino, R

    2014-01-01

    Quality assurance exercises and networking on the detection of highly infectious pathogens (QUANDHIP) is a joint action initiative set up in 2011 that has successfully unified the primary objectives of the European Network on Highly Pathogenic Bacteria (ENHPB) and of P4-laboratories (ENP4-Lab) both of which aimed to improve the efficiency, effectiveness, and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries. The specific objectives and achievements include the initiation and establishment of a recognized and acceptable quality assurance scheme, including practical external quality assurance exercises, comprising living agents, that aims to improve laboratory performance, accuracy, and detection capabilities in support of patient management and public health responses; recognized training schemes for diagnostics and handling of highly pathogenic agents; international repositories comprising highly pathogenic bacteria and viruses for the development of standardized reference material; a standardized and transparent Biosafety and Biosecurity strategy protecting healthcare personnel and the community in dealing with high consequence pathogens; the design and organization of response capabilities dealing with cross-border events with highly infectious pathogens including the consideration of diagnostic capabilities of individual European laboratories. The project tackled several sensitive issues regarding Biosafety, Biosecurity and "dual use" concerns. The article will give an overview of the project outcomes and discuss the assessment of potential "dual use" issues.

  5. Benefits of a European Project on Diagnostics of Highly Pathogenic Agents and Assessment of Potential “Dual Use” Issues

    PubMed Central

    Grunow, Roland; Ippolito, G.; Jacob, D.; Sauer, U.; Rohleder, A.; Di Caro, A.; Iacovino, R.

    2014-01-01

    Quality assurance exercises and networking on the detection of highly infectious pathogens (QUANDHIP) is a joint action initiative set up in 2011 that has successfully unified the primary objectives of the European Network on Highly Pathogenic Bacteria (ENHPB) and of P4-laboratories (ENP4-Lab) both of which aimed to improve the efficiency, effectiveness, and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries. The specific objectives and achievements include the initiation and establishment of a recognized and acceptable quality assurance scheme, including practical external quality assurance exercises, comprising living agents, that aims to improve laboratory performance, accuracy, and detection capabilities in support of patient management and public health responses; recognized training schemes for diagnostics and handling of highly pathogenic agents; international repositories comprising highly pathogenic bacteria and viruses for the development of standardized reference material; a standardized and transparent Biosafety and Biosecurity strategy protecting healthcare personnel and the community in dealing with high consequence pathogens; the design and organization of response capabilities dealing with cross-border events with highly infectious pathogens including the consideration of diagnostic capabilities of individual European laboratories. The project tackled several sensitive issues regarding Biosafety, Biosecurity and “dual use” concerns. The article will give an overview of the project outcomes and discuss the assessment of potential “dual use” issues. PMID:25426479

  6. Semi-quantitative assessment of disease risks at the human, livestock, wildlife interface for the Republic of Korea using a nationwide survey of experts: A model for other countries

    USGS Publications Warehouse

    Hwang, Jusun; Lee, Kyunglee; Walsh, Daniel P.; Kim, SangWha; Sleeman, Jonathan M.; Lee, Hang

    2018-01-01

    Wildlife-associated diseases and pathogens have increased in importance; however, management of a large number of diseases and diversity of hosts is prohibitively expensive. Thus, the determination of priority wildlife pathogens and risk factors for disease emergence is warranted. We used an online questionnaire survey to assess release and exposure risks, and consequences of wildlife-associated diseases and pathogens in the Republic of Korea (ROK). We also surveyed opinions on pathways for disease exposure, and risk factors for disease emergence and spread. For the assessment of risk, we employed a two-tiered, statistical K-means clustering algorithm to group diseases into three levels (high, medium and low) of perceived risk based on release and exposure risks, societal consequences and the level of uncertainty of the experts’ opinions. To examine the experts’ perceived risk of routes of introduction of pathogens and disease amplification and spread, we used a Bayesian, multivariate normal order-statistics model. Six diseases or pathogens, including four livestock and two wildlife diseases, were identified as having high risk with low uncertainty. Similarly, 13 diseases were characterized as having high risk with medium uncertainty with three of these attributed to livestock, six associated with human disease, and the remainder having the potential to affect human, livestock and wildlife (i.e., One Health). Lastly, four diseases were described as high risk with high certainty, and were associated solely with fish diseases. Experts identified migration of wildlife, international human movement and illegal importation of wildlife as the three routes posing the greatest risk of pathogen introduction into ROK. Proximity of humans, livestock and wildlife was the most significant risk factor for promoting the spread of wildlife-associated diseases and pathogens, followed by high density of livestock populations, habitat loss and environmental degradation, and climate change. This study provides useful information to decision makers responsible for allocating resources to address disease risks. This approach provided a rapid, cost-effective method of risk assessment of wildlife-associated diseases and pathogens for which the published literature is sparse.

  7. Correlation between Detection of a Plasmid and High-Level Virulence of Vibrio nigripulchritudo, a Pathogen of the Shrimp Litopenaeus stylirostris▿

    PubMed Central

    Reynaud, Yann; Saulnier, Denis; Mazel, Didier; Goarant, Cyrille; Le Roux, Frédérique

    2008-01-01

    Vibrio nigripulchritudo, the etiological agent of Litopenaeus stylirostris summer syndrome, is responsible for mass mortalities of shrimp in New Caledonia. Epidemiological studies led to the suggestion that this disease is caused by an emergent group of pathogenic strains. Genomic subtractive hybridization was carried out between two isolates exhibiting low and high virulence. Our subtraction library was constituted of 521 specific fragments; 55 of these were detected in all virulent isolates from our collection (n = 32), and 13 were detected only in the isolates demonstrating the highest pathogenicity (n = 19), suggesting that they could be used as genetic markers for high virulence capacity. Interestingly, 10 of these markers are carried by a replicon of 11.2 kbp that contains sequences highly similar to those of a plasmid detected in Vibrio shilonii, a coral pathogen. The detection of this plasmid was correlated with the highest pathogenicity status of the isolates from our collection. The origin and consequence of this plasmid acquisition are discussed. PMID:18359828

  8. Global Warming Will Bring New Fungal Diseases for Mammals

    PubMed Central

    Garcia-Solache, Monica A.; Casadevall, Arturo

    2010-01-01

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

  9. Semi-quantitative assessment of disease risks at the human, livestock, wildlife interface for the Republic of Korea using a nationwide survey of experts: A model for other countries.

    PubMed

    Hwang, J; Lee, K; Walsh, D; Kim, S W; Sleeman, J M; Lee, H

    2018-02-01

    Wildlife-associated diseases and pathogens have increased in importance; however, management of a large number of diseases and diversity of hosts is prohibitively expensive. Thus, the determination of priority wildlife pathogens and risk factors for disease emergence is warranted. We used an online questionnaire survey to assess release and exposure risks, and consequences of wildlife-associated diseases and pathogens in the Republic of Korea (ROK). We also surveyed opinions on pathways for disease exposure, and risk factors for disease emergence and spread. For the assessment of risk, we employed a two-tiered, statistical K-means clustering algorithm to group diseases into three levels (high, medium and low) of perceived risk based on release and exposure risks, societal consequences and the level of uncertainty of the experts' opinions. To examine the experts' perceived risk of routes of introduction of pathogens and disease amplification and spread, we used a Bayesian, multivariate normal order-statistics model. Six diseases or pathogens, including four livestock and two wildlife diseases, were identified as having high risk with low uncertainty. Similarly, 13 diseases were characterized as having high risk with medium uncertainty with three of these attributed to livestock, six associated with human disease, and the remainder having the potential to affect human, livestock and wildlife (i.e., One Health). Lastly, four diseases were described as high risk with high certainty, and were associated solely with fish diseases. Experts identified migration of wildlife, international human movement and illegal importation of wildlife as the three routes posing the greatest risk of pathogen introduction into ROK. Proximity of humans, livestock and wildlife was the most significant risk factor for promoting the spread of wildlife-associated diseases and pathogens, followed by high density of livestock populations, habitat loss and environmental degradation, and climate change. This study provides useful information to decision makers responsible for allocating resources to address disease risks. This approach provided a rapid, cost-effective method of risk assessment of wildlife-associated diseases and pathogens for which the published literature is sparse. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  10. What's hot in animal biosafety?

    PubMed

    Richmond, J Y; Hill, R H; Weyant, R S; Nesby-O'Dell, S L; Vinson, P E

    2003-01-01

    In recent years, the emergence or re-emergence of critical issues in infectious disease and public health has presented new challenges and opportunities for laboratory animal care professionals. The re-emergence of bioterrorism as a threat activity of individuals or small groups has caused a heightened awareness of biosecurity and improved biosafety. The need for animal work involving high-risk or high-consequence pathogens and for arthropod-borne diseases has stimulated renewed interest in animal biosafety matters, particularly for work in containment. Application of these principles to animals retained in outdoor environments has been a consequence of disease eradication programs. The anticipated global eradication of wild poliovirus has prompted the promulgation of new biosafety guidelines for future laboratory and animal work. Increased concern regarding the use of biologically derived toxins and hazardous chemicals has stimulated a new categorization of facility containment based on risk assessment. Recognition that prion disease agents and other high-consequence pathogens require safe handling and thorough destruction during terminal decontamination treatment has led to the development of new biosafety guidelines and technologies. The implementation of these guidelines and technologies will promote state-of-the-art research while minimizing risk to laboratory animals, researchers, and the environment.

  11. The Causes and Consequences of Changes in Virulence following Pathogen Host Shifts

    PubMed Central

    Longdon, Ben; Hadfield, Jarrod D.; Day, Jonathan P.; Smith, Sophia C. L.; McGonigle, John E.; Cogni, Rodrigo; Cao, Chuan; Jiggins, Francis M.

    2015-01-01

    Emerging infectious diseases are often the result of a host shift, where the pathogen originates from a different host species. Virulence—the harm a pathogen does to its host—can be extremely high following a host shift (for example Ebola, HIV, and SARs), while other host shifts may go undetected as they cause few symptoms in the new host. Here we examine how virulence varies across host species by carrying out a large cross infection experiment using 48 species of Drosophilidae and an RNA virus. Host shifts resulted in dramatic variation in virulence, with benign infections in some species and rapid death in others. The change in virulence was highly predictable from the host phylogeny, with hosts clustering together in distinct clades displaying high or low virulence. High levels of virulence are associated with high viral loads, and this may determine the transmission rate of the virus. PMID:25774803

  12. Modify the Histone to Win the Battle: Chromatin Dynamics in Plant–Pathogen Interactions

    PubMed Central

    Ramirez-Prado, Juan S.; Piquerez, Sophie J. M.; Bendahmane, Abdelhafid; Hirt, Heribert; Raynaud, Cécile; Benhamed, Moussa

    2018-01-01

    Relying on an immune system comes with a high energetic cost for plants. Defense responses in these organisms are therefore highly regulated and fine-tuned, permitting them to respond pertinently to the attack of a microbial pathogen. In recent years, the importance of the physical modification of chromatin, a highly organized structure composed of genomic DNA and its interacting proteins, has become evident in the research field of plant–pathogen interactions. Several processes, including DNA methylation, changes in histone density and variants, and various histone modifications, have been described as regulators of various developmental and defense responses. Herein, we review the state of the art in the epigenomic aspects of plant immunity, focusing on chromatin modifications, chromatin modifiers, and their physiological consequences. In addition, we explore the exciting field of understanding how plant pathogens have adapted to manipulate the plant epigenomic regulation in order to weaken their immune system and thrive in their host, as well as how histone modifications in eukaryotic pathogens are involved in the regulation of their virulence. PMID:29616066

  13. Poultry raising systems and highly pathogenic avian influenza outbreaks in Thailand: the situation, associations, and impacts.

    PubMed

    Chantong, Wasan; Kaneene, John B

    2011-05-01

    Highly pathogenic avian influenza (HPAI), caused by the virus strain H5N1, currently occurs worldwide with the greatest burden in Southeast Asia where the disease was first reported. In Thailand where the disease was first confirmed in January 2004, the virus had been persistent as a major threat to the poultry industry and human health over the past several years. It was generally hypothesized that the main reason for the disease to circulate in Thailand was the existence of traditional backyard chickens and free-range ducks raising systems. Consequently, this study reviewed the structure of poultry raising systems, the recent outbreaks of HPAI H5N1, the disease association to the backyard and free-grazing poultry production, and consequences of the outbreaks in Thailand. Although the major outbreaks in the country had declined, the sustaining disease surveillance and prevention are still strongly recommended.

  14. Epidemiological consequences of an incursion of highly pathogenic H5N1 avian influenza into the British poultry flock

    PubMed Central

    Sharkey, Kieran J; Bowers, Roger G; Morgan, Kenton L; Robinson, Susan E; Christley, Robert M

    2007-01-01

    Highly pathogenic avian influenza and in particular the H5N1 strain has resulted in the culling of millions of birds and continues to pose a threat to poultry industries worldwide. The recent outbreak of H5N1 in the UK highlights the need for detailed assessment of the consequences of an incursion and of the efficacy of control strategies. Here, we present results from a model of H5N1 propagation within the British poultry industry. We find that although the majority of randomly seeded incursions do not spread beyond the initial infected premises, there is significant potential for widespread infection. The efficacy of the European Union strategy for disease control is evaluated and our simulations emphasize the pivotal role of duck farms in spreading H5N1. PMID:17956849

  15. Plant pathogen nanodiagnostic techniques: forthcoming changes?

    PubMed Central

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

    2014-01-01

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

  16. Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota in Cigarette Smoke-Exposed Mice

    PubMed Central

    Shen, Pamela; Whelan, Fiona J.; Schenck, L. Patrick; McGrath, Joshua J. C.; Vanderstocken, Gilles; Bowdish, Dawn M. E.; Surette, Michael G.

    2017-01-01

    ABSTRACT Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium, Gemella, and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization. PMID:28760931

  17. Risk Prioritization Tool to Identify the Public Health Risks of Wildlife Trade: The Case of Rodents from Latin America.

    PubMed

    Bueno, I; Smith, K M; Sampedro, F; Machalaba, C C; Karesh, W B; Travis, D A

    2016-06-01

    Wildlife trade (both formal and informal) is a potential driver of disease introduction and emergence. Legislative proposals aim to prevent these risks by banning wildlife imports, and creating 'white lists' of species that are cleared for importation. These approaches pose economic harm to the pet industry, and place substantial burden on importers and/or federal agencies to provide proof of low risk for importation of individual species. As a feasibility study, a risk prioritization tool was developed to rank the pathogens found in rodent species imported from Latin America into the United States with the highest risk of zoonotic consequence in the United States. Four formally traded species and 16 zoonotic pathogens were identified. Risk scores were based on the likelihood of pathogen release and human exposure, and the severity of the disease (consequences). Based on the methodology applied, three pathogens (Mycobacterium microti, Giardia spp. and Francisella tularensis) in one species (Cavia porcellus) were ranked as highest concern. The goal of this study was to present a methodological approach by which preliminary management resources can be allocated to the identified high-concern pathogen-species combinations when warranted. This tool can be expanded to other taxa and geographic locations to inform policy surrounding the wildlife trade. © 2015 Blackwell Verlag GmbH.

  18. Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota in Cigarette Smoke-Exposed Mice.

    PubMed

    Shen, Pamela; Whelan, Fiona J; Schenck, L Patrick; McGrath, Joshua J C; Vanderstocken, Gilles; Bowdish, Dawn M E; Surette, Michael G; Stämpfli, Martin R

    2017-10-01

    Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium , Gemella , and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization. Copyright © 2017 American Society for Microbiology.

  19. Collaborative Workshop on Handling, Management, and ...

    EPA Pesticide Factsheets

    Report The Water Environment Research Foundation (WERF), in partnership with the U.S. Environmental Protection Agency (EPA) National Homeland Security Research Center (NHSRC) and the National Science Foundation (NSF), hosted an expert workshop on November 17 and 18, 2015, in Alexandria, Virginia, to engage with subject matter experts and wastewater utility stakeholders on a number of topics surrounding high consequence pathogens in wastewater collection and treatment systems, should such pathogens enter the systems as a result of an emergency situation.

  20. A highly infective plant-associated bacterium influences reproductive rates in pea aphids

    PubMed Central

    Hendry, Tory A.; Clark, Kelley J.; Baltrus, David A.

    2016-01-01

    Pea aphids, Acyrthosiphon pisum, have the potential to increase reproduction as a defence against pathogens, though how frequently this occurs or how infection with live pathogens influences this response is not well understood. Here we determine the minimum infective dose of an environmentally common bacterium and possible aphid pathogen, Pseudomonas syringae, to determine the likelihood of pathogenic effects to pea aphids. Additionally, we used P. syringae infection to investigate how live pathogens may alter reproductive rates. We found that oral bacterial exposure decreased subsequent survival of aphids in a dose-dependent manner and we estimate that ingestion of less than 10 bacterial cells is sufficient to increase aphid mortality. Pathogen dose was positively related to aphid reproduction. Aphids exposed to low bacterial doses showed decreased, although statistically indistinguishable, fecundity compared to controls. Aphids exposed to high doses reproduced significantly more than low dose treatments and also more, but not significantly so, than controls. These results are consistent with previous studies suggesting that pea aphids may use fecundity compensation as a response to pathogens. Consequently, even low levels of exposure to a common plant-associated bacterium may therefore have significant effects on pea aphid survival and reproduction. PMID:26998321

  1. A highly infective plant-associated bacterium influences reproductive rates in pea aphids.

    PubMed

    Hendry, Tory A; Clark, Kelley J; Baltrus, David A

    2016-02-01

    Pea aphids, Acyrthosiphon pisum, have the potential to increase reproduction as a defence against pathogens, though how frequently this occurs or how infection with live pathogens influences this response is not well understood. Here we determine the minimum infective dose of an environmentally common bacterium and possible aphid pathogen, Pseudomonas syringae, to determine the likelihood of pathogenic effects to pea aphids. Additionally, we used P. syringae infection to investigate how live pathogens may alter reproductive rates. We found that oral bacterial exposure decreased subsequent survival of aphids in a dose-dependent manner and we estimate that ingestion of less than 10 bacterial cells is sufficient to increase aphid mortality. Pathogen dose was positively related to aphid reproduction. Aphids exposed to low bacterial doses showed decreased, although statistically indistinguishable, fecundity compared to controls. Aphids exposed to high doses reproduced significantly more than low dose treatments and also more, but not significantly so, than controls. These results are consistent with previous studies suggesting that pea aphids may use fecundity compensation as a response to pathogens. Consequently, even low levels of exposure to a common plant-associated bacterium may therefore have significant effects on pea aphid survival and reproduction.

  2. Avian influenza virus (H5N1): a threat to human health.

    PubMed

    Peiris, J S Malik; de Jong, Menno D; Guan, Yi

    2007-04-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, and the next pandemic may well arise from a low-pathogenicity virus. The rationale for particular concern about an H5N1 pandemic is not its inevitability but its potential severity. An H5N1 pandemic is an event of low probability but one of high human health impact and poses a predicament for public health. Here, we review the ecology and evolution of highly pathogenic avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of human H5N1 disease in relation to its epidemiology, clinical presentation, pathogenesis, diagnosis, and management.

  3. NUTRIENT COMPOSITION DEGRADATION OF DAPHNIA PULICARIA BY A HIGHLY PREVALENT CHYTRIDIOMYCETE FUNGAL PATHOGEN (POLYCARYUM LEAVE) DURING NATURALLY OCCURRING LAKE-WIDE EPIDEMICS.

    EPA Science Inventory

    Despite evidence illustrating that chytridiomycete fungal infection can be highly prevalent in Daphnia (>80%) and that infected individuals are preferentially consumed by fish, no studies have measured the nutritional consequences of using chytrid-infected Daphnia as a food sourc...

  4. Methyl esterification of pectin plays a role during plant-pathogen interactions and affects plant resistance to diseases.

    PubMed

    Lionetti, Vincenzo; Cervone, Felice; Bellincampi, Daniela

    2012-11-01

    The cell wall is a complex structure mainly composed by a cellulose-hemicellulose network embedded in a cohesive pectin matrix. Pectin is synthesized in a highly methyl esterified form and is de-esterified in muro by pectin methyl esterases (PMEs). The degree and pattern of methyl esterification affect the cell wall structure and properties with consequences on both the physiological processes of the plants and their resistance to pathogens. PME activity displays a crucial role in the outcome of the plant-pathogen interactions by making pectin more susceptible to the action of the enzymes produced by the pathogens. This review focuses on the impact of pectin methyl esterification in plant-pathogen interactions and on the dynamic role of its alteration during pathogenesis. Copyright © 2012 Elsevier GmbH. All rights reserved.

  5. Mycoplasma genitalium: An Overlooked Sexually Transmitted Pathogen in Women?

    PubMed Central

    Ona, Samsiya; Molina, Rose L.; Diouf, Khady

    2016-01-01

    Mycoplasma genitalium is a facultative anaerobic organism and a recognized cause of nongonococcal urethritis in men. In women, M. genitalium has been associated with cervicitis, endometritis, pelvic inflammatory disease (PID), infertility, susceptibility to human immunodeficiency virus (HIV), and adverse birth outcomes, indicating a consistent relationship with female genital tract pathology. The global prevalence of M. genitalium among symptomatic and asymptomatic sexually active women ranges between 1 and 6.4%. M. genitalium may play a role in pathogenesis as an independent sexually transmitted pathogen or by facilitating coinfection with another pathogen. The long-term reproductive consequences of M. genitalium infection in asymptomatic individuals need to be investigated further. Though screening for this pathogen is not currently recommended, it should be considered in high-risk populations. Recent guidelines from the Centers for Disease Control regarding first-line treatment for PID do not cover M. genitalium but recommend considering treatment in patients without improvement on standard PID regimens. Prospective studies on the prevalence, pathophysiology, and long-term reproductive consequences of M. genitalium infection in the general population are needed to determine if screening protocols are necessary. New treatment regimens need to be investigated due to increasing drug resistance. PMID:27212873

  6. Effectiveness of traveller screening for emerging pathogens is shaped by epidemiology and natural history of infection

    PubMed Central

    Gostic, Katelyn M; Kucharski, Adam J; Lloyd-Smith, James O

    2015-01-01

    During outbreaks of high-consequence pathogens, airport screening programs have been deployed to curtail geographic spread of infection. The effectiveness of screening depends on several factors, including pathogen natural history and epidemiology, human behavior, and characteristics of the source epidemic. We developed a mathematical model to understand how these factors combine to influence screening outcomes. We analyzed screening programs for six emerging pathogens in the early and late stages of an epidemic. We show that the effectiveness of different screening tools depends strongly on pathogen natural history and epidemiological features, as well as human factors in implementation and compliance. For pathogens with longer incubation periods, exposure risk detection dominates in growing epidemics, while fever becomes a better target in stable or declining epidemics. For pathogens with short incubation, fever screening drives detection in any epidemic stage. However, even in the most optimistic scenario arrival screening will miss the majority of cases. DOI: http://dx.doi.org/10.7554/eLife.05564.001 PMID:25695520

  7. Epidemiology, geographical distribution, and economic consequences of swine zoonoses: a narrative review

    PubMed Central

    Uddin Khan, Salah; Atanasova, Kalina R; Krueger, Whitney S; Ramirez, Alejandro; Gray, Gregory C

    2013-01-01

    We sought to review the epidemiology, international geographical distribution, and economic consequences of selected swine zoonoses. We performed literature searches in two stages. First, we identified the zoonotic pathogens associated with swine. Second, we identified specific swine-associated zoonotic pathogen reports for those pathogens from January 1980 to October 2012. Swine-associated emerging diseases were more prevalent in the countries of North America, South America, and Europe. Multiple factors were associated with the increase of swine zoonoses in humans including: the density of pigs, poor water sources and environmental conditions for swine husbandry, the transmissibility of the pathogen, occupational exposure to pigs, poor human sanitation, and personal hygiene. Swine zoonoses often lead to severe economic consequences related to the threat of novel pathogens to humans, drop in public demand for pork, forced culling of swine herds, and international trade sanctions. Due to the complexity of swine-associated pathogen ecology, designing effective interventions for early detection of disease, their prevention, and mitigation requires an interdisciplinary collaborative “One Health” approach from veterinarians, environmental and public health professionals, and the swine industry. PMID:26038451

  8. Consequences of Nosema apis infection for male honey bees and their fertility

    PubMed Central

    Peng, Yan; Baer-Imhoof, Barbara; Harvey Millar, A.; Baer, Boris

    2015-01-01

    The queens of eusocial bees, ants and wasps mate only during a very short period early in life and males therefore produce ejaculates consisting of large numbers of high quality sperm. Such extreme selection for high fecundity resulted in males investing minimally into their somatic survival, including their immune system. However, if susceptible males are unable to protect their reproductive tissue from infections, they compromise queen fitness if they transfer pathogens during mating. We used the honey bee Apis mellifera and investigated the course of infection of the sexually transmitted pathogen Nosema apis. We predicted that honey bee males are susceptible but protect their reproductive tissues from infections. We investigated the effects of N. apis infections on the midgut, the accessory glands and the accessory testes and quantified the consequences of infection on male survival and fecundity. We found that N. apis is able to infect males, and as infections progressed, it significantly impacted fertility and survival in older males. Even though we confirm males to be able to minimize N. apis infections of their reproductive tissues, the parasite is present in ejaculates of older males. Consequently N. apis evolved alternative routes to successfully infect ejaculates and get sexually transmitted. PMID:26123530

  9. Consequences of Nosema apis infection for male honey bees and their fertility.

    PubMed

    Peng, Yan; Baer-Imhoof, Barbara; Millar, A Harvey; Baer, Boris

    2015-06-30

    The queens of eusocial bees, ants and wasps mate only during a very short period early in life and males therefore produce ejaculates consisting of large numbers of high quality sperm. Such extreme selection for high fecundity resulted in males investing minimally into their somatic survival, including their immune system. However, if susceptible males are unable to protect their reproductive tissue from infections, they compromise queen fitness if they transfer pathogens during mating. We used the honey bee Apis mellifera and investigated the course of infection of the sexually transmitted pathogen Nosema apis. We predicted that honey bee males are susceptible but protect their reproductive tissues from infections. We investigated the effects of N. apis infections on the midgut, the accessory glands and the accessory testes and quantified the consequences of infection on male survival and fecundity. We found that N. apis is able to infect males, and as infections progressed, it significantly impacted fertility and survival in older males. Even though we confirm males to be able to minimize N. apis infections of their reproductive tissues, the parasite is present in ejaculates of older males. Consequently N. apis evolved alternative routes to successfully infect ejaculates and get sexually transmitted.

  10. Armored RNA as Virus Surrogate in a Real-Time Reverse Transcriptase PCR Assay Proficiency Panel

    PubMed Central

    Hietala, S. K.; Crossley, B. M.

    2006-01-01

    In recent years testing responsibilities for high-consequence pathogens have been expanded from national reference laboratories into networks of local and regional laboratories in order to support enhanced disease surveillance and to test for surge capacity. This movement of testing of select agents and high-consequence pathogens beyond reference laboratories introduces a critical need for standardized, noninfectious surrogates of disease agents for use as training and proficiency test samples. In this study, reverse transcription-PCR assay RNA targets were developed and packaged as armored RNA for use as a noninfectious, quantifiable synthetic substitute for four high-consequence animal pathogens: classical swine fever virus; foot-and-mouth disease virus; vesicular stomatitis virus, New Jersey serogroup; and vesicular stomatitis virus, Indiana serogroup. Armored RNA spiked into oral swab fluid specimens mimicked virus-positive clinical material through all stages of the reverse transcription-PCR testing process, including RNA recovery by four different commercial extraction procedures, reverse transcription, PCR amplification, and real-time detection at target concentrations consistent with the dynamic ranges of the existing real-time PCR assays. The armored RNA concentrations spiked into the oral swab fluid specimens were stable under storage conditions selected to approximate the extremes of time and temperature expected for shipping and handling of proficiency panel samples, including 24 h at 37°C and 2 weeks at temperatures ranging from ambient room temperature to −70°C. The analytic test performance, including the reproducibility over the dynamic range of the assays, indicates that armored RNA can provide a noninfectious, quantifiable, and stable virus surrogate for specific assay training and proficiency test purposes. PMID:16390950

  11. Avian influenza virus, Streptococcus suis serotype 2, severe acute respiratory syndrome-coronavirus and beyond: molecular epidemiology, ecology and the situation in China.

    PubMed

    Ma, Ying; Feng, Youjun; Liu, Di; Gao, George F

    2009-09-27

    The outbreak and spread of severe acute respiratory syndrome-associated coronavirus and the subsequent identification of its animal origin study have heightened the world's awareness of animal-borne or zoonotic pathogens. In addition to SARS, the highly pathogenic avian influenza virus (AIV), H5N1, and the lower pathogenicity H9N2 AIV have expanded their host ranges to infect human beings and other mammalian species as well as birds. Even the 'well-known' reservoir animals for influenza virus, migratory birds, became victims of the highly pathogenic H5N1 virus. Not only the viruses, but bacteria can also expand their host range: a new disease, streptococcal toxic shock syndrome, caused by human Streptococcus suis serotype 2 infection, has been observed in China with 52 human fatalities in two separate outbreaks (1998 and 2005, respectively). Additionally, enterohaemorrhagic Escherichia coli O157:H7 infection has increased worldwide with severe disease. Several outbreaks and sporadic isolations of this pathogen in China have made it an important target for disease control. A new highly pathogenic variant of porcine reproductive and respiratory syndrome virus (PRRSV) has been isolated in both China and Vietnam recently; although PRRSV is not a zoonotic human pathogen, its severe outbreaks have implications for food safety. All of these pathogens occur in Southeast Asia, including China, with severe consequences; therefore, we discuss the issues in this article by addressing the situation of the zoonotic threat in China.

  12. A universal next generation sequencing protocol to generate non-infectious barcoded cDNA libraries from high containment RNA viruses

    USDA-ARS?s Scientific Manuscript database

    Several biosafety level (BSL)-3/4 pathogens are high consequence, single-stranded RNA viruses and their genomes, when introduced into permissive cells, are infectious. Moreover many of these viruses are Select Agents (SAs), and their genomes are also considered SAs. For this reason cDNAs and/or th...

  13. 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.

  14. 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

  15. Cheatgrass facilitates spillover of a seed bank pathogen onto native grass species

    Treesearch

    Julie Beckstead; Susan E. Meyer; Brian M. Connolly; Michael B. Huck; Laura E. Street

    2010-01-01

    Attack by pathogens can have ecological consequences for plants at many scales, such as the individual, population and community scale, although the latter is the least studied. Community-level consequences of disease in natural plant communities can drive facilitation in succession (Van der Putten, Van Dijk & Peters 1993), maintain species diversity in...

  16. Effective Chemical Inactivation of Ebola Virus

    PubMed Central

    Haddock, Elaine; Feldmann, Friederike

    2016-01-01

    Reliable inactivation of specimens before removal from high-level biocontainment is crucial for safe operation. To evaluate efficacy of methods of chemical inactivation, we compared in vitro and in vivo approaches using Ebola virus as a surrogate pathogen. Consequently, we have established parameters and protocols leading to reliable and effective inactivation. PMID:27070504

  17. Modelling the impact of co-circulating low pathogenic avian influenza viruses on epidemics of highly pathogenic avian influenza in poultry.

    PubMed

    Nickbakhsh, Sema; Hall, Matthew D; Dorigatti, Ilaria; Lycett, Samantha J; Mulatti, Paolo; Monne, Isabella; Fusaro, Alice; Woolhouse, Mark E J; Rambaut, Andrew; Kao, Rowland R

    2016-12-01

    It is well known that highly pathogenic avian influenza (HPAI) viruses emerge through mutation of precursor low pathogenic avian influenza (LPAI) viruses in domestic poultry populations. The potential for immunological cross-protection between these pathogenic variants is recognised but the epidemiological impact during co-circulation is not well understood. Here we use mathematical models to investigate whether altered flock infection parameters consequent to primary LPAI infections can impact on the spread of HPAI at the population level. First we used mechanistic models reflecting the co-circulatory dynamics of LPAI and HPAI within a single commercial poultry flock. We found that primary infections with LPAI led to HPAI prevalence being maximised under a scenario of high but partial cross-protection. We then tested the population impact in spatially-explicit simulations motivated by a major avian influenza A(H7N1) epidemic that afflicted the Italian poultry industry in 1999-2001. We found that partial cross-protection can lead to a prolongation of HPAI epidemic duration. Our findings have implications for the control of HPAI in poultry particularly for settings in which LPAI and HPAI frequently co-circulate. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Multiplex cytokine profiling with highly pathogenic material: use of formalin solution in luminex analysis.

    PubMed

    Dowall, Stuart D; Graham, Victoria A; Tipton, Thomas R W; Hewson, Roger

    2009-08-31

    Work with highly pathogenic material mandates the use of biological containment facilities, involving microbiological safety cabinets and specialist laboratory engineering structures typified by containment level 3 (CL3) and CL4 laboratories. Consequences of working in high containment are the practical difficulties associated with containing specialist assays and equipment often essential for experimental analyses. In an era of increased interest in biodefence pathogens and emerging diseases, immunological analysis has developed rapidly alongside traditional techniques in virology and molecular biology. For example, in order to maximise the use of small sample volumes, multiplexing has become a more popular and widespread approach to quantify multiple analytes simultaneously, such as cytokines and chemokines. The luminex microsphere system allows for the detection of many cytokines and chemokines in a single sample, but the detection method of using aligned lasers and fluidics means that samples often have to be analysed in low containment facilities. In order to perform cytokine analysis in materials from high containment (CL3 and CL4 laboratories), we have developed an appropriate inactivation methodology after staining steps, which although results in a reduction of median fluorescent intensity, produces statistically comparable outcomes when judged against non-inactivated samples. This methodology thus extends the use of luminex technology for material that contains highly pathogenic biological agents.

  19. Imaging O2 changes induced in tomato roots by fungal pathogen

    NASA Astrophysics Data System (ADS)

    Rubol, S.; Turco, E.; Rodeghiero, M.; Bellin, A.

    2014-12-01

    In the last decade, planar optodes have demonstrated to be a useful non-invasive tool to monitor real time oxygen concentrations in a wide range of applications. However, only limited investigations have been carried out to explore the use of optodes in plant respiration studies. In particular, their use to study plant-pathogen interactions has been not deeply investigated. Here, we present for the first time an in vitro experimental setup capable to depict the dynamical effects of the fungal pathogen Fusarium oxysporum f.sp. lycopersici (Fol) on tomato roots by the use of a recently developed optical non-invasive optode oxygen sensor (Visisens, Presens, Germany). Fol is a soil-borne pathogen and the causal agent of wilt in tomato plants, a destructive worldwide disease. The interaction Fol-tomato is widely accepted as a model system in plant pathology. In this work, oxygen concentrations are monitored continuously in time and considered a proxy for root respiration and metabolic activity. The experimental procedure reveals three different dynamic stages: 1) a uniform oxygen consumption in tomato roots earlier before pathogen colonization, 2) a progressive decrease in the oxygen concentration indicating a high metabolic activity as soon as the roots were surrounded and colonized by the fungal mycelium, and 3) absence of root respiration, as a consequence of root death. Our results suggest the ability of the fungal mycelium to move preferentially towards and along the root as a consequence of the recognition event.

  20. Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells: Opportunities and Challenges for Next-Generation Sequencing Methods

    PubMed Central

    Enguita, Francisco J.; Costa, Marina C.; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José; Leitão, Ana Lúcia

    2016-01-01

    Fungal invasive infections are an increasing health problem. The intrinsic complexity of pathogenic fungi and the unmet clinical need for new and more effective treatments requires a detailed knowledge of the infection process. During infection, fungal pathogens are able to trigger a specific transcriptional program in their host cells. The detailed knowledge of this transcriptional program will allow for a better understanding of the infection process and consequently will help in the future design of more efficient therapeutic strategies. Simultaneous transcriptomic studies of pathogen and host by high-throughput sequencing (dual RNA-seq) is an unbiased protocol to understand the intricate regulatory networks underlying the infectious process. This protocol is starting to be applied to the study of the interactions between fungal pathogens and their hosts. To date, our knowledge of the molecular basis of infection for fungal pathogens is still very limited, and the putative role of regulatory players such as non-coding RNAs or epigenetic factors remains elusive. The wider application of high-throughput transcriptomics in the near future will help to understand the fungal mechanisms for colonization and survival, as well as to characterize the molecular responses of the host cell against a fungal infection. PMID:29376924

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

    USDA-ARS?s Scientific Manuscript database

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

  2. Tick-borne pathogens in tick species infesting humans in Sibiu County, central Romania.

    PubMed

    Andersson, Martin O; Marga, Georgeta; Banu, Teofilia; Dobler, Gerhard; Chitimia-Dobler, Lidia

    2018-05-01

    Romania has a highly diverse tick fauna. Consequently, a high diversity of tick-transmitted pathogens might be a potential threat to humans. However, only a limited number of tick species regularly infest humans, and pathogens present in such species are therefore of particular interest from a medical perspective. In this study, 297 ticks were collected from humans during 2013 and 2014. Ixodes ricinus was the predominant tick species, accounting for 272 specimens or 91.6% of the ticks in the study. Nevertheless, other tick species were also found to infest humans: Dermacentor marginatus constituted 7% of the ticks found on humans (21/297), Haemaphysalis punctata 1% (3/297), and Haemaphysalis concinna 0.3% (1/297). Ticks were tested by PCR for a wide range of tick-borne pathogens. In total, 11.8% of the ticks carried human pathogenic bacteria, while no viral or protozoan pathogens were detected. The most frequently detected pathogen was Rickettsia spp., occurring in 5.4% of the ticks (16/297) and comprising three species: Rickettsia (R.) raoultii, R. monacensis, and R. helvetica. Borrelia s.l. occurred in 3% (9/297) of the ticks. "Candidatus Neoehrlichia mikurensis" occurred in 1.7% (5/297) and Anaplasma phagocytophilum in 1.3% (4/297). Anaplasma bovis was detected in an H. punctata and Borrelia miyamotoi in an I. ricinus. These results point to the need for further studies on the medical importance of tick-borne pathogens in Romania.

  3. Role of stochastic processes in maintaining discrete strain structure in antigenically diverse pathogen populations.

    PubMed

    Buckee, Caroline O; Recker, Mario; Watkins, Eleanor R; Gupta, Sunetra

    2011-09-13

    Many highly diverse pathogen populations appear to exist stably as discrete antigenic types despite evidence of genetic exchange. It has been shown that this may arise as a consequence of immune selection on pathogen populations, causing them to segregate permanently into discrete nonoverlapping subsets of antigenic variants to minimize competition for available hosts. However, discrete antigenic strain structure tends to break down under conditions where there are unequal numbers of allelic variants at each locus. Here, we show that the inclusion of stochastic processes can lead to the stable recovery of discrete strain structure through loss of certain alleles. This explains how pathogen populations may continue to behave as independently transmitted strains despite inevitable asymmetries in allelic diversity of major antigens. We present evidence for this type of structuring across global meningococcal isolates in three diverse antigens that are currently being developed as vaccine components.

  4. Adhesive Pili in UTI Pathogenesis and Drug Development.

    PubMed

    Spaulding, Caitlin N; Hultgren, Scott J

    2016-03-15

    Urinary tract infections (UTIs) are one of the most common bacterial infections, affecting 150 million people each year worldwide. High recurrence rates and increasing antimicrobial resistance among uropathogens are making it imperative to develop alternative strategies for the treatment and prevention of this common infection. In this Review, we discuss how understanding the: (i) molecular and biophysical basis of host-pathogen interactions; (ii) consequences of the molecular cross-talk at the host pathogen interface in terms of disease progression; and (iii) pathophysiology of UTIs is leading to efforts to translate this knowledge into novel therapeutics to treat and prevent these infections.

  5. Adhesive Pili in UTI Pathogenesis and Drug Development

    PubMed Central

    Spaulding, Caitlin N.; Hultgren, Scott J.

    2016-01-01

    Urinary tract infections (UTIs) are one of the most common bacterial infections, affecting 150 million people each year worldwide. High recurrence rates and increasing antimicrobial resistance among uropathogens are making it imperative to develop alternative strategies for the treatment and prevention of this common infection. In this Review, we discuss how understanding the: (i) molecular and biophysical basis of host-pathogen interactions; (ii) consequences of the molecular cross-talk at the host pathogen interface in terms of disease progression; and (iii) pathophysiology of UTIs is leading to efforts to translate this knowledge into novel therapeutics to treat and prevent these infections. PMID:26999218

  6. Lost in Translation: Bioinformatic Analysis of Variations Affecting the Translation Initiation Codon in the Human Genome.

    PubMed

    Abad, Francisco; de la Morena-Barrio, María Eugenia; Fernández-Breis, Jesualdo Tomás; Corral, Javier

    2018-06-01

    Translation is a key biological process controlled in eukaryotes by the initiation AUG codon. Variations affecting this codon may have pathological consequences by disturbing the correct initiation of translation. Unfortunately, there is no systematic study describing these variations in the human genome. Moreover, we aimed to develop new tools for in silico prediction of the pathogenicity of gene variations affecting AUG codons, because to date, these gene defects have been wrongly classified as missense. Whole-exome analysis revealed the mean of 12 gene variations per person affecting initiation codons, mostly with high (> 0:01) minor allele frequency (MAF). Moreover, analysis of Ensembl data (December 2017) revealed 11,261 genetic variations affecting the initiation AUG codon of 7,205 genes. Most of these variations (99.5%) have low or unknown MAF, probably reflecting deleterious consequences. Only 62 variations had high MAF. Genetic variations with high MAF had closer alternative AUG downstream codons than did those with low MAF. Besides, the high-MAF group better maintained both the signal peptide and reading frame. These differentiating elements could help to determine the pathogenicity of this kind of variation. Data and scripts in Perl and R are freely available at https://github.com/fanavarro/hemodonacion. jfernand@um.es. Supplementary data are available at Bioinformatics online.

  7. Co-occurrence and hybridization of anther-smut pathogens specialized on Dianthus hosts.

    PubMed

    Petit, Elsa; Silver, Casey; Cornille, Amandine; Gladieux, Pierre; Rosenthal, Lisa; Bruns, Emily; Yee, Sarah; Antonovics, Janis; Giraud, Tatiana; Hood, Michael E

    2017-04-01

    Host specialization has important consequences for the diversification and ecological interactions of obligate pathogens. The anther-smut disease of natural plant populations, caused by Microbotryum fungi, has been characterized by specialized host-pathogen interactions, which contribute in part to the isolation among these numerous fungal species. This study investigated the molecular variation of Microbotryum pathogens within the geographic and host-specific distributions on wild Dianthus species in southern European Alps. In contrast to prior studies on this pathogen genus, a range of overlapping host specificities was observed for four delineated Microbotryum lineages on Dianthus hosts, and their frequent co-occurrence within single-host populations was quantified at local and regional scales. In addition to potential consequences for direct pathogen competition, the sympatry of Microbotryum lineages led to hybridization between them in many populations, and these admixed genotypes suffered significant meiotic sterility. Therefore, this investigation of the anther-smut fungi reveals how variation in the degrees of host specificity can have major implications for ecological interactions and genetic integrity of differentiated pathogen lineages. © 2017 John Wiley & Sons Ltd.

  8. Helminths as vectors of pathogens in vertebrate hosts: a theoretical approach.

    PubMed

    Perkins, Sarah E; Fenton, Andy

    2006-07-01

    Pathogens frequently use vectors to facilitate transmission between hosts and, for vertebrate hosts, the vectors are typically ectoparasitic arthropods. However, other parasites that are intimately associated with their hosts may also be ideal candidate vectors; namely the parasitic helminths. Here, we present empirical evidence that helminth vectoring of pathogens occurs in a range of vertebrate systems by a variety of helminth taxa. Using a novel theoretical framework we explore the dynamics of helminth vectoring and determine which host-helminth-pathogen characteristics may favour the evolution of helminth vectoring. We use two theoretical models: the first is a population dynamic model amalgamated from standard macro- and microparasite models, which serves as a framework for investigation of within-host interactions between co-infecting pathogens and helminths. The second is an evolutionary model, which we use to predict the ecological conditions under which we would expect helminth vectoring to evolve. We show that, like arthropod vectors, helminth vectors increase pathogen fitness. However, unlike arthropod vectors, helminth vectoring increases the pathogenic impact on the host and may allow the evolution of high pathogen virulence. We show that concomitant infection of a host with a helminth and pathogen are not necessarily independent of one another, due to helminth vectoring of microparasites, with profound consequences for pathogen persistence and the impact of disease on the host population.

  9. Limiting damage during infection: lessons from infection tolerance for novel therapeutics.

    PubMed

    Vale, Pedro F; Fenton, Andy; Brown, Sam P

    2014-01-01

    The distinction between pathogen elimination and damage limitation during infection is beginning to change perspectives on infectious disease control, and has recently led to the development of novel therapies that focus on reducing the illness caused by pathogens (‘‘damage limitation’’)rather than reducing pathogen burdens directly (‘‘pathogen elimination’’). While beneficial at the individual host level, the population consequences of these interventions remain unclear. To address this issue,we present a simple conceptual framework for damage limitation during infection that distinguishes between therapies that are either host-centric (pro-tolerance) or pathogen-centric (anti-virulence). We then draw on recent developments from the evolutionary ecology of disease tolerance to highlight some potential epidemiological and evolutionary responses of pathogens to medical interventions that target the symptoms of infection. Just as pathogens are known to evolve in response to antimicrobial and vaccination therapies, we caution that claims of ‘‘evolution-proof’’ anti-virulence interventions may be premature, and further, that in infections where virulence and transmission are linked, reducing illness without reducing pathogen burden could have non-trivial epidemiological and evolutionary consequences that require careful examination.

  10. Tree diseases as a cause and consequence of interacting forest disturbances

    Treesearch

    Richard Cobb; Margaret Metz

    2017-01-01

    The disease triangle is a basic and highly flexible tool used extensively in forest pathology. By linking host, pathogen, and environmental factors, the model provides etiological insights into disease emergence. Landscape ecology, as a field, focuses on spatially heterogeneous environments and is most often employed to understand the dynamics of relatively large areas...

  11. Development of VNTR Markers to Assess Genetic Diversity of Mycosphaerella Fijiensis, the Causal Agent of Black Leaf Streak Disease in Bananas (Musa spp.)

    USDA-ARS?s Scientific Manuscript database

    Mycosphaerella fijiensis is the causal agent of black leaf streak (BLS) disease in bananas. This pathogen threatens global banana production as the main export cultivars are highly susceptible. As a consequence, commercial banana plantations must be protected chemically with fungicides; up to 40 app...

  12. Restoring ecosystem resilience to urban forests using Dutch elm disease-tolerant American elm trees

    Treesearch

    Charles E. Flower; Cornelia C. Pinchot; James M. Slavicek

    2017-01-01

    Urban forests contribute significantly to human health and environmental quality (Sanesi et al. 2011). As such, maintaining healthy urban forests resilient to pollution (atmospheric and soil), high temperatures, compacted soils, and poor drainage is critical. However, these forests have been hard hit by development, pests, and pathogens, consequently reshaping their...

  13. Biocontrol and Rapid Detection of Food-Borne Pathogens Using Bacteriophages and Endolysins

    PubMed Central

    Bai, Jaewoo; Kim, You-Tae; Ryu, Sangryeol; Lee, Ju-Hoon

    2016-01-01

    Bacteriophages have been suggested as natural food preservatives as well as rapid detection materials for food-borne pathogens in various foods. Since Listeria monocytogenes-targeting phage cocktail (ListShield) was approved for applications in foods, numerous phages have been screened and experimentally characterized for phage applications in foods. A single phage and phage cocktail treatments to various foods contaminated with food-borne pathogens including E. coli O157:H7, Salmonella enterica, Campylobacter jejuni, Listeria monocytogenes, Staphylococcus aureus, Cronobacter sakazakii, and Vibrio spp. revealed that they have great potential to control various food-borne pathogens and may be alternative for conventional food preservatives. In addition, phage-derived endolysins with high host specificity and host lysis activities may be preferred to food applications rather than phages. For rapid detection of food-borne pathogens, cell-wall binding domains (CBDs) from endolysins have been suggested due to their high host-specific binding. Fluorescence-tagged CBDs have been successfully evaluated and suggested to be alternative materials of expensive antibodies for various detection applications. Most recently, reporter phage systems have been developed and tested to confirm their usability and accuracy for specific detection. These systems revealed some advantages like rapid detection of only viable pathogenic cells without interference by food components in a very short reaction time, suggesting that these systems may be suitable for monitoring of pathogens in foods. Consequently, phage is the next-generation biocontrol agent as well as rapid detection tool to confirm and even identify the food-borne pathogens present in various foods. PMID:27092128

  14. A generic risk-based surveying method for invading plant pathogens

    USDA-ARS?s Scientific Manuscript database

    Invasive plant pathogens are increasing with international trade and travel with damaging environmental and economic consequences. Recent examples include tree diseases such as Sudden Oak Death in the Western US and Ash Dieback in Europe. To control an invading pathogen it is crucial that newly in...

  15. High prevalence of campylobacter excretors among Liberian children related to environmental conditions.

    PubMed

    Mølbak, K; Højlyng, N; Gaarslev, K

    1988-04-01

    Campylobacter was the bacterial pathogen most prevalent in 859 children, aged 6-59 months, examined in a house-to-house diarrhoea survey in two Liberian communities. 44.9% of the children from an urban slum and 28.4% from a rural area were excretors. Since the prevalence of diarrhoea was very high and consequently many convalescent carriers were found, it was not possible to evaluate the pathogenic role of campylobacter. The excretor rate increased with age and was significantly correlated to the use of supplementary feeding, inversely correlated to the quality of the water supply, and also associated with helminthic infestation. Results from re-examination of 172 children suggested a high intensity of transmission. The findings all indicate the existence of a heavy environmental contamination with campylobacter, probably of both human and animal faecal origin.

  16. High prevalence of campylobacter excretors among Liberian children related to environmental conditions.

    PubMed Central

    Mølbak, K.; Højlyng, N.; Gaarslev, K.

    1988-01-01

    Campylobacter was the bacterial pathogen most prevalent in 859 children, aged 6-59 months, examined in a house-to-house diarrhoea survey in two Liberian communities. 44.9% of the children from an urban slum and 28.4% from a rural area were excretors. Since the prevalence of diarrhoea was very high and consequently many convalescent carriers were found, it was not possible to evaluate the pathogenic role of campylobacter. The excretor rate increased with age and was significantly correlated to the use of supplementary feeding, inversely correlated to the quality of the water supply, and also associated with helminthic infestation. Results from re-examination of 172 children suggested a high intensity of transmission. The findings all indicate the existence of a heavy environmental contamination with campylobacter, probably of both human and animal faecal origin. PMID:3356221

  17. The Janus face of reactive oxygen species in resistance and susceptibility of plants to necrotrophic and biotrophic pathogens.

    PubMed

    Barna, B; Fodor, J; Harrach, B D; Pogány, M; Király, Z

    2012-10-01

    Plant pathogens can be divided into biotrophs and necrotrophs according to their different life styles; biotrophs prefer living, while necrotrophs prefer dead cells for nutritional purposes. Therefore tissue necrosis caused by reactive oxygen species (ROS) during pathogen infection increases host susceptibility to necrotrophic, but resistance to biotrophic pathogen. Consequently, elevation of antioxidant capacity of plants enhances their tolerance to development of necroses caused by necrotrophic pathogens. Plant hormones can strongly influence induction of ROS and antioxidants, thereby influencing susceptibility or resistance of plants to pathogens. Pathogen-induced ROS themselves are considered as signaling molecules. Generally, salicylic acid (SA) signaling induces defense against biotrophic pathogens, whereas jasmonic acid (JA) against necrotrophic pathogens. Furthermore pathogens can modify plant's defense signaling network for their own benefit by changing phytohormone homeostasis. On the other hand, ROS are harmful also to the pathogens, consequently they try to defend themselves by elevating antioxidant activity and secreting ROS scavengers in the infected tissue. The Janus face nature of ROS and plant cell death on biotrophic and on necrotrophic pathogens is also supported by the experiments with BAX inhibitor-1 and the mlo mutation of Mlo gene in barley. It was found that ROS and elevated plant antioxidant activity play an important role in systemic acquired resistance (SAR) and induced systemic resistance (ISR), as well as in mycorrhiza induced abiotic and biotic stress tolerance of plants. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  18. Climate change accelerates local disease extinction rates in a long-term wild host-pathogen association.

    PubMed

    Zhan, Jiasui; Ericson, Lars; Burdon, Jeremy J

    2018-02-27

    Pathogens are a significant component of all plant communities. In recent years, the potential for existing and emerging pathogens of agricultural crops to cause increased yield losses as a consequence of changing climatic patterns has raised considerable concern. In contrast, the response of naturally occurring, endemic pathogens to a warming climate has received little attention. Here, we report on the impact of a signature variable of global climate change - increasing temperature - on the long-term epidemiology of a natural host-pathogen association involving the rust pathogen Triphragmium ulmariae and its host plant Filipendula ulmaria. In a host-pathogen metapopulation involving approximately 230 host populations growing on an archipelago of islands in the Gulf of Bothnia we assessed changes in host population size and pathogen epidemiological measures over a 25-year period. We show how the incidence of disease and its severity declines over that period and most importantly demonstrate a positive association between a long-term trend of increasing extinction rates in individual pathogen populations of the metapopulation and increasing temperature. Our results are highly suggestive that changing climatic patterns, particularly mean monthly growing season (April-November) temperature, are markedly influencing the epidemiology of plant disease in this host-pathogen association. Given the important role plant pathogens have in shaping the structure of communities, changes in the epidemiology of pathogens have potentially far-reaching impacts on ecological and evolutionary processes. For these reasons, it is essential to increase understanding of pathogen epidemiology, its response to warming, and to invoke these responses in forecasts for the future. © 2018 John Wiley & Sons Ltd.

  19. Comparative genetic diversity of Lyme disease bacteria in Northern Californian ticks and their vertebrate hosts.

    PubMed

    Swei, Andrea; Bowie, Verna C; Bowie, Rauri C K

    2015-04-01

    Vector-borne pathogens are transmitted between vertebrate hosts and arthropod vectors, two immensely different environments for the pathogen. There is further differentiation among vertebrate hosts that often have complex, species-specific immunological responses to the pathogen. All this presents a heterogeneous environmental and immunological landscape with possible consequences on the population genetic structure of the pathogen. We evaluated the differential genetic diversity of the Lyme disease pathogen, Borrelia burgdorferi, in its vector, the western black-legged tick (Ixodes pacificus), and in its mammal host community using the 5S-23S rRNA intergenic spacer region. We found differences in haplotype distribution of B. burgdorferi in tick populations from two counties in California as well as between a sympatric tick and vertebrate host community. In addition, we found that three closely related haplotypes consistently occurred in high frequency in all sample types. Lastly, our study found lower species diversity of the B. burgdorferi species complex, known as B. burgdorferi sensu lato, in small mammal hosts versus the tick populations in a sympatric study area. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Resistance in persisting bat populations after white-nose syndrome invasion.

    PubMed

    Langwig, Kate E; Hoyt, Joseph R; Parise, Katy L; Frick, Winifred F; Foster, Jeffrey T; Kilpatrick, A Marm

    2017-01-19

    Increases in anthropogenic movement have led to a rise in pathogen introductions and the emergence of infectious diseases in naive host communities worldwide. We combined empirical data and mathematical models to examine changes in disease dynamics in little brown bat (Myotis lucifugus) populations following the introduction of the emerging fungal pathogen Pseudogymnoascus destructans, which causes the disease white-nose syndrome. We found that infection intensity was much lower in persisting populations than in declining populations where the fungus has recently invaded. Fitted models indicate that this is most consistent with a reduction in the growth rate of the pathogen when fungal loads become high. The data are inconsistent with the evolution of tolerance or an overall reduced pathogen growth rate that might be caused by environmental factors. The existence of resistance in some persisting populations of little brown bats offers a glimmer of hope that a precipitously declining species will persist in the face of this deadly pathogen.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

  1. 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

  2. Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Leishmania and Chlamydiales.

    PubMed

    Gupta, Neetu; Noël, Romain; Goudet, Amélie; Hinsinger, Karen; Michau, Aurélien; Pons, Valérie; Abdelkafi, Hajer; Secher, Thomas; Shima, Ayaka; Shtanko, Olena; Sakurai, Yasuteru; Cojean, Sandrine; Pomel, Sébastien; Liévin-Le Moal, Vanessa; Leignel, Véronique; Herweg, Jo-Ana; Fischer, Annette; Johannes, Ludger; Harrison, Kate; Beard, Philippa M; Clayette, Pascal; Le Grand, Roger; Rayner, Jonathan O; Rudel, Thomas; Vacus, Joël; Loiseau, Philippe M; Davey, Robert A; Oswald, Eric; Cintrat, Jean-Christophe; Barbier, Julien; Gillet, Daniel

    2017-04-01

    Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde transport that affects syntaxin-5-dependent toxins and pathogens. As a consequence, it has a broad-spectrum activity that has been demonstrated both in vitro and in vivo against ricin, Shiga toxin-producing O104:H4 entero-hemorrhagic E. coli and Leishmania sp. and in vitro against Ebola, Marburg and poxviruses and Chlamydiales. An effect is anticipated on other toxins or pathogens that use retrograde trafficking and syntaxin-5. Since Retro-2 targets cell components of the host and not directly the pathogen, no selection of resistant pathogens is expected. These lead compounds need now to be developed as drugs for human use. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. 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

  4. Progress towards the treatment of Ebola haemorrhagic fever.

    PubMed

    Ströher, Ute; Feldmann, Heinz

    2006-12-01

    Being highly pathogenic for human and nonhuman primates and the subject of former weapon programmes makes Ebola virus one of the most feared pathogens worldwide today. Due to a lack of licensed pre- and postexposure intervention, the current response depends on rapid diagnostics, proper isolation procedures and supportive care of case patients. Consequently, the development of more specific countermeasures is of high priority for the preparedness of many nations. Over the past years, enhanced research efforts directed to better understand virus replication and pathogenesis have identified potential new targets for intervention strategies. The authors discuss the most promising therapeutic approaches for Ebola haemorrhagic fever as judged by their efficacy in animal models. The current development in this field encourages discussions on how to move some of the experimental approaches towards clinical application.

  5. Development of a genetic linkage map of Mycosphaerella fijiensis, the causal agent of black leaf streak disease in bananas (Musa spp.) using SSR and DArT markers

    USDA-ARS?s Scientific Manuscript database

    Mycosphaerella fijiensis is the causal agent of black leaf streak (BLS) disease in bananas. This pathogen threatens global banana production as the main export cultivars are highly susceptible. As a consequence, commercial banana plantations must be protected chemically with fungicides; up to 40 app...

  6. 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

  7. Variant Interpretation: Functional Assays to the Rescue.

    PubMed

    Starita, Lea M; Ahituv, Nadav; Dunham, Maitreya J; Kitzman, Jacob O; Roth, Frederick P; Seelig, Georg; Shendure, Jay; Fowler, Douglas M

    2017-09-07

    Classical genetic approaches for interpreting variants, such as case-control or co-segregation studies, require finding many individuals with each variant. Because the overwhelming majority of variants are present in only a few living humans, this strategy has clear limits. Fully realizing the clinical potential of genetics requires that we accurately infer pathogenicity even for rare or private variation. Many computational approaches to predicting variant effects have been developed, but they can identify only a small fraction of pathogenic variants with the high confidence that is required in the clinic. Experimentally measuring a variant's functional consequences can provide clearer guidance, but individual assays performed only after the discovery of the variant are both time and resource intensive. Here, we discuss how multiplex assays of variant effect (MAVEs) can be used to measure the functional consequences of all possible variants in disease-relevant loci for a variety of molecular and cellular phenotypes. The resulting large-scale functional data can be combined with machine learning and clinical knowledge for the development of "lookup tables" of accurate pathogenicity predictions. A coordinated effort to produce, analyze, and disseminate large-scale functional data generated by multiplex assays could be essential to addressing the variant-interpretation crisis. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Bacterial genomics reveal the complex epidemiology of an emerging pathogen in arctic and boreal ungulates

    USGS Publications Warehouse

    Forde, Taya L.; Orsel, Karin; Zadoks, Ruth N.; Biek, Roman; Adams, Layne G.; Checkley, Sylvia L.; Davison, Tracy; De Buck, Jeroen; Dumond, Mathieu; Elkin, Brett T.; Finnegan, Laura; Macbeth, Bryan J.; Nelson, Cait; Niptanatiak, Amanda; Sather, Shane; Schwantje, Helen M.; van der Meer, Frank; Kutz, Susan J.

    2016-01-01

    Northern ecosystems are currently experiencing unprecedented ecological change, largely driven by a rapidly changing climate. Pathogen range expansion, and emergence and altered patterns of infectious disease, are increasingly reported in wildlife at high latitudes. Understanding the causes and consequences of shifting pathogen diversity and host-pathogen interactions in these ecosystems is important for wildlife conservation, and for indigenous populations that depend on wildlife. Among the key questions are whether disease events are associated with endemic or recently introduced pathogens, and whether emerging strains are spreading throughout the region. In this study, we used a phylogenomic approach to address these questions of pathogen endemicity and spread for Erysipelothrix rhusiopathiae, an opportunistic multi-host bacterial pathogen associated with recent mortalities in arctic and boreal ungulate populations in North America. We isolated E. rhusiopathiae from carcasses associated with large-scale die-offs of muskoxen in the Canadian Arctic Archipelago, and from contemporaneous mortality events and/or population declines among muskoxen in northwestern Alaska and caribou and moose in western Canada. Bacterial genomic diversity differed markedly among these locations; minimal divergence was present among isolates from muskoxen in the Canadian Arctic, while in caribou and moose populations, strains from highly divergent clades were isolated from the same location, or even from within a single carcass. These results indicate that mortalities among northern ungulates are not associated with a single emerging strain of E. rhusiopathiae, and that alternate hypotheses need to be explored. Our study illustrates the value and limitations of bacterial genomic data for discriminating between ecological hypotheses of disease emergence, and highlights the importance of studying emerging pathogens within the broader context of environmental and host factors.

  9. Investigating the production of sexual resting structures in a plant pathogen reveals unexpected self-fertility and genotype-by-environment effects.

    PubMed

    Tollenaere, C; Laine, A-L

    2013-08-01

    The sexual stage of pathogens governs recombination patterns and often also provides means of surviving the off-season. Despite its importance for evolutionary potential and between-season epidemiology, sexual systems have not been carefully investigated for many important pathogens, and what generates variation in successful sexual reproduction of pathogens remains unexplored. We surveyed the sexually produced resting structures (chasmothecia) across 86 natural populations of fungal pathogen Podosphaera plantaginis (Ascomycota) naturally infecting Plantago lanceolata in the Åland archipelago, southwestern Finland. For this pathosystem, these resting structures are a key life-history stage, as more than half of the local pathogen populations go extinct every winter. We uncovered substantial variation in the level of chasmothecia produced among populations, ranging from complete absence to presence on all infected leaves. We found that chasmothecia developed within clonal isolates (single-strain cultures). Additionally, these clonal isolates all contained both MAT1-1-1 and MAT1-2-1 genes that characterize mating types in Ascomycetes. Hence, contrary to expectations, we conclude that this species is capable of haploid selfing. In controlled inoculations, we discovered that pathogen genotypes varied in their tendency to produce chasmothecia. Production of chasmothecia was also affected by ambient temperature (E) and by the interaction between temperature and pathogen genotype (G × E). These G, E and G × E effects found both at a European scale and within the Åland archipelago may partly explain the high variability observed among populations in chasmothecia levels. Consequently, they may be key drivers of the evolutionary potential and epidemiology of this highly dynamic pathosystem. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  10. Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 1. Biosafety Level 4 Suit Laboratory Suite Entry and Exit Procedures.

    PubMed

    Janosko, Krisztina; Holbrook, Michael R; Adams, Ricky; Barr, Jason; Bollinger, Laura; Newton, Je T'aime; Ntiforo, Corrie; Coe, Linda; Wada, Jiro; Pusl, Daniela; Jahrling, Peter B; Kuhn, Jens H; Lackemeyer, Matthew G

    2016-10-03

    Biosafety level 4 (BSL-4) suit laboratories are specifically designed to study high-consequence pathogens for which neither infection prophylaxes nor treatment options exist. The hallmarks of these laboratories are: custom-designed airtight doors, dedicated supply and exhaust airflow systems, a negative-pressure environment, and mandatory use of positive-pressure ("space") suits. The risk for laboratory specialists working with highly pathogenic agents is minimized through rigorous training and adherence to stringent safety protocols and standard operating procedures. Researchers perform the majority of their work in BSL-2 laboratories and switch to BSL-4 suit laboratories when work with a high-consequence pathogen is required. Collaborators and scientists considering BSL-4 projects should be aware of the challenges associated with BSL-4 research both in terms of experimental technical limitations in BSL-4 laboratory space and the increased duration of such experiments. Tasks such as entering and exiting the BSL-4 suit laboratories are considerably more complex and time-consuming compared to BSL-2 and BSL-3 laboratories. The focus of this particular article is to address basic biosafety concerns and describe the entrance and exit procedures for the BSL-4 laboratory at the NIH/NIAID Integrated Research Facility at Fort Detrick. Such procedures include checking external systems that support the BSL-4 laboratory, and inspecting and donning positive-pressure suits, entering the laboratory, moving through air pressure-resistant doors, and connecting to air-supply hoses. We will also discuss moving within and exiting the BSL-4 suit laboratories, including using the chemical shower and removing and storing positive-pressure suits.

  11. Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 1. Biosafety Level 4 Suit Laboratory Suite Entry and Exit Procedures

    PubMed Central

    Janosko, Krisztina; Holbrook, Michael R.; Adams, Ricky; Barr, Jason; Bollinger, Laura; Newton, Je T'aime; Ntiforo, Corrie; Coe, Linda; Wada, Jiro; Pusl, Daniela; Jahrling, Peter B.; Kuhn, Jens H.; Lackemeyer, Matthew G.

    2016-01-01

    Biosafety level 4 (BSL-4) suit laboratories are specifically designed to study high-consequence pathogens for which neither infection prophylaxes nor treatment options exist. The hallmarks of these laboratories are: custom-designed airtight doors, dedicated supply and exhaust airflow systems, a negative-pressure environment, and mandatory use of positive-pressure (“space”) suits. The risk for laboratory specialists working with highly pathogenic agents is minimized through rigorous training and adherence to stringent safety protocols and standard operating procedures. Researchers perform the majority of their work in BSL-2 laboratories and switch to BSL-4 suit laboratories when work with a high-consequence pathogen is required. Collaborators and scientists considering BSL-4 projects should be aware of the challenges associated with BSL-4 research both in terms of experimental technical limitations in BSL-4 laboratory space and the increased duration of such experiments. Tasks such as entering and exiting the BSL-4 suit laboratories are considerably more complex and time-consuming compared to BSL-2 and BSL-3 laboratories. The focus of this particular article is to address basic biosafety concerns and describe the entrance and exit procedures for the BSL-4 laboratory at the NIH/NIAID Integrated Research Facility at Fort Detrick. Such procedures include checking external systems that support the BSL-4 laboratory, and inspecting and donning positive-pressure suits, entering the laboratory, moving through air pressure-resistant doors, and connecting to air-supply hoses. We will also discuss moving within and exiting the BSL-4 suit laboratories, including using the chemical shower and removing and storing positive-pressure suits. PMID:27768063

  12. The Tick Microbiome: Why Non-pathogenic Microorganisms Matter in Tick Biology and Pathogen Transmission

    PubMed Central

    Bonnet, Sarah I.; Binetruy, Florian; Hernández-Jarguín, Angelica M.; Duron, Olivier

    2017-01-01

    Ticks are among the most important vectors of pathogens affecting humans and other animals worldwide. They do not only carry pathogens however, as a diverse group of commensal and symbiotic microorganisms are also present in ticks. Unlike pathogens, their biology and their effect on ticks remain largely unexplored, and are in fact often neglected. Nonetheless, they can confer multiple detrimental, neutral, or beneficial effects to their tick hosts, and can play various roles in fitness, nutritional adaptation, development, reproduction, defense against environmental stress, and immunity. Non-pathogenic microorganisms may also play a role in driving transmission of tick-borne pathogens (TBP), with many potential implications for both human and animal health. In addition, the genetic proximity of some pathogens to mutualistic symbionts hosted by ticks is evident when studying phylogenies of several bacterial genera. The best examples are found within members of the Rickettsia, Francisella, and Coxiella genera: while in medical and veterinary research these bacteria are traditionally recognized as highly virulent vertebrate pathogens, it is now clear to evolutionary ecologists that many (if not most) Coxiella, Francisella, and Rickettsia bacteria are actually non-pathogenic microorganisms exhibiting alternative lifestyles as mutualistic ticks symbionts. Consequently, ticks represent a compelling yet challenging system in which to study microbiomes and microbial interactions, and to investigate the composition, functional, and ecological implications of bacterial communities. Ultimately, deciphering the relationships between tick microorganisms as well as tick symbiont interactions will garner invaluable information, which may aid in the future development of arthropod pest and vector-borne pathogen transmission control strategies. PMID:28642842

  13. The Tick Microbiome: Why Non-pathogenic Microorganisms Matter in Tick Biology and Pathogen Transmission.

    PubMed

    Bonnet, Sarah I; Binetruy, Florian; Hernández-Jarguín, Angelica M; Duron, Olivier

    2017-01-01

    Ticks are among the most important vectors of pathogens affecting humans and other animals worldwide. They do not only carry pathogens however, as a diverse group of commensal and symbiotic microorganisms are also present in ticks. Unlike pathogens, their biology and their effect on ticks remain largely unexplored, and are in fact often neglected. Nonetheless, they can confer multiple detrimental, neutral, or beneficial effects to their tick hosts, and can play various roles in fitness, nutritional adaptation, development, reproduction, defense against environmental stress, and immunity. Non-pathogenic microorganisms may also play a role in driving transmission of tick-borne pathogens (TBP), with many potential implications for both human and animal health. In addition, the genetic proximity of some pathogens to mutualistic symbionts hosted by ticks is evident when studying phylogenies of several bacterial genera. The best examples are found within members of the Rickettsia, Francisella , and Coxiella genera: while in medical and veterinary research these bacteria are traditionally recognized as highly virulent vertebrate pathogens, it is now clear to evolutionary ecologists that many (if not most) Coxiella, Francisella , and Rickettsia bacteria are actually non-pathogenic microorganisms exhibiting alternative lifestyles as mutualistic ticks symbionts. Consequently, ticks represent a compelling yet challenging system in which to study microbiomes and microbial interactions, and to investigate the composition, functional, and ecological implications of bacterial communities. Ultimately, deciphering the relationships between tick microorganisms as well as tick symbiont interactions will garner invaluable information, which may aid in the future development of arthropod pest and vector-borne pathogen transmission control strategies.

  14. Implications of climate change (global warming) for the healthcare system.

    PubMed

    Raffa, R B; Eltoukhy, N S; Raffa, K F

    2012-10-01

    Temperature-sensitive pathogenic species and their vectors and hosts are emerging in previously colder regions as a consequence of several factors, including global warming. As a result, an increasing number of people will be exposed to pathogens against which they have not previously needed defences. We illustrate this with a specific example of recent emergence of Cryptococcus gattii infections in more temperate climates. The outbreaks in more temperate climates of the highly virulent--but usually tropically restricted--C. gattii is illustrative of an anticipated growing challenge for the healthcare system. There is a need for preparedness by healthcare professionals in anticipation and for management of such outbreaks, including other infections whose recent increased prevalence in temperate climates can be at least partly associated with global warming. (Re)emergence of temperature-sensitive pathogenic species in more temperate climates will present new challenges for healthcare systems. Preparation for outbreaks should precede their occurrence. © 2012 Blackwell Publishing Ltd.

  15. Isolation and characterization of highly pathogenic avian influenza virus subtype H5N1 from donkeys

    PubMed Central

    2010-01-01

    Background The highly pathogenic H5N1 is a major avian pathogen that crosses species barriers and seriously affects humans as well as some mammals. It mutates in an intensified manner and is considered a potential candidate for the possible next pandemic with all the catastrophic consequences. Methods Nasal swabs were collected from donkeys suffered from respiratory distress. The virus was isolated from the pooled nasal swabs in specific pathogen free embryonated chicken eggs (SPF-ECE). Reverse transcriptase polymerase chain reaction (RT-PCR) and sequencing of both haemagglutingin and neuraminidase were performed. H5 seroconversion was screened using haemagglutination inhibition (HI) assay on 105 donkey serum samples. Results We demonstrated that H5N1 jumped from poultry to another mammalian host; donkeys. Phylogenetic analysis showed that the virus clustered within the lineage of H5N1 from Egypt, closely related to 2009 isolates. It harboured few genetic changes compared to the closely related viruses from avian and humans. The neuraminidase lacks oseltamivir resistant mutations. Interestingly, HI screening for antibodies to H5 haemagglutinins in donkeys revealed high exposure rate. Conclusions These findings extend the host range of the H5N1 influenza virus, possess implications for influenza virus epidemiology and highlight the need for the systematic surveillance of H5N1 in animals in the vicinity of backyard poultry units especially in endemic areas. PMID:20398268

  16. Plant defenses against parasitic plants show similarities to those induced by herbivores and pathogens

    Treesearch

    Justin B. Runyon; Mark C. Mescher; Consuelo M. De Moraes

    2010-01-01

    Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling and response to herbivores and pathogens has expanded rapidly in recent years...

  17. The role of natural environments in the evolution of resistance traits in pathogenic bacteria.

    PubMed

    Martinez, Jose L

    2009-07-22

    Antibiotics are among the most valuable compounds used for fighting human diseases. Unfortunately, pathogenic bacteria have evolved towards resistance. One important and frequently forgotten aspect of antibiotics and their resistance genes is that they evolved in non-clinical (natural) environments before the use of antibiotics by humans. Given that the biosphere is mainly formed by micro-organisms, learning the functional role of antibiotics and their resistance elements in nature has relevant implications both for human health and from an ecological perspective. Recent works have suggested that some antibiotics may serve for signalling purposes at the low concentrations probably found in natural ecosystems, whereas some antibiotic resistance genes were originally selected in their hosts for metabolic purposes or for signal trafficking. However, the high concentrations of antibiotics released in specific habitats (for instance, clinical settings) as a consequence of human activity can shift those functional roles. The pollution of natural ecosystems by antibiotics and resistance genes might have consequences for the evolution of the microbiosphere. Whereas antibiotics produce transient and usually local challenges in microbial communities, antibiotic resistance genes present in gene-transfer units can spread in nature with consequences for human health and the evolution of environmental microbiota that are largely ignored.

  18. [Scientific progress and new biological weapons].

    PubMed

    Berche, Patrick

    2006-02-01

    The biological weapons are different from conventional weapons, because living germs hold an extraordinary and predictable potential for multiplication, propagation and genetic variation during their dissemination in a susceptible population. Only natural pathogens (1rst generation weapons) have been used in the past (smallpox virus, plague, anthrax, toxins...). However, new threats are emerging, due to the rapid progress of scientific knowledge and its exponential worldwide diffusion. It is possible to synthesize microorganisms from in silico sequences widely diffused on Internet (poliovirus, influenza...), thus resulting in the accessibility of very dangerous virus confined today in high-security laboratories (virus Ebola...). It is possible also to "improve" pathogens by genetic manipulations, becoming more resistant or virulent (2nd generation weapons). Finally, one can now create de novo new pathogens by molecular breeding (DNA shuffling), potentially highly dangerous for naive populations (3rd generation weapons). Making biological weapons does not require too much technological resources and appears accessible to terrorists, due to low cost and easy use. Although the destructive consequences are difficult to predict, the psychological and social damages should be considerable, because of the highly emotional burden in the population associated to the transgression by man of a taboo of life.

  19. Detection of bacterial pathogens including potential new species in human head lice from Mali

    PubMed Central

    Amanzougaghene, Nadia; Fenollar, Florence; Sangaré, Abdoul Karim; Sissoko, Mahamadou S.; Doumbo, Ogobara K.; Raoult, Didier

    2017-01-01

    In poor African countries, where no medical and biological facilities are available, the identification of potential emerging pathogens of concern at an early stage is challenging. Head lice, Pediculus humanus capitis, have a short life, feed only on human blood and do not transmit pathogens to their progeny. They are, therefore, a perfect tool for the xenodiagnosis of current or recent human infection. This study assessed the occurrence of bacterial pathogens from head lice collected in two rural villages from Mali, where a high frequency of head lice infestation had previously been reported, using molecular methods. Results show that all 600 head lice, collected from 117 individuals, belonged to clade E, specific to West Africa. Bartonella quintana, the causative agent of trench fever, was identified in three of the 600 (0.5%) head lice studied. Our study also shows, for the first time, the presence of the DNA of two pathogenic bacteria, namely Coxiella burnetii (5.1%) and Rickettsia aeschlimannii (0.6%), detected in human head lice, as well as the DNA of potential new species from the Anaplasma and Ehrlichia genera of unknown pathogenicity. The finding of several Malian head lice infected with B. quintana, C. burnetii, R. aeschlimannii, Anaplasma and Ehrlichia is alarming and highlights the need for active survey programs to define the public health consequences of the detection of these emerging bacterial pathogens in human head lice. PMID:28931077

  20. Detection of bacterial pathogens including potential new species in human head lice from Mali.

    PubMed

    Amanzougaghene, Nadia; Fenollar, Florence; Sangaré, Abdoul Karim; Sissoko, Mahamadou S; Doumbo, Ogobara K; Raoult, Didier; Mediannikov, Oleg

    2017-01-01

    In poor African countries, where no medical and biological facilities are available, the identification of potential emerging pathogens of concern at an early stage is challenging. Head lice, Pediculus humanus capitis, have a short life, feed only on human blood and do not transmit pathogens to their progeny. They are, therefore, a perfect tool for the xenodiagnosis of current or recent human infection. This study assessed the occurrence of bacterial pathogens from head lice collected in two rural villages from Mali, where a high frequency of head lice infestation had previously been reported, using molecular methods. Results show that all 600 head lice, collected from 117 individuals, belonged to clade E, specific to West Africa. Bartonella quintana, the causative agent of trench fever, was identified in three of the 600 (0.5%) head lice studied. Our study also shows, for the first time, the presence of the DNA of two pathogenic bacteria, namely Coxiella burnetii (5.1%) and Rickettsia aeschlimannii (0.6%), detected in human head lice, as well as the DNA of potential new species from the Anaplasma and Ehrlichia genera of unknown pathogenicity. The finding of several Malian head lice infected with B. quintana, C. burnetii, R. aeschlimannii, Anaplasma and Ehrlichia is alarming and highlights the need for active survey programs to define the public health consequences of the detection of these emerging bacterial pathogens in human head lice.

  1. Predicting pathogen introduction: West Nile virus spread to Galáipagos.

    PubMed

    Kilpatrick, A Marm; Daszak, Peter; Goodman, Simon J; Rogg, Helmuth; Kramer, Laura D; Cedeño, Virna; Cunningham, Andrew A

    2006-08-01

    Emerging infectious diseases are a key threat to conservation and public health, yet predicting and preventing their emergence is notoriously difficult. We devised a predictive model for the introduction of a zoonotic vector-borne pathogen by considering each of the pathways by which it may be introduced to a new area and comparing the relative risk of each pathway. This framework is an adaptation of pest introduction models and estimates the number of infectious individuals arriving in a location and the duration of their infectivity. We used it to determine the most likely route for the introduction of West Nile virus to Galápagos and measures that can be taken to reduce the risk of introduction. The introduction of this highly pathogenic virus to this unique World Heritage Site could have devastating consequences, similar to those seen following introductions of pathogens into other endemic island faunas. Our model identified the transport of mosquitoes on airplanes as the highest risk for West Nile virus introduction. Pathogen dissemination through avian migration and the transportation of day-old chickens appeared to be less important pathways. Infected humans and mosquitoes transported in sea containers, in tires, or by wind all represented much lower risk. Our risk-assessment framework has broad applicability to other pathogens and other regions and depends only on the availability of data on the transport of goods and animals and the epidemiology of the pathogen.

  2. Development of a Multiplex PCR Method to Detect Fungal Pathogens for Quarantine on Exported Cacti

    PubMed Central

    Cho, Hyun ji; Hong, Seong Won; Kim, Hyun-ju; Kwak, Youn-Sig

    2016-01-01

    Major diseases in grafted cacti have been reported and Fusarium oxysporum, Bipolaris cactivora, Phytophthora spp. and Collectotrichum spp. are known as causal pathogens. These pathogens can lead to plant death after infection. Therefore, some European countries have quarantined imported cacti that are infected with specific fungal pathogens. Consequently, we developed PCR detection methods to identify four quarantined fungal pathogens and reduce export rejection rates of Korean grafted cacti. The pathogen specific primer sets F.oF-F.oR, B.CF-B.CR, P.nF-P.nR, and P.cF-P.CR were tested for F. oxysporum, B. cactivora, P. nicotinae, and P. cactorum, respectively. The F.oF-F.oR primer set was designed from the Fusarium ITS region; the B.CF-B.CR and P.nF-P.nR primers respectively from Bipolaris and Phytophthora ITS1; and the P.cF-P.CR primer set from the Ypt1protein gene region. The quarantine fungal pathogen primer pairs were amplified to the specific number of base pairs in each of the following fungal pathogens: 210-bp (F. oxysporum), 510-bp (B. cactivora), 313-bp (P. nicotinae), and 447-bp (P. cactorum). The detection limit for the mono- and multiplex PCR primer sets was 0.1 ng of template DNA under in vitro conditions. Therefore, each primer set successfully diagnosed contamination of quarantine pathogens in export grafted cacti. Consequently, our methodology is a viable tool to screen contamination of the fungal pathogen in exported grafted cacti. PMID:26889115

  3. Costs and benefits of group living with disease: a case study of pneumonia in bighorn lambs (Ovis canadensis).

    PubMed

    Manlove, Kezia R; Cassirer, E Frances; Cross, Paul C; Plowright, Raina K; Hudson, Peter J

    2014-12-22

    Group living facilitates pathogen transmission among social hosts, yet temporally stable host social organizations can actually limit transmission of some pathogens. When there are few between-subpopulation contacts for the duration of a disease event, transmission becomes localized to subpopulations. The number of per capita infectious contacts approaches the subpopulation size as pathogen infectiousness increases. Here, we illustrate that this is the case during epidemics of highly infectious pneumonia in bighorn lambs (Ovis canadensis). We classified individually marked bighorn ewes into disjoint seasonal subpopulations, and decomposed the variance in lamb survival to weaning into components associated with individual ewes, subpopulations, populations and years. During epidemics, lamb survival varied substantially more between ewe-subpopulations than across populations or years, suggesting localized pathogen transmission. This pattern of lamb survival was not observed during years when disease was absent. Additionally, group sizes in ewe-subpopulations were independent of population size, but the number of ewe-subpopulations increased with population size. Consequently, although one might reasonably assume that force of infection for this highly communicable disease scales with population size, in fact, host social behaviour modulates transmission such that disease is frequency-dependent within populations, and some groups remain protected during epidemic events. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  4. Costs and benefits of group living with disease: a case study of pneumonia in bighorn lambs (Ovis canadensis)

    PubMed Central

    Manlove, Kezia R.; Cassirer, E. Frances; Cross, Paul C.; Plowright, Raina K.; Hudson, Peter J.

    2014-01-01

    Group living facilitates pathogen transmission among social hosts, yet temporally stable host social organizations can actually limit transmission of some pathogens. When there are few between-subpopulation contacts for the duration of a disease event, transmission becomes localized to subpopulations. The number of per capita infectious contacts approaches the subpopulation size as pathogen infectiousness increases. Here, we illustrate that this is the case during epidemics of highly infectious pneumonia in bighorn lambs (Ovis canadensis). We classified individually marked bighorn ewes into disjoint seasonal subpopulations, and decomposed the variance in lamb survival to weaning into components associated with individual ewes, subpopulations, populations and years. During epidemics, lamb survival varied substantially more between ewe-subpopulations than across populations or years, suggesting localized pathogen transmission. This pattern of lamb survival was not observed during years when disease was absent. Additionally, group sizes in ewe-subpopulations were independent of population size, but the number of ewe-subpopulations increased with population size. Consequently, although one might reasonably assume that force of infection for this highly communicable disease scales with population size, in fact, host social behaviour modulates transmission such that disease is frequency-dependent within populations, and some groups remain protected during epidemic events. PMID:25377464

  5. Costs and benefits of group living with disease: a case study of pneumonia in bighorn lambs (Ovis canadensis)

    USGS Publications Warehouse

    Manlove, Kezia R.; Cassirer, E. Frances; Cross, Paul C.; Plowright, Raina K.; Hudson, Peter J.

    2014-01-01

    Group living facilitates pathogen transmission among social hosts, yet temporally stable host social organizations can actually limit transmission of some pathogens. When there are few between-subpopulation contacts for the duration of a disease event, transmission becomes localized to subpopulations. The number of per capita infectious contacts approaches the subpopulation size as pathogen infectiousness increases. Here, we illustrate that this is the case during epidemics of highly infectious pneumonia in bighorn lambs (Ovis canadensis). We classified individually marked bighorn ewes into disjoint seasonal subpopulations, and decomposed the variance in lamb survival to weaning into components associated with individual ewes, subpopulations, populations and years. During epidemics, lamb survival varied substantially more between ewe-subpopulations than across populations or years, suggesting localized pathogen transmission. This pattern of lamb survival was not observed during years when disease was absent. Additionally, group sizes in ewe-subpopulations were independent of population size, but the number of ewe-subpopulations increased with population size. Consequently, although one might reasonably assume that force of infection for this highly communicable disease scales with population size, in fact, host social behaviour modulates transmission such that disease is frequency-dependent within populations, and some groups remain protected during epidemic events.

  6. Effects of helminths and Mycobacterium tuberculosis infection on HIV-1: a cellular immunological perspective.

    PubMed

    Mouser, Emily E I M; Pollakis, Georgios; Paxton, William A

    2012-05-01

    In many regions of the world, a high prevalence of HIV-1, helminthic and Mycobacterium tuberculosis (Mtb) infections can be found. Here, we summarize the types of immune responses induced and/or modulated by these pathogens and the consequences for HIV-1 disease. Helminths predominantly induce strong T helper (Th) 2 cellular responses which are downregulated in chronic disease. The anatomical niche populated by helminths plays a key factor in the effect these parasites have on HIV-1 transmission and subsequent replication. Gut-associated helminths have been found to increase HIV-1 transmission via the lesions they provide. In spite of this, the many immune modulatory molecules secreted by the parasites may inhibit or slow HIV-1 infection. In contrast, Mtb is mainly restricted to the lung and the Mtb-specific Th cells induced are highly susceptible to HIV-1 infection and replication. Antigens from both pathogens have immunomodulatory activity that can skew cellular immune responses in specific directions. The effect of helminths and Mtb on modulating immune responses is varied and complex with both their location and phenotype potentially influencing HIV-1 disease. These pathogens have evolved a complex array of molecules which have the capacity to modulate immunity and preserve pathogen survival.

  7. An epidemiologic simulation model of the spread and control of highly pathogenic avian influenza (H5N1) among commercial and backyard poultry flocks in South Carolina, United States.

    PubMed

    Patyk, Kelly A; Helm, Julie; Martin, Michael K; Forde-Folle, Kimberly N; Olea-Popelka, Francisco J; Hokanson, John E; Fingerlin, Tasha; Reeves, Aaron

    2013-07-01

    Epidemiologic simulation modeling of highly pathogenic avian influenza (HPAI) outbreaks provides a useful conceptual framework with which to estimate the consequences of HPAI outbreaks and to evaluate disease control strategies. The purposes of this study were to establish detailed and informed input parameters for an epidemiologic simulation model of the H5N1 strain of HPAI among commercial and backyard poultry in the state of South Carolina in the United States using a highly realistic representation of this poultry population; to estimate the consequences of an outbreak of HPAI in this population with a model constructed from these parameters; and to briefly evaluate the sensitivity of model outcomes to several parameters. Parameters describing disease state durations; disease transmission via direct contact, indirect contact, and local-area spread; and disease detection, surveillance, and control were established through consultation with subject matter experts, a review of the current literature, and the use of several computational tools. The stochastic model constructed from these parameters produced simulated outbreaks ranging from 2 to 111 days in duration (median 25 days), during which 1 to 514 flocks were infected (median 28 flocks). Model results were particularly sensitive to the rate of indirect contact that occurs among flocks. The baseline model established in this study can be used in the future to evaluate various control strategies, as a tool for emergency preparedness and response planning, and to assess the costs associated with disease control and the economic consequences of a disease outbreak. Published by Elsevier B.V.

  8. Advanced biosensors for detection of pathogens related to livestock and poultry.

    PubMed

    Vidic, Jasmina; Manzano, Marisa; Chang, Chung-Ming; Jaffrezic-Renault, Nicole

    2017-02-21

    Infectious animal diseases caused by pathogenic microorganisms such as bacteria and viruses threaten the health and well-being of wildlife, livestock, and human populations, limit productivity and increase significantly economic losses to each sector. The pathogen detection is an important step for the diagnostics, successful treatment of animal infection diseases and control management in farms and field conditions. Current techniques employed to diagnose pathogens in livestock and poultry include classical plate-based methods and conventional biochemical methods as enzyme-linked immunosorbent assays (ELISA). These methods are time-consuming and frequently incapable to distinguish between low and highly pathogenic strains. Molecular techniques such as polymerase chain reaction (PCR) and real time PCR (RT-PCR) have also been proposed to be used to diagnose and identify relevant infectious disease in animals. However these DNA-based methodologies need isolated genetic materials and sophisticated instruments, being not suitable for in field analysis. Consequently, there is strong interest for developing new swift point-of-care biosensing systems for early detection of animal diseases with high sensitivity and specificity. In this review, we provide an overview of the innovative biosensing systems that can be applied for livestock pathogen detection. Different sensing strategies based on DNA receptors, glycan, aptamers and antibodies are presented. Besides devices still at development level some are validated according to standards of the World Organization for Animal Health and are commercially available. Especially, paper-based platforms proposed as an affordable, rapid and easy to perform sensing systems for implementation in field condition are included in this review.

  9. Bovine mastitis disease/pathogenicity: evidence of the potential role of microbial biofilms.

    PubMed

    Gomes, Fernanda; Saavedra, Maria José; Henriques, Mariana

    2016-04-01

    Bovine mastitis (BM) is a disease with high incidence worldwide and one of the most relevant bovine pathologies and the most costly to the dairy industry. BM is an inflammation of the udder and represents one of the most difficult veterinary diseases to control. Biofilm formation is considered a selective advantage for pathogens causing mastitis, facilitating bacterial persistence in the udder. In fact, recently some authors drew attention to the biofilm formation ability presented by several mastitis causing pathogens and to its possible relation with recurrent mastitis infections and with the increased resistance to antimicrobial agents and host immune defence system. Actually, up to now, several researchers reported the potential role of cells in this mode of growth in the previous facts mentioned. As a consequence of the presence of biofilms, the infection here focused is more difficult to treat and eradicate, making this problem a more relevant pressing issue. Thus, we believe that a deeper knowledge of these structures in mastitis can help to determine the best control strategy to be used in veterinary practice in order to reduce losses in the dairy industry and to ensure milk safety and quality. The aim of this paper was to review the existing research and consequently to provide an overview of the role of biofilms in BM infections. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Environmental Persistence Influences Infection Dynamics for a Butterfly Pathogen

    PubMed Central

    Altizer, Sonia; Williams, Mary-Kate; Hall, Richard J.

    2017-01-01

    Many pathogens, including those infecting insects, are transmitted via dormant stages shed into the environment, where they must persist until encountering a susceptible host. Understanding how abiotic conditions influence environmental persistence and how these factors influence pathogen spread are crucial for predicting patterns of infection risk. Here, we explored the consequences of environmental transmission for infection dynamics of a debilitating protozoan parasite (Ophryocystis elektroscirrha) that infects monarch butterflies (Danaus plexippus). We first conducted an experiment to observe the persistence of protozoan spores exposed to natural conditions. Experimental results showed that, contrary to our expectations, pathogen doses maintained high infectivity even after 16 days in the environment, although pathogens did yield infections with lower parasite loads after environmental exposure. Because pathogen longevity exceeded the time span of our experiment, we developed a mechanistic model to better explore environmental persistence for this host-pathogen system. Model analysis showed that, in general, longer spore persistence led to higher infection prevalence and slightly smaller monarch population sizes. The model indicated that typical parasite doses shed onto milkweed plants must remain viable for a minimum of 3 weeks for prevalence to increase during the summer-breeding season, and for 11 weeks or longer to match levels of infection commonly reported from the wild, assuming moderate values for parasite shedding rate. Our findings showed that transmission stages of this butterfly pathogen are long-lived and indicated that this is a necessary condition for the protozoan to persist in local monarch populations. This study provides a modeling framework for future work examining the dynamics of an ecologically important pathogen in an iconic insect. PMID:28099501

  11. OVERVIEW OF RISK ASSESSMENT FOR TOXIC AND PATHOGENIC AGENTS

    EPA Science Inventory

    Risk assessment is a process that defines the adverse health consequences of exposure to toxic or pathogenic agents. hen used in regulatory decision making, risk assessment is an important component of risk management, which "combines the risk assessment with the directives of re...

  12. Phenotypic and functional consequences of different isolation protocols on skin mononuclear phagocytes.

    PubMed

    Botting, Rachel A; Bertram, Kirstie M; Baharlou, Heeva; Sandgren, Kerrie J; Fletcher, James; Rhodes, Jake W; Rana, Hafsa; Plasto, Toby M; Wang, Xin Maggie; Lim, Jake J K; Barnouti, Laith; Kohout, Mark P; Papadopoulos, Tim; Merten, Steve; Olbourne, Norman; Cunningham, Anthony L; Haniffa, Muzlifah; Harman, Andrew N

    2017-06-01

    Mononuclear phagocytes are present in skin and mucosa and represent one of the first lines of defense against invading pathogens, which they detect via an array of pathogen-binding receptors expressed on their surface. However, their extraction from tissue is difficult, and the isolation technique used has functional consequences on the cells obtained. Here, we compare mononuclear phagocytes isolated from human skin using either enzymatic digestion or spontaneous migration. Cells isolated via enzymatic digestion are in an immature state, and all subsets are easily defined. However, cells isolated by spontaneous migration are in a mature state, and CD141 cross-presenting DCs (cDC1) are more difficult to define. Different pathogen-binding receptors are susceptible to cleavage by blends of collagenase, demonstrating that great care must be taken in choosing the correct enzyme blend to digest tissue if carrying out pathogen-interaction assays. Finally, we have optimized mononuclear phagocyte culture conditions to enhance their survival after liberation from the tissue. © The Author(s).

  13. Phenotypic and functional consequences of different isolation protocols on skin mononuclear phagocytes

    PubMed Central

    Botting, Rachel A.; Bertram, Kirstie M.; Baharlou, Heeva; Sandgren, Kerrie J.; Fletcher, James; Rhodes, Jake W.; Rana, Hafsa; Plasto, Toby M.; Wang, Xin Maggie; Lim, Jake J. K.; Barnouti, Laith; Kohout, Mark P.; Papadopoulos, Tim; Merten, Steve; Olbourne, Norman; Cunningham, Anthony L.; Haniffa, Muzlifah; Harman, Andrew N.

    2017-01-01

    Mononuclear phagocytes are present in skin and mucosa and represent one of the first lines of defense against invading pathogens, which they detect via an array of pathogen-binding receptors expressed on their surface. However, their extraction from tissue is difficult, and the isolation technique used has functional consequences on the cells obtained. Here, we compare mononuclear phagocytes isolated from human skin using either enzymatic digestion or spontaneous migration. Cells isolated via enzymatic digestion are in an immature state, and all subsets are easily defined. However, cells isolated by spontaneous migration are in a mature state, and CD141 cross-presenting DCs (cDC1) are more difficult to define. Different pathogen-binding receptors are susceptible to cleavage by blends of collagenase, demonstrating that great care must be taken in choosing the correct enzyme blend to digest tissue if carrying out pathogen-interaction assays. Finally, we have optimized mononuclear phagocyte culture conditions to enhance their survival after liberation from the tissue. PMID:28270408

  14. Social barriers to pathogen transmission in wild animal populations

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

    Loehle, C.

    Diseases and pathogens are receiving increasing recognition as sources of mortality in animal populations. Immune system strength is clearly important in fending off pathogen attack. Physical barriers to pathogen entry are also important. Various individual behaviors are efficacious in reducing contact with diseases and pests. This paper focuses on a fourth mode of defense: social barriers to transmission. Various social behaviors have pathogen transmission consequences. Selective pressures on these social behaviors may therefore exist. Effects on pathogen transmission of mating strategies, social avoidance, group size, group isolation, and other behaviors are explored. It is concluded that many of these behaviorsmore » may have been affected by selection pressures to reduce transmission of pathogens. 84 refs., 1 tab.« less

  15. Development of imaging techniques to study the pathogenesis of biosafety level 2/3 infectious agents

    PubMed Central

    Rella, Courtney E.; Ruel, Nancy; Eugenin, Eliseo A.

    2015-01-01

    Despite significant advances in microbiology and molecular biology over the last decades, several infectious diseases remain global concerns, resulting in the death of millions of people worldwide each year. According to the Center for Disease Control (CDC) in 2012, there were 34 million people infected with HIV, 8.7 million new cases of tuberculosis, 500 million cases of hepatitis, and 50–100 million people infected with dengue. Several of these pathogens, despite high incidence, do not have reliable clinical detection methods. New or improved protocols have been generated to enhance detection and quantitation of several pathogens using high-end microscopy (light, confocal, and STORM microscopy) and imaging software. In the current manuscript, we discuss these approaches and the theories behind these methodologies. Thus, advances in imaging techniques will open new possibilities to discover therapeutic interventions to reduce or eliminate the devastating consequences of infectious diseases. PMID:24990818

  16. Microbial diversity and structure are drivers of the biological barrier effect against Listeria monocytogenes in soil.

    PubMed

    Vivant, Anne-Laure; Garmyn, Dominique; Maron, Pierre-Alain; Nowak, Virginie; Piveteau, Pascal

    2013-01-01

    Understanding the ecology of pathogenic organisms is important in order to monitor their transmission in the environment and the related health hazards. We investigated the relationship between soil microbial diversity and the barrier effect against Listeria monocytogenes invasion. By using a dilution-to-extinction approach, we analysed the consequence of eroding microbial diversity on L. monocytogenes population dynamics under standardised conditions of abiotic parameters and microbial abundance in soil microcosms. We demonstrated that highly diverse soil microbial communities act as a biological barrier against L. monocytogenes invasion and that phylogenetic composition of the community also has to be considered. This suggests that erosion of diversity may have damaging effects regarding circulation of pathogenic microorganisms in the environment.

  17. Modeling of Virion Collisions in Cervicovaginal Mucus Reveals Limits on Agglutination as the Protective Mechanism of Secretory Immunoglobulin A

    PubMed Central

    Chen, Alex; McKinley, Scott A.; Shi, Feng; Wang, Simi; Mucha, Peter J.; Harit, Dimple; Forest, M. Gregory; Lai, Samuel K.

    2015-01-01

    Secretory immunoglobulin A (sIgA), a dimeric antibody found in high quantities in the gastrointestinal mucosa, is broadly associated with mucosal immune protection. A distinguishing feature of sIgA is its ability to crosslink pathogens, thereby creating pathogen/sIgA aggregates that are too large to traverse the dense matrix of mucin fibers in mucus layers overlying epithelial cells and consequently reducing infectivity. Here, we use modeling to investigate this mechanism of “immune exclusion” based on sIgA-mediated agglutination, in particular the potential use of sIgA to agglutinate HIV in cervicovaginal mucus (CVM) and prevent HIV transmission. Utilizing reported data on HIV diffusion in CVM and semen, we simulate HIV collision kinetics in physiologically-thick mucus layers–a necessary first step for sIgA-induced aggregation. We find that even at the median HIV load in semen of acutely infected individuals possessing high viral titers, over 99% of HIV virions will penetrate CVM and reach the vaginal epithelium without colliding with another virion. These findings imply that agglutination is unlikely to be the dominant mechanism of sIgA-mediated protection against HIV or other sexually transmitted pathogens. Rather, we surmise that agglutination is most effective against pathogens either present at exceedingly high concentrations or that possess motility mechanisms other than Brownian diffusion that significantly enhance encounter rates. PMID:26132216

  18. Evaluating High-Throughput Ab Initio Gene Finders to Discover Proteins Encoded in Eukaryotic Pathogen Genomes Missed by Laboratory Techniques

    PubMed Central

    Goodswen, Stephen J.; Kennedy, Paul J.; Ellis, John T.

    2012-01-01

    Next generation sequencing technology is advancing genome sequencing at an unprecedented level. By unravelling the code within a pathogen’s genome, every possible protein (prior to post-translational modifications) can theoretically be discovered, irrespective of life cycle stages and environmental stimuli. Now more than ever there is a great need for high-throughput ab initio gene finding. Ab initio gene finders use statistical models to predict genes and their exon-intron structures from the genome sequence alone. This paper evaluates whether existing ab initio gene finders can effectively predict genes to deduce proteins that have presently missed capture by laboratory techniques. An aim here is to identify possible patterns of prediction inaccuracies for gene finders as a whole irrespective of the target pathogen. All currently available ab initio gene finders are considered in the evaluation but only four fulfil high-throughput capability: AUGUSTUS, GeneMark_hmm, GlimmerHMM, and SNAP. These gene finders require training data specific to a target pathogen and consequently the evaluation results are inextricably linked to the availability and quality of the data. The pathogen, Toxoplasma gondii, is used to illustrate the evaluation methods. The results support current opinion that predicted exons by ab initio gene finders are inaccurate in the absence of experimental evidence. However, the results reveal some patterns of inaccuracy that are common to all gene finders and these inaccuracies may provide a focus area for future gene finder developers. PMID:23226328

  19. Avian flu school: a training approach to prepare for H5N1 highly pathogenic avian influenza.

    PubMed

    Beltran-Alcrudo, Daniel; Bunn, David A; Sandrock, Christian E; Cardona, Carol J

    2008-01-01

    Since the reemergence of highly pathogenic avian influenza (H5N1 HPAI) in 2003, a panzootic that is historically unprecedented in the number of infected flocks, geographic spread, and economic consequences for agriculture has developed. The epidemic has affected a wide range of birds and mammals, including humans. The ineffective management of outbreaks, mainly due to a lack of knowledge among those involved in detection, prevention, and response, points to the need for training on H5N1 HPAI. The main challenges are the multidisciplinary approach required, the lack of experts, the need to train at all levels, and the diversity of outbreak scenarios. Avian Flu School addresses these challenges through a three-level train-the-trainer program intended to minimize the health and economic impacts of H5N1 HPAI by improving a community's ability to prevent and respond, while protecting themselves and others. The course teaches need-to-know facts using highly flexible, interactive, and relevant materials.

  20. Recent Advances in Understanding Enteric Pathogenic Escherichia coli

    PubMed Central

    Croxen, Matthew A.; Law, Robyn J.; Scholz, Roland; Keeney, Kristie M.; Wlodarska, Marta

    2013-01-01

    SUMMARY Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli. PMID:24092857

  1. Prevalence of tick-borne pathogens in questing Ixodes ricinus ticks in urban and suburban areas of Switzerland.

    PubMed

    Oechslin, Corinne P; Heutschi, Daniel; Lenz, Nicole; Tischhauser, Werner; Péter, Olivier; Rais, Olivier; Beuret, Christian M; Leib, Stephen L; Bankoul, Sergei; Ackermann-Gäumann, Rahel

    2017-11-09

    Throughout Europe, Ixodes ricinus transmits numerous pathogens. Its widespread distribution is not limited to rural but also includes urbanized areas. To date, comprehensive data on pathogen carrier rates of I. ricinus ticks in urban areas of Switzerland is lacking. Ixodes ricinus ticks sampled at 18 (sub-) urban collection sites throughout Switzerland showed carrier rates of 0% for tick-borne encephalitis virus, 18.0% for Borrelia burgdorferi (sensu lato), 2.5% for Borrelia miyamotoi, 13.5% for Rickettsia spp., 1.4% for Anaplasma phagocytophilum, 6.2% for "Candidatus Neoehrlichia mikurensis", and 0.8% for Babesia venatorum (Babesia sp., EU1). Site-specific prevalence at collection sites with n > 45 ticks (n = 9) significantly differed for B. burgdorferi (s.l.), Rickettsia spp., and "Ca. N. mikurensis", but were not related to the habitat type. Three hundred fifty eight out of 1078 I. ricinus ticks (33.2%) tested positive for at least one pathogen. Thereof, about 20% (71/358) were carrying two or three different potentially disease-causing agents. Using next generation sequencing, we could detect true pathogens, tick symbionts and organisms of environmental or human origin in ten selected samples. Our data document the presence of pathogens in the (sub-) urban I. ricinus tick population in Switzerland, with carrier rates as high as those in rural regions. Carriage of multiple pathogens was repeatedly observed, demonstrating the risk of acquiring multiple infections as a consequence of a tick bite.

  2. Global Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions

    DTIC Science & Technology

    2016-12-01

    Award Number: W81XWH-11-2-0175 TITLE: Global Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions PRINCIPAL...Positioning Systems (GPS) Technology to Study Vector-Pathogen-Host Interactions 5b. GRANT NUMBER W81XWH-11-2-0175 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...objective of this project is to examine the evolutionary consequences of introducing a tetravalent live- attenuated dengue virus vaccine into children in

  3. Biosensors for plant pathogen detection.

    PubMed

    Khater, Mohga; de la Escosura-Muñiz, Alfredo; Merkoçi, Arben

    2017-07-15

    Infectious plant diseases are caused by pathogenic microorganisms such as fungi, bacteria, viruses, viroids, phytoplasma and nematodes. Worldwide, plant pathogen infections are among main factors limiting crop productivity and increasing economic losses. Plant pathogen detection is important as first step to manage a plant disease in greenhouses, field conditions and at the country boarders. Current immunological techniques used to detect pathogens in plant include enzyme-linked immunosorbent assays (ELISA) and direct tissue blot immunoassays (DTBIA). DNA-based techniques such as polymerase chain reaction (PCR), real time PCR (RT-PCR) and dot blot hybridization have also been proposed for pathogen identification and detection. However these methodologies are time-consuming and require complex instruments, being not suitable for in-situ analysis. Consequently, there is strong interest for developing new biosensing systems for early detection of plant diseases with high sensitivity and specificity at the point-of-care. In this context, we revise here the recent advancement in the development of advantageous biosensing systems for plant pathogen detection based on both antibody and DNA receptors. The use of different nanomaterials such as nanochannels and metallic nanoparticles for the development of innovative and sensitive biosensing systems for the detection of pathogens (i.e. bacteria and viruses) at the point-of-care is also shown. Plastic and paper-based platforms have been used for this purpose, offering cheap and easy-to-use really integrated sensing systems for rapid on-site detection. Beside devices developed at research and development level a brief revision of commercially available kits is also included in this review. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. 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.

  5. The role of diet on gut microbiota composition.

    PubMed

    Bibbò, S; Ianiro, G; Giorgio, V; Scaldaferri, F; Masucci, L; Gasbarrini, A; Cammarota, G

    2016-11-01

    Gut microbiota is characterized by an inter-individual variability due to genetic and environmental factors. Among the environmental ones, dietary habits play a key role in the modulation of gut microbiota composition. There are main differences between the intestinal microbiota of subjects fed with prevalent Western diet and that of subjects with a diet rich in fibers. Specific changes in the composition of gut microbiota have been demonstrated among subjects according to a different dietary intake. A particular diet may promote the growth of specific bacterial strains, driving hosts to a consequent alteration of fermentative metabolism, with a direct effect on intestinal pH, which can be responsible for the development of a pathogenic flora. Moreover, a high-fat diet can promote the development of a pro-inflammatory gut microbiota, with a consequent increase of intestinal permeability and, consequently, of circulating levels of lipopolysaccharides. In this review, we discuss the direct role of the diet in the composition of gut microbiota and about the possible clinical consequences.

  6. Pathogenic Germline Variants in 10,389 Adult Cancers.

    PubMed

    Huang, Kuan-Lin; Mashl, R Jay; Wu, Yige; Ritter, Deborah I; Wang, Jiayin; Oh, Clara; Paczkowska, Marta; Reynolds, Sheila; Wyczalkowski, Matthew A; Oak, Ninad; Scott, Adam D; Krassowski, Michal; Cherniack, Andrew D; Houlahan, Kathleen E; Jayasinghe, Reyka; Wang, Liang-Bo; Zhou, Daniel Cui; Liu, Di; Cao, Song; Kim, Young Won; Koire, Amanda; McMichael, Joshua F; Hucthagowder, Vishwanathan; Kim, Tae-Beom; Hahn, Abigail; Wang, Chen; McLellan, Michael D; Al-Mulla, Fahd; Johnson, Kimberly J; Lichtarge, Olivier; Boutros, Paul C; Raphael, Benjamin; Lazar, Alexander J; Zhang, Wei; Wendl, Michael C; Govindan, Ramaswamy; Jain, Sanjay; Wheeler, David; Kulkarni, Shashikant; Dipersio, John F; Reimand, Jüri; Meric-Bernstam, Funda; Chen, Ken; Shmulevich, Ilya; Plon, Sharon E; Chen, Feng; Ding, Li

    2018-04-05

    We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Harbouring public good mutants within a pathogen population can increase both fitness and virulence.

    PubMed

    Lindsay, Richard J; Kershaw, Michael J; Pawlowska, Bogna J; Talbot, Nicholas J; Gudelj, Ivana

    2016-12-28

    Existing theory, empirical, clinical and field research all predict that reducing the virulence of individuals within a pathogen population will reduce the overall virulence, rendering disease less severe. Here, we show that this seemingly successful disease management strategy can fail with devastating consequences for infected hosts. We deploy cooperation theory and a novel synthetic system involving the rice blast fungus Magnaporthe oryzae . In vivo infections of rice demonstrate that M. oryzae virulence is enhanced, quite paradoxically, when a public good mutant is present in a population of high-virulence pathogens. We reason that during infection, the fungus engages in multiple cooperative acts to exploit host resources. We establish a multi-trait cooperation model which suggests that the observed failure of the virulence reduction strategy is caused by the interference between different social traits. Multi-trait cooperative interactions are widespread, so we caution against the indiscriminant application of anti-virulence therapy as a disease-management strategy.

  8. Animal Models of Ebolavirus Infection

    PubMed Central

    Claire, Marisa C St; Ragland, Dan R; Bollinger, Laura; Jahrling, Peter B

    2017-01-01

    Ebola virus is a highly pathogenic member of the family Filoviridae that causes a severe hemorrhagic disease in humans and NHP. The 2013–2016 West African outbreak has increased interest in the development and refinement of animal models of Ebola virus disease. These models are used to test countermeasures and vaccines, gain scientific insights into the mechanisms of disease progression and transmission, and study key correlates of immunology. Ebola virus is classified as a BSL4 pathogen and Category A agent, for which the United States government requires preparedness in case of bioterrorism. Rodents, such as Syrian golden hamsters (Mesocricetus auratus), mice (Mus musculus), and guinea pigs (Cavia porcellus), are the most common research species. However, NHP, especially macaques, are favored for Ebola virus disease research due to similarities with humans regarding the pathogenesis, clinical presentation, laboratory findings, and causes of fatality. To satisfy the regulatory requirements for approval of countermeasures against high-consequence pathogens, the FDA instituted the Animal Rule, which permits efficacy studies in animal models in place of human clinical data when such studies are not feasible or ethical. This review provides a comprehensive summary of various animal models and their use in Ebola virus disease research. PMID:28662754

  9. Efficacy of accelerated hydrogen peroxide® disinfectant on foot-and-mouth disease virus, swine vesicular disease virus and Senecavirus A.

    PubMed

    Hole, K; Ahmadpour, F; Krishnan, J; Stansfield, C; Copps, J; Nfon, C

    2017-03-01

    In a laboratory, disinfectants used to inactivate pathogens on contaminated surfaces and to prevent spread of diseases often have adverse side effects on personnel and the environment. It is, therefore, essential to find safer, fast-acting and yet effective disinfectants. The objective of this study was to evaluate an accelerated hydrogen peroxide ® (AHP ® )-based disinfectant against high consequence foreign animal disease pathogens such as foot-and-mouth disease virus (FMDV) and swine vesicular disease virus (SVDV), as well as Senecavirus A (SVA), which causes similar lesions as FMDV and SVDV. We tested varying dilutions and contact times of AHP against FMDV, SVDV and SVA by the standard US EPA and modified methods. AHP was effective against all three viruses, albeit at a higher concentration and double the manufacturer recommended contact time when testing wet films of SVDV. AHP is an effective disinfectant against FMDV, SVDV and SVA. AHP-based disinfectant can, therefore, be used in high containment laboratories working with FMDV, SVDV and related pathogens. © 2016 The Canadian Food Inspection Agency. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of The Society for Applied Microbiology.

  10. Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 2. General Practices.

    PubMed

    Mazur, Steven; Holbrook, Michael R; Burdette, Tracey; Joselyn, Nicole; Barr, Jason; Pusl, Daniela; Bollinger, Laura; Coe, Linda; Jahrling, Peter B; Lackemeyer, Matthew G; Wada, Jiro; Kuhn, Jens H; Janosko, Krisztina

    2016-10-03

    Work in a biosafety level 4 (BSL-4) containment laboratory requires time and great attention to detail. The same work that is done in a BSL-2 laboratory with non-high-consequence pathogens will take significantly longer in a BSL-4 setting. This increased time requirement is due to a multitude of factors that are aimed at protecting the researcher from laboratory-acquired infections, the work environment from potential contamination and the local community from possible release of high-consequence pathogens. Inside the laboratory, movement is restricted due to air hoses attached to the mandatory full-body safety suits. In addition, disinfection of every item that is removed from Class II biosafety cabinets (BSCs) is required. Laboratory specialists must be trained in the practices of the BSL-4 laboratory and must show high proficiency in the skills they are performing. The focus of this article is to outline proper procedures and techniques to ensure laboratory biosafety and experimental accuracy using a standard viral plaque assay as an example procedure. In particular, proper techniques to work safely in a BSL-4 environment when performing an experiment will be visually emphasized. These techniques include: setting up a Class II BSC for experiments, proper cleaning of the Class II BSC when finished working, waste management and safe disposal of waste generated inside a BSL-4 laboratory, and the removal of inactivated samples from inside a BSL-4 laboratory to the BSL-2 laboratory.

  11. In vivo imaging of the pathophysiological changes and neutrophil dynamics in influenza virus-infected mouse lungs.

    PubMed

    Ueki, Hiroshi; Wang, I-Hsuan; Fukuyama, Satoshi; Katsura, Hiroaki; da Silva Lopes, Tiago Jose; Neumann, Gabriele; Kawaoka, Yoshihiro

    2018-06-25

    The pathophysiological changes that occur in lungs infected with influenza viruses are poorly understood. Here we established an in vivo imaging system that combines two-photon excitation microscopy and fluorescent influenza viruses of different pathogenicity. This approach allowed us to monitor and correlate several parameters and physiological changes including the spread of infection, pulmonary permeability, pulmonary perfusion speed, number of recruited neutrophils in infected lungs, and neutrophil motion in the lungs of live mice. Several physiological changes were larger and occurred earlier in mice infected with a highly pathogenic H5N1 influenza virus compared with those infected with a mouse-adapted human strain. These findings demonstrate the potential of our in vivo imaging system to provide novel information about the pathophysiological consequences of virus infections.

  12. Microbial Diversity and Structure Are Drivers of the Biological Barrier Effect against Listeria monocytogenes in Soil

    PubMed Central

    Vivant, Anne-Laure; Garmyn, Dominique; Maron, Pierre-Alain; Nowak, Virginie; Piveteau, Pascal

    2013-01-01

    Understanding the ecology of pathogenic organisms is important in order to monitor their transmission in the environment and the related health hazards. We investigated the relationship between soil microbial diversity and the barrier effect against Listeria monocytogenes invasion. By using a dilution-to-extinction approach, we analysed the consequence of eroding microbial diversity on L. monocytogenes population dynamics under standardised conditions of abiotic parameters and microbial abundance in soil microcosms. We demonstrated that highly diverse soil microbial communities act as a biological barrier against L. monocytogenes invasion and that phylogenetic composition of the community also has to be considered. This suggests that erosion of diversity may have damaging effects regarding circulation of pathogenic microorganisms in the environment. PMID:24116193

  13. Plant-Pathogen Effectors: Cellular Probes Interfering with Plant Defenses in Spatial and Temporal Manners

    PubMed Central

    Toruño, Tania Y.; Stergiopoulos, Ioannis; Coaker, Gitta

    2017-01-01

    Plants possess large arsenals of immune receptors capable of recognizing all pathogen classes. To cause disease, pathogenic organisms must be able to overcome physical barriers, suppress or evade immune perception, and derive nutrients from host tissues. Consequently, to facilitate some of these processes, pathogens secrete effector proteins that promote colonization. This review covers recent advances in the field of effector biology, focusing on conserved cellular processes targeted by effectors from diverse pathogens. The ability of effectors to facilitate pathogen entry into the host interior, suppress plant immune perception, and alter host physiology for pathogen benefit is discussed. Pathogens also deploy effectors in a spatial and temporal manner, depending on infection stage. Recent advances have also enhanced our understanding of effectors acting in specific plant organs and tissues. Effectors are excellent cellular probes that facilitate insight into biological processes as well as key points of vulnerability in plant immune signaling networks. PMID:27359369

  14. Disease intelligence for highly pathogenic avian influenza.

    PubMed

    Domenech, J; Slingenbergh, J; Martin, V; McLeod, A; Lubroth, J; Sims, L D

    2007-01-01

    A comprehensive approach to highly pathogenic avian influenza (HPAI) is crucial for identifying all the factors that contribute to its emergence, spread and persistence. Epidemiological understanding makes it possible to predict the evolution of the virus and to prevent and control the socioeconomic, environmental, institutional and policy consequences. At FAO, risk assessment and intelligence with regard to HPAI are based on lessons learnt from assisting countries to design strategies and on implementation of technical assistance programmes, which reveal important elements, such as the roles of ducks, live-bird markets and trade. Wild birds were found to contribute, by transporting the H5N1 virus over long distances. The contributions of different poultry farming systems and market chains in the epidemiology of HPAI are well recognized; however, the respective roles of smallholder systems and commercial farms are unclear. FAO considers that smallholders will continue to be an important factor and should be taken into account in control and prevention programmes. Changes in poultry farming are essentially driven by the private sector and market forces and could have negative consequences on the livelihoods of smallholders and on ecologically balanced production systems and agricultural biodiversity. Biosecurity can, however, be improved at the level of farms and markets. Institutional factors, such as the capacity of animal health systems to deliver control programmes, are also important, requiring strengthening and innovation in risk analysis and management.

  15. Linking social and spatial networks to viral community phylogenetics reveals subtype-specific transmission dynamics in African lions.

    PubMed

    Fountain-Jones, Nicholas M; Packer, Craig; Troyer, Jennifer L; VanderWaal, Kimberly; Robinson, Stacie; Jacquot, Maude; Craft, Meggan E

    2017-10-01

    Heterogeneity within pathogen species can have important consequences for how pathogens transmit across landscapes; however, discerning different transmission routes is challenging. Here, we apply both phylodynamic and phylogenetic community ecology techniques to examine the consequences of pathogen heterogeneity on transmission by assessing subtype-specific transmission pathways in a social carnivore. We use comprehensive social and spatial network data to examine transmission pathways for three subtypes of feline immunodeficiency virus (FIV Ple ) in African lions (Panthera leo) at multiple scales in the Serengeti National Park, Tanzania. We used FIV Ple molecular data to examine the role of social organization and lion density in shaping transmission pathways and tested to what extent vertical (i.e., father- and/or mother-offspring relationships) or horizontal (between unrelated individuals) transmission underpinned these patterns for each subtype. Using the same data, we constructed subtype-specific FIV Ple co-occurrence networks and assessed what combination of social networks, spatial networks or co-infection best structured the FIV Ple network. While social organization (i.e., pride) was an important component of FIV Ple transmission pathways at all scales, we find that FIV Ple subtypes exhibited different transmission pathways at within- and between-pride scales. A combination of social and spatial networks, coupled with consideration of subtype co-infection, was likely to be important for FIV Ple transmission for the two major subtypes, but the relative contribution of each factor was strongly subtype-specific. Our study provides evidence that pathogen heterogeneity is important in understanding pathogen transmission, which could have consequences for how endemic pathogens are managed. Furthermore, we demonstrate that community phylogenetic ecology coupled with phylodynamic techniques can reveal insights into the differential evolutionary pressures acting on virus subtypes, which can manifest into landscape-level effects. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

  16. Pathogen evolution under host avoidance plasticity.

    PubMed

    McLeod, David V; Day, Troy

    2015-09-07

    Host resistance consists of defences that limit pathogen burden, and can be classified as either adaptations targeting recovery from infection or those focused upon infection avoidance. Conventional theory treats avoidance as a fixed strategy which does not vary from one interaction to the next. However, there is increasing empirical evidence that many avoidance strategies are triggered by external stimuli, and thus should be treated as phenotypically plastic responses. Here, we consider the implications of avoidance plasticity for host-pathogen coevolution. We uncover a number of predictions challenging current theory. First, in the absence of pathogen trade-offs, plasticity can restrain pathogen evolution; moreover, the pathogen exploits conditions in which the host would otherwise invest less in resistance, causing resistance escalation. Second, when transmission trades off with pathogen-induced mortality, plasticity encourages avirulence, resulting in a superior fitness outcome for both host and pathogen. Third, plasticity ensures the sterilizing effect of pathogens has consequences for pathogen evolution. When pathogens castrate hosts, selection forces them to minimize mortality virulence; moreover, when transmission trades off with sterility alone, resistance plasticity is sufficient to prevent pathogens from evolving to fully castrate. © 2015 The Author(s).

  17. Modeling the effect of seasonal variation in ambient temperature on the transmission dynamics of a pathogen with a free-living stage: example of Escherichia coli O157:H7 in a dairy herd.

    PubMed

    Gautam, Raju; Bani-Yaghoub, Majid; Neill, William H; Döpfer, Dörte; Kaspar, Charles; Ivanek, Renata

    2011-10-01

    To explore the potential role of ambient temperature on infection transmission dynamics for pathogens, we used Escherichia coli O157:H7 in a dairy herd and the surrounding farm environment as a model system. For this system, we developed a mathematical model in which a Susceptible-Infectious-Susceptible (SIS) model of infection spread through the host population is coupled with a metapopulation model of E. coli O157:H7 free-living stage in the environment allowing bacterial growth to be influenced by ambient temperature. Model results indicate that seasonal variation in ambient temperature could have a considerable impact on pathogen populations in the environment, specifically on barn surfaces and in water troughs, and consequently on the prevalence of infection in the host population. Based on model assumptions, contaminated drinking water was the most important pathway of E. coli O157:H7 transmission to cattle. Sensitivity analysis indicated that water-borne transmission is amplified during the warmer months if the amount of standing drinking water available to the cattle herd is high. This is because warmer ambient temperature favors faster pathogen replication which when combined with slower water replacement-rate due to high amount of available standing water leads to a greater pathogen load in drinking water. These results offer a possible explanation of the seasonal variation in E. coli O157:H7 prevalence in cattle and suggest that improved drinking-water management could be used for control of this infection in cattle. Our study demonstrates how consideration of ambient temperature in transmission cycles of pathogens able to survive and grow in the environment outside the host could offer novel perspectives on the spread and control of infections caused by such pathogens. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. High-Throughput Intracellular Antimicrobial Susceptibility Testing of Legionella pneumophila.

    PubMed

    Chiaraviglio, Lucius; Kirby, James E

    2015-12-01

    Legionella pneumophila is a Gram-negative opportunistic human pathogen that causes a severe pneumonia known as Legionnaires' disease. Notably, in the human host, the organism is believed to replicate solely within an intracellular compartment, predominantly within pulmonary macrophages. Consequently, successful therapy is predicated on antimicrobials penetrating into this intracellular growth niche. However, standard antimicrobial susceptibility testing methods test solely for extracellular growth inhibition. Here, we make use of a high-throughput assay to characterize intracellular growth inhibition activity of known antimicrobials. For select antimicrobials, high-resolution dose-response analysis was then performed to characterize and compare activity levels in both macrophage infection and axenic growth assays. Results support the superiority of several classes of nonpolar antimicrobials in abrogating intracellular growth. Importantly, our assay results show excellent correlations with prior clinical observations of antimicrobial efficacy. Furthermore, we also show the applicability of high-throughput automation to two- and three-dimensional synergy testing. High-resolution isocontour isobolograms provide in vitro support for specific combination antimicrobial therapy. Taken together, findings suggest that high-throughput screening technology may be successfully applied to identify and characterize antimicrobials that target bacterial pathogens that make use of an intracellular growth niche. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. High-Throughput Intracellular Antimicrobial Susceptibility Testing of Legionella pneumophila

    PubMed Central

    Chiaraviglio, Lucius

    2015-01-01

    Legionella pneumophila is a Gram-negative opportunistic human pathogen that causes a severe pneumonia known as Legionnaires' disease. Notably, in the human host, the organism is believed to replicate solely within an intracellular compartment, predominantly within pulmonary macrophages. Consequently, successful therapy is predicated on antimicrobials penetrating into this intracellular growth niche. However, standard antimicrobial susceptibility testing methods test solely for extracellular growth inhibition. Here, we make use of a high-throughput assay to characterize intracellular growth inhibition activity of known antimicrobials. For select antimicrobials, high-resolution dose-response analysis was then performed to characterize and compare activity levels in both macrophage infection and axenic growth assays. Results support the superiority of several classes of nonpolar antimicrobials in abrogating intracellular growth. Importantly, our assay results show excellent correlations with prior clinical observations of antimicrobial efficacy. Furthermore, we also show the applicability of high-throughput automation to two- and three-dimensional synergy testing. High-resolution isocontour isobolograms provide in vitro support for specific combination antimicrobial therapy. Taken together, findings suggest that high-throughput screening technology may be successfully applied to identify and characterize antimicrobials that target bacterial pathogens that make use of an intracellular growth niche. PMID:26392509

  20. Eastern equine encephalitis virus: high seroprevalence in horses from Southern Quebec, Canada, 2012.

    PubMed

    Rocheleau, Jean-Philippe; Arsenault, Julie; Lindsay, L Robbin; DiBernardo, Antonia; Kulkarni, Manisha A; Côté, Nathalie; Michel, Pascal

    2013-10-01

    Eastern equine encephalitis virus (EEEV) is a highly pathogenic arbovirus that infects humans, horses, and other animals. There has been a significant increase in EEEV activity in southeastern Canada since 2008. Few data are available regarding nonlethal EEEV infections in mammals, and consequently the distribution and pathogenicity spectrum of EEEV infections in these hosts is poorly understood. This cross-sectional study focuses on the evaluation of viral activity in southern Quebec's horses by seroprevalence estimation. A total of 196 horses, 18 months and older, which had never been vaccinated against EEEV and have never traveled outside Canada, were sampled from 92 barns distributed throughout three administrative regions of southern Quebec. Blood samples were taken from each horse and titrated for EEEV antibodies by plaque reduction neutralization test (PRNT). Equine population vaccination coverage was estimated by surveying horse owners and equine practitioners. PRNT results revealed an EEEV seroprevalence up to 8.7%, with 95% confidence limits ranging from 4.4% to 13.0%. Vaccination coverage was estimated to be at least 79%. Our study reveals for the first time in Canada a measure of EEEV seroprevalence in horses. High seroprevalence in unvaccinated animals challenges the perception that EEEV is a highly lethal pathogen in horses. Monitoring high-risk vector-borne infections such as EEEV in animal populations can be an important element of a public health surveillance strategy, population risk assessment and early detection of epidemics.

  1. Effect of climate change on runoff of Campylobacter and Cryptosporidium from land to surface water.

    PubMed

    Sterk, Ankie; Schijven, Jack; de Roda Husman, Ana Maria; de Nijs, Ton

    2016-05-15

    Faeces originating from wildlife, domestic animals or manure-fertilized fields, is considered an important source of zoonotic pathogens to which people may be exposed by, for instance, bathing or drinking-water consumption. An increase in runoff, and associated wash-off of animal faeces from fields, is assumed to contribute to the increase of disease outbreaks during periods of high precipitation. Climate change is expected to increase winter precipitation and extreme precipitation events during summer, but has simultaneously also other effects such as temperature rise and changes in evapotranspiration. The question is to what extent the combination of these effects influence the input of zoonotic pathogens to the surface waters. To quantitatively analyse the impacts of climate change on pathogen runoff, pathogen concentrations reaching surface waters through runoff were calculated by combining an input model for catchment pathogen loads with the Wageningen Lowland Runoff Simulator (WALRUS). Runoff of Cryptosporidium and Campylobacter was evaluated under different climate change scenarios and by applying different scenarios for sources of faecal pollution in the catchments, namely dairy cows and geese and manure fertilization. Model evaluation of these scenarios shows that climate change has little overall impact on runoff of Campylobacter and Cryptosporidium from land to the surface waters. Even though individual processes like runoff fluxes, pathogen release and dilution are affected, either positively or negatively, the net effect on the pathogen concentration in surface waters and consequently also on infection risks through recreation seems limited. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Within-host evolution decreases virulence in an opportunistic bacterial pathogen.

    PubMed

    Mikonranta, Lauri; Mappes, Johanna; Laakso, Jouni; Ketola, Tarmo

    2015-08-19

    Pathogens evolve in a close antagonistic relationship with their hosts. The conventional theory proposes that evolution of virulence is highly dependent on the efficiency of direct host-to-host transmission. Many opportunistic pathogens, however, are not strictly dependent on the hosts due to their ability to reproduce in the free-living environment. Therefore it is likely that conflicting selection pressures for growth and survival outside versus within the host, rather than transmission potential, shape the evolution of virulence in opportunists. We tested the role of within-host selection in evolution of virulence by letting a pathogen Serratia marcescens db11 sequentially infect Drosophila melanogaster hosts and then compared the virulence to strains that evolved only in the outside-host environment. We found that the pathogen adapted to both Drosophila melanogaster host and novel outside-host environment, leading to rapid evolutionary changes in the bacterial life-history traits including motility, in vitro growth rate, biomass yield, and secretion of extracellular proteases. Most significantly, selection within the host led to decreased virulence without decreased bacterial load while the selection lines in the outside-host environment maintained the same level of virulence with ancestral bacteria. This experimental evidence supports the idea that increased virulence is not an inevitable consequence of within-host adaptation even when the epidemiological restrictions are removed. Evolution of attenuated virulence could occur because of immune evasion within the host. Alternatively, rapid fluctuation between outside-host and within-host environments, which is typical for the life cycle of opportunistic bacterial pathogens, could lead to trade-offs that lower pathogen virulence.

  3. Electrochemical Methodologies for the Detection of Pathogens.

    PubMed

    Amiri, Mandana; Bezaatpour, Abolfazl; Jafari, Hamed; Boukherroub, Rabah; Szunerits, Sabine

    2018-05-25

    Bacterial infections remain one of the principal causes of morbidity and mortality worldwide. The number of deaths due to infections is declining every year by only 1% with a forecast of 13 million deaths in 2050. Among the 1400 recognized human pathogens, the majority of infectious diseases is caused by just a few, about 20 pathogens only. While the development of vaccinations and novel antibacterial drugs and treatments are at the forefront of research, and strongly financially supported by policy makers, another manner to limit and control infectious outbreaks is targeting the development and implementation of early warning systems, which indicate qualitatively and quantitatively the presence of a pathogen. As toxin contaminated food and drink are a potential threat to human health and consequently have a significant socioeconomic impact worldwide, the detection of pathogenic bacteria remains not only a big scientific challenge but also a practical problem of enormous significance. Numerous analytical methods, including conventional culturing and staining techniques as well as molecular methods based on polymerase chain reaction amplification and immunological assays, have emerged over the years and are used to identify and quantify pathogenic agents. While being highly sensitive in most cases, these approaches are highly time, labor, and cost consuming, requiring trained personnel to perform the frequently complex assays. A great challenge in this field is therefore to develop rapid, sensitive, specific, and if possible miniaturized devices to validate the presence of pathogens in cost and time efficient manners. Electrochemical sensors are well accepted powerful tools for the detection of disease-related biomarkers and environmental and organic hazards. They have also found widespread interest in the last years for the detection of waterborne and foodborne pathogens due to their label free character and high sensitivity. This Review is focused on the current electrochemical-based microorganism recognition approaches and putting them into context of other sensing devices for pathogens such as culturing the microorganism on agar plates and the polymer chain reaction (PCR) method, able to identify the DNA of the microorganism. Recent breakthroughs will be highlighted, including the utilization of microfluidic devices and immunomagnetic separation for multiple pathogen analysis in a single device. We will conclude with some perspectives and outlooks to better understand shortcomings. Indeed, there is currently no adequate solution that allows the selective and sensitive binding to a specific microorganism, that is fast in detection and screening, cheap to implement, and able to be conceptualized for a wide range of biologically relevant targets.

  4. Challenges of Designing and Implementing High Consequence Infectious Disease Response.

    PubMed

    King, Joan M; Tiwari, Chetan; Mikler, Armin R; O'Neill, Martin

    2018-03-19

    Ebola is a high consequence infectious disease-a disease with the potential to cause outbreaks, epidemics, or pandemics with deadly possibilities, highly infectious, pathogenic, and virulent. Ebola's first reported cases in the United States in September 2014 led to the development of preparedness capabilities for the mitigation of possible rapid outbreaks, with the Centers for Disease Control and Prevention (CDC) providing guidelines to assist public health officials in infectious disease response planning. These guidelines include broad goals for state and local agencies and detailed information concerning the types of resources needed at health care facilities. However, the spatial configuration of populations and existing health care facilities is neglected. An incomplete understanding of the demand landscape may result in an inefficient and inequitable allocation of resources to populations. Hence, this paper examines challenges in implementing CDC's guidance for Ebola preparedness and mitigation in the context of geospatial allocation of health resources and discusses possible strategies for addressing such challenges. (Disaster Med Public Health Preparedness. 2018;page 1 of 4).

  5. Diseases of Forest Trees: Consequences of Exotic Ecosystems?

    Treesearch

    William J. Otrosina

    1998-01-01

    Much attention is now given to risks and impacts of exotic pest introductions in forest ecosystems. This concern is for good reason because, once introduced, an exotic pathogen or insect encounters little resistance in the native plant population and can produce catastrophic losses in relatively short periods of time. Most native fungal pathogens of forest trees have...

  6. Adult trees cause density-dependent mortality in conspecific seedlings by regulating the frequency of pathogenic soil fungi.

    PubMed

    Liang, Minxia; Liu, Xubing; Gilbert, Gregory S; Zheng, Yi; Luo, Shan; Huang, Fengmin; Yu, Shixiao

    2016-12-01

    Negative density-dependent seedling mortality has been widely detected in tropical, subtropical and temperate forests, with soil pathogens as a major driver. Here we investigated how host density affects the composition of soil pathogen communities and consequently influences the strength of plant-soil feedbacks. In field censuses of six 1-ha permanent plots, we found that survival was much lower for newly germinated seedlings that were surrounded by more conspecific adults. The relative abundance of pathogenic fungi in soil increased with increasing conspecific tree density for five of nine tree species; more soil pathogens accumulated around roots where adult tree density was higher, and this greater pathogen frequency was associated with lower seedling survival. Our findings show how tree density influences populations of soil pathogens, which creates plant-soil feedbacks that contribute to community-level and population-level compensatory trends in seedling survival. © 2016 John Wiley & Sons Ltd/CNRS.

  7. Strain-specific antibodies reduce co-feeding transmission of the Lyme disease pathogen, Borrelia afzelii.

    PubMed

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

    2016-03-01

    Vector-borne pathogens use a diversity of strategies to evade the vertebrate immune system. Co-feeding transmission is a potential immune evasion strategy because the vector-borne pathogen minimizes the time spent in the vertebrate host. We tested whether the Lyme disease pathogen, Borrelia afzelii, can use co-feeding transmission to escape the acquired immune response in the vertebrate host. We induced a strain-specific, protective antibody response by immunizing mice with one of two variants of OspC (A3 and A10), the highly variable outer surface protein C of Borrelia pathogens. Immunized mice were challenged via tick bite with B. afzelii strains A3 or A10 and infested with larval ticks at days 2 and 34 post-infection to measure co-feeding and systemic transmission respectively. Antibodies against a particular OspC variant significantly reduced co-feeding transmission of the targeted (homologous) strain but not the non-targeted (heterologous) strain. Cross-immunity between OspC antigens had no effect in co-feeding ticks but reduced the spirochaete load twofold in ticks infected via systemic transmission. In summary, OspC-specific antibodies reduced co-feeding transmission of a homologous but not a heterologous strain of B. afzelii. Co-feeding transmission allowed B. afzelii to evade the negative consequences of cross-immunity on the tick spirochaete load. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  8. Consequences of organ choice in describing bacterial pathogen assemblages in a rodent population.

    PubMed

    Villette, P; Afonso, E; Couval, G; Levret, A; Galan, M; Tatard, C; Cosson, J F; Giraudoux, P

    2017-10-01

    High-throughput sequencing technologies now allow for rapid cost-effective surveys of multiple pathogens in many host species including rodents, but it is currently unclear if the organ chosen for screening influences the number and identity of bacteria detected. We used 16S rRNA amplicon sequencing to identify bacterial pathogens in the heart, liver, lungs, kidneys and spleen of 13 water voles (Arvicola terrestris) collected in Franche-Comté, France. We asked if bacterial pathogen assemblages within organs are similar and if all five organs are necessary to detect all of the bacteria present in an individual animal. We identified 24 bacteria representing 17 genera; average bacterial richness for each organ ranged from 1·5 ± 0·4 (mean ± standard error) to 2·5 ± 0·4 bacteria/organ and did not differ significantly between organs. The average bacterial richness when organ assemblages were pooled within animals was 4·7 ± 0·6 bacteria/animal; Operational Taxonomic Unit accumulation analysis indicates that all five organs are required to obtain this. Organ type influences bacterial assemblage composition in a systematic way (PERMANOVA, 999 permutations, pseudo-F 4,51 = 1·37, P = 0·001). Our results demonstrate that the number of organs sampled influences the ability to detect bacterial pathogens, which can inform sampling decisions in public health and wildlife ecology.

  9. Thermal physiology, disease, and amphibian declines on the eastern slopes of the Andes.

    PubMed

    Catenazzi, Alessandro; Lehr, Edgar; Vredenburg, Vance T

    2014-04-01

    Rising temperatures, a widespread consequence of climate change, have been implicated in enigmatic amphibian declines from habitats with little apparent human impact. The pathogenic fungus Batrachochytrium dendrobatidis (Bd), now widespread in Neotropical mountains, may act in synergy with climate change causing collapse in thermally stressed hosts. We measured the thermal tolerance of frogs along a wide elevational gradient in the Tropical Andes, where frog populations have collapsed. We used the difference between critical thermal maximum and the temperature a frog experiences in nature as a measure of tolerance to high temperatures. Temperature tolerance increased as elevation increased, suggesting that frogs at higher elevations may be less sensitive to rising temperatures. We tested the alternative pathogen optimal growth hypothesis that prevalence of the pathogen should decrease as temperatures fall outside the optimal range of pathogen growth. Our infection-prevalence data supported the pathogen optimal growth hypothesis because we found that prevalence of Bd increased when host temperatures matched its optimal growth range. These findings suggest that rising temperatures may not be the driver of amphibian declines in the eastern slopes of the Andes. Zoonotic outbreaks of Bd are the most parsimonious hypothesis to explain the collapse of montane amphibian faunas; but our results also reveal that lowland tropical amphibians, despite being shielded from Bd by higher temperatures, are vulnerable to climate-warming stress. © 2013 Society for Conservation Biology.

  10. Antimicrobial susceptibility of foodborne pathogens in organic or natural production systems: an overview.

    PubMed

    Jacob, Megan E; Fox, James Trent; Reinstein, Shelby L; Nagaraja, T G

    2008-12-01

    Organic and natural food production systems are increasing in popularity, at least partially because consumers perceive that these niche markets provide healthier and safer food products. One major difference between these niche markets and conventional production systems is the use of antimicrobials. Because antimicrobial agents exert selective pressures for antimicrobial resistance, relating antimicrobial susceptibility of foodborne bacteria to niche market production systems is of interest. Other differences between production systems might also influence the susceptibility of foodborne pathogens. The objective of this review is to compare the impact of food animal production systems on the antimicrobial susceptibility of common foodborne bacterial pathogens. Studies comparing the susceptibility of such pathogens were diverse in terms of geographic location, procedures, species of bacteria, and antimicrobials evaluated; thus, it was difficult to draw conclusions. The literature is highly variable in terms of production type and practices and susceptibility associations, although few studies have compared truly organic and conventional practices. When statistical associations were found between production type and minimum inhibitory concentrations or percentage of isolates resistant for a particular pathogen, the isolates from conventionally reared animals/products were more commonly resistant than the comparison group (organic, antibiotic free, etc.). Therefore, further studies are needed to better assess public health consequences of antimicrobial resistance and food animal production systems, specifically organic or natural versus conventional.

  11. Development of imaging techniques to study the pathogenesis of biosafety level 2/3 infectious agents.

    PubMed

    Rella, Courtney E; Ruel, Nancy; Eugenin, Eliseo A

    2014-12-01

    Despite significant advances in microbiology and molecular biology over the last decades, several infectious diseases remain global concerns, resulting in the death of millions of people worldwide each year. According to the Center for Disease Control (CDC) in 2012, there were 34 million people infected with HIV, 8.7 million new cases of tuberculosis, 500 million cases of hepatitis, and 50-100 million people infected with dengue. Several of these pathogens, despite high incidence, do not have reliable clinical detection methods. New or improved protocols have been generated to enhance detection and quantitation of several pathogens using high-end microscopy (light, confocal, and STORM microscopy) and imaging software. In the current manuscript, we discuss these approaches and the theories behind these methodologies. Thus, advances in imaging techniques will open new possibilities to discover therapeutic interventions to reduce or eliminate the devastating consequences of infectious diseases. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  12. Anti-Immune Strategies of Pathogenic Fungi

    PubMed Central

    Marcos, Caroline M.; de Oliveira, Haroldo C.; de Melo, Wanessa de Cássia M. Antunes; da Silva, Julhiany de Fátima; Assato, Patrícia A.; Scorzoni, Liliana; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Mendes-Giannini, Maria J. S.; Fusco-Almeida, Ana M.

    2016-01-01

    Pathogenic fungi have developed many strategies to evade the host immune system. Multiple escape mechanisms appear to function together to inhibit attack by the various stages of both the adaptive and the innate immune response. Thus, after entering the host, such pathogens fight to overcome the immune system to allow their survival, colonization and spread to different sites of infection. Consequently, the establishment of a successful infectious process is closely related to the ability of the pathogen to modulate attack by the immune system. Most strategies employed to subvert or exploit the immune system are shared among different species of fungi. In this review, we summarize the main strategies employed for immune evasion by some of the major pathogenic fungi. PMID:27896220

  13. Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica

    PubMed Central

    Vercken, Elodie; Fontaine, Michael C.; Gladieux, Pierre; Hood, Michael E.; Jonot, Odile; Giraud, Tatiana

    2010-01-01

    Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization patterns. PMID:21187901

  14. Threats and opportunities of plant pathogenic bacteria.

    PubMed

    Tarkowski, Petr; Vereecke, Danny

    2014-01-01

    Plant pathogenic bacteria can have devastating effects on plant productivity and yield. Nevertheless, because these often soil-dwelling bacteria have evolved to interact with eukaryotes, they generally exhibit a strong adaptivity, a versatile metabolism, and ingenious mechanisms tailored to modify the development of their hosts. Consequently, besides being a threat for agricultural practices, phytopathogens may also represent opportunities for plant production or be useful for specific biotechnological applications. Here, we illustrate this idea by reviewing the pathogenic strategies and the (potential) uses of five very different (hemi)biotrophic plant pathogenic bacteria: Agrobacterium tumefaciens, A. rhizogenes, Rhodococcus fascians, scab-inducing Streptomyces spp., and Pseudomonas syringae. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Rodents as potential couriers for bioterrorism agents.

    PubMed

    Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

    2013-09-01

    Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control.

  16. Legionella Risk Management and Control in Potable Water Systems: Argument for the Abolishment of Routine Testing.

    PubMed

    Whiley, Harriet

    2016-12-24

    Legionella is an opportunistic pathogen of public health significance. One of the main sources of Legionella is potable water systems. As a consequence of aging populations there is an increasing demographic considered at high risk for Legionellosis and, as such, a review of the guidelines is required. Worldwide, Legionella has been detected from many potable water sources, suggesting it is ubiquitous in this environment. Previous studies have identified the limitations of the current standard method for Legionella detection and the high possibility of it returning both false negative and false positive results. There is also huge variability in Legionella test results for the same water sample when conducted at different laboratories. However, many guidelines still recommend the testing of water systems. This commentary argues for the removal of routine Legionella monitoring from all water distribution guidelines. This procedure is financially consuming and false negatives may result in managers being over-confident with a system or a control mechanism. Instead, the presence of the pathogen should be assumed and focus spent on managing appropriate control measures and protecting high-risk population groups.

  17. Legionella Risk Management and Control in Potable Water Systems: Argument for the Abolishment of Routine Testing

    PubMed Central

    Whiley, Harriet

    2016-01-01

    Legionella is an opportunistic pathogen of public health significance. One of the main sources of Legionella is potable water systems. As a consequence of aging populations there is an increasing demographic considered at high risk for Legionellosis and, as such, a review of the guidelines is required. Worldwide, Legionella has been detected from many potable water sources, suggesting it is ubiquitous in this environment. Previous studies have identified the limitations of the current standard method for Legionella detection and the high possibility of it returning both false negative and false positive results. There is also huge variability in Legionella test results for the same water sample when conducted at different laboratories. However, many guidelines still recommend the testing of water systems. This commentary argues for the removal of routine Legionella monitoring from all water distribution guidelines. This procedure is financially consuming and false negatives may result in managers being over-confident with a system or a control mechanism. Instead, the presence of the pathogen should be assumed and focus spent on managing appropriate control measures and protecting high-risk population groups. PMID:28029126

  18. Blood parasites shape extreme major histocompatibility complex diversity in a migratory passerine.

    PubMed

    Biedrzycka, Aleksandra; Bielański, Wojciech; Ćmiel, Adam; Solarz, Wojciech; Zając, Tadeusz; Migalska, Magdalena; Sebastian, Alvaro; Westerdahl, Helena; Radwan, Jacek

    2018-06-01

    Pathogens are one of the main forces driving the evolution and maintenance of the highly polymorphic genes of the vertebrate major histocompatibility complex (MHC). Although MHC proteins are crucial in pathogen recognition, it is still poorly understood how pathogen-mediated selection promotes and maintains MHC diversity, and especially so in host species with highly duplicated MHC genes. Sedge warblers (Acrocephalus schoenobaenus) have highly duplicated MHC genes, and using data from high-throughput MHC genotyping, we were able to investigate to what extent avian malaria parasites explain temporal MHC class I supertype fluctuations in a long-term study population. We investigated infection status and infection intensities of two different strains of Haemoproteus, that is avian malaria parasites that are known to have significant fitness consequences in sedge warblers. We found that prevalence of avian malaria in carriers of specific MHC class I supertypes was a significant predictor of their frequency changes between years. This finding suggests that avian malaria infections partly drive the temporal fluctuations of the MHC class I supertypes. Furthermore, we found that individuals with a large number of different supertypes had higher resistance to avian malaria, but there was no evidence for an optimal MHC class I diversity. Thus, the two studied malaria parasite strains appear to select for a high MHC class I supertype diversity. Such selection may explain the maintenance of the extremely high number of MHC class I gene copies in sedge warblers and possibly also in other passerines where avian malaria is a common disease. © 2018 John Wiley & Sons Ltd.

  19. Changing epidemiology of melioidosis? A case of acute pulmonary melioidosis with fatal outcome imported from Brazil.

    PubMed Central

    Aardema, H.; Luijnenburg, E. M.; Salm, E. F.; Bijlmer, H. A.; Visser, C. E.; Van't Wout, J. W.

    2005-01-01

    Melioidosis is an infectious disease caused by Burkholderia pseudomallei. It is endemic in South East Asia and tropical regions of Northern Australia. Sporadic cases have been described elsewhere. In this article we present a case of acute pulmonary melioidosis with fatal outcome imported from Brazil. The most common pathogen causing severe community-acquired pneumonia in Brazil is Streptococcus pneumoniae. Other possible pathogens include Legionella spp., Mycoplasma pneumonia, Gram-negative rods and viruses. There are few reports of melioidosis in the Americas. This article represents the second known human case of melioidosis from Brazil. Recognition of melioidosis as a possible cause of severe pneumonia, even if a patient has not been travelling in a highly endemic area, is important because of the therapeutic consequences. The epidemiology of melioidosis will be reviewed. PMID:16181507

  20. Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

    PubMed Central

    2014-01-01

    SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced. PMID:25278574

  1. Characteristics and consequences of root diseases in forests of Western North America

    Treesearch

    D.J. Goheen; W.J. Otrosina

    1998-01-01

    Root diseases are somewhat mysterious. Operating as they do within the soil, it is difficult to actually view root pathogens or follow their progress in causing disease. The signs and symptoms that they produce can be quite subtle and variable. Just identifying which pathogen occurs in a specific situation is often challenging. Nevertheless, in the past two decades,...

  2. Root diseases: primary agents and secondary consequences of disturbance

    Treesearch

    William J. Otrosina; George T. Ferrell

    1995-01-01

    The fact that endemic root disease causing pathogens have evolved with forest ecosystems does not necessarily mean they are inconsequential. A pathogen such as the P group of Heterobasidion annosum has become an intractable problem in many Sierra east side pine stands in California because the fungus is adapted to colonization of freshly cut stump surfaces. The S group...

  3. The consequences of the intracellular retention of pathogen-derived T-cell-independent antigens on protein presentation to T cells.

    PubMed

    Leyva-Cobián, F; Outschoorn, I M; Carrasco-Marín, E; Alvarez-Domínguez, C

    1997-10-01

    Intracellular pathogens can be considered as particulate antigens chemically composed of a complex mixture of T-cell-dependent antigens (TD) (peptides and proteins) and T-cell-independent antigens (TI) (glycolipids and complex polysaccharides). A large range of saccharides (from oligosaccharides to complex polysaccharides) derived from pathogenic microorganisms are being isolated and characterized. They are currently implicated in signaling systems and concomitant host-parasite relationships. However, there are not many structure-function relationships described for these pathogens. This is particularly true of polysaccharides. In this report we have reviewed the role of defined TI antigens in the processing and presentation of defined TD antigens to specific T cells by antigen-presenting cells (APC). We also considered the importance of some of the chemical characteristics shared by different carbohydrates implicated in the inhibition of antigen presentation. These findings are discussed in relation to the clear immunopathological consequences of long retention periods of complex carbohydrate molecules derived from intracellular parasites inside certain APC and the absence of antigen presentation impairment in physiological situations such as the removal of senescent or damaged red blood cells by splenic macrophages or intracellular accumulation of carbohydrates in colostrum and milk macrophages during lactation.

  4. Chlorine-rich plasma polymer coating for the prevention of attachment of pathogenic fungal cells onto materials surfaces

    NASA Astrophysics Data System (ADS)

    Lamont-Friedrich, Stephanie J.; Michl, Thomas D.; Giles, Carla; Griesser, Hans J.; Coad, Bryan R.

    2016-07-01

    The attachment of pathogenic fungal cells onto materials surfaces, which is often followed by biofilm formation, causes adverse consequences in a wide range of areas. Here we have investigated the ability of thin film coatings from chlorinated molecules to deter fungal colonization of solid materials by contact killing of fungal cells reaching the surface of the coating. Coatings were deposited onto various substrate materials via plasma polymerization, which is a substrate-independent process widely used for industrial coating applications, using 1,1,2-trichloroethane as the process vapour. XPS surface analysis showed that the coatings were characterized by a highly chlorinated hydrocarbon polymer nature, with only a very small amount of oxygen incorporated. The activity of these coatings against human fungal pathogens was quantified using a recently developed, modified yeast assay and excellent antifungal activity was observed against Candida albicans and Candida glabrata. Plasma polymer surface coatings derived from chlorinated hydrocarbon molecules may therefore offer a promising solution to preventing yeast and mould biofilm formation on materials surfaces, for applications such as air conditioners, biomedical devices, food processing equipment, and others.

  5. Deformability Assessment of Waterborne Protozoa Using a Microfluidic-Enabled Force Microscopy Probe

    PubMed Central

    Seddon, James R. T.; Lai, Stanley C. S.; Lemay, Serge G.; Bridle, Helen L.

    2016-01-01

    Many modern filtration technologies are incapable of the complete removal of Cryptosporidium oocysts from drinking-water. Consequently, Cryptosporidium-contaminated drinking-water supplies can severely implicate both water utilities and consumers. Existing methods for the detection of Cryptosporidium in drinking-water do not discern between non-pathogenic and pathogenic species, nor between viable and non-viable oocysts. Using FluidFM, a novel force spectroscopy method employing microchannelled cantilevers for single-cell level manipulation, we assessed the size and deformability properties of two species of Cryptosporidium that pose varying levels of risk to human health. A comparison of such characteristics demonstrated the ability of FluidFM to discern between Cryptosporidium muris and Cryptosporidium parvum with 86% efficiency, whilst using a measurement throughput which exceeded 50 discrete oocysts per hour. In addition, we measured the deformability properties for untreated and temperature-inactivated oocysts of the highly infective, human pathogenic C. parvum to assess whether deformability may be a marker of viability. Our results indicate that untreated and temperature-inactivated C. parvum oocysts had overlapping but significantly different deformability distributions. PMID:26938220

  6. Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks

    PubMed Central

    Flentie, Kelly; Garner, Ashley L.

    2016-01-01

    Regulating responses to stress is critical for all bacteria, whether they are environmental, commensal, or pathogenic species. For pathogenic bacteria, successful colonization and survival in the host are dependent on adaptation to diverse conditions imposed by the host tissue architecture and the immune response. Once the bacterium senses a hostile environment, it must enact a change in physiology that contributes to the organism's survival strategy. Inappropriate responses have consequences; hence, the execution of the appropriate response is essential for survival of the bacterium in its niche. Stress responses are most often regulated at the level of gene expression and, more specifically, transcription. This minireview focuses on mechanisms of regulating transcription initiation that are required by Mycobacterium tuberculosis to respond to the arsenal of defenses imposed by the host during infection. In particular, we highlight how certain features of M. tuberculosis physiology allow this pathogen to respond swiftly and effectively to host defenses. By enacting highly integrated and coordinated gene expression changes in response to stress, M. tuberculosis is prepared for battle against the host defense and able to persist within the human population. PMID:26883824

  7. [Relationship of consequences of anastomotic insufficiency and bacterial flora of oral cavity in patients with esophageal and cardia cancer].

    PubMed

    Balázs, Ákos; Winkler, Beáta; Kristóf, Katalin; Harsányi, László; Bokor, Lívia

    2017-01-01

    In the course of anastomotic insufficiency following resection of esophageal cancers the bacterial compound of the esophageal substance has a remarkable, presumable role in the outcome of complications. The purpose of this study is to compare the consequences of the anastomotic leak with the bacterial flora of patients' oral cavity. In this prospective study a total of 131 patients were investigated directly before the surgical intervention taking a bacterial sample. Bacterial flora of patients' oral cavity was analysed; and the correlation between the consequences of the anastomotic leak and the content of the bacterial flora was examined. Pathogenic bacteria in the oral microflora in 50 cases (38.2%) was found. Statistically significant, moderate correlation was found between the severity of the complication and the incidence of pathogenic bacteria (r s = 0.553; p≤0.05). Pathogenic agent in the microbial flora might induce higher risk and more severe outcome in case of anastomotic leakage and it might be evaluated as a determinative factor. Consideration of the bacterial flora of the oral cavity requires more attention in the preoperative preparation than before and it demands the change of the current practice. Orv. Hetil., 2017, 158(1), 25-30.

  8. Increased seawater temperature increases the abundance and alters the structure of natural Vibrio populations associated with the coral Pocillopora damicornis

    PubMed Central

    Tout, Jessica; Siboni, Nachshon; Messer, Lauren F.; Garren, Melissa; Stocker, Roman; Webster, Nicole S.; Ralph, Peter J.; Seymour, Justin R.

    2015-01-01

    Rising seawater temperature associated with global climate change is a significant threat to coral health and is linked to increasing coral disease and pathogen-related bleaching events. We performed heat stress experiments with the coral Pocillopora damicornis, where temperature was increased to 31°C, consistent with the 2–3°C predicted increase in summer sea surface maxima. 16S rRNA amplicon sequencing revealed a large shift in the composition of the bacterial community at 31°C, with a notable increase in Vibrio, including known coral pathogens. To investigate the dynamics of the naturally occurring Vibrio community, we performed quantitative PCR targeting (i) the whole Vibrio community and (ii) the coral pathogen Vibrio coralliilyticus. At 31°C, Vibrio abundance increased by 2–3 orders of magnitude and V. coralliilyticus abundance increased by four orders of magnitude. Using a Vibrio-specific amplicon sequencing assay, we further demonstrated that the community composition shifted dramatically as a consequence of heat stress, with significant increases in the relative abundance of known coral pathogens. Our findings provide quantitative evidence that the abundance of potential coral pathogens increases within natural communities of coral-associated microbes as a consequence of rising seawater temperature and highlight the potential negative impacts of anthropogenic climate change on coral reef ecosystems. PMID:26042096

  9. [Change of host's behavior including man under the influence of parasites].

    PubMed

    Sergiev, V P

    2010-01-01

    Directed modulation of hosts' behavior favouring transmission of pathogen was noted in many parasites and, above all, in helminthes, which life cycle includes the consequent change of several hosts. It turned out that parasites use the same neuromediators for change of behavior of both mammals and hosts belonging to other animal classes. In fishes as well as in mammals, monoamines-neurotransmitters assist in brain functioning. Norepinephrine, dopamine and serotonin affect the alimentation, motion activity, aggression and social behaviour. Changes in concentration ratio of serotonin and its metabolites in invaded species were more pronounced, which pointed to directed effects of pathogens on serotonin activity. The same effect of some pathogens on human behaviour does not have selective significance because humans are not an essential link in life cycle of many parasites. Although the mentioned effect on behaviour could lead to negative consequences. For examples, persons with latent toxoplasmosis are significantly more frequent become members or victims of traffic accidents due to decreased ability for concentration of attention.

  10. The standardised freight container: vector of vectors and vector-borne diseases.

    PubMed

    Reiter, P

    2010-04-01

    The standardised freight container was one of the most important innovations of the 20th Century. Containerised cargoes travel from their point of origin to their destination by ship, road and rail as part of a single journey, without unpacking. This simple concept is the key element in cheap, rapid transport by land and sea, and has led to a phenomenal growth in global trade. Likewise, containerised air cargo has led to a remarkable increase in the inter-continental transportation of goods, particularly perishable items such as flowers, fresh vegetables and live animals. In both cases, containerisation offers great advantages in speed and security, but reduces the opportunity to inspect cargoes in transit. An inevitable consequence is the globalisation of undesirable species of animals, plants and pathogens. Moreover, cheap passenger flights offer worldwide travel for viral and parasitic pathogens in infected humans. The continued emergence of exotic pests, vectors and pathogens throughout the world is an unavoidable consequence of these advances in transportation technology.

  11. Planning for compliance: OSHA's bloodborne pathogen rule.

    PubMed

    Bednar, B; Duke, M C

    1990-11-01

    Overall, the bloodborne pathogen rule constitutes a reasonable response to a significant threat to workplace safety. The risks to dialysis workers from HBV and HIV must be minimized or eliminated and the rule is generally consistent with the consensus approach. Unfortunately for dialysis providers, the rule is not exempt from the law of unintended consequences: government regulation will always have impact beyond its object. Promulgation of the final rule will immediately increase the expenses of dialysis providers. Additionally, the enormity of the HBV and HIV problem coupled with the open-ended nature of the rule's key provisions will almost certainly bring additional costs. So long as dialysis reimbursement remains flat, the unintended consequence of the bloodborne pathogen rule may be to quicken the pace of consolidation in the dialysis service market. The added burden of compliance may be too much for small independent facilities. Only large chains may have the resources to comply and survive. To forestall this effect and to provide employees with maximum protection, all dialysis providers should plan now for compliance.

  12. Mortality and community changes drive sudden oak death impacts on litterfall and soil nitrogen cycling.

    PubMed

    Cobb, Richard C; Eviner, Valerie T; Rizzo, David M

    2013-10-01

    Few studies have quantified pathogen impacts to ecosystem processes, despite the fact that pathogens cause or contribute to regional-scale tree mortality. We measured litterfall mass, litterfall chemistry, and soil nitrogen (N) cycling associated with multiple hosts along a gradient of mortality caused by Phytophthora ramorum, the cause of sudden oak death. In redwood forests, the epidemiological and ecological characteristics of the major overstory species determine disease patterns and the magnitude and nature of ecosystem change. Bay laurel (Umbellularia californica) has high litterfall N (0.992%), greater soil extractable NO3 -N, and transmits infection without suffering mortality. Tanoak (Notholithocarpus densiflorus) has moderate litterfall N (0.723%) and transmits infection while suffering extensive mortality that leads to higher extractable soil NO3 -N. Redwood (Sequoia sempervirens) has relatively low litterfall N (0.519%), does not suffer mortality or transmit the pathogen, but dominates forest biomass. The strongest impact of pathogen-caused mortality was the potential shift in species composition, which will alter litterfall chemistry, patterns and dynamics of litterfall mass, and increase soil NO3 -N availability. Patterns of P. ramorum spread and consequent mortality are closely associated with bay laurel abundances, suggesting this species will drive both disease emergence and subsequent ecosystem function. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  13. Strain-Specific Transfer of Antibiotic Resistance from an Environmental Plasmid to Foodborne Pathogens

    PubMed Central

    Van Meervenne, Eva; Van Coillie, Els; Kerckhof, Frederiek-Maarten; Devlieghere, Frank; Herman, Lieve; De Gelder, Leen S. P.; Top, Eva M.; Boon, Nico

    2012-01-01

    Pathogens resistant to multiple antibiotics are rapidly emerging, entailing important consequences for human health. This study investigated if the broad-host-range multiresistance plasmid pB10, isolated from a wastewater treatment plant, harbouring amoxicillin, streptomycin, sulfonamide, and tetracycline resistance genes, was transferable to the foodborne pathogens Salmonella spp. or E. coli O157:H7 and how this transfer alters the phenotype of the recipients. The transfer ratio was determined by both plating and flow cytometry. Antibiotic resistance profiles were determined for both recipients and transconjugants using the disk diffusion method. For 14 of the 15 recipient strains, transconjugants were detected. Based on plating, transfer ratios were between 6.8 × 10−9 and 3.0 × 10−2 while using flow cytometry, transfer ratios were between <1.0 × 10−5 and 1.9 × 10−2. With a few exceptions, the transconjugants showed phenotypically increased resistance, indicating that most of the transferred resistance genes were expressed. In summary, we showed that an environmental plasmid can be transferred into foodborne pathogenic bacteria at high transfer ratios. However, the transfer ratio seemed to be recipient strain dependent. Moreover, the newly acquired resistance genes could turn antibiotic susceptible strains into resistant ones, paving the way to compromise human health. PMID:22791963

  14. Highly dynamic animal contact network and implications on disease transmission

    PubMed Central

    Chen, Shi; White, Brad J.; Sanderson, Michael W.; Amrine, David E.; Ilany, Amiyaal; Lanzas, Cristina

    2014-01-01

    Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R0 < 2). PMID:24667241

  15. Sequestration and Scavenging of Iron in Infection

    PubMed Central

    Parrow, Nermi L.; Fleming, Robert E.

    2013-01-01

    The proliferative capability of many invasive pathogens is limited by the bioavailability of iron. Pathogens have thus developed strategies to obtain iron from their host organisms. In turn, host defense strategies have evolved to sequester iron from invasive pathogens. This review explores the mechanisms employed by bacterial pathogens to gain access to host iron sources, the role of iron in bacterial virulence, and iron-related genes required for the establishment or maintenance of infection. Host defenses to limit iron availability for bacterial growth during the acute-phase response and the consequences of iron overload conditions on susceptibility to bacterial infection are also examined. The evidence summarized herein demonstrates the importance of iron bioavailability in influencing the risk of infection and the ability of the host to clear the pathogen. PMID:23836822

  16. Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

    PubMed Central

    Hörger, Anja C.; Ilyas, Muhammad; Stephan, Wolfgang; Tellier, Aurélien; van der Hoorn, Renier A. L.; Rose, Laura E.

    2012-01-01

    Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant–pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the “Guard-Hypothesis,” R proteins (the “guards”) can sense modification of target molecules in the host (the “guardees”) by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the “guardee-effector” interface for pathogen recognition, natural selection acts on the “guard-guardee” interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen. PMID:22829777

  17. Power Ultrasound to Process Dairy Products

    NASA Astrophysics Data System (ADS)

    Bermúdez-Aguirre, Daniela; Barbosa-Cánovas, Gustavo V.

    Conventional methods of pasteurizing milk involve the use of heat regardless of treatment (batch, high temperature short time - HTST or ultra high temperature - UHT sterilization), and the quality of the milk is affected because of the use of high temperatures. Consequences of thermal treatment are a decrease in nutritional properties through the destruction of vitamins or denaturation of proteins, and sometimes the flavor of milk is undesirably changed. These changes are produced at the same time that the goal of the pasteurization process is achieved, which is to have a microbiological safe product, free of pathogenic bacteria, and to reduce the load of deteriorative microorganisms and enzymes, resulting in a product with a longer storage life.

  18. Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data.

    PubMed

    Hammitt, Laura L; Feikin, Daniel R; Scott, J Anthony G; Zeger, Scott L; Murdoch, David R; O'Brien, Katherine L; Deloria Knoll, Maria

    2017-06-15

    Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  19. Prediction of BRCA1 and BRCA2 mutation status using post-irradiation assays of lymphoblastoid cell lines is compromised by inter-cell-line phenotypic variability.

    PubMed

    Lovelock, Paul K; Wong, Ee Ming; Sprung, Carl N; Marsh, Anna; Hobson, Karen; French, Juliet D; Southey, Melissa; Sculley, Tom; Pandeya, Nirmala; Brown, Melissa A; Chenevix-Trench, Georgia; Spurdle, Amanda B; McKay, Michael J

    2007-09-01

    Assays to determine the pathogenicity of unclassified sequence variants in disease-associated genes include the analysis of lymphoblastoid cell lines (LCLs). We assessed the ability of several assays of LCLs to distinguish carriers of germline BRCA1 and BRCA2 gene mutations from mutation-negative controls to determine their utility for use in a diagnostic setting. Post-ionising radiation cell viability and micronucleus formation, and telomere length were assayed in LCLs carrying BRCA1 or BRCA2 mutations, and in unaffected mutation-negative controls. Post-irradiation cell viability and micronucleus induction assays of LCLs from individuals carrying pathogenic BRCA1 mutations, unclassified BRCA1 sequence variants or wildtype BRCA1 sequence showed significant phenotypic heterogeneity within each group. Responses were not consistent with predicted functional consequences of known pathogenic or normal sequences. Telomere length was also highly heterogeneous within groups of LCLs carrying pathogenic BRCA1 or BRCA2 mutations, and normal BRCA1 sequences, and was not predictive of mutation status. Given the significant degree of phenotypic heterogeneity of LCLs after gamma-irradiation, and the lack of association with BRCA1 or BRCA2 mutation status, we conclude that the assays evaluated in this study should not be used as a means of differentiating pathogenic and non-pathogenic sequence variants for clinical application. We suggest that a range of normal controls must be included in any functional assays of LCLs to ensure that any observed differences between samples reflect the genotype under investigation rather than generic inter-individual variation.

  20. Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data

    PubMed Central

    Feikin, Daniel R.; Scott, J. Anthony G.; Zeger, Scott L.; Murdoch, David R.; O’Brien, Katherine L.; Deloria Knoll, Maria

    2017-01-01

    Abstract Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data. PMID:28575372

  1. The Pathogenic Potential of a Microbe

    PubMed Central

    2017-01-01

    ABSTRACT Virulence is a microbial property that is realized only in susceptible hosts. There is no absolute measurement for virulence, and consequently it is always measured relative to a standard, usually another microbe or host. This article introduces the concept of pathogenic potential, which provides a new approach to measuring the capacity of microbes for virulence. The pathogenic potential is proportional to the fraction of individuals who become symptomatic after infection with a defined inoculum and can include such attributes as mortality, communicability, and the time from infection to disease. The calculation of the pathogenic potential has significant advantages over the use of the lethal dose that kills 50% of infected individuals (LD50) and allows direct comparisons between individual microbes. An analysis of the pathogenic potential of several microbes for mice reveals a continuum, which in turn supports the view that there is no dividing line between pathogenic and nonpathogenic microbes. PMID:28251180

  2. Live plant imports: the major pathway for forest insect and pathogen invasions of the US

    Treesearch

    Andrew M. Liebhold; Eckehard G. Brockerhoff; Lynn J. Garrett; Jennifer L. Parke

    2012-01-01

    Trade in live plants has been recognized worldwide as an important invasion pathway for non-native plant pests. Such pests can have severe economic and ecological consequences. Nearly 70% of damaging forest insects and pathogens established in the US between 1860 and 2006 most likely entered on imported live plants. The current regulation of plant imports is outdated...

  3. Insect-plant-pathogen interactions as shaped by future climate: effects on biology, distribution, and implications for agriculture.

    PubMed

    Trębicki, Piotr; Dáder, Beatriz; Vassiliadis, Simone; Fereres, Alberto

    2017-12-01

    Carbon dioxide (CO 2 ) is the main anthropogenic gas which has drastically increased since the industrial revolution, and current concentrations are projected to double by the end of this century. As a consequence, elevated CO 2 is expected to alter the earths' climate, increase global temperatures and change weather patterns. This is likely to have both direct and indirect impacts on plants, insect pests, plant pathogens and their distribution, and is therefore problematic for the security of future food production. This review summarizes the latest findings and highlights current knowledge gaps regarding the influence of climate change on insect, plant and pathogen interactions with an emphasis on agriculture and food production. Direct effects of climate change, including increased CO 2 concentration, temperature, patterns of rainfall and severe weather events that impact insects (namely vectors of plant pathogens) are discussed. Elevated CO 2 and temperature, together with plant pathogen infection, can considerably change plant biochemistry and therefore plant defense responses. This can have substantial consequences on insect fecundity, feeding rates, survival, population size, and dispersal. Generally, changes in host plant quality due to elevated CO 2 (e.g., carbon to nitrogen ratios in C3 plants) negatively affect insect pests. However, compensatory feeding, increased population size and distribution have also been reported for some agricultural insect pests. This underlines the importance of additional research on more targeted, individual insect-plant scenarios at specific locations to fully understand the impact of a changing climate on insect-plant-pathogen interactions. © 2017 Institute of Zoology, Chinese Academy of Sciences.

  4. Association and Host Selectivity in Multi-Host Pathogens

    PubMed Central

    Malpica, José M.; Sacristán, Soledad; Fraile, Aurora; García-Arenal, Fernando

    2006-01-01

    The distribution of multi-host pathogens over their host range conditions their population dynamics and structure. Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution. Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host. To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations. Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively. Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens. Analyses also showed that viruses tended to associate positively in co-infected hosts. The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens. PMID:17183670

  5. Development of the adaptive NK cell response to human cytomegalovirus in the context of aging.

    PubMed

    López-Botet, Miguel; Muntasell, Aura; Martínez-Rodríguez, José E; López-Montañés, María; Costa-García, Marcel; Pupuleku, Aldi

    2016-09-01

    Human cytomegalovirus (HCMV) establishes a highly prevalent life-long latent infection. Though generally subclinical, HCMV infection may have severe consequences during fetal development and in immunocompromised individuals. Based on epidemiological studies HCMV(+) serology has been associated with the development of atherosclerosis, immune senescence and an increase mortality rate in elderly people. Such long-term detrimental effects of the viral infection presumably result from an inefficient immune control of the pathogen, depending on the quality and evolution of the individual host-pathogen relationship. Together with antigen-specific T lymphocytes, NK cells play an important role in anti-viral immune defense. HCMV promotes in some individuals the differentiation and persistent steady state expansion of an NK cell subset bearing the CD94/NKG2C activating receptor. The relationship between this adaptive NK cell response to HCMV and aging is overviewed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Bacterium-Dependent Induction of Cytokines in Mononuclear Cells and Their Pathologic Consequences In Vivo

    PubMed Central

    Jiang, Yanling; Magli, Luciano; Russo, Michael

    1999-01-01

    Viridans streptococci are a heterogeneous group of gram-positive bacteria that are normal inhabitants of the mouth. These organisms are thought to contribute significantly to the etiology of infective endocarditis, although recently they have been implicated in serious infections in other settings. Another group of oral bacteria, gram-negative anaerobes, is associated with chronic dental infections, such as periodontal diseases or endodontic lesion formation. We evaluated the ability of the oral pathogens Streptococcus mutans and Porphyromonas endodontalis to induce a pathogenic response in vivo, with the goal of quantifying the inflammatory response in soft tissue by measuring leukocyte recruitment and hard tissues by measuring osteoclastogenesis. S. mutans induced a strong inflammatory response and was a potent inducer of osteoclast formation, while P. endodontalis was not. To further study the mechanisms by which P. endodontalis and S. mutans elicit significantly different levels of inflammatory responses in vivo, we tested the capacity of each to induce production of cytokines by mononuclear cells in vitro. S. mutans stimulated high levels of interleukin-12 (IL-12), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), all of which are associated with inflammation, enhanced monocyte function, and generation of a Th1 response. In contrast, P. endodontalis stimulated production of IL-10 but not of TNF-α, IL-12, or IFN-γ. These results demonstrate that oral pathogens differ dramatically in their abilities to induce inflammatory and immunoregulatory cytokines. Moreover, there is a high degree of correlation between the cytokine profile induced by these bacteria in vitro and their pathogenic capacity in vivo. PMID:10225864

  7. Bacterium-dependent induction of cytokines in mononuclear cells and their pathologic consequences in vivo.

    PubMed

    Jiang, Y; Magli, L; Russo, M

    1999-05-01

    Viridans streptococci are a heterogeneous group of gram-positive bacteria that are normal inhabitants of the mouth. These organisms are thought to contribute significantly to the etiology of infective endocarditis, although recently they have been implicated in serious infections in other settings. Another group of oral bacteria, gram-negative anaerobes, is associated with chronic dental infections, such as periodontal diseases or endodontic lesion formation. We evaluated the ability of the oral pathogens Streptococcus mutans and Porphyromonas endodontalis to induce a pathogenic response in vivo, with the goal of quantifying the inflammatory response in soft tissue by measuring leukocyte recruitment and hard tissues by measuring osteoclastogenesis. S. mutans induced a strong inflammatory response and was a potent inducer of osteoclast formation, while P. endodontalis was not. To further study the mechanisms by which P. endodontalis and S. mutans elicit significantly different levels of inflammatory responses in vivo, we tested the capacity of each to induce production of cytokines by mononuclear cells in vitro. S. mutans stimulated high levels of interleukin-12 (IL-12), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), all of which are associated with inflammation, enhanced monocyte function, and generation of a Th1 response. In contrast, P. endodontalis stimulated production of IL-10 but not of TNF-alpha, IL-12, or IFN-gamma. These results demonstrate that oral pathogens differ dramatically in their abilities to induce inflammatory and immunoregulatory cytokines. Moreover, there is a high degree of correlation between the cytokine profile induced by these bacteria in vitro and their pathogenic capacity in vivo.

  8. The endosomal recycling of FgSnc1 by FgSnx41-FgSnx4 heterodimer is essential for polarized growth and pathogenicity in Fusarium graminearum.

    PubMed

    Zheng, Wenhui; Lin, Yahong; Fang, Wenqin; Zhao, Xu; Lou, Yi; Wang, Guanghui; Zheng, Huawei; Liang, Qifu; Abubakar, Yakubu Saddeeq; Olsson, Stefan; Zhou, Jie; Wang, Zonghua

    2018-04-20

    Endosomal sorting machineries regulate the transport of their cargoes among intracellular compartments. However, the molecular nature of such intracellular trafficking processes in pathogenic fungal development and pathogenicity remains unclear. Here, we dissect the roles and molecular mechanisms of two sorting nexin proteins and their cargoes in endosomal recycling in Fusarium graminearum using high-resolution microscopy and high-throughput co-immunoprecipitation strategies. We show that the sorting nexins, FgSnx41 and FgSnx4, interact with each other and assemble into a functionally interdependent heterodimer through their respective BAR domains. Further analyses demonstrate that the dimer localizes to the early endosomal membrane and coordinates endosomal sorting. The small GTPase FgRab5 regulates the correct localization of FgSnx41-FgSnx4 and is consequently required for its trafficking function. The protein FgSnc1 is a cargo of FgSnx41-FgSnx4 and regulates the fusion of secreted vesicles with the fungal growing apex and plasma membrane. In the absence of FgSnx41 or FgSnx4, FgSnc1 is mis-sorted and degraded in the vacuole, and null deletion of either component causes defects in the fungal polarized growth and virulence. Overall, for the first time, our results reveal the mechanism of FgSnc1 endosomal recycling by FgSnx41-FgSnx4 heterodimer which is essential for polarized growth and pathogenicity in F. graminearum. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  9. Changing geographic ranges of ticks and tick-borne pathogens: drivers, mechanisms and consequences for pathogen diversity

    PubMed Central

    Ogden, Nick H.; Mechai, Samir; Margos, Gabriele

    2013-01-01

    The geographic ranges of ticks and tick-borne pathogens are changing due to global and local environmental (including climatic) changes. In this review we explore current knowledge of the drivers for changes in the ranges of ticks and tick-borne pathogen species and strains via effects on their basic reproduction number (R0), and the mechanisms of dispersal that allow ticks and tick-borne pathogens to invade suitable environments. Using the expanding geographic distribution of the vectors and agent of Lyme disease as an example we then investigate what could be expected of the diversity of tick-borne pathogens during the process of range expansion, and compare this with what is currently being observed. Lastly we explore how historic population and range expansions and contractions could be reflected in the phylogeography of ticks and tick-borne pathogens seen in recent years, and conclude that combined study of currently changing tick and tick-borne pathogen ranges and diversity, with phylogeographic analysis, may help us better predict future patterns of invasion and diversity. PMID:24010124

  10. Changing geographic ranges of ticks and tick-borne pathogens: drivers, mechanisms and consequences for pathogen diversity.

    PubMed

    Ogden, Nick H; Mechai, Samir; Margos, Gabriele

    2013-01-01

    The geographic ranges of ticks and tick-borne pathogens are changing due to global and local environmental (including climatic) changes. In this review we explore current knowledge of the drivers for changes in the ranges of ticks and tick-borne pathogen species and strains via effects on their basic reproduction number (R 0), and the mechanisms of dispersal that allow ticks and tick-borne pathogens to invade suitable environments. Using the expanding geographic distribution of the vectors and agent of Lyme disease as an example we then investigate what could be expected of the diversity of tick-borne pathogens during the process of range expansion, and compare this with what is currently being observed. Lastly we explore how historic population and range expansions and contractions could be reflected in the phylogeography of ticks and tick-borne pathogens seen in recent years, and conclude that combined study of currently changing tick and tick-borne pathogen ranges and diversity, with phylogeographic analysis, may help us better predict future patterns of invasion and diversity.

  11. Sea fan immunity and disease is influenced by metal pollution, host demography, and multiple stressors

    NASA Astrophysics Data System (ADS)

    Tracy, A. M.; Weil, E.; Harvell, C. D.

    2016-02-01

    Organisms in natural populations experience an onslaught of stressful conditions that may compromise their ability to fight pathogens, particularly if multiple stressors impact a host at the same time. Environmental stressors can also influence the pathogens. Despite the clear importance of environmental factors for coral host-pathogen interactions and the potential for population-level consequences, there is relatively little research to date on multiple stressors. The population of Caribbean sea fans, Gorgonia ventalina, in Parguera, Puerto Rico is a tractable system in which to study the effects of multiple stressors on two pathogens. Sea fans are dominant members of reefs that provide food and habitat for diverse reef inhabitants. In addition, there is already a foundation of research on sea fan disease and immunity. We first conducted field surveys of 15 sites to assess the effects of demographic and environmental factors on the prevalence and severity of multifocal purple spots (MFPS) and a Labyrinthulid stramenopile pathogen, as well as the host's cellular immune response to each pathogen. We complemented the field survey with a fully factorial, clonally replicated experiment on the separate and combined effects of thermal stress and copper pollution on both the host and the pathogen. Although water quality has been linked to coral disease, there are no studies investigating the role of metal or chemical pollutants, which are high at some of our study sites. Preliminary results show that the sea fan immune response to the Labyrinthulid depends on interactive effects of copper and thermal stress. The field survey identifies colony size as the main driver of MFPS. This in-depth perspective on sea fan disease speaks to the immune capabilities of cnidarians, highlights factors that modify those capabilities, and reflects the complex interaction of host, pathogens, and environment in this ecologically important coral.

  12. Polar bear encephalitis: establishment of a comprehensive next-generation pathogen analysis pipeline for captive and free-living wildlife.

    PubMed

    Szentiks, C A; Tsangaras, K; Abendroth, B; Scheuch, M; Stenglein, M D; Wohlsein, P; Heeger, F; Höveler, R; Chen, W; Sun, W; Damiani, A; Nikolin, V; Gruber, A D; Grobbel, M; Kalthoff, D; Höper, D; Czirják, G Á; Derisi, J; Mazzoni, C J; Schüle, A; Aue, A; East, M L; Hofer, H; Beer, M; Osterrieder, N; Greenwood, A D

    2014-05-01

    This report describes three possibly related incidences of encephalitis, two of them lethal, in captive polar bears (Ursus maritimus). Standard diagnostic methods failed to identify pathogens in any of these cases. A comprehensive, three-stage diagnostic 'pipeline' employing both standard serological methods and new DNA microarray and next generation sequencing-based diagnostics was developed, in part as a consequence of this initial failure. This pipeline approach illustrates the strengths, weaknesses and limitations of these tools in determining pathogen caused deaths in non-model organisms such as wildlife species and why the use of a limited number of diagnostic tools may fail to uncover important wildlife pathogens. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Vacated niches, competitive release and the community ecology of pathogen eradication

    PubMed Central

    Lloyd-Smith, James O.

    2013-01-01

    A recurring theme in the epidemiological literature on disease eradication is that each pathogen occupies an ecological niche, and eradication of one pathogen leaves a vacant niche that favours the emergence of new pathogens to replace it. However, eminent figures have rejected this view unequivocally, stating that there is no basis to fear pathogen replacement and even that pathogen niches do not exist. After exploring the roots of this controversy, I propose resolutions to disputed issues by drawing on broader ecological theory, and advance a new consensus based on robust mechanistic principles. I argue that pathogen eradication (and cessation of vaccination) leads to a ‘vacated niche’, which could be re-invaded by the original pathogen if introduced. Consequences for other pathogens will vary, with the crucial mechanisms being competitive release, whereby the decline of one species allows its competitors to perform better, and evolutionary adaptation. Hence, eradication can cause a quantitative rise in the incidence of another infection, but whether this leads to emergence as an endemic pathogen depends on additional factors. I focus on the case study of human monkeypox and its rise following smallpox eradication, but also survey how these ideas apply to other pathogens and discuss implications for eradication policy. PMID:23798698

  14. Biocontainment laboratory risk assessment: perspectives and considerations.

    PubMed

    Patterson, Amy; Fennington, Kelly; Bayha, Ryan; Wax, Diane; Hirschberg, Rona; Boyd, Nancy; Kurilla, Michael

    2014-07-01

    The ability to respond to public health emergencies involving infectious diseases as well as our ability to adequately prepare for as yet unknown or unrecognized emerging infectious diseases requires suitable facilities within which scientific investigations can take place. To ensure the safe conduct of such investigations so that laboratory workers and the general public are protected from potential consequences of accidental or intentional release of high consequence pathogens, special containment facilities have been designed and constructed. Evaluation of the adequacy of containment for these types of investigations requires a risk assessment (RA) as part of the overall construction project for these types of laboratories. A discussion of the RA process along with considerations that impact the design of such studies and the overall results is presented. Published 2014. This article is a US Government work and is in the public domain in the USA.

  15. Superficial veterinary mycoses.

    PubMed

    Bond, Ross

    2010-03-04

    Dermatophytes are significant pathogens in animal health due to their zoonotic potential, the economic consequences of infection in farm animal and fur production systems, and the distressing lesions they cause in small domestic pets. Malassezia spp are normal commensal and occasional pathogens of the skin of many veterinary species. Malassezia pachydermatis is a very common cause of otitis and pruritic dermatitis in dogs but is of less importance in other veterinary species. Dermatophytosis, and Malassezia otitis and dermatitis, represent the superficial mycoses of greatest significance in companion and farm animal health. Although the dermatophytes and Malassezia spp both exist in the stratum corneum of mammalian skin, there are important differences in the epidemiology, pathogenesis, and clinical consequences of infection. Dermatophytes are significant due to their zoonotic potential, the economic consequences of infection in farm animal and fur production systems, and the concern for owners of pets with inflammatory skin disease that is sometimes severe. Malassezia spp are normal commensals and occasional pathogens of the skin for many veterinary species, and M pachydermatis is a very common cause of otitis and pruritic dermatitis in dogs. This chapter will focus on the epidemiologic, clinical, diagnostic, and therapeutic aspects of dermatophytosis and Malassezia dermatitis in veterinary species. There are generally only sporadic reports of other superficial mycoses, such as candidiasis, piedra, and Rhodotorula dermatitis in veterinary medicine, and these are not included here. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Climate extremes promote fatal co-infections during canine distemper epidemics in African lions.

    PubMed

    Munson, Linda; Terio, Karen A; Kock, Richard; Mlengeya, Titus; Roelke, Melody E; Dubovi, Edward; Summers, Brian; Sinclair, Anthony R E; Packer, Craig

    2008-06-25

    Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five "silent" CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become increasingly common if climate extremes disrupt historic stable relationships between co-existing pathogens and their susceptible hosts.

  17. Climate Extremes Promote Fatal Co-Infections during Canine Distemper Epidemics in African Lions

    PubMed Central

    Munson, Linda; Terio, Karen A.; Kock, Richard; Mlengeya, Titus; Roelke, Melody E.; Dubovi, Edward; Summers, Brian; Sinclair, Anthony R. E.; Packer, Craig

    2008-01-01

    Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five “silent” CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become increasingly common if climate extremes disrupt historic stable relationships between co-existing pathogens and their susceptible hosts. PMID:18575601

  18. Frequent combination of antimicrobial multiresistance and extraintestinal pathogenicity in Escherichia coli isolates from urban rats (Rattus norvegicus) in Berlin, Germany.

    PubMed

    Guenther, Sebastian; Bethe, Astrid; Fruth, Angelika; Semmler, Torsten; Ulrich, Rainer G; Wieler, Lothar H; Ewers, Christa

    2012-01-01

    Urban rats present a global public health concern as they are considered a reservoir and vector of zoonotic pathogens, including Escherichia coli. In view of the increasing emergence of antimicrobial resistant E. coli strains and the on-going discussion about environmental reservoirs, we intended to analyse whether urban rats might be a potential source of putatively zoonotic E. coli combining resistance and virulence. For that, we took fecal samples from 87 brown rats (Rattus norvegicus) and tested at least three E. coli colonies from each animal. Thirty two of these E. coli strains were pre-selected from a total of 211 non-duplicate isolates based on their phenotypic resistance to at least three antimicrobial classes, thus fulfilling the definition of multiresistance. As determined by multilocus sequence typing (MLST), these 32 strains belonged to 24 different sequence types (STs), indicating a high phylogenetic diversity. We identified STs, which frequently occur among extraintestinal pathogenic E. coli (ExPEC), such as STs 95, 131, 70, 428, and 127. Also, the detection of a number of typical virulence genes confirmed that the rats tested carried ExPEC-like strains. In particular, the finding of an Extended-spectrum beta-lactamase (ESBL)-producing strain which belongs to a highly virulent, so far mainly human- and avian-restricted ExPEC lineage (ST95), which expresses a serogroup linked with invasive strains (O18:NM:K1), and finally, which produces an ESBL-type frequently identified among human strains (CTX-M-9), pointed towards the important role, urban rats might play in the transmission of multiresistant and virulent E. coli strains. Indeed, using a chicken infection model, this strain showed a high in vivo pathogenicity. Imagining the high numbers of urban rats living worldwide, the way to the transmission of putatively zoonotic, multiresistant, and virulent strains might not be far ahead. The unforeseeable consequences of such an emerging public health threat need careful consideration in the future.

  19. A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses

    PubMed Central

    Moser, Lindsey A.; Ramirez-Carvajal, Lisbeth; Puri, Vinita; Pauszek, Steven J.; Matthews, Krystal; Dilley, Kari A.; Mullan, Clancy; McGraw, Jennifer; Khayat, Michael; Beeri, Karen; Yee, Anthony; Dugan, Vivien; Heise, Mark T.; Frieman, Matthew B.; Rodriguez, Luis L.; Bernard, Kristen A.; Wentworth, David E.

    2016-01-01

    ABSTRACT Several biosafety level 3 and/or 4 (BSL-3/4) pathogens are high-consequence, single-stranded RNA viruses, and their genomes, when introduced into permissive cells, are infectious. Moreover, many of these viruses are select agents (SAs), and their genomes are also considered SAs. For this reason, cDNAs and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral RNA before transfer out of the BSL-3/4 and/or SA laboratory. This tremendously limits the capacity to conduct viral genomic research, particularly the application of next-generation sequencing (NGS). Here, we present a sequence-independent method to rapidly amplify viral genomic RNA while simultaneously abolishing both viral and genomic RNA infectivity across multiple single-stranded positive-sense RNA (ssRNA+) virus families. The process generates barcoded DNA amplicons that range in length from 300 to 1,000 bp, which cannot be used to rescue a virus and are stable to transport at room temperature. Our barcoding approach allows for up to 288 barcoded samples to be pooled into a single library and run across various NGS platforms without potential reconstitution of the viral genome. Our data demonstrate that this approach provides full-length genomic sequence information not only from high-titer virion preparations but it can also recover specific viral sequence from samples with limited starting material in the background of cellular RNA, and it can be used to identify pathogens from unknown samples. In summary, we describe a rapid, universal standard operating procedure that generates high-quality NGS libraries free of infectious virus and infectious viral RNA. IMPORTANCE This report establishes and validates a standard operating procedure (SOP) for select agents (SAs) and other biosafety level 3 and/or 4 (BSL-3/4) RNA viruses to rapidly generate noninfectious, barcoded cDNA amenable for next-generation sequencing (NGS). This eliminates the burden of testing all processed samples derived from high-consequence pathogens prior to transfer from high-containment laboratories to lower-containment facilities for sequencing. Our established protocol can be scaled up for high-throughput sequencing of hundreds of samples simultaneously, which can dramatically reduce the cost and effort required for NGS library construction. NGS data from this SOP can provide complete genome coverage from viral stocks and can also detect virus-specific reads from limited starting material. Our data suggest that the procedure can be implemented and easily validated by institutional biosafety committees across research laboratories. PMID:27822536

  20. Constitutive Expression of Mammalian Nitric Oxide Synthase in Tobacco Plants Triggers Disease Resistance to Pathogens

    PubMed Central

    Chun, Hyun Jin; Park, Hyeong Cheol; Koo, Sung Cheol; Lee, Ju Huck; Park, Chan Young; Choi, Man Soo; Kang, Chang Ho; Baek, Dongwon; Cheong, Yong Hwa; Yun, Dae-Jin; Chung, Woo Sik; Cho, Moo Je; Kim, Min Chul

    2012-01-01

    Nitric oxide (NO) is known for its role in the activation of plant defense responses. To examine the involvement and mode of action of NO in plant defense responses, we introduced calmodulin-dependent mammalian neuronal nitric oxide synthase (nNOS), which controls the CaMV35S promoter, into wild-type and NahG tobacco plants. Constitutive expression of nNOS led to NO production and triggered spontaneous induction of leaf lesions. Transgenic plants accumulated high amounts of H2O2, with catalase activity lower than that in the wild type. nNOS transgenic plants contained high levels of salicylic acid (SA), and they induced an array of SA-, jasmonic acid (JA)-, and/or ethylene (ET)-related genes. Consequently, NahG co-expression blocked the induction of systemic acquired resistance (SAR)-associated genes in transgenic plants, implying SA is involved in NO-mediated induction of SAR genes. The transgenic plants exhibited enhanced resistance to a spectrum of pathogens, including bacteria, fungi, and viruses. Our results suggest a highly ranked regulatory role for NO in SA-, JA-, and/or ET-dependent pathways that lead to disease resistance. PMID:23124383

  1. The effect of tar spot pathogen on host plant carbon balance and its possible consequences on a tundra ecosystem.

    PubMed

    Masumoto, Shota; Uchida, Masaki; Tojo, Motoaki; Herrero, Maria Luz; Mori, Akira S; Imura, Satoshi

    2018-03-01

    In Arctic tundra, plant pathogens have substantial effects on the growth and survival of hosts, and impacts on the carbon balance at the scale of ecological systems. To understand these effects on carbon dynamics across different scales including plant organ, individual, population and ecosystem, we focused on two primary factors: host productivity reduction and carbon consumption by the pathogen. We measured the effect of the pathogen on photosynthetic and respiratory activity in the host. We also measured respiration and the amount of carbon in the pathogen. We constructed a model based on these two factors, and calculated pathogenic effects on the carbon balance at different organismal and ecological scales. We found that carbon was reduced in infected leaves by 118% compared with healthy leaves; the major factor causing this loss was pathogenic carbon consumption. The carbon balance at the population and ecosystem levels decreased by 35% and 20%, respectively, at an infection rate of 30%. This case study provides the first evidence that a host plant can lose more carbon through pathogenic carbon consumption than through a reduction in productivity. Such a pathogenic effect could greatly change ecosystem carbon cycling without decreasing annual productivity.

  2. Attenuated Salmonella Typhimurium Lacking the Pathogenicity Island-2 Type 3 Secretion System Grow to High Bacterial Numbers inside Phagocytes in Mice

    PubMed Central

    Grant, Andrew J.; Morgan, Fiona J. E.; McKinley, Trevelyan J.; Foster, Gemma L.; Maskell, Duncan J.; Mastroeni, Pietro

    2012-01-01

    Intracellular replication within specialized vacuoles and cell-to-cell spread in the tissue are essential for the virulence of Salmonella enterica. By observing infection dynamics at the single-cell level in vivo, we have discovered that the Salmonella pathogenicity island 2 (SPI-2) type 3 secretory system (T3SS) is dispensable for growth to high intracellular densities. This challenges the concept that intracellular replication absolutely requires proteins delivered by SPI-2 T3SS, which has been derived largely by inference from in vitro cell experiments and from unrefined measurement of net growth in mouse organs. Furthermore, we infer from our data that the SPI-2 T3SS mediates exit from infected cells, with consequent formation of new infection foci resulting in bacterial spread in the tissues. This suggests a new role for SPI-2 in vivo as a mediator of bacterial spread in the body. In addition, we demonstrate that very similar net growth rates of attenuated salmonellae in organs can be derived from very different underlying intracellular growth dynamics. PMID:23236281

  3. Overexpression of an ABC transporter and mutations of GyrA, GyrB, and ParC in contributing to high-level ciprofloxacin resistance in Streptococcus suis type 2.

    PubMed

    Yao, Jie; Shang, Kexin; Huang, Jinhu; Ran, Wei; Kashif, Jam; Wang, Liping

    2014-04-01

    Streptococcus suis is a pathogen of zoonotic diseases. Moreover, the emergence of fluoro-quinolones (FQs) resistance in this pathogen has severe consequences for pigs and human health. In this study, the molecular mechanism of FQs resistance in S. suis type 2 (SS2) sensitive strains isolated from pigs was assessed after in vitro induction of resistance against the most frequently used FQs: ciprofloxacin, norfloxacin, and enrofloxacin. Proteome analysis, sequencing and real-time RT-PCR results strongly established an overexpression of an ABC transporter protein (other than SatAB) and topoisomerase mutations in GyrA (Ser81Arg), GyrB (Glu354Lys), and ParC (Ser79Phe) in contributing to high level ciprofloxacin resistance in SS2. Due to the overexpression of the ABC transporter, intracellular ciprofloxacin concentrations were significantly lower in the resistant strains than those of sensitive strains after 20, 35, and 60 min exposures to ciprofloxacin (p < 0.05). It was concluded that improper use of FQs is one of the main causes of the emergence of this zoonotic pathogen as a multiresistant organism against commonly used antibiotics. The existence of an efflux-like protein is an incentive to find new drug targets to avoid the spread of FQs-resistant S. suis isolates in pigs and the human population.

  4. THE CONSEQUENCES OF CROSSING BARRIERS AND BOUNDARIES

    EPA Science Inventory

    This is a brief, general ecological theory presentation which explains concepts of physically defining habitational zones, ecological barriers, ecological boundaries and vehicles, plus biologically defining pathogens, hosts, and vectors.

  5. Microbial mito-pathogens: fact or fiction?

    PubMed

    Bongaerts, Ger P A; van den Heuvel, Lambert P

    2008-01-01

    Mitochondria are bacteria-like semi-autonomous intracellular organelles that function as the powerhouses of eukaryotic cells. Inactivation or destruction of these organelles may have far-reaching consequences regarding the viability of the cells and thus of tissues, organs and finally even the body. Since mitochondria resemble (degenerated) bacteria, we have extrapolated from both cytological and microbiological facts the existence of various (kinds of) mitochondrion-specific microbial pathogens, i.e., pathogenic micro-organisms that may damage or destroy the mitochondria from within. These mito-pathogens may include mitoviruses, mitoviroids and mitobacteria. Although these mito-pathogens have not yet been demonstrated in humans, their theoretical degenerative effect regarding energy production from energy-rich substrates, such as carbohydrates and fats, might explain diseases that have not yet been understood, such as prion diseases and post-traumatic muscle dystrophy. Therefore, these kinds of micro-organisms should be kept in mind.

  6. Biosensor for the detection of Listeria monocytogenes: emerging trends.

    PubMed

    Soni, Dharmendra Kumar; Ahmad, Rafiq; Dubey, Suresh Kumar

    2018-05-23

    The early detection of Listeria monocytogenes (L. monocytogenes) and understanding the disease burden is of paramount interest. The failure to detect pathogenic bacteria in the food industry may have terrible consequences, and poses deleterious effects on human health. Therefore, integration of methods to detect and trace the route of pathogens along the entire food supply network might facilitate elucidation of the main contamination sources. Recent research interest has been oriented towards the development of rapid and affordable pathogen detection tools/techniques. An innovative and new approach like biosensors has been quite promising in revealing the foodborne pathogens. In spite of the existing knowledge, advanced research is still needed to substantiate the expeditious nature and sensitivity of biosensors for rapid and in situ analysis of foodborne pathogens. This review summarizes recent developments in optical, piezoelectric, cell-based, and electrochemical biosensors for Listeria sp. detection in clinical diagnostics, food analysis, and environmental monitoring, and also lists their drawbacks and advantages.

  7. The poultry red mite (Dermanyssus gallinae): a potential vector of pathogenic agents.

    PubMed

    Valiente Moro, Claire; De Luna, Carlos J; Tod, Alexander; Guy, Jonathan H; Sparagano, Olivier A E; Zenner, Lionel

    2009-06-01

    The poultry red mite, D. gallinae has been involved in the transmission of many pathogenic agents, responsible for serious diseases both in animals and humans. Nowadays, few effective methods are available to control the ectoparasite in poultry farms. Consequently, this is an emerging problem which must be taken into account to maintain good health in commercial egg production. This paper addresses the vector capacity of the ectoparasite with special emphasis on salmonellae, pathogenic agents responsible for many of the most important outbreaks of food-borne diseases worlwide. It has been experimentally shown that D. gallinae could act as a biological vector of S. enteritidis and natural carriage of these bacteria by the mite on poultry premises has also been reported. It was also found that D. gallinae carried other pathogens such as E. coli, Shigella sp., and Staphylococcus, thus increasing the list of pathogenic agents potentially transmitted by the mite.

  8. Enteric porcine viruses in farmed shellfish in Denmark.

    PubMed

    Krog, J S; Larsen, L E; Schultz, A C

    2014-09-01

    Bivalve shellfish are at constant risk of being exposed to pathogens as a consequence of contamination of the shellfish beds with human or animal waste originating from sewage treatment plants or slurry fertilized fields. Consumption of contaminated oysters and mussels are frequently reported as causes of disease outbreaks caused by norovirus or hepatitis A virus. Other zoonotic pathogens such as hepatitis E virus (HEV), rotavirus (RV) and Salmonella from livestock may also be transmitted to shellfish via this route. In this study, 29 pooled samples from commercial Danish blue mussels were tested for porcine pathogens and indicator bacteria Escherichia coli (E. coli). All samples tested negative for HEV, RV and Salmonella, whereas E. coli and the highly stable porcine circovirus type 2 (PCV2) were detected in eight and 12 samples, respectively. This is the first study to report the detection of PCV2 in commercial mussels. Based on the detection of PCV2 in clean areas with low prevalence of the normally applied fecal indicator E. coli, testing for PCV2 may be a more sensitive and robust specific porcine waste indicator in shellfish harvesting areas. Copyright © 2014. Published by Elsevier B.V.

  9. Unbiased Strain-Typing of Arbovirus Directly from Mosquitoes Using Nanopore Sequencing: A Field-forward Biosurveillance Protocol.

    PubMed

    Russell, Joseph A; Campos, Brittany; Stone, Jennifer; Blosser, Erik M; Burkett-Cadena, Nathan; Jacobs, Jonathan L

    2018-04-03

    The future of infectious disease surveillance and outbreak response is trending towards smaller hand-held solutions for point-of-need pathogen detection. Here, samples of Culex cedecei mosquitoes collected in Southern Florida, USA were tested for Venezuelan Equine Encephalitis Virus (VEEV), a previously-weaponized arthropod-borne RNA-virus capable of causing acute and fatal encephalitis in animal and human hosts. A single 20-mosquito pool tested positive for VEEV by quantitative reverse transcription polymerase chain reaction (RT-qPCR) on the Biomeme two3. The virus-positive sample was subjected to unbiased metatranscriptome sequencing on the Oxford Nanopore MinION and shown to contain Everglades Virus (EVEV), an alphavirus in the VEEV serocomplex. Our results demonstrate, for the first time, the use of unbiased sequence-based detection and subtyping of a high-consequence biothreat pathogen directly from an environmental sample using field-forward protocols. The development and validation of methods designed for field-based diagnostic metagenomics and pathogen discovery, such as those suitable for use in mobile "pocket laboratories", will address a growing demand for public health teams to carry out their mission where it is most urgent: at the point-of-need.

  10. Pathogen prevalence predicts human cross-cultural variability in individualism/collectivism.

    PubMed

    Fincher, Corey L; Thornhill, Randy; Murray, Damian R; Schaller, Mark

    2008-06-07

    Pathogenic diseases impose selection pressures on the social behaviour of host populations. In humans (Homo sapiens), many psychological phenomena appear to serve an antipathogen defence function. One broad implication is the existence of cross-cultural differences in human cognition and behaviour contingent upon the relative presence of pathogens in the local ecology. We focus specifically on one fundamental cultural variable: differences in individualistic versus collectivist values. We suggest that specific behavioural manifestations of collectivism (e.g. ethnocentrism, conformity) can inhibit the transmission of pathogens; and so we hypothesize that collectivism (compared with individualism) will more often characterize cultures in regions that have historically had higher prevalence of pathogens. Drawing on epidemiological data and the findings of worldwide cross-national surveys of individualism/collectivism, our results support this hypothesis: the regional prevalence of pathogens has a strong positive correlation with cultural indicators of collectivism and a strong negative correlation with individualism. The correlations remain significant even when controlling for potential confounding variables. These results help to explain the origin of a paradigmatic cross-cultural difference, and reveal previously undocumented consequences of pathogenic diseases on the variable nature of human societies.

  11. Bacterial and parasitic diseases of parrots.

    PubMed

    Doneley, Robert J T

    2009-09-01

    As wild-caught birds become increasingly rare in aviculture, there is a corresponding decline in the incidence of bacterial and parasitic problems and an increase in the recognition of the importance of maintaining health through better nutrition and husbandry. Nevertheless, the relatively close confines of captivity mean an increased pathogen load in the environment in which companion and aviary parrots live. This increased pathogen load leads to greater exposure of these birds to bacteria and parasites, and consequently a greater risk of infection and disease. This article discusses bacterial and parasitic infections in companion and aviary parrots. It includes the origins, pathogens, diagnosis, treatment, and some of the associated risk factors.

  12. Draft genome sequence of Enterococcus faecium strain LMG 8148.

    PubMed

    Michiels, Joran E; Van den Bergh, Bram; Fauvart, Maarten; Michiels, Jan

    2016-01-01

    Enterococcus faecium, traditionally considered a harmless gut commensal, is emerging as an important nosocomial pathogen showing increasing rates of multidrug resistance. We report the draft genome sequence of E. faecium strain LMG 8148, isolated in 1968 from a human in Gothenburg, Sweden. The draft genome has a total length of 2,697,490 bp, a GC-content of 38.3 %, and 2,402 predicted protein-coding sequences. The isolation of this strain predates the emergence of E. faecium as a nosocomial pathogen. Consequently, its genome can be useful in comparative genomic studies investigating the evolution of E. faecium as a pathogen.

  13. Conversations between kingdoms: small RNAs.

    PubMed

    Weiberg, Arne; Bellinger, Marschal; Jin, Hailing

    2015-04-01

    Humans, animals, and plants are constantly under attack from pathogens and pests, resulting in severe consequences on global human health and crop production. Small RNA (sRNA)-mediated RNA interference (RNAi) is a conserved regulatory mechanism that is involved in almost all eukaryotic cellular processes, including host immunity and pathogen virulence. Recent evidence supports the significant contribution of sRNAs and RNAi to the communication between hosts and some eukaryotic pathogens, pests, parasites, or symbiotic microorganisms. Mobile silencing signals—most likely sRNAs—are capable of translocating from the host to its interacting organism, and vice versa. In this review, we will provide an overview of sRNA communications between different kingdoms, with a primary focus on the advances in plant-pathogen interaction systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Human quarantine: Toward reducing infectious pressure on chimpanzees at the Taï Chimpanzee Project, Côte d'Ivoire.

    PubMed

    Grützmacher, Kim; Keil, Verena; Leinert, Vera; Leguillon, Floraine; Henlin, Arthur; Couacy-Hymann, Emmanuel; Köndgen, Sophie; Lang, Alexander; Deschner, Tobias; Wittig, Roman M; Leendertz, Fabian H

    2018-01-01

    Due to their genetic relatedness, great apes are highly susceptible to common human respiratory pathogens. Although most respiratory pathogens, such as human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), rarely cause severe disease in healthy human adults, they are associated with considerable morbidity and mortality in wild great apes habituated to humans for research or tourism. To prevent pathogen transmission, most great ape projects have established a set of hygiene measures ranging from keeping a specific distance, to the use of surgical masks and establishment of quarantines. This study investigates the incidence of respiratory symptoms and human respiratory viruses in humans at a human-great ape interface, the Taï Chimpanzee Project (TCP) in Côte d'Ivoire, and consequently, the effectiveness of a 5-day quarantine designed to reduce the risk of potential exposure to human respiratory pathogens. To assess the impact of quarantine as a preventative measure, we monitored the quarantine process and tested 262 throat swabs for respiratory viruses, collected during quarantine over a period of 1 year. Although only 1 subject tested positive for a respiratory virus (HRSV), 17 subjects developed symptoms of infection while in quarantine and were subsequently kept from approaching the chimpanzees, preventing potential exposure in 18 cases. Our results suggest that quarantine-in combination with monitoring for symptoms-is effective in reducing the risk of potential pathogen exposure. This research contributes to our understanding of how endangered great apes can be protected from human-borne infectious disease. © 2017 Wiley Periodicals, Inc.

  15. Quantifying climate change impacts on runoff of zoonotic pathogens from land

    NASA Astrophysics Data System (ADS)

    Sterk, Ankie; de Roda Husman, Ana Maria; Stergiadi, Maria; de Nijs, Ton; Schijven, Jack

    2013-04-01

    Several studies have shown a correlation between rainfall and waterborne disease outbreaks. One of the mechanisms whereby rainfall may cause outbreaks is through an increase in runoff of animal faeces from fields to surface waters. Faeces originating from wildlife, domestic animals or manure-fertilized fields, is considered an important source of zoonotic pathogens to which people may be exposed by water recreation or drinking-water consumption. Climate changes affect runoff because of increasing winter precipitation and more extreme precipitation events, as well as changes in evaporation. Furthermore, drier summers are leading to longer periods of high soil moisture deficits, increasing the hydrophobicity of soil and consequently changing infiltration capacities. A conceptual model is designed to describe the impacts of climate changes on the terrestrial and aquatic ecosystems, which are both directly and indirectly affecting pathogen loads in the environment and subsequent public health risks. One of the major outcomes was the lack of quantitative data and limited qualitative analyses of impacts of climate changes on pathogen runoff. Quantifying the processes by which micro-organisms are transported from fields to waters is important to be able to estimate such impacts to enable targeted implementation of effective intervention measures. A quantitative model using Mathematica software will be developed to estimate concentrations of pathogens originating from overland flow during runoff events. Different input sources will be included by applying different land-use scenarios, including point source faecal pollution from dairy cows and geese and diffuse source pollution by fertilization. Zoonotic pathogens, i.e. Cryptosporidium and Campylobacter, were selected based on transport properties, faecal loads and disease burden. Transport and survival rates of these pathogens are determined including effects of changes in precipitation but also temperature induced changes on die-off. Moreover, besides climate and surface variables, changes in soil or vegetation and adjustments in agricultural policy are considered. Output of this model can be used to assess how expected climate changes could affect pathogen concentrations in surface waters. The long term aim is to include this information in a larger framework, to quantify the impact of climate change on the infection and eventual disease risks due to exposure to water transmitted pathogens.

  16. Removal of enteric bacteria in constructed treatment wetlands with emergent macrophytes: a review.

    PubMed

    Vymazal, Jan

    2005-01-01

    Domestic and municipal sewage contains various pathogenic or potentially pathogenic microorganisms which, depending on species concentration, pose a potential risk to human health and whose presence must therefore be reduced in the course of wastewater treatment. The removal of microbiological pollution is seldom a primary target for constructed treatment wetlands (CWs). However, wetlands are known to act as excellent biofilters through a complex of physical, chemical and biological factors which all participate in the reduction of the number of bacteria. Measurement of human pathogenic organisms in untreated and treated wastewater is expensive and technically challenging. Consequently, environmental engineers have sought indicator organisms that are (1) easy to monitor and (2) correlate with population of pathogenic organisms. The most frequently used indicators are total coliforms, fecal coliforms, fecal streptococci and Escherichia coli. The literature survey of 60 constructed wetlands with emergent vegetation around the world revealed that removal of total and fecal coliforms in constructed wetlands with emergent macrophytes is high, usually 95 to > 99% while removal of fecal streptococci is lower, usually 80-95%. Because bacterial removal efficiency is a function of inflow bacteria number, the high removal effects are achieved for untreated or mechanically pretreated wastewater. Therefore, the outflow numbers of bacteria are more important. For TC and FC the outflow concentrations are usually in the range of 10(2) to 10(5) CFU/ 100 ml while for FS the range is between 10(2) and 10(4) CFU/ 100 ml. Results from operating systems suggest that enteric microbe removal efficiency in CWs with emergent macrophytes is primarily influenced by hydraulic loading rate (HLR) and the resultant hydraulic residence time (HRT) and the presence of vegetation. Removal of enteric bacteria follows approximately a first-order relationship.

  17. Expert Elicitation Provides a Rapid Alternative to Formal Case-Control Study of an H7N9 Avian Influenza Outbreak in the United States.

    PubMed

    Gustafson, L; Jones, R; Dufour-Zavala, L; Jensen, E; Malinak, C; McCarter, S; Opengart, K; Quinn, J; Slater, T; Delgado, A; Talbert, M; Garber, L; Remmenga, M; Smeltzer, M

    2018-06-01

    An expert elicitation was staged to rapidly decipher plausible routes and risks of pathogen transmission in the 2017 H7N9 avian influenza (AI) outbreak in the four-state region of Tennessee, Alabama, Georgia, and Kentucky. The process included the identification of risk factors found in a preponderance of commercial broiler breeder case farms over matched controls and an opinion-based weighting of risks and mitigations perceived influential to this outbreak. Although the two highly pathogenic AI case farms had general location and company ownership in common, obvious connections were lacking for the remainder of H7N9-infected (all low pathogenicity) commercial farms. Expert elicitation of differences between known cases and controls suggested a key role for environmental rather than lateral (business network) pathways in the distribution of low pathogenicity AI across commercial broiler breeder operations. Factors with greatest strength as predictors of disease, whether or not they were causal, included mesopredator or rodent incursions, enclosure defects, and habitat disturbance that might attract wildlife to the farm (e.g., feed spills and vacating of neighboring properties). Business affiliations that may have facilitated farm-to-farm transfer, in contrast, were limited. Biosecurity standards varied across this study group but were no more or less stringent among cases over controls. However, results from a parallel hypothetical scenario staged to address field data gaps suggest that uniformity and consistency in the implementation of biosecurity practices may impact risk of disease introduction. Importantly, this study was conducted within a few weeks and with little disruption to emergency response activities. As such, the approach offers an alternative model for interim field investigation of new or emerging high-consequence diseases with immediate decision support needs.

  18. The niche reduction approach: an opportunity for optimal control of infectious diseases in low-income countries?

    PubMed

    Roche, Benjamin; Broutin, Hélène; Choisy, Marc; Godreuil, Sylvain; de Magny, Guillaume Constantin; Chevaleyre, Yann; Zucker, Jean-Daniel; Breban, Romulus; Cazelles, Bernard; Simard, Frédéric

    2014-07-25

    During the last century, WHO led public health interventions that resulted in spectacular achievements such as the worldwide eradication of smallpox and the elimination of malaria from the Western world. However, besides major successes achieved worldwide in infectious diseases control, most elimination/control programs remain frustrating in many tropical countries where specific biological and socio-economical features prevented implementation of disease control over broad spatial and temporal scales. Emblematic examples include malaria, yellow fever, measles and HIV. There is consequently an urgent need to develop affordable and sustainable disease control strategies that can target the core of infectious diseases transmission in highly endemic areas. Meanwhile, although most pathogens appear so difficult to eradicate, it is surprising to realize that human activities are major drivers of the current high rate of extinction among upper organisms through alteration of their ecology and evolution, i.e., their "niche". During the last decades, the accumulation of ecological and evolutionary studies focused on infectious diseases has shown that the niche of a pathogen holds more dimensions than just the immune system targeted by vaccination and treatment. Indeed, it is situated at various intra- and inter- host levels involved on very different spatial and temporal scales. After developing a precise definition of the niche of a pathogen, we detail how major advances in the field of ecology and evolutionary biology of infectious diseases can enlighten the planning and implementation of infectious diseases control in tropical countries with challenging economic constraints. We develop how the approach could translate into applied cases, explore its expected benefits and constraints, and we conclude on the necessity of such approach for pathogen control in low-income countries.

  19. Disease resistance in Atlantic salmon (Salmo salar): coinfection of the intracellular bacterial pathogen Piscirickettsia salmonis and the sea louse Caligus rogercresseyi.

    PubMed

    Lhorente, Jean Paul; Gallardo, José A; Villanueva, Beatriz; Carabaño, María J; Neira, Roberto

    2014-01-01

    Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection. In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections. C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h2SI = 0.23 ± 0.07; h2LC = 0.17 ± 0.08; h2HC = 0.24 ± 0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (rg LC-HC = 0.99 ± 0.01) but not between the single and coinfection treatments (rg SI-LC = -0.14 ± 0.33; rg SI-HC = 0.32 ± 0.34). C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation.

  20. Experimental Adaptation of Burkholderia cenocepacia to Onion Medium Reduces Host Range ▿ † ‡

    PubMed Central

    Ellis, Crystal N.; Cooper, Vaughn S.

    2010-01-01

    It is unclear whether adaptation to a new host typically broadens or compromises host range, yet the answer bears on the fate of emergent pathogens and symbionts. We investigated this dynamic using a soil isolate of Burkholderia cenocepacia, a species that normally inhabits the rhizosphere, is related to the onion pathogen B. cepacia, and can infect the lungs of cystic fibrosis patients. We hypothesized that adaptation of B. cenocepacia to a novel host would compromise fitness and virulence in alternative hosts. We modeled adaptation to a specific host by experimentally evolving 12 populations of B. cenocepacia in liquid medium composed of macerated onion tissue for 1,000 generations. The mean fitness of all populations increased by 78% relative to the ancestor, but significant variation among lines was observed. Populations also varied in several phenotypes related to host association, including motility, biofilm formation, and quorum-sensing function. Together, these results suggest that each population adapted by fixing different sets of adaptive mutations. However, this adaptation was consistently accompanied by a loss of pathogenicity to the nematode Caenorhabditis elegans; by 500 generations most populations became unable to kill nematodes. In conclusion, we observed a narrowing of host range as a consequence of prolonged adaptation to an environment simulating a specific host, and we suggest that emergent pathogens may face similar consequences if they become host-restricted. PMID:20154121

  1. Incorporating risk communication into highly pathogenic avian influenza preparedness and response efforts.

    PubMed

    Voss, Shauna J; Malladi, Sasidhar; Sampedro, Fernando; Snider, Tim; Goldsmith, Timothy; Hueston, William D; Lauer, Dale C; Halvorson, David A

    2012-12-01

    A highly pathogenic avian influenza (HPAI) outbreak in the United States will initiate a federal emergency response effort that will consist of disease control and eradication efforts, including quarantine and movement control measures. These movement control measures will not only apply to live animals but also to animal products. However, with current egg industry "just-in-time" production practices, limited storage is available to hold eggs. As a result, stop movement orders can have significant unintended negative consequences, including severe disruptions to the food supply chain. Because stakeholders' perceptions of risk vary, waiting to initiate communication efforts until an HPAI event occurs can hinder disease control efforts, including the willingness of producers to comply with the response, and also can affect consumers' demand for the product. A public-private-academic partnership was formed to assess actual risks involved in the movement of egg industry products during an HPAI event through product specific, proactive risk assessments. The risk analysis process engaged a broad representation of stakeholders and promoted effective risk management and communication strategies before an HPAI outbreak event. This multidisciplinary team used the risk assessments in the development of the United States Department of Agriculture, Highly Pathogenic Avian Influenza Secure Egg Supply Plan, a comprehensive response plan that strives to maintain continuity of business. The collaborative approach that was used demonstrates how a proactive risk communication strategy that involves many different stakeholders can be valuable in the development of a foreign animal disease response plan and build working relationships, trust, and understanding.

  2. Panzootics and the poor: devising a global livestock disease prioritisation framework for poverty alleviation.

    PubMed

    Heffernan, C

    2009-12-01

    Panzootics such as highly pathogenic avian influenza and Rift Valley fever have originated from the South, largely among poor communities. On a global level, approximately two-thirds of those individuals living on less than US$2 per day keep livestock. Consequently, there is a need to better target animal health interventions for poverty reduction using an evidence-based approach. Therefore, the paper offers a three-step prioritisation framework using calculations derived from standard poverty measures: the poverty gap and the head count ratio. Data from 265 poor livestock-keeping households in Kenya informed the study. The results demonstrate that, across a spectrum of producers, the dependence upon particular species varies. Furthermore, the same livestock disease has differing impacts on the depth and severity of poverty. Consequently, animal health interventions need to account for variability in income effects at the species and disease levels.

  3. Animal health economics: an aid to decisionmaking on animal health interventions - case studies in the United States of America.

    PubMed

    Marsh, T L; Pendell, D; Knippenberg, R

    2017-04-01

    For animal disease events the outcomes and consequences often remain unclear or uncertain, including the expected changes in benefits (e.g. profit to firms, prices to consumers) and in costs (e.g. response, clean-up). Moreover, the measurement of changes in benefits and costs across alternative interventions used to control animal disease events may be inexact. For instance, the economic consequences of alternative vaccination strategies to mitigate a disease can vary in magnitude due to trade embargoes and other factors. The authors discuss the economic measurement of animal disease outbreaks and interventions and how measurement is used in private and public decision-making. Two illustrative case studies in the United States of America are provided: a hypothetical outbreak of foot and mouth disease in cattle, and the 2014-2015 outbreak of highly pathogenic avian influenza in poultry.

  4. Olive anthracnose: a yield- and oil quality-degrading disease caused by several species of Colletotrichum that differ in virulence, host preference and geographical distribution.

    PubMed

    Talhinhas, Pedro; Loureiro, Andreia; Oliveira, Helena

    2018-03-08

    Olive anthracnose causes fruit rot leading to its drop or mummification, resulting in yield losses and the degradation of oil quality. The disease is caused by diverse species of Colletotrichum, mostly clustering in the C. acutatum species complex. Colletotrichum nymphaeae and C. godetiae are the prevalent species in the Northern Hemisphere, whereas C. acutatum sensu stricto is the most frequent species in the Southern Hemisphere, although it is recently and quickly emerging in the Northern Hemisphere. The disease has been reported from all continents, but it attains higher incidence and severity in the west of the Mediterranean Basin, where it is endemic in traditional orchards of susceptible cultivars. The pathogens are able to survive on vegetative organs. On the fruit surface, infections remain quiescent until fruit maturity, when typical anthracnose symptoms develop. Under severe epidemics, defoliation and death of branches can also occur. Pathogen species differ in virulence, although this depends on the cultivar. The selection of resistant cultivars depends strongly on pathogen diversity and environmental conditions, posing added difficulties to breeding efforts. Chemical disease control is normally achieved with copper-based fungicides, although this may be insufficient under highly favourable disease conditions and causes concern because of the presence of fungicide residues in the oil. In areas in which the incidence is high, farmers tend to anticipate harvest, with consequences in yield and oil characteristics. Olive production systems, harvest and post-harvest processing have experienced profound changes in recent years, namely new training systems using specific cultivars, new harvest and processing techniques and new organoleptic market requests. Changes are also occurring in both the geographical distribution of pathogen populations and the taxonomic framework. In addition, stricter rules concerning pesticide use are likely to have a strong impact on control strategies. A detailed knowledge of pathogen diversity, population dynamics and host-pathogen interactions is basal for the deployment of durable and effective disease control strategies, whether based on resistance breeding, agronomic practices or biological or chemical control. © 2018 BSPP AND JOHN WILEY & SONS LTD.

  5. Evaluation of effects of Mycoplasma mastitis on milk composition in dairy cattle from South Australia.

    PubMed

    Al-Farha, Abd Al-Bar; Hemmatzadeh, Farhid; Khazandi, Manouchehr; Hoare, Andrew; Petrovski, Kiro

    2017-11-25

    Mycoplasma mastitis is increasingly posing significant impact on dairy industry. Although the effects of major conventional mastitis pathogens on milk components has been widely addressed in the literature, limited data on the effects of different Mycoplasma and Acholeplasma spp. on milk quality and quantity is available. The aim of this study was to determine the casual relationship of Mycoplasma spp. and A. laidlawii to mastitis and compare them to subclinical mastitis caused by conventional mastitis pathogens from a single dairy herd in South Australia; Mycoplasma spp. and A. laidlawii were detected using PCR applied directly to milk samples. The herd had mastitis problem with high somatic cell count and low response rate to conventional antimicrobial therapy. A total of 288 cow-level milk samples were collected aseptically and used in this study. Conventional culture showed a predominance of coagulase-negative staphylococci, followed by coagulase-positive staphylococci, Streptococcus spp., Enterococcus spp., E. coli, and Klebsiella spp. PCR results showed a high prevalence of mycoplasmas (76.7%), including A. laidlawii (10.8%), M. bovis (6.2%), M. bovirhinis (5.6%), M. arginini (2%), and (52.1%) of cows were co-infected with two or more Mycoplasma and Acholeplasma species. Mycoplasma co-infection significantly increased somatic cell counts (SCC) similar to conventional mastitis pathogens and compared to non-infected cows with 389.3, 550.3 and 67.3 respectively; and decreased the milk yield with 29.0, 29.9 and 34.4 l, respectively. Mycoplasma co-infection caused significant increase in protein percentage, and significant decrease in fat percentage and total milk solids, similar to other conventional mastitis pathogens. In contrast, changes in milk composition and yield caused by various individual Mycoplasma species were non-significant. Mycoplasma mastitis had on-farm economic consequences similar to common conventional mastitis pathogens. Results of our study indicate that co-infection Mycoplasma mastitis caused similar effect on milk composition to other mastitis pathogens and we hope these findings raise the awareness of the importance of their detection on routine diagnostic panels.

  6. Characterization of the 2012 highly pathogenic avian influenza H7N3 virus isolated from poultry in an outbreak in Mexico: pathobiology and vaccine protection.

    PubMed

    Kapczynski, Darrell R; Pantin-Jackwood, Mary; Guzman, Sofia G; Ricardez, Yadira; Spackman, Erica; Bertran, Kateri; Suarez, David L; Swayne, David E

    2013-08-01

    In June of 2012, an H7N3 highly pathogenic avian influenza (HPAI) virus was identified as the cause of a severe disease outbreak in commercial laying chicken farms in Mexico. The purpose of this study was to characterize the Mexican 2012 H7N3 HPAI virus (A/chicken/Jalisco/CPA1/2012) and determine the protection against the virus conferred by different H7 inactivated vaccines in chickens. Both adult and young chickens intranasally inoculated with the virus became infected and died at between 2 and 4 days postinoculation (p.i.). High virus titers and viral replication in many tissues were demonstrated at 2 days p.i. in infected birds. The virus from Jalisco, Mexico, had high sequence similarity of greater than 97% to the sequences of wild bird viruses from North America in all eight gene segments. The hemagglutinin gene of the virus contained a 24-nucleotide insert at the hemagglutinin cleavage site which had 100% sequence identity to chicken 28S rRNA, suggesting that the insert was the result of nonhomologous recombination with the host genome. For vaccine protection studies, both U.S. H7 low-pathogenic avian influenza (LPAI) viruses and a 2006 Mexican H7 LPAI virus were tested as antigens in experimental oil emulsion vaccines and injected into chickens 3 weeks prior to challenge. All H7 vaccines tested provided ≥90% protection against clinical disease after challenge and decreased the number of birds shedding virus and the titers of virus shed. This study demonstrates the pathological consequences of the infection of chickens with the 2012 Mexican lineage H7N3 HPAI virus and provides support for effective programs of vaccination against this virus in poultry.

  7. Treatment of ME/CFS in Children

    MedlinePlus

    ... a little better, do too much once again). Depression, Stress, and Anxiety Adjusting to any chronic illness ... Consequence Pathogens and Pathology (DHCPP) Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

  8. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Treatment

    MedlinePlus

    ... practitioner, might help with pain for some patients. Depression, Stress, and Anxiety Adjusting to a chronic, debilitating ... Consequence Pathogens and Pathology (DHCPP) Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

  9. Pathogens gone wild? Medical anthropology and the "swine flu" pandemic.

    PubMed

    Singer, Merrill

    2009-07-01

    Beginning in April 2009, global attention began focusing on the emergence in Mexico of a potentially highly lethal new influenza strain of porcine origin that has successfully jumped species barriers and is now being transmitted around the world. Reported on extensively by the mass media, commented on by public health and government officials across the globe, and focused on with nervous attention by the general public, the so-called swine flu pandemic raises important questions, addressed here, concerning the capacity of medical anthropology to respond usefully to such disease outbreaks and their health and social consequences.

  10. GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects

    PubMed Central

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah; Winschel, Alexander; Chen, Wenjuan; Hu, Chun; Kusumoto, Hirofumi; Heyne, Henrike O; Helbig, Katherine L; Tang, Sha; Willing, Marcia C; Tinkle, Brad T; Adams, Darius J; Depienne, Christel; Keren, Boris; Mignot, Cyril; Frengen, Eirik; Strømme, Petter; Biskup, Saskia; Döcker, Dennis; Strom, Tim M; Mefford, Heather C; Myers, Candace T; Muir, Alison M; LaCroix, Amy; Sadleir, Lynette; Scheffer, Ingrid E; Brilstra, Eva; van Haelst, Mieke M; van der Smagt, Jasper J; Bok, Levinus A; Møller, Rikke S; Jensen, Uffe B; Millichap, John J; Berg, Anne T; Goldberg, Ethan M; De Bie, Isabelle; Fox, Stephanie; Major, Philippe; Jones, Julie R; Zackai, Elaine H; Jamra, Rami Abou; Rolfs, Arndt; Leventer, Richard J; Lawson, John A; Roscioli, Tony; Jansen, Floor E; Ranza, Emmanuelle; Korff, Christian M; Lehesjoki, Anna-Elina; Courage, Carolina; Linnankivi, Tarja; Smith, Douglas R; Stanley, Christine; Mintz, Mark; McKnight, Dianalee; Decker, Amy; Tan, Wen-Hann; Tarnopolsky, Mark A; Brady, Lauren I; Wolff, Markus; Dondit, Lutz; Pedro, Helio F; Parisotto, Sarah E; Jones, Kelly L; Patel, Anup D; Franz, David N; Vanzo, Rena; Marco, Elysa; Ranells, Judith D; Di Donato, Nataliya; Dobyns, William B; Laube, Bodo; Traynelis, Stephen F; Lemke, Johannes R

    2017-01-01

    Background We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Methods Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care. Results Overall, de novo variants in 86 patients were classified as pathogenic/likely pathogenic. Patients presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense variants cluster in transmembrane segments and ligand-binding sites. Functional consequences of variants were diverse, revealing various potential gain-of-function and loss-of-function mechanisms and a retained sensitivity to the use-dependent blocker memantine. However, an objectifiable beneficial treatment response in the respective patients still remains to be demonstrated. Conclusions In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies. PMID:28377535

  11. Within-host evolution of bacterial pathogens

    PubMed Central

    Didelot, Xavier; Walker, A. Sarah; Peto, Tim E.; Crook, Derrick W.; Wilson, Daniel J.

    2016-01-01

    Whole genome sequencing has opened the way to investigating the dynamics and genomic evolution of bacterial pathogens during colonization and infection of humans. The application of this technology to the longitudinal study of adaptation in the infected host — in particular, the evolution of drug resistance and host adaptation in patients chronically infected with opportunistic pathogens — has revealed remarkable patterns of convergent evolution, pointing to an inherent repeatability of evolution. In this Review, we describe how these studies have advanced our understanding of the mechanisms and principles of within-host genome evolution, and we consider the consequences of findings such as a potent adaptive potential for pathogenicity. Finally, we discuss the possibility that genomics may be used in the future to predict the clinical progression of bacterial infections, and to suggest the best treatment option. PMID:26806595

  12. Within-host evolution of bacterial pathogens.

    PubMed

    Didelot, Xavier; Walker, A Sarah; Peto, Tim E; Crook, Derrick W; Wilson, Daniel J

    2016-03-01

    Whole-genome sequencing has opened the way for investigating the dynamics and genomic evolution of bacterial pathogens during the colonization and infection of humans. The application of this technology to the longitudinal study of adaptation in an infected host--in particular, the evolution of drug resistance and host adaptation in patients who are chronically infected with opportunistic pathogens--has revealed remarkable patterns of convergent evolution, suggestive of an inherent repeatability of evolution. In this Review, we describe how these studies have advanced our understanding of the mechanisms and principles of within-host genome evolution, and we consider the consequences of findings such as a potent adaptive potential for pathogenicity. Finally, we discuss the possibility that genomics may be used in the future to predict the clinical progression of bacterial infections and to suggest the best option for treatment.

  13. Mycobacterium tuberculosis in the Face of Host-Imposed Nutrient Limitation

    PubMed Central

    BERNEY, MICHAEL; BERNEY-MEYER, LINDA

    2017-01-01

    Coevolution of pathogens and host has led to many metabolic strategies employed by intracellular pathogens to deal with the immune response and the scarcity of food during infection. Simply put, bacterial pathogens are just looking for food. As a consequence, the host has developed strategies to limit nutrients for the bacterium by containment of the intruder in a pathogen-containing vacuole and/or by actively depleting nutrients from the intracellular space, a process called nutritional immunity. Since metabolism is a prerequisite for virulence, such pathways could potentially be good targets for antimicrobial therapies. In this chapter, we review the current knowledge about the in vivo diet of Mycobacterium tuberculosis, with a focus on amino acid and cofactors, discuss evidence for the bacilli’s nutritionally independent lifestyle in the host, and evaluate strategies for new chemotherapeutic interventions. PMID:28597811

  14. Mycobacterium tuberculosis in the Face of Host-Imposed Nutrient Limitation.

    PubMed

    Berney, Michael; Berney-Meyer, Linda

    2017-06-01

    Coevolution of pathogens and host has led to many metabolic strategies employed by intracellular pathogens to deal with the immune response and the scarcity of food during infection. Simply put, bacterial pathogens are just looking for food. As a consequence, the host has developed strategies to limit nutrients for the bacterium by containment of the intruder in a pathogen-containing vacuole and/or by actively depleting nutrients from the intracellular space, a process called nutritional immunity. Since metabolism is a prerequisite for virulence, such pathways could potentially be good targets for antimicrobial therapies. In this chapter, we review the current knowledge about the in vivo diet of Mycobacterium tuberculosis , with a focus on amino acid and cofactors, discuss evidence for the bacilli's nutritionally independent lifestyle in the host, and evaluate strategies for new chemotherapeutic interventions.

  15. Hydroxamate Production as a High Affinity Iron Acquisition Mechanism in Paracoccidioides Spp

    PubMed Central

    Silva-Bailão, Mirelle Garcia; Bailão, Elisa Flávia Luiz Cardoso; Lechner, Beatrix Elisabeth; Gauthier, Gregory M.; Lindner, Herbert; Bailão, Alexandre Melo; Haas, Hubertus; de Almeida Soares, Célia Maria

    2014-01-01

    Iron is a micronutrient required by almost all living organisms, including fungi. Although this metal is abundant, its bioavailability is low either in aerobic environments or within mammalian hosts. As a consequence, pathogenic microorganisms evolved high affinity iron acquisition mechanisms which include the production and uptake of siderophores. Here we investigated the utilization of these molecules by species of the Paracoccidioides genus, the causative agents of a systemic mycosis. It was demonstrated that iron starvation induces the expression of Paracoccidioides ortholog genes for siderophore biosynthesis and transport. Reversed-phase HPLC analysis revealed that the fungus produces and secretes coprogen B, which generates dimerumic acid as a breakdown product. Ferricrocin and ferrichrome C were detected in Paracoccidioides as the intracellular produced siderophores. Moreover, the fungus is also able to grow in presence of siderophores as the only iron sources, demonstrating that beyond producing, Paracoccidioides is also able to utilize siderophores for growth, including the xenosiderophore ferrioxamine. Exposure to exogenous ferrioxamine and dimerumic acid increased fungus survival during co-cultivation with macrophages indicating that these molecules play a role during host-pathogen interaction. Furthermore, cross-feeding experiments revealed that Paracoccidioides siderophores promotes growth of Aspergillus nidulans strain unable to produce these iron chelators. Together, these data denote that synthesis and utilization of siderophores is a mechanism used by Paracoccidioides to surpass iron limitation. As iron paucity is found within the host, siderophore production may be related to fungus pathogenicity. PMID:25157575

  16. Negative impact of laws regarding biosecurity and bioterrorism on real diseases.

    PubMed

    Wurtz, N; Grobusch, M P; Raoult, D

    2014-06-01

    Research on highly pathogenic microorganisms in biosafety level 3 and 4 laboratories is very important for human public health, as it provides opportunities for the development of vaccines and novel therapeutics as well as diagnostic methods to prevent epidemics. However, in recent years, after the anthrax and World Trade Center attacks in 2001 in the USA, the threat of bioterrorism has grown for both the public and the authorities. As a result, technical and physical containment measures and biosafety and biosecurity practices have been implemented in laboratories handling these dangerous pathogens. Working with selected biological agents and toxins is now highly regulated, owing to their potential to pose a threat to public health and safety, despite the fact that the anthrax attack was found to be the result of a lack of security at a US Army laboratory. Thus, these added regulations have been associated with a large amount of fruitless investment. Herein, we describe the limitations of research in these facilities, and the multiple consequences of the increased regulations. These limitations have seriously negatively impacted on the number of collaborations, the size of research projects, and, more generally, scientific research on microbial pathogens. Clearly, the actual number of known victims and fatalities caused by the intentional use of microorganisms has been negligible as compared with those caused by naturally acquired human infections. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  17. Fermentation of Foc TR4-infected bananas and Trichoderma spp.

    PubMed

    Yang, J; Li, B; Liu, S W; Biswas, M K; Liu, S; Wei, Y R; Zuo, C W; Deng, G M; Kuang, R B; Hu, C H; Yi, G J; Li, C Y

    2016-10-17

    Fusarium wilt (also known as Panama disease) is one of the most destructive banana diseases, and greatly hampers the global production of bananas. Consequently, it has been very detrimental to the Chinese banana industry. An infected plant is one of the major causes of the spread of Fusarium wilt to nearby regions. It is essential to develop an efficient and environmentally sustainable disease control method to restrict the spread of Fusarium wilt. We isolated Trichoderma spp from the rhizosphere soil, roots, and pseudostems of banana plants that showed Fusarium wilt symptoms in the infected areas. Their cellulase activities were measured by endoglucanase activity, β-glucosidase activity, and filter paper activity assays. Safety analyses of the Trichoderma isolates were conducted by inoculating them into banana plantlets. The antagonistic effects of the Trichoderma spp on the Fusarium pathogen Foc tropical Race 4 (Foc TR4) were tested by the dual culture technique. Four isolates that had high cellulase activity, no observable pathogenicity to banana plants, and high antagonistic capability were identified. The isolates were used to biodegrade diseased banana plants infected with GFP-tagged Foc TR4, and the compost was tested for biological control of the infectious agent; the results showed that the fermentation suppressed the incidence of wilt and killed the pathogen. This study indicates that Trichoderma isolates have the potential to eliminate the transmission of Foc TR4, and may be developed into an environmentally sustainable treatment for controlling Fusarium wilt in banana plants.

  18. Buried treasure: evolutionary perspectives on microbial iron piracy

    PubMed Central

    Barber, Matthew F.; Elde, Nels C.

    2015-01-01

    Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a critical innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of `iron piracy' to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution, but also microbial community interactions. Here we highlight recent and potential future areas of investigation on the evolutionary implications of microbial iron piracy in relation to molecular arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease. PMID:26431675

  19. A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies.

    PubMed

    Orr, Miranda E; Sullivan, A Campbell; Frost, Bess

    2017-07-01

    There are currently no disease-modifying therapies for the treatment of tauopathies, a group of progressive neurodegenerative disorders that are pathologically defined by the presence of tau protein aggregates in the brain. Current challenges for the treatment of tauopathies include the inability to diagnose early and to confidently discriminate between distinct tauopathies in patients, alongside an incomplete understanding of the cellular mechanisms involved in pathogenic tau-induced neuronal death and dysfunction. In this review, we describe current diagnostic and therapeutic strategies, known drivers of pathogenic tau formation, recent contributions to our current mechanistic understanding of how pathogenic tau induces neuronal death, and potential diagnostic and therapeutic approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Prevalence and persistence of potentially pathogenic and antibiotic resistant bacteria during anaerobic digestion treatment of cattle manure.

    PubMed

    Resende, Juliana Alves; Silva, Vânia Lúcia; de Oliveira, Tamara Lopes Rocha; de Oliveira Fortunato, Samuel; da Costa Carneiro, Jailton; Otenio, Marcelo Henrique; Diniz, Cláudio Galuppo

    2014-02-01

    Anaerobic digestion figures as a sustainable alternative to avoid discharge of cattle manure in the environment, which results in biogas and biofertilizer. Persistence of potentially pathogenic and drug-resistant bacteria during anaerobic digestion of cattle manure was evaluated. Selective cultures were performed for enterobacteria (ENT), non-fermenting Gram-negative rods (NFR) and Gram-positive cocci (GPC). Antimicrobial susceptibility patterns were determined and a decay of all bacterial groups was observed after 60days. Multidrug-resistant bacteria were detected both the influent and effluent. GPC, the most prevalent group was highly resistant against penicillin and levofloxacin, whereas resistance to ampicillin, ampicillin-sulbactam and chloramphenicol was frequently observed in the ENT and NFR groups. The data point out the need of discussions to better address management of biodigesters and the implementation of sanitary and microbiological safe treatments of animal manures to avoid consequences to human, animal and environmental health. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Diagnostics for Lassa Fever: Detecting Host Antibody Responses.

    PubMed

    Salvato, Maria S; Lukashevich, Igor S; Medina-Moreno, Sandra; Zapata, Juan Carlos

    2018-01-01

    There are two types of viral diagnostics: (1) those that detect components of the pathogen (like viral RNA or proteins) and (2) those that detect host molecules that rise or fall as a consequence of pathogen infection (like anti-viral antibodies or virus-induced inflammatory cytokines). Quantitative PCR to detect Lassa RNA, and clinical chemistry to detect high liver enzymes (AST/ALT) are commonly used to diagnose Lassa fever. Here, we discuss the various types of diagnostics for Lassa fever and the urgent need for early diagnosis. We also describe a protocol for using the attenuated Lassa vaccine candidate, ML29 , as an antigen for detecting Lassa-specific antibodies. Since antibodies are developed late in the progression of Lassa fever disease, this is not an early diagnostic, but is more useful in surveillance of the population to determine the sero-prevalence of antibodies to Lassa virus (LASV ), and to define treatment options for people in close contact with a Lassa-infected person.

  2. Vector-borne diseases in Haiti: a review.

    PubMed

    Ben-Chetrit, Eli; Schwartz, Eli

    2015-01-01

    Haiti lies on the western third of the island of Hispaniola in the Caribbean, and is one of the poorest nations in the Western hemisphere. Haiti attracts a lot of medical attention and support due to severe natural disasters followed by disastrous health consequences. Vector-borne infections are still prevalent there with some unique aspects comparing it to Latin American countries and other Caribbean islands. Although vector-borne viral diseases such as dengue and recently chikungunya can be found in many of the Caribbean islands, including Haiti, there is an apparent distinction of the vector-borne parasitic diseases. Contrary to neighboring Carribbean islands, Haiti is highly endemic for malaria, lymphatic filariasis and mansonellosis. Affected by repeat natural disasters, poverty and lack of adequate infrastructure, control of transmission within Haiti and prevention of dissemination of vector-borne pathogens to other regions is challenging. In this review we summarize some aspects concerning diseases caused by vector-borne pathogens in Haiti. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Unisexual versus bisexual mating in Cryptococcus neoformans: Consequences and biological impacts

    PubMed Central

    Fu, Ci; Sun, Sheng; Billmyre, R. Blake; Roach, Kevin C.; Heitman, Joseph

    2014-01-01

    Cryptococcus neoformans is an opportunistic human fungal pathogen and can undergo both bisexual and unisexual mating. Despite the fact that one mating type is dispensable for unisexual mating, the two sexual cycles share surprisingly similar features. Both mating cycles are affected by similar environmental factors and regulated by the same pheromone response pathway. Recombination takes place during unisexual reproduction in a fashion similar to bisexual reproduction and can both admix pre-existing genetic diversity and also generate diversity de novo just like bisexual reproduction. These common features may allow the unisexual life cycle to provide phenotypic and genotypic plasticity for the natural Cryptococcus population, which is predominantly α mating type, and to avoid Muller’s ratchet. The morphological transition from yeast to hyphal growth during both bisexual and unisexual mating may provide increased opportunities for outcrossing and the ability to forage for nutrients at a distance. The unisexual life cycle is a key evolutionary factor for Cryptococcus as a highly successful global fungal pathogen. PMID:25173822

  4. Taxonomy, Physiology, and Natural Products of Actinobacteria.

    PubMed

    Barka, Essaid Ait; Vatsa, Parul; Sanchez, Lisa; Gaveau-Vaillant, Nathalie; Jacquard, Cedric; Meier-Kolthoff, Jan P; Klenk, Hans-Peter; Clément, Christophe; Ouhdouch, Yder; van Wezel, Gilles P

    2016-03-01

    Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Taxonomy, Physiology, and Natural Products of Actinobacteria

    PubMed Central

    Vatsa, Parul; Sanchez, Lisa; Gaveau-Vaillant, Nathalie; Jacquard, Cedric; Klenk, Hans-Peter; Clément, Christophe; Ouhdouch, Yder

    2015-01-01

    SUMMARY Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum. PMID:26609051

  6. [Modes of action of agrochemicals against plant pathogenic organisms].

    PubMed

    Leroux, Pierre

    2003-01-01

    The chemical control of plant pathogens concerns mainly fungal diseases of crops. Most of the available fungicides act directly on essential fungal functions such as respiration, sterol biosynthesis or cell division. Consequently, these compounds can exhibit undesirable toxicological and environmental effects and sometimes select fungal resistant strains. Plant activators are expected to provide sustainable disease management in several crops because the development of resistance is not expected. Considering the future, the discovery of novel antifungal molecules will reap advantage from throughput screening methodologies and functional genomics.

  7. MALDI-TOF mass spectrometry and high-consequence bacteria: safety and stability of biothreat bacterial sample testing in clinical diagnostic laboratories.

    PubMed

    Tracz, Dobryan M; Tober, Ashley D; Antonation, Kym S; Corbett, Cindi R

    2018-03-01

    We considered the application of MALDI-TOF mass spectrometry for BSL-3 bacterial diagnostics, with a focus on the biosafety of live-culture direct-colony testing and the stability of stored extracts. Biosafety level 2 (BSL-2) bacterial species were used as surrogates for BSL-3 high-consequence pathogens in all live-culture MALDI-TOF experiments. Viable BSL-2 bacteria were isolated from MALDI-TOF mass spectrometry target plates after 'direct-colony' and 'on-plate' extraction testing, suggesting that the matrix chemicals alone cannot be considered sufficient to inactivate bacterial culture and spores in all samples. Sampling of the instrument interior after direct-colony analysis did not recover viable organisms, suggesting that any potential risks to the laboratory technician are associated with preparation of the MALDI-TOF target plate before or after testing. Secondly, a long-term stability study (3 years) of stored MALDI-TOF extracts showed that match scores can decrease below the threshold for reliable species identification (<1.7), which has implications for proficiency test panel item storage and distribution.

  8. Historical precedence and technical requirements of biological weapons use : a threat assessment.

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

    Estes, Daniel P.; Vogel, Kathleen Margaret; Gaudioso, Jennifer Marie

    2004-05-01

    The threat from biological weapons is assessed through both a comparative historical analysis of the patterns of biological weapons use and an assessment of the technological hurdles to proliferation and use that must be overcome. The history of biological weapons is studied to learn how agents have been acquired and what types of states and substate actors have used agents. Substate actors have generally been more willing than states to use pathogens and toxins and they have focused on those agents that are more readily available. There has been an increasing trend of bioterrorism incidents over the past century, butmore » states and substate actors have struggled with one or more of the necessary technological steps. These steps include acquisition of a suitable agent, production of an appropriate quantity and form, and effective deployment. The technological hurdles associated with the steps present a real barrier to producing a high consequence event. However, the ever increasing technological sophistication of society continually lowers the barriers, resulting in a low but increasing probability of a high consequence bioterrorism event.« less

  9. Recovery Estimation of Dried Foodborne Pathogens Is Directly Related to Rehydration Kinetics

    PubMed Central

    Lang, Emilie; Zoz, Fiona; Iaconelli, Cyril; Guyot, Stéphane; Alvarez-Martin, Pablo; Beney, Laurent; Perrier-Cornet, Jean-Marie; Gervais, Patrick

    2016-01-01

    Drying is a common process which is used to preserve food products and technological microorganisms, but which is deleterious for the cells. The aim of this study is to differentiate the effects of drying alone from the effects of the successive and necessary rehydration. Rehydration of dried bacteria is a critical step already studied in starter culture but not for different kinetics and not for pathogens. In the present study, the influence of rehydration kinetics was investigated for three foodborne pathogens involved in neonatal diseases caused by the consumption of rehydrated milk powder: Salmonella enterica subsp. enterica serovar Typhimurium, Salmonella enterica subsp. enterica serovar Senftenberg and Cronobacter sakazakii. Bacteria were dried in controlled relative humidity atmospheres and then rehydrated using different methods. Our results showed that the survival of the three pathogens was strongly related to rehydration kinetics. Consequently, rehydration is an important step to consider during food safety assessment or during studies of dried foodborne pathogens. Also, it has to be considered with more attention in consumers’ homes during the preparation of food, like powdered infant formula, to avoid pathogens recovery. PMID:27494169

  10. Immune defence strategies of generalist and specialist insect herbivores

    PubMed Central

    Barthel, Andrea; Kopka, Isabell; Vogel, Heiko; Zipfel, Peter; Heckel, David G.; Groot, Astrid T.

    2014-01-01

    Ecological immunology examines the adaptive responses of animals to pathogens in relation to other environmental factors and explores the consequences of trade-offs between investment in immune function and other life-history traits. Among species of herbivorous insects, diet breadth may vary greatly, with generalists consuming a wide variety of plant families and specialists restricted to a few species. Generalists may thus be exposed to a wider range of pathogens exerting stronger selection on the innate immune system. To examine whether this produces an increase in the robustness of the immune response, we compared larvae of the generalist herbivore Heliothis virescens and the specialist Heliothis subflexa challenged by entomopathogenic and non-pathogenic bacteria. Heliothis virescens larvae showed lower mortality, a lower number of recoverable bacteria, lower proliferation of haemocytes and higher phagocytic activity. These results indicate a higher tolerance to entomopathogenic bacteria by the generalist, which is associated with a more efficient cell-mediated immune response by mechanisms that differ between these closely related species. Our findings provide novel insights into the consequences of diet breadth and related environmental factors, which may be significant in further studies to understand the ecological forces and investment trade-offs that shape the evolution of innate immunity. PMID:24943370

  11. The Small GTPase MoSec4 Is Involved in Vegetative Development and Pathogenicity by Regulating the Extracellular Protein Secretion in Magnaporthe oryzae

    PubMed Central

    Zheng, Huakun; Chen, Simiao; Chen, Xiaofeng; Liu, Shuyan; Dang, Xie; Yang, Chengdong; Giraldo, Martha C.; Oliveira-Garcia, Ely; Zhou, Jie; Wang, Zonghua; Valent, Barbara

    2016-01-01

    The Rab GTPase proteins play important roles in the membrane trafficking, and consequently protein secretion and development of eukaryotic organisms. However, little is known about the function of Rab GTPases in Magnaporthe oryzae. To further explore the function of Rab GTPases, we deleted the ortholog of the yeast Sec4p protein in M. oryzae, namely MoSEC4. The ΔMosec4 mutant is defective in polarized growth and conidiation, and it displays decreased appressorium turgor pressure and attenuated pathogenicity. Notably, the biotrophic invasive hyphae produced in rice cells are more bulbous and compressed in the ΔMosec4 mutant. Further studies showed that deletion of the MoSEC4 gene resulted in decreased secretion of extracellular enzymes and mislocalization of the cytoplasmic effector PWL2-mCherry-NLS. In accordance with a role in secretion, the GFP-MoSec4 fusion protein mainly accumulates at tips of growing vegetative hyphae. Our results suggest that the MoSec4 protein plays important roles in the secretion of extracellular proteins and consequently hyphal development and pathogenicity in the rice blast fungus. PMID:27729922

  12. Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery

    PubMed Central

    Sykes, Melissa L.; Jones, Amy J.; Shelper, Todd B.; Simpson, Moana; Lang, Rebecca; Poulsen, Sally-Ann; Sleebs, Brad E.

    2017-01-01

    ABSTRACT Open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages in vitro. Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this in vitro biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research. PMID:28674055

  13. Pathogen prevalence predicts human cross-cultural variability in individualism/collectivism

    PubMed Central

    Fincher, Corey L; Thornhill, Randy; Murray, Damian R; Schaller, Mark

    2008-01-01

    Pathogenic diseases impose selection pressures on the social behaviour of host populations. In humans (Homo sapiens), many psychological phenomena appear to serve an antipathogen defence function. One broad implication is the existence of cross-cultural differences in human cognition and behaviour contingent upon the relative presence of pathogens in the local ecology. We focus specifically on one fundamental cultural variable: differences in individualistic versus collectivist values. We suggest that specific behavioural manifestations of collectivism (e.g. ethnocentrism, conformity) can inhibit the transmission of pathogens; and so we hypothesize that collectivism (compared with individualism) will more often characterize cultures in regions that have historically had higher prevalence of pathogens. Drawing on epidemiological data and the findings of worldwide cross-national surveys of individualism/collectivism, our results support this hypothesis: the regional prevalence of pathogens has a strong positive correlation with cultural indicators of collectivism and a strong negative correlation with individualism. The correlations remain significant even when controlling for potential confounding variables. These results help to explain the origin of a paradigmatic cross-cultural difference, and reveal previously undocumented consequences of pathogenic diseases on the variable nature of human societies. PMID:18302996

  14. Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery.

    PubMed

    Duffy, Sandra; Sykes, Melissa L; Jones, Amy J; Shelper, Todd B; Simpson, Moana; Lang, Rebecca; Poulsen, Sally-Ann; Sleebs, Brad E; Avery, Vicky M

    2017-09-01

    Open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages in vitro Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this in vitro biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research. Copyright © 2017 Duffy et al.

  15. Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

    PubMed

    Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J

    2018-01-01

    Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

  16. Land cover and forest connectivity alter the interactions among host, pathogen and skin microbiome.

    PubMed

    Becker, C G; Longo, A V; Haddad, C F B; Zamudio, K R

    2017-08-30

    Deforestation has detrimental consequences on biodiversity, affecting species interactions at multiple scales. The associations among vertebrates, pathogens and their commensal/symbiotic microbial communities (i.e. microbiomes) have important downstream effects for biodiversity conservation, yet we know little about how deforestation contributes to changes in host microbial diversity and pathogen abundance. Here, we tested the effects of landcover, forest connectivity and infection by the chytrid fungus Batrachochytrium dendrobatidis ( Bd ) on amphibian skin bacterial diversity along deforestation gradients in Brazilian landscapes. If disturbance to natural habitat alters skin microbiomes as it does in vertebrate host communities, then we would expect higher host bacterial diversity in natural forest habitats. Bd infection loads are also often higher in these closed-canopy forests, which may in turn impact skin-associated bacterial communities. We found that forest corridors shaped composition of host skin microbiomes; high forest connectivity predicted greater similarity of skin bacterial communities among host populations. In addition, we found that host skin bacterial diversity and Bd loads increased towards natural vegetation. Because symbiotic bacteria can potentially buffer hosts from Bd infection, we also evaluated the bi-directional microbiome- Bd link but failed to find a significant effect of skin bacterial diversity reducing Bd infections. Although weak, we found support for Bd increasing bacterial diversity and/or for core bacteria dominance reducing Bd loads. Our research incorporates a critical element in the study of host microbiomes by linking environmental heterogeneity of landscapes to the host-pathogen-microbiome triangle. © 2017 The Author(s).

  17. Evolutionary suicide through a non-catastrophic bifurcation: adaptive dynamics of pathogens with frequency-dependent transmission.

    PubMed

    Boldin, Barbara; Kisdi, Éva

    2016-03-01

    Evolutionary suicide is a riveting phenomenon in which adaptive evolution drives a viable population to extinction. Gyllenberg and Parvinen (Bull Math Biol 63(5):981-993, 2001) showed that, in a wide class of deterministic population models, a discontinuous transition to extinction is a necessary condition for evolutionary suicide. An implicit assumption of their proof is that the invasion fitness of a rare strategy is well-defined also in the extinction state of the population. Epidemic models with frequency-dependent incidence, which are often used to model the spread of sexually transmitted infections or the dynamics of infectious diseases within herds, violate this assumption. In these models, evolutionary suicide can occur through a non-catastrophic bifurcation whereby pathogen adaptation leads to a continuous decline of host (and consequently pathogen) population size to zero. Evolutionary suicide of pathogens with frequency-dependent transmission can occur in two ways, with pathogen strains evolving either higher or lower virulence.

  18. Application of polymerase chain reaction for detection of Vibrio parahaemolyticus associated with tropical seafoods and coastal environment.

    PubMed

    Dileep, V; Kumar, H S; Kumar, Y; Nishibuchi, M; Karunasagar, Indrani; Karunasagar, Iddya

    2003-01-01

    To study the incidence of Vibrio parahaemolyticus in seafoods, water and sediment by molecular techniques vs conventional microbiological methods. Of 86 samples analysed, 28 recorded positive for V. parahaemolyticus by conventional microbiological method, while 53 were positive by the toxR-targeted PCR, performed directly on enrichment broth lysates. While one sample of molluscan shellfish was positive for tdh gene, trh gene was detected in three enrichment broths of molluscan shellfish. Direct application of PCR to enrichment broths will be useful for the rapid and sensitive detection of potentially pathogenic strains of V. parahemolyticus in seafoods. Vibrio parahaemolyticus is an important human pathogen responsible for food-borne gastroenteritis world-wide. As, both pathogenic and non-pathogenic strains of V. parahaemolyticus exist in the seafood, application of PCR specific for the virulence genes (tdh & trh) will help in detection of pathogenic strains of V. parahaemolyticus and consequently reduce the risk of food-borne illness.

  19. Reactive oxygen species, essential molecules, during plant-pathogen interactions.

    PubMed

    Camejo, Daymi; Guzmán-Cedeño, Ángel; Moreno, Alexander

    2016-06-01

    Reactive oxygen species (ROS) are continually generated as a consequence of the normal metabolism in aerobic organisms. Accumulation and release of ROS into cell take place in response to a wide variety of adverse environmental conditions including salt, temperature, cold stresses and pathogen attack, among others. In plants, peroxidases class III, NADPH oxidase (NOX) locates in cell wall and plasma membrane, respectively, may be mainly enzymatic systems involving ROS generation. It is well documented that ROS play a dual role into cells, acting as important signal transduction molecules and as toxic molecules with strong oxidant power, however some aspects related to its function during plant-pathogen interactions remain unclear. This review focuses on the principal enzymatic systems involving ROS generation addressing the role of ROS as signal molecules during plant-pathogen interactions. We described how the chloroplasts, mitochondria and peroxisomes perceive the external stimuli as pathogen invasion, and trigger resistance response using ROS as signal molecule. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance

    PubMed Central

    Houlden, Ashley; Hayes, Kelly S.; Bancroft, Allison J.; Worthington, John J.; Wang, Ping; Grencis, Richard K.; Roberts, Ian S.

    2015-01-01

    Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation. PMID:25938477

  1. Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance.

    PubMed

    Houlden, Ashley; Hayes, Kelly S; Bancroft, Allison J; Worthington, John J; Wang, Ping; Grencis, Richard K; Roberts, Ian S

    2015-01-01

    Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation.

  2. Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients.

    PubMed

    de Steenhuijsen Piters, Wouter A A; Huijskens, Elisabeth G W; Wyllie, Anne L; Biesbroek, Giske; van den Bergh, Menno R; Veenhoven, Reinier H; Wang, Xinhui; Trzciński, Krzysztof; Bonten, Marc J; Rossen, John W A; Sanders, Elisabeth A M; Bogaert, Debby

    2016-01-01

    Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.

  3. [Dermatomycoses due to pets and farm animals : neglected infections?].

    PubMed

    Nenoff, P; Handrick, W; Krüger, C; Vissiennon, T; Wichmann, K; Gräser, Y; Tchernev, G

    2012-11-01

    Dermatomycoses due to contact with pets and livestock frequently affect children and young adults. Zoophilic dermatophytes are the main important causative agents. It has long been known that the often high inflammatory dermatophytoses of the skin and the scalp are caused mostly by Microsporum canis. Due to an absence of an obligation for reporting fungal infections of the skin to the Public Health Office in Germany, an unnoticed but significant change in responsible pathogens has occurred. Today an increasing number of infections due to zoophilic strains of Trichophyton interdigitale (formerly Trichophyton mentagrophytes) and Trichophyton species of Arthroderma benhamiae are found. The latter mentioned dermatophyte is the anamorph species of the teleomorph Arthroderma benhamiae, which originally was isolated in the Far East (Japan). Source of infection of these dermatophytes are small rodents, in particular guinea pigs. These animals are bought in pet shops by the parents of those children who later are affected by the fungal infection. The coincidental purchase of the relevant fungal pathogen is not obvious to the parents. As a consequence, highly contagious dermatophytoses occur, often tinea capitis sometimes with kerion formation. Further dermatophytes should be considered as cause of a zoophilic dermatomycosis. Both Trichophyton verrucosum, the cause of the ringworm in cattle, and Trichophyton erinacei following contact to hedgehogs are worthy of note. Yeasts cannot be ignored as cause of dermatomycosis, especially Malassezia pachydermatis, the only non-lipophilic species within the genus Malassezia, which can be transferred from dog to men. Cryptococcus neoformans also comes from animal sources. The mucous yeast occurs in bird's dropping, and it causes both pulmonary and central nervous system infections, but also primary and secondary cutaneous cryptococcosis in immunocompromised patients (HIV/AIDS) as possible consequence after contact to these animals.

  4. A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host–Pathogen Interaction Networks

    PubMed Central

    Wu, Chia-Chou; Chen, Bor-Sen

    2016-01-01

    Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host–pathogen dynamic interaction networks. The consideration of host–pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host–pathogen molecular interaction networks, and consequent inferences of the host–pathogen relationship could be translated into biomedical applications. PMID:26881892

  5. A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks.

    PubMed

    Wu, Chia-Chou; Chen, Bor-Sen

    2016-01-01

    Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications.

  6. The Immunology of Mammary Gland of Dairy Ruminants between Healthy and Inflammatory Conditions

    PubMed Central

    Ezzat Alnakip, Mohamed; Quintela-Baluja, Marcos; Fernández-No, Inmaculada; Caamaño-Antelo, Sonia; Calo-Mata, Pillar; Barros-Velázquez, Jorge

    2014-01-01

    The health of dairy animals, particularly the milk-producing mammary glands, is essential to the dairy industry because of the crucial hygienic and economic aspects of ensuring production of high quality milk. Due to its high prevalence, mastitis is considered the most important threat to dairy industry, due to its impacts on animal health and milk production and thus on economic benefits. The MG is protected by several defence mechanisms that prevent microbial penetration and surveillance. However, several factors can attenuate the host immune response (IR), and the possession of various virulence and resistance factors by different mastitis-causing microorganisms greatly limits immune defences and promotes establishment of intramammary infections (IMIs). A comprehensive understanding of MG immunity in both healthy and inflammatory conditions will be an important key to understand the nature of IMIs caused by specific pathogens and greatly contributes to the development of effective control methods and appropriate detection techniques. Consequently, this review aims to provide a detailed overview of antimicrobial defences in the MG under healthy and inflammatory conditions. In this sense, we will focus on pathogen-dependent variations in IRs mounted by the host during IMI and discuss the potential ramifications of these variations. PMID:26464939

  7. [Anthropocene and Emerging viral diseases].

    PubMed

    Chastel, C

    2016-08-01

    We propose to bring together the new geologic concept of Anthropocene and its consequences on our environment with the observed increasing emergence of new viruses - a pathogen for both humans and animals, mainly since the mid of the twentieth century.

  8. “Nanofiltration” Enabled by Super-Absorbent Polymer Beads for Concentrating Microorganisms in Water Samples

    NASA Astrophysics Data System (ADS)

    Xie, Xing; Bahnemann, Janina; Wang, Siwen; Yang, Yang; Hoffmann, Michael R.

    2016-02-01

    Detection and quantification of pathogens in water is critical for the protection of human health and for drinking water safety and security. When the pathogen concentrations are low, large sample volumes (several liters) are needed to achieve reliable quantitative results. However, most microbial identification methods utilize relatively small sample volumes. As a consequence, a concentration step is often required to detect pathogens in natural waters. Herein, we introduce a novel water sample concentration method based on superabsorbent polymer (SAP) beads. When SAP beads swell with water, small molecules can be sorbed within the beads, but larger particles are excluded and, thus, concentrated in the residual non-sorbed water. To illustrate this approach, millimeter-sized poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) beads are synthesized and successfully applied to concentrate water samples containing two model microorganisms: Escherichia coli and bacteriophage MS2. Experimental results indicate that the size of the water channel within water swollen P(AM-co-IA) hydrogel beads is on the order of several nanometers. The millimeter size coupled with a negative surface charge of the beads are shown to be critical in order to achieve high levels of concentration. This new concentration procedure is very fast, effective, scalable, and low-cost with no need for complex instrumentation.

  9. Helicase-dependent isothermal amplification: a novel tool in the development of molecular-based analytical systems for rapid pathogen detection.

    PubMed

    Barreda-García, Susana; Miranda-Castro, Rebeca; de-Los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J; Lobo-Castañón, María Jesús

    2018-01-01

    Highly sensitive testing of nucleic acids is essential to improve the detection of pathogens, which pose a major threat for public health worldwide. Currently available molecular assays, mainly based on PCR, have a limited utility in point-of-need control or resource-limited settings. Consequently, there is a strong interest in developing cost-effective, robust, and portable platforms for early detection of these harmful microorganisms. Since its description in 2004, isothermal helicase-dependent amplification (HDA) has been successfully applied in the development of novel molecular-based technologies for rapid, sensitive, and selective detection of viruses and bacteria. In this review, we highlight relevant analytical systems using this simple nucleic acid amplification methodology that takes place at a constant temperature and that is readily compatible with microfluidic technologies. Different strategies for monitoring HDA amplification products are described. In addition, we present technological advances for integrating sample preparation, HDA amplification, and detection. Future perspectives and challenges toward point-of-need use not only for clinical diagnosis but also in food safety testing and environmental monitoring are also discussed. Graphical Abstract Expanding the analytical toolbox for the detection of DNA sequences specific of pathogens with isothermal helicase dependent amplification (HDA).

  10. Viral pathogen production in a wild grass host driven by host growth and soil nitrogen.

    PubMed

    Whitaker, Briana K; Rúa, Megan A; Mitchell, Charles E

    2015-08-01

    Nutrient limitation is a basic ecological constraint that has received little attention in studies on virus production and disease dynamics. Nutrient availability could directly limit the production of viral nucleic acids and proteins, or alternatively limit host growth and thus indirectly limit metabolic pathways necessary for viral replication. In order to compare direct and indirect effects of nutrient limitation on virus production within hosts, we manipulated soil nitrogen (N) and phosphorus (P) availability in a glasshouse for the wild grass host Bromus hordeaceus and the viral pathogen Barley yellow dwarf virus-PAV. We found that soil N additions increased viral concentrations within host tissues, and the effect was mediated by host growth. Specifically, in statistical models evaluating the roles of host biomass production, leaf N and leaf P, viral production depended most strongly on host biomass, rather than the concentration of either nutrient. Furthermore, at low soil N, larger plants supported greater viral concentrations than smaller ones, whereas at high N, smaller plants supported greater viral concentrations. Our results suggest that enhanced viral productivity under N enrichment is an indirect consequence of nutrient stimulation to host growth rate. Heightened pathogen production in plants has important implications for a world facing increasing rates of nutrient deposition. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  11. The structural identifiability and parameter estimation of a multispecies model for the transmission of mastitis in dairy cows with postmilking teat disinfection.

    PubMed

    White, L J; Evans, N D; Lam, T J G M; Schukken, Y H; Medley, G F; Godfrey, K R; Chappell, M J

    2002-01-01

    A mathematical model for the transmission of two interacting classes of mastitis causing bacterial pathogens in a herd of dairy cows is presented and applied to a specific data set. The data were derived from a field trial of a specific measure used in the control of these pathogens, where half the individuals were subjected to the control and in the others the treatment was discontinued. The resultant mathematical model (eight non-linear simultaneous ordinary differential equations) therefore incorporates heterogeneity in the host as well as the infectious agent and consequently the effects of control are intrinsic in the model structure. A structural identifiability analysis of the model is presented demonstrating that the scope of the novel method used allows application to high order non-linear systems. The results of a simultaneous estimation of six unknown system parameters are presented. Previous work has only estimated a subset of these either simultaneously or individually. Therefore not only are new estimates provided for the parameters relating to the transmission and control of the classes of pathogens under study, but also information about the relationships between them. We exploit the close link between mathematical modelling, structural identifiability analysis, and parameter estimation to obtain biological insights into the system modelled.

  12. "Nanofiltration" Enabled by Super-Absorbent Polymer Beads for Concentrating Microorganisms in Water Samples.

    PubMed

    Xie, Xing; Bahnemann, Janina; Wang, Siwen; Yang, Yang; Hoffmann, Michael R

    2016-02-15

    Detection and quantification of pathogens in water is critical for the protection of human health and for drinking water safety and security. When the pathogen concentrations are low, large sample volumes (several liters) are needed to achieve reliable quantitative results. However, most microbial identification methods utilize relatively small sample volumes. As a consequence, a concentration step is often required to detect pathogens in natural waters. Herein, we introduce a novel water sample concentration method based on superabsorbent polymer (SAP) beads. When SAP beads swell with water, small molecules can be sorbed within the beads, but larger particles are excluded and, thus, concentrated in the residual non-sorbed water. To illustrate this approach, millimeter-sized poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) beads are synthesized and successfully applied to concentrate water samples containing two model microorganisms: Escherichia coli and bacteriophage MS2. Experimental results indicate that the size of the water channel within water swollen P(AM-co-IA) hydrogel beads is on the order of several nanometers. The millimeter size coupled with a negative surface charge of the beads are shown to be critical in order to achieve high levels of concentration. This new concentration procedure is very fast, effective, scalable, and low-cost with no need for complex instrumentation.

  13. “Nanofiltration” Enabled by Super-Absorbent Polymer Beads for Concentrating Microorganisms in Water Samples

    PubMed Central

    Xie, Xing; Bahnemann, Janina; Wang, Siwen; Yang, Yang; Hoffmann, Michael R.

    2016-01-01

    Detection and quantification of pathogens in water is critical for the protection of human health and for drinking water safety and security. When the pathogen concentrations are low, large sample volumes (several liters) are needed to achieve reliable quantitative results. However, most microbial identification methods utilize relatively small sample volumes. As a consequence, a concentration step is often required to detect pathogens in natural waters. Herein, we introduce a novel water sample concentration method based on superabsorbent polymer (SAP) beads. When SAP beads swell with water, small molecules can be sorbed within the beads, but larger particles are excluded and, thus, concentrated in the residual non-sorbed water. To illustrate this approach, millimeter-sized poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) beads are synthesized and successfully applied to concentrate water samples containing two model microorganisms: Escherichia coli and bacteriophage MS2. Experimental results indicate that the size of the water channel within water swollen P(AM-co-IA) hydrogel beads is on the order of several nanometers. The millimeter size coupled with a negative surface charge of the beads are shown to be critical in order to achieve high levels of concentration. This new concentration procedure is very fast, effective, scalable, and low-cost with no need for complex instrumentation. PMID:26876979

  14. Arthropods and associated arthropod-borne diseases transmitted by migrating birds. The case of ticks and tick-borne pathogens.

    PubMed

    Sparagano, Olivier; George, David; Giangaspero, Annunziata; Špitalská, Eva

    2015-09-30

    Geographic spread of parasites and pathogens poses a constant risk to animal health and welfare, particularly given that climate change is expected to potentially expand appropriate ranges for many key species. The spread of deleterious organisms via trade routes and human travelling is relatively closely controlled, though represents only one possible means of parasite/pathogen distribution. The transmission via natural parasite/pathogen movement between geographic locales, is far harder to manage. Though the extent of such movement may be limited by the relative inability of many parasites and pathogens to actively migrate, passive movement over long distances may still occur via migratory hosts. This paper reviews the potential role of migrating birds in the transfer of ectoparasites and pathogens between geographic locales, focusing primarily on ticks. Bird-tick-pathogen relationships are considered, and evidence provided of long-range parasite/pathogen transfer from one location to another during bird migration events. As shown in this paper not only many different arthropod species are carried by migrating birds but consequently these pests carry many different pathogens species which can be transmitted to the migrating birds or to other animal species when those arthropods are dropping during these migrations. Data available from the literature are provided highlighting the need to understand better dissemination paths and disease epidemiology. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The host protease TMPRSS2 plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses.

    PubMed

    Sakai, Kouji; Ami, Yasushi; Tahara, Maino; Kubota, Toru; Anraku, Masaki; Abe, Masako; Nakajima, Noriko; Sekizuka, Tsuyoshi; Shirato, Kazuya; Suzaki, Yuriko; Ainai, Akira; Nakatsu, Yuichiro; Kanou, Kazuhiko; Nakamura, Kazuya; Suzuki, Tadaki; Komase, Katsuhiro; Nobusawa, Eri; Maenaka, Katsumi; Kuroda, Makoto; Hasegawa, Hideki; Kawaoka, Yoshihiro; Tashiro, Masato; Takeda, Makoto

    2014-05-01

    Proteolytic cleavage of the hemagglutinin (HA) protein is essential for influenza A virus (IAV) to acquire infectivity. This process is mediated by a host cell protease(s) in vivo. The type II transmembrane serine protease TMPRSS2 is expressed in the respiratory tract and is capable of activating a variety of respiratory viruses, including low-pathogenic (LP) IAVs possessing a single arginine residue at the cleavage site. Here we show that TMPRSS2 plays an essential role in the proteolytic activation of LP IAVs, including a recently emerged H7N9 subtype, in vivo. We generated TMPRSS2 knockout (KO) mice. The TMPRSS2 KO mice showed normal reproduction, development, and growth phenotypes. In TMPRSS2 KO mice infected with LP IAVs, cleavage of HA was severely impaired, and consequently, the majority of LP IAV progeny particles failed to gain infectivity, while the viruses were fully activated proteolytically in TMPRSS2+/+ wild-type (WT) mice. Accordingly, in contrast to WT mice, TMPRSS2 KO mice were highly tolerant of challenge infection by LP IAVs (H1N1, H3N2, and H7N9) with ≥1,000 50% lethal doses (LD50) for WT mice. On the other hand, a high-pathogenic H5N1 subtype IAV possessing a multibasic cleavage site was successfully activated in the lungs of TMPRSS2 KO mice and killed these mice, as observed for WT mice. Our results demonstrate that recently emerged H7N9 as well as seasonal IAVs mainly use the specific protease TMPRSS2 for HA cleavage in vivo and, thus, that TMPRSS2 expression is essential for IAV replication in vivo. Influenza A virus (IAV) is a leading pathogen that infects and kills many humans every year. We clarified that the infectivity and pathogenicity of IAVs, including a recently emerged H7N9 subtype, are determined primarily by a host protease, TMPRSS2. Our data showed that TMPRSS2 is the key host protease that activates IAVs in vivo through proteolytic cleavage of their HA proteins. Hence, TMPRSS2 is a good target for the development of anti-IAV drugs. Such drugs could also be effective for many other respiratory viruses, including the recently emerged Middle East respiratory syndrome (MERS) coronavirus, because they are also activated by TMPRSS2 in vitro. Consequently, the present paper could have a large impact on the battle against respiratory virus infections and contribute greatly to human health.

  16. Applications of High and Ultra High Pressure Homogenization for Food Safety.

    PubMed

    Patrignani, Francesca; Lanciotti, Rosalba

    2016-01-01

    Traditionally, the shelf-life and safety of foods have been achieved by thermal processing. Low temperature long time and high temperature short time treatments are the most commonly used hurdles for the pasteurization of fluid foods and raw materials. However, the thermal treatments can reduce the product quality and freshness. Consequently, some non-thermal pasteurization process have been proposed during the last decades, including high hydrostatic pressure, pulsed electric field, ultrasound (US), and high pressure homogenization (HPH). This last technique has been demonstrated to have a great potential to provide "fresh-like" products with prolonged shelf-life. Moreover, the recent developments in high-pressure-homogenization technology and the design of new homogenization valves able to withstand pressures up to 350-400 MPa have opened new opportunities to homogenization processing in the food industries and, consequently, permitted the development of new products differentiated from traditional ones by sensory and structural characteristics or functional properties. For this, this review deals with the principal mechanisms of action of HPH against microorganisms of food concern in relation to the adopted homogenizer and process parameters. In addition, the effects of homogenization on foodborne pathogenic species inactivation in relation to the food matrix and food chemico-physical and process variables will be reviewed. Also the combined use of this alternative technology with other non-thermal technologies will be considered.

  17. Applications of High and Ultra High Pressure Homogenization for Food Safety

    PubMed Central

    Patrignani, Francesca; Lanciotti, Rosalba

    2016-01-01

    Traditionally, the shelf-life and safety of foods have been achieved by thermal processing. Low temperature long time and high temperature short time treatments are the most commonly used hurdles for the pasteurization of fluid foods and raw materials. However, the thermal treatments can reduce the product quality and freshness. Consequently, some non-thermal pasteurization process have been proposed during the last decades, including high hydrostatic pressure, pulsed electric field, ultrasound (US), and high pressure homogenization (HPH). This last technique has been demonstrated to have a great potential to provide “fresh-like” products with prolonged shelf-life. Moreover, the recent developments in high-pressure-homogenization technology and the design of new homogenization valves able to withstand pressures up to 350–400 MPa have opened new opportunities to homogenization processing in the food industries and, consequently, permitted the development of new products differentiated from traditional ones by sensory and structural characteristics or functional properties. For this, this review deals with the principal mechanisms of action of HPH against microorganisms of food concern in relation to the adopted homogenizer and process parameters. In addition, the effects of homogenization on foodborne pathogenic species inactivation in relation to the food matrix and food chemico-physical and process variables will be reviewed. Also the combined use of this alternative technology with other non-thermal technologies will be considered. PMID:27536270

  18. Tracer-aided modelling to explore non-linearities in flow paths, hydrological connectivity and faecal contamination risk

    NASA Astrophysics Data System (ADS)

    Neill, A. J.; Tetzlaff, D.; Strachan, N.; Soulsby, C.

    2016-12-01

    The non-linearities of runoff generation processes are strongly influenced by the connectivity of hillslopes and channel networks, particularly where overland flow is an important runoff mechanism. Despite major advances in understanding hydrological connectivity and runoff generation, the role of connectivity in the contamination of potable water supplies by faecal pathogens from grazing animals remains unclear. This is a water quality issue with serious implications for public health. Here, we sought to understand the dynamics of hydrological connectivity, flow paths and linked faecal pathogen transport in a montane catchment in Scotland with high deer populations. We firstly calibrated, within an uncertainty framework, a parsimonious tracer-aided hydrological model to daily discharge and stream isotope data. The model, developed on the basis of past empirical and tracer studies, conceptualises the catchment as three interacting hydrological source areas (dynamic saturation zone, dynamic hillslope, and groundwater) for which water fluxes, water ages and storage-based connectivity can be simulated. We next coupled several faecal indicator organism (FIO; a common indicator of faecal pathogen contamination) behaviour and transport schemes to the robust hydrological models. A further calibration was then undertaken based on the ability of each coupled model to simulate daily FIO concentrations. This gave us a final set of coupled behavioural models from which we explored how in-stream FIO dynamics could be related to the changing connectivity between the three hydrological source areas, flow paths, water ages and consequent dominant runoff generation processes. We found that high levels of FIOs were transient and episodic, and strongly correlated with periods of high connectivity through overland flow. This non-linearity in connectivity and FIO flux was successfully captured within our dynamic, tracer-aided hydrological model.

  19. Effect of the bacterium Serratia marcescens SCBI on the longevity and reproduction of the nematode Caenorhabditis briggsae KT0001.

    PubMed

    Lancaster, Jeremiah D; Mohammad, Budour; Abebe, Eyualem

    2012-12-20

    Extensive research effort has advanced our understanding of Caenorhabditis as a model system, but its natural association with bacteria remains to be explored in an ecological context. Explored associations vary vastly from mutualistic to parasitic. Serratia marcescens has been shown to be pathogenic to Caenorhabditis with a fitness cost. The recent isolation of an entomopathogenic Caenorhabditis briggsae KT0001/S. marcescens SCBI association from the wild has allowed us to examine under laboratory conditions whether such an association poses a serious cost to Caenorhabditis as previously surmised for other Serratia. A fecundity table of Caenorhabditis briggsae KT0001 fed on S. marcescens SCBI and the control fed on E. coli OP50 is presented. We found no significant difference in survivorship or total fecundity between the S. marcescens SCBI fed and E. coli OP50 fed Caenorhabditis briggsae KT0001. Only the mean onset of reproduction was significantly different between the two groups with E. coli fed C. briggsae maturing earlier (2.12 days) than those fed on Serratia (2.42 days). S. marcescens SCBI is not highly pathogenic to C. briggsae KT0001 indicating that the entomopathogenicity reported for this association may be beneficial for both the nematode and bacteria. In light of the fact that hitherto conducted experimental tests conform to widely held view that Serratia are highly pathogenic to Caenorhabditis, the absence of a high fitness cost for C. briggsae we report here may indicate that this entomopathogenic association is non-transient suggesting nematode/bacterial associations in the wild may vary greatly. Consequently, broad generalizations about nematode/bacterial associations should be interpreted with care.

  20. Effect of the bacterium Serratia marcescens SCBI on the longevity and reproduction of the nematode Caenorhabditis briggsae KT0001

    PubMed Central

    2012-01-01

    Background Extensive research effort has advanced our understanding of Caenorhabditis as a model system, but its natural association with bacteria remains to be explored in an ecological context. Explored associations vary vastly from mutualistic to parasitic. Serratia marcescens has been shown to be pathogenic to Caenorhabditis with a fitness cost. The recent isolation of an entomopathogenic Caenorhabditis briggsae KT0001/S. marcescens SCBI association from the wild has allowed us to examine under laboratory conditions whether such an association poses a serious cost to Caenorhabditis as previously surmised for other Serratia. Results A fecundity table of Caenorhabditis briggsae KT0001 fed on S. marcescens SCBI and the control fed on E. coli OP50 is presented. We found no significant difference in survivorship or total fecundity between the S. marcescens SCBI fed and E. coli OP50 fed Caenorhabditis briggsae KT0001. Only the mean onset of reproduction was significantly different between the two groups with E. coli fed C. briggsae maturing earlier (2.12 days) than those fed on Serratia (2.42 days). Conclusion S. marcescens SCBI is not highly pathogenic to C. briggsae KT0001 indicating that the entomopathogenicity reported for this association may be beneficial for both the nematode and bacteria. In light of the fact that hitherto conducted experimental tests conform to widely held view that Serratia are highly pathogenic to Caenorhabditis, the absence of a high fitness cost for C. briggsae we report here may indicate that this entomopathogenic association is non-transient suggesting nematode/bacterial associations in the wild may vary greatly. Consequently, broad generalizations about nematode/bacterial associations should be interpreted with care. PMID:23256850

  1. Entamoeba histolytica-Induced Mucin Exocytosis Is Mediated by VAMP8 and Is Critical in Mucosal Innate Host Defense.

    PubMed

    Cornick, Steve; Moreau, France; Gaisano, Herbert Y; Chadee, Kris

    2017-10-03

    Intestinal mucus secretion is critical in maintaining mucosal host defense against a myriad of pathogens by preventing direct association with the epithelium. Entamoeba histolytica specifically binds colonic MUC2 mucin and also induces potent hypersecretion from goblet cells; however, characterization of the nature of the mechanisms controlling mucus release remains elusive. In this report, we identify vesicle SNARE vesicle-associated membrane protein 8 (VAMP8) present on mucin granules as orchestrating regulated exocytosis in human goblet cells in response to the presence of E. histolytica VAMP8 was specifically activated during E. histolytica infection, and ablation of VAMP8 led to impaired mucin secretion. As a consequence, loss of VAMP8 increased E. histolytica adherence to epithelial cells associated with enhanced cell death through apoptosis characterized by caspase 3 and 9 cleavages and DNA fragmentation. With the mucosal barrier compromised in Vamp8 -/- animals, E. histolytica induced an aggressive proinflammatory response with elevated levels of interleukin-1 alpha (IL-1α), IL-1β, and tumor necrosis factor alpha (TNF-α) secretion. This report is the first to characterize regulated mucin exocytosis in intestinal goblet cells in response to a pathogen and the downstream consequences of improper mucin secretion in mucosal barrier defense. IMPORTANCE The intestinal tract is exposed to countless substances and pathogens, and yet homeostasis is maintained, in part by the mucus layer that houses the microbiota and spatially separates potential threats from the underlying single layer of epithelium. Despite the critical role of mucus in innate host defense, characterization of the mechanisms by which mucus is secreted from specialized goblet cells in the gut remains elusive. Here, we describe the machinery that regulates mucus secretion as well as the consequence during infection with the colonic pathogen Entamoeba histolytica Abolishment of the key machinery protein VAMP8 abrogated mucus release in cultured human colonic goblet cells and during E. histolytica infection in Vamp8 -/- mice, which showed enhanced amoeba contact and killing of epithelial cells, triggering a potent proinflammatory response. This report highlights the importance of the VAMP8 secretory machinery in facilitating mucus release from intestinal goblet cells and the dire consequences that occur during disease pathogenesis if these pathways are not functional. Copyright © 2017 Cornick et al.

  2. Cage size, movement in and out of housing during daily care, and other environmental and population health risk factors for feline upper respiratory disease in nine North American animal shelters.

    PubMed

    Wagner, Denae C; Kass, Philip H; Hurley, Kate F

    2018-01-01

    Upper respiratory infection (URI) is not an inevitable consequence of sheltering homeless cats. This study documents variation in risk of URI between nine North American shelters; determines whether this reflects variation in pathogen frequency on intake or differences in transmission and expression of disease; and identifies modifiable environmental and group health factors linked to risk for URI. This study demonstrated that although periodic introduction of pathogens into shelter populations may be inevitable, disease resulting from those pathogens is not. Housing and care of cats, particularly during their first week of stay in an animal shelter environment, significantly affects the rate of upper respiratory infection.

  3. Coinfection by the tick-borne pathogens Babesia microti and Borrelia burgdorferi: ecological, epidemiological and clinical consequences

    PubMed Central

    Diuk-Wasser, Maria A.; Vannier, Edouard

    2015-01-01

    Ixodes ticks maintain a large and diverse array of human pathogens in the enzootic cycle, including Borrelia burgdorferi and Babesia microti. Despite the poor ecological fitness of B. microti, babesiosis has recently emerged in areas endemic for Lyme disease. Studies in ticks, reservoir hosts and humans indicate that coinfection with B. burgdorferi and B. microti is common, promotes transmission and emergence of B. microti in the enzootic cycle, and causes greater disease severity and duration in humans. These integrative studies may serve as a paradigm for the study of other vector-borne coinfections. Identifying ecological drivers of pathogen emergence and host factors that fuel disease severity will help guide the design of effective curative and prevention strategies. PMID:26613664

  4. Kinetoplastids: related protozoan pathogens, different diseases

    PubMed Central

    Stuart, Ken; Brun, Reto; Croft, Simon; Fairlamb, Alan; Gürtler, Ricardo E.; McKerrow, Jim; Reed, Steve; Tarleton, Rick

    2008-01-01

    Kinetoplastids are a group of flagellated protozoans that include the species Trypanosoma and Leishmania, which are human pathogens with devastating health and economic effects. The sequencing of the genomes of some of these species has highlighted their genetic relatedness and underlined differences in the diseases that they cause. As we discuss in this Review, steady progress using a combination of molecular, genetic, immunologic, and clinical approaches has substantially increased understanding of these pathogens and important aspects of the diseases that they cause. Consequently, the paths for developing additional measures to control these “neglected diseases” are becoming increasingly clear, and we believe that the opportunities for developing the drugs, diagnostics, vaccines, and other tools necessary to expand the armamentarium to combat these diseases have never been better. PMID:18382742

  5. Behavioral, metabolic, and immune consequences of chronic alcohol or cannabinoids on HIV/AIDs: Studies in the Non-Human Primate SIV model

    PubMed Central

    Molina, Patricia E.; Amedee, Angela M.; Winsauer, Peter; Nelson, Steve; Bagby, Gregory; Simon, Liz

    2015-01-01

    HIV-associated mortality has been significantly reduced with antiretroviral therapy (ART), and HIV infection has become a chronic disease that frequently coexists with many disorders, including substance abuse (Azar et al. 2010; Phillips et al. 2001). Alcohol and drugs of abuse may modify host-pathogen interactions at various levels including behavioral, metabolic, and immune consequences of HIV infection, as well as the ability of the virus to integrate into the genome and replicate in host cells. Identifying mechanisms responsible for these interactions is complicated by many factors, such as the tissue specific responses to viral infection, multiple cellular mechanisms involved in inflammatory responses, neuroendocrine and localized responses to infection, and kinetics of viral replication. An integrated physiological analysis of the biomedical consequences of chronic alcohol and drug use or abuse on disease progression is possible using rhesus macaques infected with simian immunodeficiency virus (SIV), a relevant model of HIV infection. This review will provide an overview of the data gathered using this model to show that chronic administration of two of the most commonly abused substances, alcohol and cannabinoids (Δ9-Tetrahydrocannabinol; THC), affect host-pathogen interactions. PMID:25795088

  6. Update in Pathogenesis and Prospective in Treatment of Necrotizing Enterocolitis

    PubMed Central

    Terrin, Gianluca; Scipione, Antonella; De Curtis, Mario

    2014-01-01

    Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high. Improvements in the understanding of pathogenesis of NEC may have therapeutic consequences. Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC. This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives. PMID:25147804

  7. Engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens

    NASA Astrophysics Data System (ADS)

    Seo, Youngmin; Kim, Ji-Eun; Jeong, Yoon; Lee, Kwan Hong; Hwang, Jangsun; Hong, Jongwook; Park, Hansoo; Choi, Jonghoon

    2016-01-01

    Many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. Given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Vaccinia virus) is highly desirable. Here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capturing antibodies against four different high-risk pathogens for simple and rapid isolation, and (2) genetically engineered apoferritin nanoparticles conjugated with multiple quantum dots and detection antibodies against four different high-risk pathogens for signal amplification. For each high-risk pathogen, we demonstrated at least 10-fold increase in sensitivity compared to traditional lateral flow devices that utilize enzyme-based detection methods. Multiplexed detection of high-risk pathogens in a sample was also successful by using the nanoconstructs harboring the dye molecules with fluorescence at different wavelengths. We ultimately envision the use of this novel nanoprobe detection platform in future applications that require highly sensitive on-site detection of high-risk pathogens.

  8. 76 FR 24793 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    .... APHIS-2006-0074] RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal and Plant Health... any subtype of highly pathogenic avian influenza is considered to exist. The interim rule also imposed... avian influenza, or that have moved through regions where any subtype of highly pathogenic avian...

  9. Host persistence or extinction from emerging infectious disease: insights from white-nose syndrome in endemic and invading regions

    PubMed Central

    Hoyt, Joseph R.; Langwig, Kate E.; Sun, Keping; Lu, Guanjun; Parise, Katy L.; Jiang, Tinglei; Foster, Jeffrey T.; Feng, Jiang; Kilpatrick, A. Marm

    2016-01-01

    Predicting species' fates following the introduction of a novel pathogen is a significant and growing problem in conservation. Comparing disease dynamics between introduced and endemic regions can offer insight into which naive hosts will persist or go extinct, with disease acting as a filter on host communities. We examined four hypothesized mechanisms for host–pathogen persistence by comparing host infection patterns and environmental reservoirs for Pseudogymnoascus destructans (the causative agent of white-nose syndrome) in Asia, an endemic region, and North America, where the pathogen has recently invaded. Although colony sizes of bats and hibernacula temperatures were very similar, both infection prevalence and fungal loads were much lower on bats and in the environment in Asia than North America. These results indicate that transmission intensity and pathogen growth are lower in Asia, likely due to higher host resistance to pathogen growth in this endemic region, and not due to host tolerance, lower transmission due to smaller populations, or lower environmentally driven pathogen growth rate. Disease filtering also appears to be favouring initially resistant species in North America. More broadly, determining the mechanisms allowing species persistence in endemic regions can help identify species at greater risk of extinction in introduced regions, and determine the consequences for disease dynamics and host–pathogen coevolution. PMID:26962138

  10. Sources and contamination routes of microbial pathogens to fresh produce during field cultivation: A review.

    PubMed

    Alegbeleye, Oluwadara Oluwaseun; Singleton, Ian; Sant'Ana, Anderson S

    2018-08-01

    Foodborne illness resulting from the consumption of contaminated fresh produce is a common phenomenon and has severe effects on human health together with severe economic and social impacts. The implications of foodborne diseases associated with fresh produce have urged research into the numerous ways and mechanisms through which pathogens may gain access to produce, thereby compromising microbiological safety. This review provides a background on the various sources and pathways through which pathogenic bacteria contaminate fresh produce; the survival and proliferation of pathogens on fresh produce while growing and potential methods to reduce microbial contamination before harvest. Some of the established bacterial contamination sources include contaminated manure, irrigation water, soil, livestock/ wildlife, and numerous factors influence the incidence, fate, transport, survival and proliferation of pathogens in the wide variety of sources where they are found. Once pathogenic bacteria have been introduced into the growing environment, they can colonize and persist on fresh produce using a variety of mechanisms. Overall, microbiological hazards are significant; therefore, ways to reduce sources of contamination and a deeper understanding of pathogen survival and growth on fresh produce in the field are required to reduce risk to human health and the associated economic consequences. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. A faster infection assay for Armillaria using Herbaceous plants

    USDA-ARS?s Scientific Manuscript database

    Armillaria (honey fungus) is a virulent necrotrophic pathogen that causes Armillaria root disease. Conventional Armillaria inoculation assays use young saplings as hosts and consequently are cumbersome, frequently conducted outdoors and take many years from establishment to analysis of infection. We...

  12. Host-pathogen interactions in a varying environment: temperature, behavioural fever and fitness.

    PubMed Central

    Elliot, Sam L; Blanford, Simon; Thomas, Matthew B

    2002-01-01

    We demonstrate how variable temperatures, mediated by host thermoregulation and behavioural fever, critically affect the interaction between a host (the desert locust, Schistocerca gregaria) and a pathogen (the fungus Metarhizium anisopliae var. acridum). By means of behavioural thermoregulation, infected locusts can raise their body temperatures to fever levels. The adaptive value of this behaviour was examined using three thermal regimes wherein maximum body temperatures achievable were: (i) below, or (ii) at normally preferred temperatures, or were (iii) unrestricted, allowing heightened fever temperatures. All infected locusts ultimately succumbed to disease, with median survival times of 8, 15 and 21 days post-infection, respectively. Crucially, only those locusts able to fever produced viable offspring. This represents, to our knowledge, the first demonstration of the adaptive value of behavioural fever following infection with a naturally occurring pathogen. By contrast, although normal host thermoregulation moderately reduced pathogen reproduction (by 35%), there was no additional negative effect of fever, resulting in an asymmetry in the fitness consequences of fever for the host and the pathogen. The dependency of the host-pathogen interaction upon external abiotic conditions has implications for how virulence and resistance are treated both theoretically and in the management of pests and diseases. PMID:12184830

  13. Biodiversity decreases disease through predictable changes in host community competence.

    PubMed

    Johnson, Pieter T J; Preston, Daniel L; Hoverman, Jason T; Richgels, Katherine L D

    2013-02-14

    Accelerating rates of species extinctions and disease emergence underscore the importance of understanding how changes in biodiversity affect disease outcomes. Over the past decade, a growing number of studies have reported negative correlations between host biodiversity and disease risk, prompting suggestions that biodiversity conservation could promote human and wildlife health. Yet the generality of the diversity-disease linkage remains conjectural, in part because empirical evidence of a relationship between host competence (the ability to maintain and transmit infections) and the order in which communities assemble has proven elusive. Here we integrate high-resolution field data with multi-scale experiments to show that host diversity inhibits transmission of the virulent pathogen Ribeiroia ondatrae and reduces amphibian disease as a result of consistent linkages among species richness, host composition and community competence. Surveys of 345 wetlands indicated that community composition changed nonrandomly with species richness, such that highly competent hosts dominated in species-poor assemblages whereas more resistant species became progressively more common in diverse assemblages. As a result, amphibian species richness strongly moderated pathogen transmission and disease pathology among 24,215 examined hosts, with a 78.4% decline in realized transmission in richer assemblages. Laboratory and mesocosm manipulations revealed an approximately 50% decrease in pathogen transmission and host pathology across a realistic diversity gradient while controlling for host density, helping to establish mechanisms underlying the diversity-disease relationship and their consequences for host fitness. By revealing a consistent link between species richness and community competence, these findings highlight the influence of biodiversity on infection risk and emphasize the benefit of a community-based approach to understanding infectious diseases.

  14. Disease Resistance in Atlantic Salmon (Salmo salar): Coinfection of the Intracellular Bacterial Pathogen Piscirickettsia salmonis and the Sea Louse Caligus rogercresseyi

    PubMed Central

    Lhorente, Jean Paul; Gallardo, José A.; Villanueva, Beatriz; Carabaño, María J.; Neira, Roberto

    2014-01-01

    Background Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection. Methodology In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections. Main Findings C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h 2 SI = 0.23±0.07; h 2 LC = 0.17±0.08; h 2 HC = 0.24±0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (rg LC-HC = 0.99±0.01) but not between the single and coinfection treatments (rg SI-LC = −0.14±0.33; rg SI-HC = 0.32±0.34). Conclusions/Significance C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation. PMID:24736323

  15. Bleeding sap and old wood are the two main sources of contamination of merging organs of vine plants by Xylophilus ampelinus, the causal agent of bacterial necrosis.

    PubMed

    Grall, S; Roulland, C; Guillaumès, J; Manceau, C

    2005-12-01

    The spatial distribution of vine plants contaminated by Xylophilus ampelinus, the agent responsible for bacterial necrosis, was studied over a 5-year period within two vineyards in the Cognac area. Both vineyards were planted with Vitis vinifera cv. Ugni blanc but were different in age and agronomic location. The emission of X. ampelinus in contaminated bleeding sap was observed during vine sprouting. Contaminated bleeding sap is an important source of inoculum for external contamination due to the high susceptibility of young merging shoots to the pathogen. X. ampelinus emission by bleeding sap was not affected by the age of the plants or the location of the vineyards. However, its emission was irregular with time, and it varied between two fruit canes from individual plants and between plants as well as between years. Moreover, the two vineyards appeared to be entirely contaminated. Consequently, the behavior of the pathogen is not predictable. The distribution of the pathogen inside vine plant organs was analyzed through the four growing seasons. The old wood was contaminated throughout the year and constituted a stock inoculum for endophytic contamination of crude sap during the winter and the spring. Despite the fact that most of the young green shoots were contaminated in May, X.ampelinus was not found in green shoots in June and September, refuting the hypothesis of an epiphytic life of the pathogen under natural conditions. Although all plants were entirely contaminated in both vineyards, symptoms were rare and were observed on different plants each year.

  16. Bleeding Sap and Old Wood Are the Two Main Sources of Contamination of Merging Organs of Vine Plants by Xylophilus ampelinus, the Causal Agent of Bacterial Necrosis

    PubMed Central

    Grall, S.; Roulland, C.; Guillaumès, J.; Manceau, C.

    2005-01-01

    The spatial distribution of vine plants contaminated by Xylophilus ampelinus, the agent responsible for bacterial necrosis, was studied over a 5-year period within two vineyards in the Cognac area. Both vineyards were planted with Vitis vinifera cv. Ugni blanc but were different in age and agronomic location. The emission of X. ampelinus in contaminated bleeding sap was observed during vine sprouting. Contaminated bleeding sap is an important source of inoculum for external contamination due to the high susceptibility of young merging shoots to the pathogen. X. ampelinus emission by bleeding sap was not affected by the age of the plants or the location of the vineyards. However, its emission was irregular with time, and it varied between two fruit canes from individual plants and between plants as well as between years. Moreover, the two vineyards appeared to be entirely contaminated. Consequently, the behavior of the pathogen is not predictable. The distribution of the pathogen inside vine plant organs was analyzed through the four growing seasons. The old wood was contaminated throughout the year and constituted a stock inoculum for endophytic contamination of crude sap during the winter and the spring. Despite the fact that most of the young green shoots were contaminated in May, X.ampelinus was not found in green shoots in June and September, refuting the hypothesis of an epiphytic life of the pathogen under natural conditions. Although all plants were entirely contaminated in both vineyards, symptoms were rare and were observed on different plants each year. PMID:16332815

  17. The Roles of Inflammation, Nutrient Availability and the Commensal Microbiota in Enteric Pathogen Infection.

    PubMed

    Stecher, Bärbel

    2015-06-01

    The healthy human intestine is colonized by as many as 1014 bacteria belonging to more than 500 different species forming a microbial ecosystem of unsurpassed diversity, termed the microbiota. The microbiota's various bacterial members engage in a physiological network of cooperation and competition within several layers of complexity. Within the last 10 years, technological progress in the field of next-generation sequencing technologies has tremendously advanced our understanding of the wide variety of physiological and pathological processes that are influenced by the commensal microbiota (1, 2). An increasing number of human disease conditions, such as inflammatory bowel diseases (IBD), type 2 diabetes, obesity, allergies and colorectal cancer are linked with altered microbiota composition (3). Moreover, a clearer picture is emerging of the composition of the human microbiota in healthy individuals, its variability over time and between different persons and how the microbiota is shaped by environmental factors (i.e., diet) and the host's genetic background (4). A general feature of a normal, healthy gut microbiota can generate conditions in the gut that disfavor colonization of enteric pathogens. This is termed colonization-resistance (CR). Upon disturbance of the microbiota, CR can be transiently disrupted, and pathogens can gain the opportunity to grow to high levels. This disruption can be caused by exposure to antibiotics (5, 6), changes in diet (7, 8), application of probiotics and drugs (9), and a variety of diseases (3). Breakdown of CR can boost colonization by intrinsic pathogens or increase susceptibility to infections (10). One consequence of pathogen expansion is the triggering of inflammatory host responses and pathogen-mediated disease. Interestingly, human enteric pathogens are part of a small group of bacterial families that belong to the Proteobacteria: the Enterobacteriaceae (E. coli, Yersinia spp., Salmonella spp., Shigella spp.), the Vibrionaceae (Vibrio cholerae) and the Campylobacteriaceae (Campylobacter spp.). In general, members of these families (be it commensals or pathogens) only constitute a minority of the intestinal microbiota. However, proteobacterial "blooms" are a characteristic trait of an abnormal microbiota such as in the course of antibiotic therapy, dietary changes or inflammation (11). It has become clear that the gut microbiota not only plays a major role in priming and regulating mucosal and systemic immunity, but that the immune system also contributes to host control over microbiota composition. These two ways of mutual communication between the microbiota and the immune system were coined as "outside-in" and "inside-out," respectively (12). The significance of those interactions for human health is particularly evident in Crohn's disease (CD) and Ulcerative Colitis (UC). The symptoms of these recurrent, chronic types of gut inflammation are caused by an excessive immune response against one's own commensal microbiota (13). It is assumed that deregulated immune responses can be caused by a genetic predisposition, leading to, for example, the impairment of intestinal barrier function or disruption of mucosal T-cell homeostasis. In CD or UC patients, an abnormally composed microbiota, referred to as "dysbiosis," is commonly observed (discussed later). This is often characterized by an increased relative abundance of facultative anaerobic bacteria (e.g., Enterobacteriaeceae, Bacilli) and, at the same time, depletion of obligate anaerobic bacteria of the classes Bacteroidia and Clostridia. So far, it is unclear whether dysbiosis is a cause or a consequence of inflammatory bowel disease (IBD). In fact, both scenarios are equally conceivable. Recent work suggests that inflammatory immune responses in the gut (both IBD and pathogen-induced) can alter the gut luminal milieu in a way that favors dysbiosis (14). In this chapter, I present a survey on our current state of understanding of the characteristics and mechanisms underlying gut inflammation-associated dysbiosis. The role of dysbiosis in enteric infections and human IBD is discussed. In addition, I will focus on competition of enteric pathogens and the gut microbiota in the inflamed gut and the role of dysbiotic microbiota alterations (e.g., "Enterobacterial blooms" (11)) for the evolution of pathogenicity.

  18. The ectopic expression of a pectin methyl esterase inhibitor increases pectin methyl esterification and limits fungal diseases in wheat.

    PubMed

    Volpi, Chiara; Janni, Michela; Lionetti, Vincenzo; Bellincampi, Daniela; Favaron, Francesco; D'Ovidio, Renato

    2011-09-01

    Cell wall pectin methyl esterification can influence plant resistance because highly methyl-esterified pectin can be less susceptible to the hydrolysis by pectic enzymes such as fungal endopolygalacturonases (PG). Pectin is secreted into the cell wall in a highly methyl-esterified form and, here, is de-methyl esterified by pectin methyl esterase (PME). The activity of PME is controlled by specific protein inhibitors called PMEI; consequently, an increased inhibition of PME by PMEI might modify the pectin methyl esterification. In order to test the possibility of improving wheat resistance by modifying the methyl esterification of pectin cell wall, we have produced durum wheat transgenic lines expressing the PMEI from Actinidia chinensis (AcPMEI). The expression of AcPMEI endows wheat with a reduced endogenous PME activity, and transgenic lines expressing a high level of the inhibitor showed a significant increase in the degree of methyl esterification. These lines showed a significant reduction of disease symptoms caused by the fungal pathogens Bipolaris sorokiniana or Fusarium graminearum. This increased resistance was related to the impaired ability of these fungal pathogens to grow on methyl-esterified pectin and to a reduced activity of the fungal PG to hydrolyze methyl-esterified pectin. In addition to their importance for wheat improvement, these results highlight the primary role of pectin despite its low content in the wheat cell wall.

  19. T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection.

    PubMed

    Wang, George C; Dash, Pradyot; McCullers, Jonathan A; Doherty, Peter C; Thomas, Paul G

    2012-04-04

    A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8⁺ TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV)-specific CD8⁺ T cells recovered directly ex vivo. We found that CD8⁺ TCRαβ repertoire diversity, but not the size of the CD8⁺ T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8⁺ T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.

  20. Novel organisms: comparing invasive species, GMOs, and emerging pathogens.

    PubMed

    Jeschke, Jonathan M; Keesing, Felicia; Ostfeld, Richard S

    2013-09-01

    Invasive species, range-expanding species, genetically modified organisms (GMOs), synthetic organisms, and emerging pathogens increasingly affect the human environment. We propose a framework that allows comparison of consecutive stages that such novel organisms go through. The framework provides a common terminology for novel organisms, facilitating knowledge exchange among researchers, managers, and policy makers that work on, or have to make effective decisions about, novel organisms. The framework also indicates that knowledge about the causes and consequences of stage transitions for the better studied novel organisms, such as invasive species, can be transferred to more poorly studied ones, such as GMOs and emerging pathogens. Finally, the framework advances understanding of how climate change can affect the establishment, spread, and impacts of novel organisms, and how biodiversity affects, and is affected by, novel organisms.

  1. Consequences of germline variation disrupting the constitutional translational initiation codon start sites of MLH1 and BRCA2: use of potential alternative start sites and implications for predicting variant pathogenicity

    PubMed Central

    Parsons, Michael T.; Whiley, Phillip J.; Beesley, Jonathan; Drost, Mark; de Wind, Niels; Thompson, Bryony A.; Marquart, Louise; Hopper, John L.; Jenkins, Mark A.; Brown, Melissa A.; Tucker, Kathy; Warwick, Linda; Buchanan, Daniel D.; Spurdle, Amanda B.

    2014-01-01

    Variants that disrupt the translation initiation sequences in cancer predisposition genes are generally assumed to be deleterious. However few studies have validated these assumptions with functional and clinical data. Two cancer syndrome gene variants likely to affect native translation initiation were identified by clinical genetic testing: MLH1:c.1A>G p.(Met1?) and BRCA2:c.67+3A>G. In vitro GFP-reporter assays were conducted to assess the consequences of translation initiation disruption on alternative downstream initiation codon usage. Analysis of MLH1:c.1A>G p.(Met1?) showed that translation was mostly initiated at an in-frame position 103 nucleotides downstream, but also at two ATG sequences downstream. The protein product encoded by the in-frame transcript initiating from position c.103 showed loss of in vitro mismatch repair activity comparable to known pathogenic mutations. BRCA2:c.67+3A>G was shown by mRNA analysis to result in an aberrantly spliced transcript deleting exon 2 and the consensus ATG site. In the absence of exon 2, translation initiated mostly at an out-of-frame ATG 323 nucleotides downstream, and to a lesser extent at an in-frame ATG 370 nucleotides downstream. Initiation from any of the downstream alternative sites tested in both genes would lead to loss of protein function, but further clinical data is required to confirm if these variants are associated with a high cancer risk. Importantly, our results highlight the need for caution in interpreting the functional and clinical consequences of variation that leads to disruption of the initiation codon, since translation may not necessarily occur from the first downstream alternative start site, or from a single alternative start site. PMID:24302565

  2. Highly pathogenic avian influenza A(H7N9) virus, Tennessee, USA, March 2017

    USDA-ARS?s Scientific Manuscript database

    In March 2017, highly pathogenic avian influenza A(H7N9) was detected at 2 poultry farms in Tennessee, USA. Surveillance data and genetic analyses indicated multiple introductions of low pathogenicity avian influenza virus before mutation to high pathogenicity and interfarm transmission. Poultry sur...

  3. Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 4. Medical Imaging Procedures.

    PubMed

    Byrum, Russell; Keith, Lauren; Bartos, Christopher; St Claire, Marisa; Lackemeyer, Matthew G; Holbrook, Michael R; Janosko, Krisztina; Barr, Jason; Pusl, Daniela; Bollinger, Laura; Wada, Jiro; Coe, Linda; Hensley, Lisa E; Jahrling, Peter B; Kuhn, Jens H; Lentz, Margaret R

    2016-10-03

    Medical imaging using animal models for human diseases has been utilized for decades; however, until recently, medical imaging of diseases induced by high-consequence pathogens has not been possible. In 2014, the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Integrated Research Facility at Fort Detrick opened an Animal Biosafety Level 4 (ABSL-4) facility to assess the clinical course and pathology of infectious diseases in experimentally infected animals. Multiple imaging modalities including computed tomography (CT), magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography are available to researchers for these evaluations. The focus of this article is to describe the workflow for safely obtaining a CT image of a live guinea pig in an ABSL-4 facility. These procedures include animal handling, anesthesia, and preparing and monitoring the animal until recovery from sedation. We will also discuss preparing the imaging equipment, performing quality checks, communication methods from "hot side" (containing pathogens) to "cold side," and moving the animal from the holding room to the imaging suite.

  4. A Review of Roof Harvested Rainwater in Australia

    PubMed Central

    Whiley, Harriet; Edwards, John W.; Ross, Kirstin E.

    2018-01-01

    To address concern regarding water sustainability, the Australian Federal Government and many state governments have implemented regulatory mechanisms and incentives to support households to purchase and install rainwater harvesting systems. This has led to an increase in rainwater harvesting in regional and urban Australia. This review examines the implementation of the regulatory mechanisms across Australia. In addition, the literature investigating the potential health consequences of rainwater consumption in Australia was explored. Studies demonstrated that although trace metals such as arsenic, cadmium, chromium, lead, and iron were present in Australian rainwater, these metallic elements were generally found below the health limit guideline, except in high industrial areas. In addition, pathogenic or indicator microorganisms that include, but are not limited to, Escherichia coli, total and faecal coliforms, Campylobacter, Salmonella, Legionella, Pseudomonas, Cryptosporidium, Enterococci, Giardia, Aeromonas, and Mycobacterium avium Complex (MAC) have been detected in rainwater collected in Australia. However, epidemiological evidence suggests that drinking rainwater does not increase the risk of gastrointestinal disease. It was also identified that there is a need for further research investigating the potential for rainwater to be a source of infection for opportunistic pathogens. PMID:29606962

  5. Evaluation of the Efficacy of Iodophor Disinfection of Walleye and Northern Pike Eggs to Eliminate Viral Hemorrhagic Septicemia Virus

    USGS Publications Warehouse

    Tuttle-Lau, M.T.; Phillips, K.A.; Gaikowski, M.P.

    2009-01-01

    Viral hemorrhagic septicemia virus (VHSv) is a serious fish pathogen that has been responsible for large-scale fish kills in the Great Lakes since 2005. It causes high mortality and resulting outbreaks have severe economic consequences for aquaculture. Iodophor disinfection of salmonid eggs is a standard hatchery practice to reduce the risk of pathogen transfer during gamete collection ('spawning') operations and is thus a leading candidate for reducing VHSv transmission during and after spawning of nonsalmonid fishes. However, before it is incorporated by hatcheries during nonsalmonid fish spawning efforts, its safety and effectiveness needs to be evaluated. The USGS Fact Sheet 2009-3107, 'Evaluation of the Efficacy of Iodophor Disinfection of Walleye and Northern Pike Eggs to Eliminate Viral Hemorrhagic Septicemia Virus' presents the results of a study to assess the effectiveness of iodophor disinfection for eliminating VHSv (strain IVb) from fertilized eggs of walleye and northern pike intentionally challenged with VHSv following egg fertilization. Walleye and northern pike egg survival (hatch) following iodophor egg disinfection also was assessed.

  6. Land-Use Change Alters Host and Vector Communities and May Elevate Disease Risk.

    PubMed

    Guo, Fengyi; Bonebrake, Timothy C; Gibson, Luke

    2018-04-24

    Land-use change has transformed most of the planet. Concurrently, recent outbreaks of various emerging infectious diseases have raised great attention to the health consequences of anthropogenic environmental degradation. Here, we assessed the global impacts of habitat conversion and other land-use changes on community structures of infectious disease hosts and vectors, using a meta-analysis of 37 studies. From 331 pairwise comparisons of disease hosts/vectors in pristine (undisturbed) and disturbed areas, we found a decrease in species diversity but an increase in body size associated with land-use changes, potentially suggesting higher risk of infectious disease transmission in disturbed habitats. Neither host nor vector abundance, however, changed significantly following disturbance. When grouped by subcategories like disturbance type, taxonomic group, pathogen type and region, changes in host/vector community composition varied considerably. Fragmentation and agriculture in particular benefit host and vector communities and therefore might elevate disease risk. Our results indicate that while habitat disturbance could alter disease host/vector communities in ways that exacerbate pathogen prevalence, the relationship is highly context-dependent and influenced by multiple factors.

  7. Characterization of the 2012 Highly Pathogenic Avian Influenza H7N3 Virus Isolated from Poultry in an Outbreak in Mexico: Pathobiology and Vaccine Protection

    PubMed Central

    Pantin-Jackwood, Mary; Guzman, Sofia G.; Ricardez, Yadira; Spackman, Erica; Bertran, Kateri; Suarez, David L.; Swayne, David E.

    2013-01-01

    In June of 2012, an H7N3 highly pathogenic avian influenza (HPAI) virus was identified as the cause of a severe disease outbreak in commercial laying chicken farms in Mexico. The purpose of this study was to characterize the Mexican 2012 H7N3 HPAI virus (A/chicken/Jalisco/CPA1/2012) and determine the protection against the virus conferred by different H7 inactivated vaccines in chickens. Both adult and young chickens intranasally inoculated with the virus became infected and died at between 2 and 4 days postinoculation (p.i.). High virus titers and viral replication in many tissues were demonstrated at 2 days p.i. in infected birds. The virus from Jalisco, Mexico, had high sequence similarity of greater than 97% to the sequences of wild bird viruses from North America in all eight gene segments. The hemagglutinin gene of the virus contained a 24-nucleotide insert at the hemagglutinin cleavage site which had 100% sequence identity to chicken 28S rRNA, suggesting that the insert was the result of nonhomologous recombination with the host genome. For vaccine protection studies, both U.S. H7 low-pathogenic avian influenza (LPAI) viruses and a 2006 Mexican H7 LPAI virus were tested as antigens in experimental oil emulsion vaccines and injected into chickens 3 weeks prior to challenge. All H7 vaccines tested provided ≥90% protection against clinical disease after challenge and decreased the number of birds shedding virus and the titers of virus shed. This study demonstrates the pathological consequences of the infection of chickens with the 2012 Mexican lineage H7N3 HPAI virus and provides support for effective programs of vaccination against this virus in poultry. PMID:23760232

  8. An enteric pathogen Salmonella enterica serovar Typhimurium suppresses tumor growth by downregulating CD44high and CD4T regulatory (Treg) cell expression in mice: the critical role of lipopolysaccharide and Braun lipoprotein in modulating tumor growth.

    PubMed

    Liu, T; Chopra, A K

    2010-02-01

    An antitumor activity associated with several bacterial pathogens, including Salmonella enterica serovar Typhimurium, has been reported; however, the underlying immunological mechanism(s) that lead to an antitumor effect are currently unclear. Furthermore, such pathogens cannot be used to suppress tumor growth because of their potential for causing sepsis. Recently, we reported the characterization of S. Typhimurium isogenic mutants from which Braun lipoprotein genes (lppA and B) and the multicopy repressor of high temperature requirement (msbB) gene were deleted. In a mouse infection model, two mutants, namely, lppB/msbB and lppAB/msbB, minimally induced proinflammatory cytokine production at high doses and were nonlethal to animals. We showed that immunization of mice with these mutants, followed by challenge with the wild-type S. Typhimurium, could significantly suppress tumor growth, as evidenced by an 88% regression in tumor size in lppB/msbB mutant-immunized animals over a 24-day period. However, the lppAB/msbB mutant alone was not effective in modulating tumor growth in mice, although the lppB/msbB mutant alone caused marginal regression in tumor size. Importantly, we showed that CD44(+) cells grew much faster than CD44(-) cells from human liver tumors in mice, leading us to examine the possibility that S. Typhimurium might downregulate CD44 in tumors and splenocytes of mice. Consequently, we found in S. Typhimurium-infected mice that tumor size regression could indeed be related to the downregulation of CD44(high) and CD4(+)CD25(+) T(reg) cells. Importantly, the role of lipopolysaccharide and Braun lipoprotein was critical in S. Typhimurium-induced antitumor immune responses. Taken together, we have defined new immune mechanisms leading to tumor suppression in mice by S. Typhimurium.

  9. Electrochemical immunosensors for Salmonella detection in food

    USDA-ARS?s Scientific Manuscript database

    Pathogen detection is a critical point for the identification and the prevention of problems related to food safety. Failures at detecting contaminations in food may cause outbreaks with drastic consequences to public health. In spite of the real need for obtaining analytical results in the shortest...

  10. GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects.

    PubMed

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah; Winschel, Alexander; Chen, Wenjuan; Hu, Chun; Kusumoto, Hirofumi; Heyne, Henrike O; Helbig, Katherine L; Tang, Sha; Willing, Marcia C; Tinkle, Brad T; Adams, Darius J; Depienne, Christel; Keren, Boris; Mignot, Cyril; Frengen, Eirik; Strømme, Petter; Biskup, Saskia; Döcker, Dennis; Strom, Tim M; Mefford, Heather C; Myers, Candace T; Muir, Alison M; LaCroix, Amy; Sadleir, Lynette; Scheffer, Ingrid E; Brilstra, Eva; van Haelst, Mieke M; van der Smagt, Jasper J; Bok, Levinus A; Møller, Rikke S; Jensen, Uffe B; Millichap, John J; Berg, Anne T; Goldberg, Ethan M; De Bie, Isabelle; Fox, Stephanie; Major, Philippe; Jones, Julie R; Zackai, Elaine H; Abou Jamra, Rami; Rolfs, Arndt; Leventer, Richard J; Lawson, John A; Roscioli, Tony; Jansen, Floor E; Ranza, Emmanuelle; Korff, Christian M; Lehesjoki, Anna-Elina; Courage, Carolina; Linnankivi, Tarja; Smith, Douglas R; Stanley, Christine; Mintz, Mark; McKnight, Dianalee; Decker, Amy; Tan, Wen-Hann; Tarnopolsky, Mark A; Brady, Lauren I; Wolff, Markus; Dondit, Lutz; Pedro, Helio F; Parisotto, Sarah E; Jones, Kelly L; Patel, Anup D; Franz, David N; Vanzo, Rena; Marco, Elysa; Ranells, Judith D; Di Donato, Nataliya; Dobyns, William B; Laube, Bodo; Traynelis, Stephen F; Lemke, Johannes R

    2017-07-01

    We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care. Overall, de novo variants in 86 patients were classified as pathogenic/likely pathogenic. Patients presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense variants cluster in transmembrane segments and ligand-binding sites. Functional consequences of variants were diverse, revealing various potential gain-of-function and loss-of-function mechanisms and a retained sensitivity to the use-dependent blocker memantine. However, an objectifiable beneficial treatment response in the respective patients still remains to be demonstrated. In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Direction of interaction between mountain pine beetle (Dendroctonus ponderosae) and resource-sharing wood-boring beetles depends on plant parasite infection.

    PubMed

    Klutsch, Jennifer G; Najar, Ahmed; Cale, Jonathan A; Erbilgin, Nadir

    2016-09-01

    Plant pathogens can have cascading consequences on insect herbivores, though whether they alter competition among resource-sharing insect herbivores is unknown. We experimentally tested whether the infection of a plant pathogen, the parasitic plant dwarf mistletoe (Arceuthobium americanum), on jack pine (Pinus banksiana) altered the competitive interactions among two groups of beetles sharing the same resources: wood-boring beetles (Coleoptera: Cerambycidae) and the invasive mountain pine beetle (Dendroctonus ponderosae) (Coleoptera: Curculionidae). We were particularly interested in identifying potential mechanisms governing the direction of interactions (from competition to facilitation) between the two beetle groups. At the lowest and highest disease severity, wood-boring beetles increased their consumption rate relative to feeding levels at moderate severity. The performance (brood production and feeding) of mountain pine beetle was negatively associated with wood-boring beetle feeding and disease severity when they were reared separately. However, when both wood-boring beetles and high severity of plant pathogen infection occurred together, mountain pine beetle escaped from competition and improved its performance (increased brood production and feeding). Species-specific responses to changes in tree defense compounds and quality of resources (available phloem) were likely mechanisms driving this change of interactions between the two beetle groups. This is the first study demonstrating that a parasitic plant can be an important force in mediating competition among resource-sharing subcortical insect herbivores.

  12. Extracellular HtrA serine proteases: An emerging new strategy in bacterial pathogenesis.

    PubMed

    Backert, Steffen; Bernegger, Sabine; Skórko-Glonek, Joanna; Wessler, Silja

    2018-03-26

    The HtrA family of chaperones and serine proteases is important for regulating stress responses and controlling protein quality in the periplasm of bacteria. HtrA is also associated with infectious diseases since inactivation of htrA genes results in significantly reduced virulence properties by various bacterial pathogens. These virulence features of HtrA can be attributed to reduced fitness of the bacteria, higher susceptibility to environmental stress and/or diminished secretion of virulence factors. In some Gram-negative and Gram-positive pathogens, HtrA itself can be exposed to the extracellular environment promoting bacterial colonisation and invasion of host tissues. Most of our knowledge on the function of exported HtrAs stems from research on Helicobacter pylori, Campylobacter jejuni, Borrelia burgdorferi, Bacillus anthracis, and Chlamydia species. Here, we discuss recent progress showing that extracellular HtrAs are able to cleave cell-to-cell junction factors including E-cadherin, occludin, and claudin-8, as well as extracellular matrix proteins such as fibronectin, aggrecan, and proteoglycans, disrupting the epithelial barrier and producing substantial host cell damage. We propose that the export of HtrAs is a newly discovered strategy, also applied by additional bacterial pathogens. Consequently, exported HtrA proteases represent highly attractive targets for antibacterial treatment by inhibiting their proteolytic activity or application in vaccine development. © 2018 John Wiley & Sons Ltd.

  13. Biomimicry of volatile-based microbial control for managing emerging fungal pathogens.

    PubMed

    Gabriel, K T; Joseph Sexton, D; Cornelison, C T

    2018-05-01

    Volatile organic compounds (VOCs) are known to be produced by a wide range of micro-organisms and for a number of purposes. Volatile-based microbial inhibition in environments such as soil is well-founded, with numerous antimicrobial VOCs having been identified. Inhibitory VOCs are of interest as microbial control agents, as low concentrations of gaseous VOCs can elicit significant antimicrobial effects. Volatile organic compounds are organic chemicals typically characterized as having low molecular weight, low solubility in water, and high vapour pressure. Consequently, VOCs readily evaporate to the gaseous phase at standard temperature and pressure. This contact-independent antagonism presents unique advantages over traditional, contact-dependent microbial control methods, including increased surface exposure and reduced environmental persistence. This approach has been the focus of our recent research, with positive results suggesting it may be particularly promising for the management of emerging fungal pathogens, such as the causative agents of white-nose syndrome of bats and snake fungal disease, which are difficult or impossible to treat using traditional approaches. Here, we review the history of volatile-based microbial control, discuss recent progress in formulations that mimic naturally antagonistic VOCs, outline the development of a novel treatment device, and highlight areas where further work is needed to successfully deploy VOCs against existing and emerging fungal pathogens. © 2017 The Society for Applied Microbiology.

  14. [Invasion of microorganisms in bronchial mucosa of liquidators of the Chernobyl accident consequences].

    PubMed

    Poliakova, V A; Suchko, V A; Tereshchenko, V P; Bazyka, D A; Golovnia, O M; Rudavskaia, G A

    2001-01-01

    Bronchial bioptates of 97 liquidators of the Chernobyl accident consequences with chronic bronchitis and 23 patients of control nosological group as well as sputum (174 persons) and BAL (22 persons) of liquidators with chronic obstructive lung disease (COLD) were studied to define pathogenic role of automicroflora in the development of lung diseases. Such methods as electron microscopy, immunohistochemistry and microbiology were used. The revealed invasion of microorganisms occurred against the background of pathology of superficial bronchial epithelium with a decrease of HLA-DR and CD23 lymphocytes and increase of CD1c lymphocytes in lamina propria of bronchial mucosa of the liquidators. Verification of microorganisms characteristic of the upper respiratory tracts and atypical presence of Escherichia coli were found in the contents of the lower parts of broncho-pulmonary system of the liquidators. The obtained results testify to the activation of automicroflora and appearance of pathogenic microorganisms were caused by deterioration of specific and non-specific immune protection in liquidators with COLD.

  15. The RpoB H481Y Rifampicin Resistance Mutation and an Active Stringent Response Reduce Virulence and Increase Resistance to Innate Immune Responses in Staphylococcus aureus

    PubMed Central

    Gao, Wei; Cameron, David R.; Davies, John K.; Kostoulias, Xenia; Stepnell, Justin; Tuck, Kellie L.; Yeaman, Michael R.; Peleg, Anton Y.; Stinear, Timothy P.; Howden, Benjamin P.

    2013-01-01

    The occurrence of mutations in methicillin-resistant Staphylococcus aureus (MRSA) during persistent infection leads to antimicrobial resistance but may also impact host-pathogen interactions. Here, we investigate the host-pathogen consequences of 2 mutations arising in clinical MRSA during persistent infection: RpoB H481Y, which is linked to rifampicin resistance, and RelA F128Y, which is associated with an active stringent response. Allelic exchange experiments showed that both mutations cause global transcriptional changes, leading to upregulation of capsule production, with attenuated virulence in a murine bacteremia model and reduced susceptibility to both antimicrobial peptides and whole-blood killing. Disruption of capsule biosynthesis reversed these impacts on innate immune function. These data clearly link MRSA persistence and reduced virulence to the same mechanisms that alter antimicrobial susceptibility. Our study highlights the wider consequences of suboptimal antimicrobial use, where drug resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure. PMID:23255563

  16. Human health implications of avian influenza viruses and paramyxoviruses.

    PubMed

    Capua, I; Alexander, D J

    2004-01-01

    Among avian influenza viruses and avian paramyxoviruses are the aetiological agents of two of the most devastating diseases of the animal kingdom: (i). the highly pathogenic form of avian influenza, caused by some viruses of the H5 and H7 subtypes, and (ii). Newcastle disease, caused by virulent strains of APMV type 1. Mortality rates due to these agents can exceed 50% in naïve bird populations, and, for some strains of AI, nearly 100%. These viruses may also be responsible for clinical conditions in humans. The virus responsible for Newcastle disease has been known to cause conjunctivitis in humans since the 1940s. The conjunctivitis is self-limiting and does not have any permanent consequences. Until 1997, reports of human infection with avian influenza viruses were sporadic and frequently associated with conjunctivitis. Recently, however, avian influenza virus infections have been associated with fatalities in human beings. These casualties have highlighted the potential risk that this type of infection poses to public health. In particular, the pathogenetic mechanisms of highly pathogenic avian influenza viruses in birds and the possibility of reassortment between avian and human viruses in the human host represent serious threats to human health. For this reason, any suspected case should be investigated thoroughly.

  17. The microbiome of a striped dolphin (Stenella coeruleoalba) stranded in Portugal.

    PubMed

    Godoy-Vitorino, Filipa; Rodriguez-Hilario, Arnold; Alves, Ana Luísa; Gonçalves, Filipa; Cabrera-Colon, Beatriz; Mesquita, Cristina Sousa; Soares-Castro, Pedro; Ferreira, Marisa; Marçalo, Ana; Vingada, José; Eira, Catarina; Santos, Pedro Miguel

    2017-01-01

    Infectious diseases with epizootic consequences have not been fully studied in marine mammals. Presently, the unprecedented depth of sequencing, made available by high-throughput approaches, allows detailed comparisons of the microbiome in health and disease. This is the first report of the striped dolphin microbiome in different body sites. Samples from one striped female edematous dolphin were acquired from a variety of body niches, including the blowhole, oral cavity, oral mucosa, tongue, stomach, intestines and genital mucosa. Detailed 16S rRNA analysis of over half a million sequences identified 235 OTUs. Beta diversity analyses indicated that microbial communities vary in structure and cluster by sample origin. Pathogenic, Gram-negative, facultative and obligate anaerobic taxa were significantly detected, including Cetobacterium, Fusobacterium and Ureaplasma. Phocoenobacter and Arcobacter dominated the oral-type samples, while Cardiobacteriaceae and Vibrio were associated with the blowhole and Photobacterium were abundant in the gut. We report for the first time the association of Epulopiscium with a marine mammal gut. The striped dolphin microbiota shows variation in structure and diversity according to the organ type. The high dominance of Gram-negative anaerobic pathogens evidences a cetacean microbiome affected by human-related bacteria. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  18. A risk assessment of campylobacteriosis and salmonellosis linked to chicken meals prepared in households in Dakar, Senegal.

    PubMed

    Pouillot, Régis; Garin, Benoit; Ravaonindrina, Noro; Diop, Kane; Ratsitorahina, Mahery; Ramanantsoa, Domoina; Rocourt, Jocelyne

    2012-10-01

    We used a quantitative microbiological risk assessment model to describe the risk of Campylobacter and Salmonella infection linked to chicken meals prepared in households in Dakar, Senegal. The model uses data collected specifically for this study, such as the prevalence and level of bacteria on the neck skin of chickens bought in Dakar markets, time-temperature profiles recorded from purchase to consumption, an observational survey of meal preparation in private kitchens, and detection and enumeration of pathogens on kitchenware and cooks' hands. Thorough heating kills all bacteria present on chicken during cooking, but cross-contamination of cooked chicken or ready-to-eat food prepared for the meal via kitchenware and cooks' hands leads to a high expected frequency of pathogen ingestion. Additionally, significant growth of Salmonella is predicted during food storage at ambient temperature before and after meal preparation. These high exposures lead to a high estimated risk of campylobacteriosis and/or salmonellosis in Dakar households. The public health consequences could be amplified by the high level of antimicrobial resistance of Salmonella and Campylobacter observed in this setting. A significant decrease in the number of ingested bacteria and in the risk could be achieved through a reduction of the prevalence of chicken contamination at slaughter, and by the use of simple hygienic measures in the kitchen. There is an urgent need to reinforce the hygiene education of food handlers in Senegal. © 2012 Society for Risk Analysis.

  19. NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA

    PubMed Central

    Alvarez, Luis A.; Kovačič, Lidija; Rodríguez, Javier; Gosemann, Jan-Hendrik; Kubica, Malgorzata; Pircalabioru, Gratiela G.; Friedmacher, Florian; Cean, Ada; Ghişe, Alina; Sărăndan, Mihai B.; Puri, Prem; Daff, Simon; Plettner, Erika; von Kriegsheim, Alex; Bourke, Billy; Knaus, Ulla G.

    2016-01-01

    Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host–pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches. PMID:27562167

  20. The role of hyperparasitism in microbial pathogen ecology and evolution.

    PubMed

    Parratt, Steven R; Laine, Anna-Liisa

    2016-08-01

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

  1. NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA.

    PubMed

    Alvarez, Luis A; Kovačič, Lidija; Rodríguez, Javier; Gosemann, Jan-Hendrik; Kubica, Malgorzata; Pircalabioru, Gratiela G; Friedmacher, Florian; Cean, Ada; Ghişe, Alina; Sărăndan, Mihai B; Puri, Prem; Daff, Simon; Plettner, Erika; von Kriegsheim, Alex; Bourke, Billy; Knaus, Ulla G

    2016-09-13

    Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host-pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches.

  2. Applying horizontal gene transfer phenomena to enhance non-viral gene therapy

    PubMed Central

    Elmer, Jacob J.; Christensen, Matthew D.; Rege, Kaushal

    2014-01-01

    Horizontal gene transfer (HGT) is widespread amongst prokaryotes, but eukaryotes tend to be far less promiscuous with their genetic information. However, several examples of HGT from pathogens into eukaryotic cells have been discovered and mimicked to improve non-viral gene delivery techniques. For example, several viral proteins and DNA sequences have been used to significantly increase cytoplasmic and nuclear gene delivery. Plant genetic engineering is routinely performed with the pathogenic bacterium Agrobacterium tumefaciens and similar pathogens (e.g. Bartonella henselae) may also be able to transform human cells. Intracellular parasites like Trypanosoma cruzi may also provide new insights into overcoming cellular barriers to gene delivery. Finally, intercellular nucleic acid transfer between host cells will also be briefly discussed. This article will review the unique characteristics of several different viruses and microbes and discuss how their traits have been successfully applied to improve non-viral gene delivery techniques. Consequently, pathogenic traits that originally caused diseases may eventually be used to treat many genetic diseases. PMID:23994344

  3. Pathology during acute infections: contributions of intracellular pathogens and the CTL response.

    PubMed

    Ganusov, Vitaly V; Antia, Rustom

    2005-06-22

    Previous work has shown how, in the case of cytotoxic T-lymphocyte (CTL) responses to persistent viral infections, pathology may arise as a consequence of cell destruction directly by the virus or indirectly due to the CTL response, leading to maximum pathology at intermediate efficacy of the immune response. We expand these studies to consider pathology arising during acute infections with intracellular pathogens controlled by the CTL response. We show that, in contrast to persistent infections, pathology during acute infections is minimized with increasing efficacy of the immune response. The implications of these results for vaccination are discussed.

  4. Host persistence or extinction from emerging infectious disease: insights from white-nose syndrome in endemic and invading regions.

    PubMed

    Hoyt, Joseph R; Langwig, Kate E; Sun, Keping; Lu, Guanjun; Parise, Katy L; Jiang, Tinglei; Frick, Winifred F; Foster, Jeffrey T; Feng, Jiang; Kilpatrick, A Marm

    2016-03-16

    Predicting species' fates following the introduction of a novel pathogen is a significant and growing problem in conservation. Comparing disease dynamics between introduced and endemic regions can offer insight into which naive hosts will persist or go extinct, with disease acting as a filter on host communities. We examined four hypothesized mechanisms for host-pathogen persistence by comparing host infection patterns and environmental reservoirs for Pseudogymnoascus destructans (the causative agent of white-nose syndrome) in Asia, an endemic region, and North America, where the pathogen has recently invaded. Although colony sizes of bats and hibernacula temperatures were very similar, both infection prevalence and fungal loads were much lower on bats and in the environment in Asia than North America. These results indicate that transmission intensity and pathogen growth are lower in Asia, likely due to higher host resistance to pathogen growth in this endemic region, and not due to host tolerance, lower transmission due to smaller populations, or lower environmentally driven pathogen growth rate. Disease filtering also appears to be favouring initially resistant species in North America. More broadly, determining the mechanisms allowing species persistence in endemic regions can help identify species at greater risk of extinction in introduced regions, and determine the consequences for disease dynamics and host-pathogen coevolution. © 2016 The Author(s).

  5. BATS RECOVERING FROM WHITE-NOSE SYNDROME ELEVATE METABOLIC RATE DURING WING HEALING IN SPRING.

    PubMed

    Meierhofer, Melissa B; Johnson, Joseph S; Field, Kenneth A; Lumadue, Shayne S; Kurta, Allen; Kath, Joseph A; Reeder, DeeAnn M

    2018-04-04

      Host responses to infection with novel pathogens are costly and require trade-offs among physiologic systems. One such pathogen is the fungus Pseudogymnoascus destructans (Pd) that causes white-nose syndrome (WNS) and has led to mass mortality of hibernating bats in eastern North America. Although infection with Pd does not always result in death, we hypothesized that bats that survive infection suffer significant consequences that negatively impact the ability of females to reproduce. To understand the physiologic consequences of surviving infection with Pd, we assessed differences in wing damage, mass-specific resting metabolic rate, and reproductive rate between little brown myotis ( Myotis lucifugus) that survived a winter in captivity after inoculation with Pd (WNS survivors) and comparable, uninfected bats. Survivors of WNS had significantly more damaged wing tissue and displayed elevated mass-specific metabolic rates compared with Pd-uninfected bats after emergence from hibernation. The WNS survivors and Pd-uninfected bats did not significantly differ in their reproductive capacity, at least in captivity. However, our metabolic data demonstrated greater energetic costs during spring in WNS survivors compared with uninfected bats, which may have led to other consequences for postpartum fitness. We suggest that, after surviving the energetic constraints of winter, temperate hibernating bats infected with Pd faced a second energetic bottleneck after emerging from hibernation.

  6. Coastal development and precipitation drive pathogen flow from land to sea: evidence from a Toxoplasma gondii and felid host system

    PubMed Central

    VanWormer, Elizabeth; Carpenter, Tim E; Singh, Purnendu; Shapiro, Karen; Wallender, Wesley W.; Conrad, Patricia A.; Largier, John L.; Maneta, Marco P.; Mazet, Jonna A. K.

    2016-01-01

    Rapidly developing coastal regions face consequences of land use and climate change including flooding and increased sediment, nutrient, and chemical runoff, but these forces may also enhance pathogen runoff, which threatens human, animal, and ecosystem health. Using the zoonotic parasite Toxoplasma gondii in California, USA as a model for coastal pathogen pollution, we examine the spatial distribution of parasite runoff and the impacts of precipitation and development on projected pathogen delivery to the ocean. Oocysts, the extremely hardy free-living environmental stage of T. gondii shed in faeces of domestic and wild felids, are carried to the ocean by freshwater runoff. Linking spatial pathogen loading and transport models, we show that watersheds with the highest levels of oocyst runoff align closely with regions of increased sentinel marine mammal T. gondii infection. These watersheds are characterized by higher levels of coastal development and larger domestic cat populations. Increases in coastal development and precipitation independently raised oocyst delivery to the ocean (average increases of 44% and 79%, respectively), but dramatically increased parasite runoff when combined (175% average increase). Anthropogenic changes in landscapes and climate can accelerate runoff of diverse pathogens from terrestrial to aquatic environments, influencing transmission to people, domestic animals, and wildlife. PMID:27456911

  7. Coastal development and precipitation drive pathogen flow from land to sea: evidence from a Toxoplasma gondii and felid host system.

    PubMed

    VanWormer, Elizabeth; Carpenter, Tim E; Singh, Purnendu; Shapiro, Karen; Wallender, Wesley W; Conrad, Patricia A; Largier, John L; Maneta, Marco P; Mazet, Jonna A K

    2016-07-26

    Rapidly developing coastal regions face consequences of land use and climate change including flooding and increased sediment, nutrient, and chemical runoff, but these forces may also enhance pathogen runoff, which threatens human, animal, and ecosystem health. Using the zoonotic parasite Toxoplasma gondii in California, USA as a model for coastal pathogen pollution, we examine the spatial distribution of parasite runoff and the impacts of precipitation and development on projected pathogen delivery to the ocean. Oocysts, the extremely hardy free-living environmental stage of T. gondii shed in faeces of domestic and wild felids, are carried to the ocean by freshwater runoff. Linking spatial pathogen loading and transport models, we show that watersheds with the highest levels of oocyst runoff align closely with regions of increased sentinel marine mammal T. gondii infection. These watersheds are characterized by higher levels of coastal development and larger domestic cat populations. Increases in coastal development and precipitation independently raised oocyst delivery to the ocean (average increases of 44% and 79%, respectively), but dramatically increased parasite runoff when combined (175% average increase). Anthropogenic changes in landscapes and climate can accelerate runoff of diverse pathogens from terrestrial to aquatic environments, influencing transmission to people, domestic animals, and wildlife.

  8. Global Transport Networks and Infectious Disease Spread

    PubMed Central

    Tatem, A.J.; Rogers, D.J.; Hay, S.I.

    2011-01-01

    Air, sea and land transport networks continue to expand in reach, speed of travel and volume of passengers and goods carried. Pathogens and their vectors can now move further, faster and in greater numbers than ever before. Three important consequences of global transport network expansion are infectious disease pandemics, vector invasion events and vector-borne pathogen importation. This review briefly examines some of the important historical examples of these disease and vector movements, such as the global influenza pandemics, the devastating Anopheles gambiae invasion of Brazil and the recent increases in imported Plasmodium falciparum malaria cases. We then outline potential approaches for future studies of disease movement, focussing on vector invasion and vector-borne disease importation. Such approaches allow us to explore the potential implications of international air travel, shipping routes and other methods of transport on global pathogen and vector traffic. PMID:16647974

  9. Cannibalism amplifies the spread of vertically transmitted pathogens.

    PubMed

    Sadeh, Asaf; Rosenheim, Jay A

    2016-08-01

    Cannibalism is a widespread behavior. Abundant empirical evidence demonstrates that cannibals incur a risk of contracting pathogenic infections when they consume infected conspecifics. However, current theory suggests that cannibalism generally impedes disease spread, because each victim is usually consumed by a single cannibal, such that cannibalism does not function as a spreading process. Consequently, cannibalism cannot be the only mode of transmission of most parasites. We develop simple, but general epidemiological models to analyze the interaction of cannibalism and vertical transmission. We show that cannibalism increases the prevalence of vertically transmitted pathogens whenever the host population density is not solely regulated by cannibalism. This mechanism, combined with additional, recently published, theoretical mechanisms, presents a strong case for the role of cannibalism in the spread of infectious diseases across a wide range of parasite-host systems. © 2016 by the Ecological Society of America.

  10. The consequences of human actions on risks for infectious diseases: a review

    PubMed Central

    Lindahl, Johanna F.; Grace, Delia

    2015-01-01

    The human population is growing, requiring more space for food production, and needing more animals to feed it. Emerging infectious diseases are increasing, causing losses in both human and animal lives, as well as large costs to society. Many factors are contributing to disease emergence, including climate change, globalization and urbanization, and most of these factors are to some extent caused by humans. Pathogens may be more or less prone to emergence in themselves, and rapidly mutating viruses are more common among the emerging pathogens. The climate-sensitive vector-borne diseases are likely to be emerging due to climate changes and environmental changes, such as increased irrigation. This review lists the factors within pathogens that make them prone to emergence, and the modes of transmission that are affected. The anthropogenic changes contributing to disease emergence are described, as well as how they directly and indirectly cause either increased numbers of susceptible or exposed individuals, or cause increased infectivity. Many actions may have multiple direct or indirect effects, and it may be difficult to assess what the consequences may be. In addition, most anthropogenic drivers are related to desired activities, such as logging, irrigation, trade, and travelling, which the society is requiring. It is important to research more about the indirect and direct effects of the different actions to understand both the benefits and the risks. PMID:26615822

  11. Strategies for Pathogen Biocontrol Using Lactic Acid Bacteria and Their Metabolites: A Focus on Meat Ecosystems and Industrial Environments

    PubMed Central

    Castellano, Patricia; Pérez Ibarreche, Mariana; Fontana, Cecilia; Vignolo, Graciela M.

    2017-01-01

    The globalization of trade and lifestyle ensure that the factors responsible for the emergence of diseases are more present than ever. Despite biotechnology advancements, meat-based foods are still under scrutiny because of the presence of pathogens, which causes a loss of consumer confidence and consequently a fall in demand. In this context, Lactic Acid Bacteria (LAB) as GRAS organisms offer an alternative for developing pathogen-free foods, particularly avoiding Listeria monocytogenes, with minimal processing and fewer additives while maintaining the foods’ sensorial characteristics. The use of LAB strains, enabling us to produce antimicrobial peptides (bacteriocins) in addition to lactic acid, with an impact on quality and safety during fermentation, processing, and/or storage of meat and ready-to-eat (RTE) meat products, constitutes a promising tool. A number of bacteriocin-based strategies including the use of bioprotective cultures, purified and/or semi-purified bacteriocins as well as their inclusion in varied packaging materials under different storage conditions, have been investigated. The application of bacteriocins as part of hurdle technology using non-thermal technologies was explored for the preservation of RTE meat products. Likewise, considering that food contamination with L. monocytogenes is a consequence of the post-processing manipulation of RTE foods, the role of bacteriocinogenic LAB in the control of biofilms formed on industrial surfaces is also discussed. PMID:28696370

  12. Induction of thyroiditis in mice with thyrotropin receptor lacking serologically dominant regions

    PubMed Central

    Wang, S H; Carayanniotis, G; Zhang, Y; Gupta, M; Mcgregor, A M; Banga, J P

    1998-01-01

    Grave's disease (GD) is characterized by pathogenic autoantibodies to the human thyrotropin receptor (hTSH-R), and is frequently associated with a lymphocytic infiltrate of the thyroid gland. In attempts to establish a murine model of GD, we and others have previously shown that immunization of mice with recombinant preparations of the hTSH-R ectodomain induces high titres of specific antibodies, which, however, are not pathogenic, nor is the response accompanied by the development of thyroiditis. Since earlier reports identified the serological immunodominant determinants within the N- and C-terminal regions of hTSH-R ectodomain, we reasoned that immunization of mice with truncated fragments of ectodomain lacking these dominant regions might result in skewing of the response to other determinants of the molecule, with consequent induction of immunopathological features present in GD. We show here that multiple challenge of BALB/c mice with an amino acid fragment of residues 43–282 generates antibodies directed at hTSH-R peptides 37–56, 157–176, 217–236 and 232–251. This reactivity pattern is distinct from that induced previously with the whole ectodomain of hTSH-R in BALB/c animals. Thyroid function remained unaffected in these mice, suggesting that pathogenic antibodies were not being induced. Interestingly, some animals developed lymphocytic infiltration of the thyroid gland, clearly indicating the presence of pathogenic T cell determinants within the 43–282 fragment. Challenge with the related fragment 43–316 produced the same pattern of serological response to the synthetic peptides as fragment 43–282, but was not accompanied by thyroiditis. The results demonstrate: (i) the presence of thyroiditogenic determinants within hTSH-R, and (ii) that these pathogenic determinants are likely to be cryptic, as their effect is exhibited only when the hierarchy of immunodominance within hTSH-R is drastically altered. PMID:9697994

  13. [Strategies to prevent the transmission of multidrug-resistant pathogens and their practical implementation in oupatient care].

    PubMed

    Adler, A C; Spegel, H; Wilke, J; Höller, C; Herr, C

    2012-10-01

    Multidrugresistant pathogens which are highly relevant for infection control in hospitals and other health-care facilities are a serious public health problem and a big challenge for all players in the health sector. In order to prevent the spread of multi-resistant pathogens the Commission for Hospital Hygiene of the Robert Koch-Institute (RKI) has published guidelines. These recommendations refer to the consequent implementation of an infection control management in all health care settings, including outpatient care. In Germany there are only few data available concerning infection control management and the implementation of preventive strategies in outpatient care. To what extent are national guidelines concerning infection control of multidrugresistant pathogens (i.e. methicillin-resistant Staphylococcus aureus, MRSA) feasible and practicable in outpatient care? And what are the reasons not to practice these strategies. In outpatient care the status of the infection control management and the implementation of prevention strategies was surveyed and assessed. Data were collected by structured interviews - a face to face method. Guidelines concerning infection control management are not always sufficiently implemented in outpatient care. There are multiple reasons for this, such as, e.g., lack of compliance with the recommendations as well as structural problems in the health-care system, and special challenges of outpatient care. Implementation of an infection control management concerning multidrug-resistant pathogens in outpatient care is problematic. Prevention strategies are commonly not known or not adequately implemented into daily practice. Actions to improve the situation should focus at the individual level (e.g., trainings in the context of the initiative "clean hands" ), the institutional level (improving networking, bonus schemes) and the social level (financial and legal support for outpatient care centres to bear the expenses of infection control management, "search and destroy"). © Georg Thieme Verlag KG Stuttgart · New York.

  14. Tinidazole inhibitory and cidal activity against anaerobic periodontal pathogens.

    PubMed

    Alou, L; Giménez, M J; Manso, F; Sevillano, D; Torrico, M; González, N; Granizo, J J; Bascones, A; Prieto, J; Maestre, J R; Aguilar, L

    2009-05-01

    The in vitro activity of tinidazole against anaerobic periodontal pathogens (25 Prevotella buccae, 18 Prevotella denticola, 10 Prevotella intermedia, 6 Prevotella melaninogenica, 5 Prevotella oralis, 10 Fusobacterium nucleatum and 8 Veillonella spp.) was determined by agar dilution. MIC(90) values (minimum inhibitory concentration for 90% of the organisms) were 8 microg/mL for Veillonella spp., 4 microg/mL for P. intermedia, 2 microg/mL for P. buccae, 1 microg/mL for Fusobacterium spp. and 0.5 microg/mL for other Prevotella spp. Cidal activity was studied by killing curves with tinidazole and amoxicillin (alone and in combination) at concentrations similar to those achieved in crevicular fluid (41.2 microg/mL tinidazole and 14.05 microg/mL amoxicillin) against an inoculum of ca. 10(7)colony-forming units/mL of four bacterial groups, each one composed of four different strains of the following periodontal isolates: Prevotella spp., Fusobacterium spp. and Veillonella spp. (anaerobes) and one amoxicillin-susceptible Streptococcus spp. (facultative) in a proportion of 1:1:1:1. When only beta-lactamase-negative Prevotella or Fusobacterium strains were tested, significantly higher reductions were found with amoxicillin (>4 log reduction at 48 h) versus controls. The presence of beta-lactamase-positive Prevotella spp. or F. nucleatum strains rendered amoxicillin inactive (no reductions at 48 h), with no differences from controls. Amoxicillin+tinidazole produced >3 log reduction at 24h and >4 log reduction at 48 h regardless of the presence or not of beta-lactamase-positive strains. The presence in crevicular fluid of beta-lactamases produced by beta-lactamase-positive periodontal pathogens may have ecological and therapeutic consequences since it may protect beta-lactamase-negative periodontal pathogens from amoxicillin treatment. In vitro, tinidazole offered high antianaerobic activity against beta-lactamase-positive and -negative periodontal pathogens, avoiding amoxicillin inactivation.

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

    PubMed

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

    2015-12-01

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

  16. Role of animal movement and indirect contact among farms in transmission of porcine epidemic diarrhea virus.

    PubMed

    VanderWaal, Kimberly; Perez, Andres; Torremorrell, Montse; Morrison, Robert M; Craft, Meggan

    2018-04-12

    Epidemiological models of the spread of pathogens in livestock populations primarily focus on direct contact between farms based on animal movement data, and in some cases, local spatial spread based on proximity between premises. The roles of other types of indirect contact among farms is rarely accounted for. In addition, data on animal movements is seldom available in the United States. However, the spread of porcine epidemic diarrhea virus (PEDv) in U.S. swine represents one of the best documented emergences of a highly infectious pathogen in the U.S. livestock industry, providing an opportunity to parameterize models of pathogen spread via direct and indirect transmission mechanisms in swine. Using observed data on pig movements during the initial phase of the PEDv epidemic, we developed a network-based and spatially explicit epidemiological model that simulates the spread of PEDv via both indirect and direct movement-related contact in order to answer unresolved questions concerning factors facilitating between-farm transmission. By modifying the likelihood of each transmission mechanism and fitting this model to observed epidemiological dynamics, our results suggest that between-farm transmission was primarily driven by direct mechanisms related to animal movement and indirect mechanisms related to local spatial spread based on geographic proximity. However, other forms of indirect transmission among farms, including contact via contaminated vehicles and feed, were responsible for high consequence transmission events resulting in the introduction of the virus into new geographic areas. This research is among the first reports of farm-level animal movements in the U.S. swine industry and, to our knowledge, represents the first epidemiological model of commercial U.S. swine using actual data on farm-level animal movement. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Pervasive effects of a dominant foliar endophytic fungus on host genetic and phenotypic expression in a tropical tree

    PubMed Central

    Mejía, Luis C.; Herre, Edward A.; Sparks, Jed P.; Winter, Klaus; García, Milton N.; Van Bael, Sunshine A.; Stitt, Joseph; Shi, Zi; Zhang, Yufan; Guiltinan, Mark J.; Maximova, Siela N.

    2014-01-01

    It is increasingly recognized that macro-organisms (corals, insects, plants, vertebrates) consist of both host tissues and multiple microbial symbionts that play essential roles in their host's ecological and evolutionary success. Consequently, identifying benefits and costs of symbioses, as well as mechanisms underlying them are research priorities. All plants surveyed under natural conditions harbor foliar endophytic fungi (FEF) in their leaf tissues, often at high densities. Despite producing no visible effects on their hosts, experiments have nonetheless shown that FEF reduce pathogen and herbivore damage. Here, combining results from three genomic, and two physiological experiments, we demonstrate pervasive genetic and phenotypic effects of the apparently asymptomatic endophytes on their hosts. Specifically, inoculation of endophyte-free (E−) Theobroma cacao leaves with Colletotrichum tropicale (E+), the dominant FEF species in healthy T. cacao, induces consistent changes in the expression of hundreds of host genes, including many with known defensive functions. Further, E+ plants exhibited increased lignin and cellulose content, reduced maximum rates of photosynthesis (Amax), and enrichment of nitrogen-15 and carbon-13 isotopes. These phenotypic changes observed in E+ plants correspond to changes in expression of specific functional genes in related pathways. Moreover, a cacao gene (Tc00g04254) highly up-regulated by C. tropicale also confers resistance to pathogen damage in the absence of endophytes or their products in host tissues. Thus, the benefits of increased pathogen resistance in E+ plants are derived in part from up-regulation of intrinsic host defense responses, and appear to be offset by potential costs including reduced photosynthesis, altered host nitrogen metabolism, and endophyte heterotrophy of host tissues. Similar effects are likely in most plant-endophyte interactions, and should be recognized in the design and interpretation of genetic and phenotypic studies of plants. PMID:25309519

  18. Black and gold howler monkeys (Alouatta caraya) as sentinels of ecosystem health: patterns of zoonotic protozoa infection relative to degree of human-primate contact.

    PubMed

    Kowalewski, Martin M; Salzer, Johanna S; Deutsch, Joseph C; Raño, Mariana; Kuhlenschmidt, Mark S; Gillespie, Thomas R

    2011-01-01

    Exponential expansion of human populations and human activities within primate habitats has resulted in high potential for pathogen exchange creating challenges for biodiversity conservation and global health. Under such conditions, resilient habitat generalists such as black and gold howler monkeys (Alouatta caraya) may act as effective sentinels to overall ecosystem health and alert us to impending epidemics in the human population. To better understand this potential, we examined noninvasively collected fecal samples from black and gold howler monkeys from remote, rural, and village populations in Northern Argentina. We examined all samples (n=90) for the zoonotic protozoa Cryptosporidium sp. and Giardia sp. via immunofluorescent antibody (IFA) detection. All samples were negative for Cryptosporidium sp. The prevalence of Giardia sp. was significantly higher at the rural site (67%) compared with the remote forest (57%) and village (40%) sites. A lack of Cryptosporidium sp. in all samples examined suggests that this pathogen is not a natural component of the howler parasite communities at these sites and that current land-use patterns and livestock contact are not exposing Argentine howler monkeys to this pathogen. High prevalence of Giardia sp. at all sites suggests that howler monkeys may serve as a viable reservoir for Giardia. Significantly higher prevalence of Giardia sp. at the rural site, where primate-livestock contact is highest, suggests the presence of multiple Giardia clades or increased exposure to Giardia through repeated zoonotic transmission among nonhuman primates, livestock, and/or people. These results highlight the need for future research into the epidemiology, cross-species transmission ecology, and clinical consequences of Giardia and other infectious agents not only in humans and livestock, but also in the wild animals that share their environments. © 2010 Wiley-Liss, Inc.

  19. Environmental fluctuations and host skin bacteria shift survival advantage between frogs and their fungal pathogen.

    PubMed

    Longo, Ana V; Zamudio, Kelly R

    2017-02-01

    Fluctuating environments can modulate host-pathogen interactions by providing a temporary advantage to one of the interacting organisms. However, we know very little about how environmental conditions facilitate beneficial interactions between hosts and their microbial communities, resulting in individual persistence with a particular pathogen. Here, we experimentally infected Eleutherodactylus coqui frogs with the fungal pathogen Batrachochytrium dendrobatidis (Bd) under environmental conditions known to confer the survival advantage to the host during the warm-wet season, or alternatively to the pathogen during the cool-dry season. We used 16S rRNA amplicon sequencing to quantify changes in bacterial richness and phylogenetic diversity, and identified operational taxonomic units (OTUs) that became overrepresented or suppressed as a consequence of Bd infection. During the warm-wet season, frogs limited Bd infections, recruited putatively beneficial bacteria and returned to pre-infection levels of richness and phylogenetic diversity. In contrast, during the cool-dry season, Bd infections kept increasing through time, and bacterial diversity remained constant. Our findings confirm that infection outcome not only depends on abiotic factors, but also on biotic interactions between hosts and their associated bacterial communities.

  20. Plant defenses against parasitic plants show similarities to those induced by herbivores and pathogens.

    PubMed

    Runyon, Justin B; Mescher, Mark C; De Moraes, Consuelo M

    2010-08-01

    Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling, and response to herbivores and pathogens has expanded rapidly in recent years, but information is generally lacking for parasitic species. In a recent paper we reported that some of the same defense responses induced by herbivores and pathogens--notably increases in jasmonic acid (JA), salicylic acid (SA), and a hypersensitive-like response (HLR)--also occur in tomato plants upon attack by the parasitic plant Cuscuta pentagona (field dodder). Parasitism induced a distinct pattern of JA and SA accumulation, and growth trials using genetically-altered tomato hosts suggested that both JA and SA govern effective defenses against the parasite, though the extent of the response varied with host plant age. Here we discuss similarities between the induced responses we observed in response to Cuscuta parasitism to those previously described for herbivores and pathogens and present new data showing that trichomes should be added to the list of plant defenses that act against multiple enemies and across Kingdoms.

  1. The biological and practical significance of antigenic variability in protective T cell responses against Theileria parva.

    PubMed

    Morrison, W I

    2007-08-19

    The evolution of antigenically distinct pathogen strains that fail to cross-protect is well documented for pathogens controlled primarily by humoral immune responses. Unlike antibodies, which recognise native proteins, protective T cells can potentially recognise epitopes in a variety of proteins that are not necessarily displayed on the pathogen surface. Moreover, individual hosts of different MHC genotypes generally respond to different sets of epitopes. It is therefore less easy to envisage how strain restricted immunity can arise for pathogens controlled by T cell responses, particularly in antigenically complex parasites. Nevertheless, strain restricted immunity is clearly a feature of a number of parasitic infections, where immunity is known to be mediated by T cell responses. One such parasite is Theileria parva which induces potent CD8 T cell responses that play an important role in immunity. CD8 T cells specific for parasitized lymphoblasts exhibit strain specificity, which appears to correlate with the ability of parasite strains to cross-protect. Studies using recently identified T. parva antigens recognised by CD8 T cells have shown that the strain restricted nature of immunity is a consequence of the CD8 T cell response in individual animals being focused on a limited number of dominant polymorphic antigenic determinants. Responses in animals of different MHC genotypes are often directed to different parasite antigens, indicating that, at the host population level, a larger number of parasite proteins can serve as targets for the protective T cell response. Nevertheless, the finding that parasite strains show overlapping antigenic profiles, probably as a consequence of sexual recombination, suggests that induction of responses to an extended but limited set of antigens in individual animals may overcome the strain restricted nature of immunity.

  2. Immune suppression in cattle: contributors and consequences

    USDA-ARS?s Scientific Manuscript database

    With a $35.7 billion Gross Domestic Value for milk produced in the U.S. during 2007, the dairy industry was the largest commodity group of the 2007 U.S. animal agriculture economic engine (when dairy beef is added). The economic value of controlling mastitis pathogens is immense. Most economic ana...

  3. Hyperspectral near-infrared reflectance imaging for detection of defect tomatoes

    USDA-ARS?s Scientific Manuscript database

    Cuticle cracks on tomatoes are potential sites of pathogenic infection that may cause deleterious consequences both to consumer health and to fresh and fresh-cut produce markets. The feasibility of a hyperspectral near-infrared imaging technique in the spectral range of 1000 nm to 1700 nm was inves...

  4. Determinant Variables, Enteric Pathogen Burden, Gut Function and Immune-related Inflammatory Biomarkers Associated With Childhood Malnutrition: A Prospective Case-Control Study in Northeastern Brazil.

    PubMed

    Lima, Aldo A M; Leite, Álvaro M; Di Moura, Alessandra; Lima, Noélia L; Soares, Alberto M; Abreu, Cláudia B; Filho, José Quirino; Mota, Rosa M S; Lima, Ila F N; Havt, Alexandre; Medeiros, Pedro H Q S; Prata, Mara M G; Guedes, Marjorie M; Cavalcante, Paloma A; Veras, Herlice N; Santos, Ana K S; Moore, Sean R; Pinkerton, Relana C; Houpt, Eric R; Guerrant, Richard L

    2017-12-01

    Malnutrition results in serious consequences for growth and cognitive development in children. We studied select child and maternal biologic factors, socioeconomic factors, enteric pathogenic burden and gut function biomarkers in 402 children 6-24 months of age in Northeastern Brazil. In this prospective case-control study, not being fed colostrum [odds ratio (OR): 3.29, 95% confidence interval (CI): 1.73-6.26], maternal age ≥18 years (OR: 1.88, 95% CI: 1.10-3.22) and no electric fan (OR: 2.46, 95% CI: 1.22-4.96) or bicycle (OR: 1.80, 95% CI: 1.10-2.95) in the household were positively associated, and higher birth weight (OR: 0.27, 95% CI: 0.19-0.38), larger head circumference (OR: 0.74, 95% CI: 0.66-0.82) and shortness of breath in the last 2 weeks (OR: 0.49, 95% CI: 0.27-0.90) were negatively associated with malnutrition. Subclinical enteric pathogen infections were common, and enteroaggregative Escherichia coli infections were more prevalent in malnourished children (P = 0.045). Biomarkers such as the lactulose-mannitol test, myeloperoxidase, neopterin and calprotectin were highly elevated in both malnourished and nourished children. Nourished children had a better systemic immune response than the malnourished children, as detected by elevated serum amyloid A-1 and soluble cluster of differentiation protein 14 biomarkers (P < 0.001). Serum amyloid A-1 and soluble cluster of differentiation protein 14 were also associated with better nutritional Z scores. Neonatal, maternal and socioeconomic factors were associated with malnutrition in children. There was a substantial subclinical enteric pathogen burden, particularly with enteroaggregative E. coli, in malnourished children.

  5. Cytotoxic Chromosomal Targeting by CRISPR/Cas Systems Can Reshape Bacterial Genomes and Expel or Remodel Pathogenicity Islands

    PubMed Central

    Vercoe, Reuben B.; Chang, James T.; Dy, Ron L.; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S.; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R.; Fineran, Peter C.

    2013-01-01

    In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas–mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA–targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity. PMID:23637624

  6. Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands.

    PubMed

    Vercoe, Reuben B; Chang, James T; Dy, Ron L; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R; Fineran, Peter C

    2013-04-01

    In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas-mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA-targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity.

  7. Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence

    PubMed Central

    Porcheron, Gaëlle; Garénaux, Amélie; Proulx, Julie; Sabri, Mourad; Dozois, Charles M.

    2013-01-01

    For all microorganisms, acquisition of metal ions is essential for survival in the environment or in their infected host. Metal ions are required in many biological processes as components of metalloproteins and serve as cofactors or structural elements for enzymes. However, it is critical for bacteria to ensure that metal uptake and availability is in accordance with physiological needs, as an imbalance in bacterial metal homeostasis is deleterious. Indeed, host defense strategies against infection either consist of metal starvation by sequestration or toxicity by the highly concentrated release of metals. To overcome these host strategies, bacteria employ a variety of metal uptake and export systems and finely regulate metal homeostasis by numerous transcriptional regulators, allowing them to adapt to changing environmental conditions. As a consequence, iron, zinc, manganese, and copper uptake systems significantly contribute to the virulence of many pathogenic bacteria. However, during the course of our experiments on the role of iron and manganese transporters in extraintestinal Escherichia coli (ExPEC) virulence, we observed that depending on the strain tested, the importance of tested systems in virulence may be different. This could be due to the different set of systems present in these strains, but literature also suggests that as each pathogen must adapt to the particular microenvironment of its site of infection, the role of each acquisition system in virulence can differ from a particular strain to another. In this review, we present the systems involved in metal transport by Enterobacteria and the main regulators responsible for their controlled expression. We also discuss the relative role of these systems depending on the pathogen and the tissues they infect. PMID:24367764

  8. A novel HRM assay for differentiating classical strains and highly pathogenic strains of type 2 porcine reproductive and respiratory syndrome virus.

    PubMed

    Sun, Junying; Bingga, Gali; Liu, Zhicheng; Zhang, Chunhong; Shen, Haiyan; Guo, Pengju; Zhang, Jianfeng

    2018-06-01

    Differentiation of classical strains and highly pathogenic strains of porcine reproductive and respiratory syndrome virus is crucial for effective vaccination programs and epidemiological studies. We used nested PCR and high resolution melting curve analysis with unlabeled probe to distinguish between the classical and the highly pathogenic strains of this virus. Two sets of primers and a 20 bp unlabeled probe were designed from the NSP3 gene. The unlabeled probe included two mutations specific for the classical and highly pathogenic strains of the virus. An additional primer set from the NSP2 gene of the highly pathogenic vaccine strain JXA1-R was used to detect its exclusive single nucleotide polymorphism. We tested 107 clinical samples, 21 clinical samples were positive for PRRSV (consistent with conventional PCR assay), among them four were positive for the classical strain with the remainder 17 for the highly pathogenic strain. Around 10 °C difference between probe melting temperatures showed the high discriminatory power of this method. Among highly pathogenic positive samples, three samples were determined as positive for JXA1-R vaccine-related strain with a 95% genotype confidence percentage. All these genotyping results using the high resolution melting curve assay were confirmed with DNA sequencing. This unlabeled probe method provides an alternative means to differentiate the classical strains from the highly pathogenic porcine reproductive and respiratory syndrome virus strains rapidly and accurately. Copyright © 2018. Published by Elsevier Ltd.

  9. Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients

    PubMed Central

    de Steenhuijsen Piters, Wouter A A; Huijskens, Elisabeth G W; Wyllie, Anne L; Biesbroek, Giske; van den Bergh, Menno R; Veenhoven, Reinier H; Wang, Xinhui; Trzciński, Krzysztof; Bonten, Marc J; Rossen, John W A; Sanders, Elisabeth A M; Bogaert, Debby

    2016-01-01

    Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research. PMID:26151645

  10. Transcriptomic profiling of a chicken lung epithelial cell line (CLEC213) reveals a mitochondrial respiratory chain activity boost during influenza virus infection.

    PubMed

    Meyer, Léa; Leymarie, Olivier; Chevalier, Christophe; Esnault, Evelyne; Moroldo, Marco; Da Costa, Bruno; Georgeault, Sonia; Roingeard, Philippe; Delmas, Bernard; Quéré, Pascale; Le Goffic, Ronan

    2017-01-01

    Avian Influenza virus (AIV) is a major concern for the global poultry industry. Since 2012, several countries have reported AIV outbreaks among domestic poultry. These outbreaks had tremendous impact on poultry production and socio-economic repercussion on farmers. In addition, the constant emergence of highly pathogenic AIV also poses a significant risk to human health. In this study, we used a chicken lung epithelial cell line (CLEC213) to gain a better understanding of the molecular consequences of low pathogenic AIV infection in their natural host. Using a transcriptome profiling approach based on microarrays, we identified a cluster of mitochondrial genes highly induced during the infection. Interestingly, most of the regulated genes are encoded by the mitochondrial genome and are involved in the oxidative phosphorylation metabolic pathway. The biological consequences of this transcriptomic induction result in a 2.5- to 4-fold increase of the ATP concentration within the infected cells. PB1-F2, a viral protein that targets the mitochondria was not found associated to the boost of activity of the respiratory chain. We next explored the possibility that ATP may act as a host-derived danger signal (through production of extracellular ATP) or as a boost to increase AIV replication. We observed that, despite the activation of the P2X7 purinergic receptor pathway, a 1mM ATP addition in the cell culture medium had no effect on the virus replication in our epithelial cell model. Finally, we found that oligomycin, a drug that inhibits the oxidative phosphorylation process, drastically reduced the AIV replication in CLEC213 cells, without apparent cellular toxicity. Collectively, our results suggest that AIV is able to boost the metabolic capacities of its avian host in order to provide the important energy needs required to produce progeny virus.

  11. Differential immune response of mallard duck peripheral blood mononuclear cells to two highly pathogenic avian influenza H5N1 viruses with distinct pathogenicity in mallard ducks.

    PubMed

    Cui, Zhu; Hu, Jiao; He, Liang; Li, Qunhui; Gu, Min; Wang, Xiaoquan; Hu, Shunlin; Liu, Huimou; Liu, Wenbo; Liu, Xiaowen; Liu, Xiufan

    2014-02-01

    CK10 and GS10 are two H5N1 highly pathogenic influenza viruses of similar genetic background but differ in their pathogenicity in mallard ducks. CK10 is highly pathogenic whereas GS10 is low pathogenic. In this study, strong inflammatory response in terms of the expression level of several cytokines was observed in mallard duck peripheral blood mononuclear cells (PBMC) infected with CK10 while mild response was triggered in those by GS10 infection. Two remarkable and intense peaks of immune response were induced by CK10 infection within 24 hours (at 8 and 24 hours post infection, respectively) without reducing the virus replication. Our observations indicated that sustained and intense innate immune responses may be central to the high pathogenicity caused by CK10 in ducks.

  12. The influence of the perceived consequences of refusing to share injection equipment among injection drug users: Balancing competing risks

    PubMed Central

    Wagner, Karla D.; Lankenau, Stephen E.; Palinkas, Lawrence A.; Richardson, Jean L.; Chou, Chih-Ping; Unger, Jennifer B.

    2011-01-01

    Injection drug users (IDUs) are at risk for HIV and other bloodborne pathogens through receptive syringe sharing (RSS) and receptive paraphernalia sharing (RPS). Research into the influence of the perceived risk of HIV infection on injection risk behavior has yielded mixed findings. One explanation may be that consequences other than HIV infection are considered when IDUs are faced with decisions about whether or not to share equipment. We investigated the perceived consequences of refusing to share injection equipment among 187 IDUs recruited from a large syringe exchange program in Los Angeles, California, assessed their influence on RSS and RPS, and evaluated gender differences. Two sub-scales of perceived consequences were identified: structural/external consequences and social/internal consequences. In multiple linear regression, the perceived social/internal consequences of refusing to share were associated with both RSS and RPS, after controlling for other psychosocial constructs and demographic variables. Few statistically significant gender differences emerged. Assessing the consequences of refusing to share injection equipment may help explain persistent injection risk behavior, and may provide promising targets for comprehensive intervention efforts designed to address both individual and structural risk factors. PMID:21498004

  13. Fate and transport of pathogens in lakes and reservoirs.

    PubMed

    Brookes, Justin D; Antenucci, Jason; Hipsey, Matthew; Burch, Michael D; Ashbolt, Nicholas J; Ferguson, Christobel

    2004-07-01

    Outbreaks of water-borne disease via public water supplies continue to be reported in developed countries even though there is increased awareness of, and treatment for, pathogen contamination. Pathogen episodes in lakes and reservoirs are often associated with rain events, and the riverine inflow is considered to be major source of pathogens. Consequently, the behaviour of these inflows is of particular importance in determining pathogen transport and distribution. Inflows are controlled by their density relative to that of the lake, such that warm inflows will flow over the surface of the lake as a buoyant surface flow and cold, dense inflows will sink beneath the lake water where they will flow along the bathymetry towards the deepest point. The fate of pathogens is determined by loss processes including settling and inactivation by temperature, UV and grazing. The general trend is for the insertion timescale to be shortest, followed by sedimentation losses and temperature inactivity. The fate of Cryptosporidium due to UV light inactivation can occur at opposite ends of the scale, depending on the location of the oocysts in the water column and the extinction coefficient for UV light. For this reason, the extinction coefficient for UV light appears to be a vitally important parameter for determining the risk of Cryptosporidium contamination. For risk assessment of pathogens in supply reservoirs, it is important to understand the role of hydrodynamics in determining the timescale of transport to the off-take relative to the timescale of inactivation. The characteristics of the riverine intrusion must also be considered when designing a sampling program for pathogens. A risk management framework is presented that accounts for pathogen fate and transport for reservoirs.

  14. Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

    DOE PAGES

    Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; ...

    2015-10-12

    Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

  15. Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

    PubMed Central

    Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; Cabelli, Diane E.; Bruns, Cami K.; Belzer, Carol A.; Gorringe, Andrew R.; Langford, Paul R.; Tabatabai, Louisa B.; Kroll, J. Simon; Tainer, John A.

    2015-01-01

    ABSTRACT Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. PMID:26459556

  16. Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus.

    PubMed

    Pratt, Ashley J; DiDonato, Michael; Shin, David S; Cabelli, Diane E; Bruns, Cami K; Belzer, Carol A; Gorringe, Andrew R; Langford, Paul R; Tabatabai, Louisa B; Kroll, J Simon; Tainer, John A; Getzoff, Elizabeth D

    2015-12-01

    Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

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

    Pratt, Ashley J.; DiDonato, Michael; Shin, David S.

    Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

  18. Meiosis Leads to Pervasive Copy-Number Variation and Distorted Inheritance of Accessory Chromosomes of the Wheat Pathogen Zymoseptoria tritici.

    PubMed

    Fouché, Simone; Plissonneau, Clémence; McDonald, Bruce A; Croll, Daniel

    2018-06-01

    Meiosis is one of the most conserved molecular processes in eukaryotes. The fidelity of pairing and segregation of homologous chromosomes has a major impact on the proper transmission of genetic information. Aberrant chromosomal transmission can have major phenotypic consequences, yet the mechanisms are poorly understood. Fungi are excellent models to investigate processes of chromosomal transmission, because many species have highly polymorphic genomes that include accessory chromosomes. Inheritance of accessory chromosomes is often unstable and chromosomal losses have little impact on fitness. We analyzed chromosomal inheritance in 477 progeny coming from two crosses of the fungal wheat pathogen Zymoseptoria tritici. For this, we developed a high-throughput screening method based on restriction site-associated DNA sequencing that generated dense coverage of genetic markers along each chromosome. We identified rare instances of chromosomal duplications (disomy) in core chromosomes. Accessory chromosomes showed high overall frequencies of disomy. Chromosomal rearrangements were found exclusively on accessory chromosomes and were more frequent than disomy. Accessory chromosomes present in only one of the parents in an analyzed cross were inherited at significantly higher rates than the expected 1:1 segregation ratio. Both the chromosome and the parental background had significant impacts on the rates of disomy, losses, rearrangements, and distorted inheritance. We found that chromosomes with higher sequence similarity and lower repeat content were inherited more faithfully. The large number of rearranged progeny chromosomes identified in this species will enable detailed analyses of the mechanisms underlying chromosomal rearrangement.

  19. A lysosomal lair for a pathogenic protein pair.

    PubMed

    Dawson, Ted M; Dawson, Valina L

    2011-07-13

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects movement. Although many of the causes of PD remain unclear, a consistent finding is the abnormal accumulation of the protein α-synuclein. In a recent issue of Cell, Mazzuli et al. provide a molecular explanation for the unexpected link between PD and Gaucher's disease, a glycolipid lysosomal storage disorder caused by loss of the enzyme glucocerebrosidase (GBA). They report a reciprocal connection between loss of GBA activity and the accumulation of α-synuclein in lysosomes that establishes a bidirectional positive feedback loop with pathogenic consequences. Understanding how lysosomes are implicated in PD may reveal new therapeutic targets for treating this disease.

  20. Microbiological Food Safety for Vulnerable People

    PubMed Central

    Lund, Barbara M.

    2015-01-01

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

  1. [Toll-like receptor in lung response to pathogens].

    PubMed

    Rivas-Santiago, Bruno; Juárez, Esmeralda

    2007-01-01

    Innate immunity plays a central role in antimicrobial defense. Advances in the understanding of pathogen recognition systems of innate cells have yielded the identification of Toll like receptors (TLR) as key elements of the lung defense mechanisms which is heavily exposed to a variety of stimuli. TLR recognition of several microbial compounds induces proinflammatory cytokines production whose contribution to the host may be either protective or detrimental. Human immune response diversity may explain the differences observed between patients facing bacterial, viral and fungal lung infections. New strategies designs that modify innate immune response may be useful to limit detrimental consequences of inflammatory processes in the lung.

  2. Natural Infection of the South American Tapir ( Tapirus terrestris ) by Theileria equi.

    PubMed

    Da Silveira, Alexandre Welzel; De Oliveira, Gustavo Gomes; Menezes Santos, Leandro; da Silva Azuaga, Lucas Bezerra; Macedo Coutinho, Claudia Regina; Echeverria, Jessica Teles; Antunes, Tamires Ramborger; do Nascimento Ramos, Carlos Alberto; Izabel de Souza, Alda

    2017-04-01

    Theileria equi is a tick-borne piroplasm considered endemic in equines in Brazil. The cohabitation of domestic and wild animals in areas of extensive cattle breeding favors the close contact between different species and the sharing of vectors and, consequently, pathogens. We report the natural infection of a young South American tapir ( Tapirus terrestris ) by T. equi in Mato Grosso do Sul, Brazil. Although it was not possible to associate the clinical and hematologic status of the animal with the infection by the protozoan parasite, our report represents an alert on the sharing of pathogens between domestic and wild animals.

  3. Differential cytokine expression in Chlamydophila psittaci genotype A-, B- or D-infected chicken macrophages after exposure to Escherichia coli O2:K1 LPS.

    PubMed

    Beeckman, Delphine Sylvie Anne; Rothwell, Lisa; Kaiser, Pete; Vanrompay, Daisy C G

    2010-08-01

    Chlamydophila (Cp.) psittaci and avian pathogenic Escherichia (E.) coli infections contribute to the respiratory disease complex observed in turkeys. Secondary infection with E. coli exacerbates Cp. psittaci pathogenicity and augments E. coli excretion. The innate immune response initiated by both pathogens in their avian host is unknown. We therefore determined the cytokine responses following Cp. psittaci infection and E. coli superinfection of avian monocytes/macrophages by examining gene transcripts of IL-1beta, IL-6, CXCLi2 (IL-8), CXCLi1 (K60), IL-10, IL-12alpha/beta, IL-18, TGF-beta4 and CCLi2 at 4h post-inoculation with different Cp. psittaci strains or 4h post-treatment with avian E. coli LPS of Cp. psittaci pre-infected HD11 cells. Cp. psittaci strains used were 84/55 and 92/1293 (highly virulent), CP3 (low virulent) and 84/2334 (phylogenetically intermediate between Cp. psittaci and Chlamydophila abortus). At 4h post chlamydial infection, an increased expression of IL-1beta and IL-6 as well as CXCLi2, CXCLi1 and CCLi2 was observed compared to levels in uninfected HD11 controls. This effect was less pronounced for the milder CP3 strain. The pro-inflammatory response of Cp. psittaci infected cells to E. coli LPS was significantly lowered compared to uninfected controls, especially when the cells were pre-infected with highly virulent Cp. psittaci strains. In both experiments, exceptionally high IL-10 and no TGF-beta4 responses were observed, and we propose that this could induce macrophage deactivation and NF-kappaB suppression. Consequently, pro-inflammatory and Th1-promoting responses to both the primary Cp. psittaci infection and E. coli would be inhibited, thus explaining the observed aggravated in vivo pathology. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. The Trk Potassium Transporter Is Required for RsmB-Mediated Activation of Virulence in the Phytopathogen Pectobacterium wasabiae.

    PubMed

    Valente, Rita S; Xavier, Karina B

    2016-01-15

    Pectobacterium wasabiae (previously known as Erwinia carotovora) is an important plant pathogen that regulates the production of plant cell wall-degrading enzymes through an N-acyl homoserine lactone-based quorum sensing system and through the GacS/GacA two-component system (also known as ExpS/ExpA). At high cell density, activation of GacS/GacA induces the expression of RsmB, a noncoding RNA that is essential for the activation of virulence in this bacterium. A genetic screen to identify regulators of RsmB revealed that mutants defective in components of a putative Trk potassium transporter (trkH and trkA) had decreased rsmB expression. Further analysis of these mutants showed that changes in potassium concentration influenced rsmB expression and consequent tissue damage in potato tubers and that this regulation required an intact Trk system. Regulation of rsmB expression by potassium via the Trk system occurred even in the absence of the GacS/GacA system, demonstrating that these systems act independently and are both required for full activation of RsmB and for the downstream induction of virulence in potato infection assays. Overall, our results identified potassium as an essential environmental factor regulating the Rsm system, and the consequent induction of virulence, in the plant pathogen P. wasabiae. Crop losses from bacterial diseases caused by pectolytic bacteria are a major problem in agriculture. By studying the regulatory pathways involved in controlling the expression of plant cell wall-degrading enzymes in Pectobacterium wasabiae, we showed that the Trk potassium transport system plays an important role in the regulation of these pathways. The data presented further identify potassium as an important environmental factor in the regulation of virulence in this plant pathogen. We showed that a reduction in virulence can be achieved by increasing the extracellular concentration of potassium. Therefore, this work highlights how elucidation of the mechanisms involved in regulating virulence can lead to the identification of environmental factors that can influence the outcome of infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. The Trk Potassium Transporter Is Required for RsmB-Mediated Activation of Virulence in the Phytopathogen Pectobacterium wasabiae

    PubMed Central

    Valente, Rita S.

    2015-01-01

    ABSTRACT Pectobacterium wasabiae (previously known as Erwinia carotovora) is an important plant pathogen that regulates the production of plant cell wall-degrading enzymes through an N-acyl homoserine lactone-based quorum sensing system and through the GacS/GacA two-component system (also known as ExpS/ExpA). At high cell density, activation of GacS/GacA induces the expression of RsmB, a noncoding RNA that is essential for the activation of virulence in this bacterium. A genetic screen to identify regulators of RsmB revealed that mutants defective in components of a putative Trk potassium transporter (trkH and trkA) had decreased rsmB expression. Further analysis of these mutants showed that changes in potassium concentration influenced rsmB expression and consequent tissue damage in potato tubers and that this regulation required an intact Trk system. Regulation of rsmB expression by potassium via the Trk system occurred even in the absence of the GacS/GacA system, demonstrating that these systems act independently and are both required for full activation of RsmB and for the downstream induction of virulence in potato infection assays. Overall, our results identified potassium as an essential environmental factor regulating the Rsm system, and the consequent induction of virulence, in the plant pathogen P. wasabiae. IMPORTANCE Crop losses from bacterial diseases caused by pectolytic bacteria are a major problem in agriculture. By studying the regulatory pathways involved in controlling the expression of plant cell wall-degrading enzymes in Pectobacterium wasabiae, we showed that the Trk potassium transport system plays an important role in the regulation of these pathways. The data presented further identify potassium as an important environmental factor in the regulation of virulence in this plant pathogen. We showed that a reduction in virulence can be achieved by increasing the extracellular concentration of potassium. Therefore, this work highlights how elucidation of the mechanisms involved in regulating virulence can lead to the identification of environmental factors that can influence the outcome of infection. PMID:26483524

  6. The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice.

    PubMed

    Wu, Xiao-Xin; Deng, Xi-Long; Yu, Dong-Shan; Yao, Wei; Ou, Hui-Lin; Weng, Tian-Hao; Hu, Chen-Yu; Hu, Feng-Yu; Wu, Nan-Ping; Yao, Hangping; Zhang, Fu-Chun; Li, Lan-Juan

    2018-01-01

    Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence. © 2018 The Author(s). Published by S. Karger AG, Basel.

  7. Destructive disinfection of infected brood prevents systemic disease spread in ant colonies.

    PubMed

    Pull, Christopher D; Ugelvig, Line V; Wiesenhofer, Florian; Grasse, Anna V; Tragust, Simon; Schmitt, Thomas; Brown, Mark Jf; Cremer, Sylvia

    2018-01-09

    In social groups, infections have the potential to spread rapidly and cause disease outbreaks. Here, we show that in a social insect, the ant Lasius neglectus , the negative consequences of fungal infections ( Metarhizium brunneum ) can be mitigated by employing an efficient multicomponent behaviour, termed destructive disinfection, which prevents further spread of the disease through the colony. Ants specifically target infected pupae during the pathogen's non-contagious incubation period, utilising chemical 'sickness cues' emitted by pupae. They then remove the pupal cocoon, perforate its cuticle and administer antimicrobial poison, which enters the body and prevents pathogen replication from the inside out. Like the immune system of a metazoan body that specifically targets and eliminates infected cells, ants destroy infected brood to stop the pathogen completing its lifecycle, thus protecting the rest of the colony. Hence, in an analogous fashion, the same principles of disease defence apply at different levels of biological organisation.

  8. The behavioural immune system and the psychology of human sociality.

    PubMed

    Schaller, Mark

    2011-12-12

    Because immunological defence against pathogens is costly and merely reactive, human anti-pathogen defence is also characterized by proactive behavioural mechanisms that inhibit contact with pathogens in the first place. This behavioural immune system comprises psychological processes that infer infection risk from perceptual cues, and that respond to these perceptual cues through the activation of aversive emotions, cognitions and behavioural impulses. These processes are engaged flexibly, producing context-contingent variation in the nature and magnitude of aversive responses. These processes have important implications for human social cognition and social behaviour-including implications for social gregariousness, person perception, intergroup prejudice, mate preferences, sexual behaviour and conformity. Empirical evidence bearing on these many implications is reviewed and discussed. This review also identifies important directions for future research on the human behavioural immune system--including the need for enquiry into underlying mechanisms, additional behavioural consequences and implications for human health and well-being.

  9. The behavioural immune system and the psychology of human sociality

    PubMed Central

    Schaller, Mark

    2011-01-01

    Because immunological defence against pathogens is costly and merely reactive, human anti-pathogen defence is also characterized by proactive behavioural mechanisms that inhibit contact with pathogens in the first place. This behavioural immune system comprises psychological processes that infer infection risk from perceptual cues, and that respond to these perceptual cues through the activation of aversive emotions, cognitions and behavioural impulses. These processes are engaged flexibly, producing context–contingent variation in the nature and magnitude of aversive responses. These processes have important implications for human social cognition and social behaviour—including implications for social gregariousness, person perception, intergroup prejudice, mate preferences, sexual behaviour and conformity. Empirical evidence bearing on these many implications is reviewed and discussed. This review also identifies important directions for future research on the human behavioural immune system—including the need for enquiry into underlying mechanisms, additional behavioural consequences and implications for human health and well-being. PMID:22042918

  10. A Xanthomonas uridine 5'-monophosphate transferase inhibits plant immune kinases.

    PubMed

    Feng, Feng; Yang, Fan; Rong, Wei; Wu, Xiaogang; Zhang, Jie; Chen, She; He, Chaozu; Zhou, Jian-Min

    2012-04-15

    Plant innate immunity is activated on the detection of pathogen-associated molecular patterns (PAMPs) at the cell surface, or of pathogen effector proteins inside the plant cell. Together, PAMP-triggered immunity and effector-triggered immunity constitute powerful defences against various phytopathogens. Pathogenic bacteria inject a variety of effector proteins into the host cell to assist infection or propagation. A number of effector proteins have been shown to inhibit plant immunity, but the biochemical basis remains unknown for the vast majority of these effectors. Here we show that the Xanthomonas campestris pathovar campestris type III effector AvrAC enhances virulence and inhibits plant immunity by specifically targeting Arabidopsis BIK1 and RIPK, two receptor-like cytoplasmic kinases known to mediate immune signalling. AvrAC is a uridylyl transferase that adds uridine 5'-monophosphate to and conceals conserved phosphorylation sites in the activation loop of BIK1 and RIPK, reducing their kinase activity and consequently inhibiting downstream signalling.

  11. Host mating system and the spread of a disease-resistant allele in a population

    USGS Publications Warehouse

    DeAngelis, D.L.; Koslow, Jennifer M.; Jiang, J.; Ruan, S.

    2008-01-01

    The model presented here modifies a susceptible-infected (SI) host-pathogen model to determine the influence of mating system on the outcome of a host-pathogen interaction. Both deterministic and stochastic (individual-based) versions of the model were used. This model considers the potential consequences of varying mating systems on the rate of spread of both the pathogen and resistance alleles within the population. We assumed that a single allele for disease resistance was sufficient to confer complete resistance in an individual, and that both homozygote and heterozygote resistant individuals had the same mean birth and death rates. When disease invaded a population with only an initial small fraction of resistant genes, inbreeding (selfing) tended to increase the probability that the disease would soon be eliminated from a small population rather than become endemic, while outcrossing greatly increased the probability that the population would become extinct due to the disease.

  12. Group B Streptococcal Maternal Colonization and Neonatal Disease: Molecular Mechanisms and Preventative Approaches

    PubMed Central

    Patras, Kathryn A.; Nizet, Victor

    2018-01-01

    Group B Streptococcus (GBS) colonizes the gastrointestinal and vaginal epithelium of a significant percentage of healthy women, with potential for ascending intrauterine infection or transmission during parturition, creating a risk of serious disease in the vulnerable newborn. This review highlights new insights on the bacterial virulence determinants, host immune responses, and microbiome interactions that underpin GBS vaginal colonization, the proximal step in newborn infectious disease pathogenesis. From the pathogen perspective, the function GBS adhesins and biofilms, β-hemolysin/cytolysin toxin, immune resistance factors, sialic acid mimicry, and two-component transcriptional regulatory systems are reviewed. From the host standpoint, pathogen recognition, cytokine responses, and the vaginal mucosal and placental immunity to the pathogen are detailed. Finally, the rationale, efficacy, and potential unintended consequences of current universal recommended intrapartum antibiotic prophylaxis are considered, with updates on new developments toward a GBS vaccine or alternative approaches to reducing vaginal colonization. PMID:29520354

  13. Disease effects on lobster fisheries, ecology, and culture: overview of DAO Special 6.

    PubMed

    Behringer, Donald C; Butler, Mark J; Stentiford, Grant D

    2012-08-27

    Lobsters are prized by commercial and recreational fishermen worldwide, and their populations are therefore buffeted by fishery practices. But lobsters also remain integral members of their benthic communities where predator-prey relationships, competitive interactions, and host-pathogen dynamics push and pull at their population dynamics. Although lobsters have few reported pathogens and parasites relative to other decapod crustaceans, the rise of diseases with consequences for lobster fisheries and aquaculture has spotlighted the importance of disease for lobster biology, population dynamics and ecology. Researchers, managers, and fishers thus increasingly recognize the need to understand lobster pathogens and parasites so they can be managed proactively and their impacts minimized where possible. At the 2011 International Conference and Workshop on Lobster Biology and Management a special session on lobster diseases was convened and this special issue of Diseases of Aquatic Organisms highlights those proceedings with a suite of articles focused on diseases discussed during that session.

  14. Detection of pathogens in food using a SERS-based assay in just a few hours

    NASA Astrophysics Data System (ADS)

    Shende, Chetan; Sengupta, Atanu; Huang, Hermes; Farquharson, Stuart

    2014-05-01

    In 2011 Escherichia, Listeria, and Salmonella species infected over 1.2 million people in the United States, resulting in over 23,000 hospitalizations and 650 deaths. In January 2013 President Obama signed into law the Food and Drug Administration (FDA) Food Safety Modernization Act (FSMA), which requires constant microbial testing of food processing equipment and food to minimize contamination and distribution of food tainted with pathogens. The challenge to preventing distribution and consumption of contaminated foods lies in the fact that just a few bacterial cells can rapidly multiply to millions, reaching infectious doses within a few days. Unfortunately, current methods used to detect these few cells rely on similar growth steps to multiply the cells to the point of detection, which also takes a few days. Consequently, there is a critical need for an analyzer that can rapidly extract and detect foodborne pathogens at 1000 colony forming units per gram of food in 1-2 hours (not days), and with a specificity that differentiates from indigenous microflora, so that false alarms are eliminated. In an effort to meet this need, we have been developing an assay that extracts such pathogens from food, selectively binds these pathogens, and produces surface-enhanced Raman spectra (SERS) when read by a Raman analyzer. Here we present SERS measurements of these pathogens in actual food samples using this assay.

  15. 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.

  16. Climate Change, Foodborne Pathogens and Illness in Higher-Income Countries.

    PubMed

    Lake, I R; Barker, G C

    2018-03-01

    We present a review of the likely consequences of climate change for foodborne pathogens and associated human illness in higher-income countries. The relationships between climate and food are complex and hence the impacts of climate change uncertain. This makes it difficult to know which foodborne pathogens will be most affected, what the specific effects will be, and on what timescales changes might occur. Hence, a focus upon current capacity and adaptation potential against foodborne pathogens is essential. We highlight a number of developments that may enhance preparedness for climate change. These include the following: Adoption of novel surveillance methods, such as syndromic methods, to speed up detection and increase the fidelity of intervention in foodborne outbreaks Genotype-based approaches to surveillance of food pathogens to enhance spatiotemporal resolution in tracing and tracking of illness Ever increasing integration of plant, animal and human surveillance systems, One Health, to maximise potential for identifying threats Increased commitment to cross-border (global) information initiatives (including big data) Improved clarity regarding the governance of complex societal issues such as the conflict between food safety and food waste Strong user-centric (social) communications strategies to engage diverse stakeholder groups The impact of climate change upon foodborne pathogens and associated illness is uncertain. This emphasises the need to enhance current capacity and adaptation potential against foodborne illness. A range of developments are explored in this paper to enhance preparedness.

  17. Listeria monocytogenes in Food-Processing Facilities, Food Contamination, and Human Listeriosis: The Brazilian Scenario.

    PubMed

    Camargo, Anderson Carlos; Woodward, Joshua John; Call, Douglas Ruben; Nero, Luís Augusto

    2017-11-01

    Listeria monocytogenes is a foodborne pathogen that contaminates food-processing environments and persists within biofilms on equipment, utensils, floors, and drains, ultimately reaching final products by cross-contamination. This pathogen grows even under high salt conditions or refrigeration temperatures, remaining viable in various food products until the end of their shelf life. While the estimated incidence of listeriosis is lower than other enteric illnesses, infections caused by L. monocytogenes are more likely to lead to hospitalizations and fatalities. Despite the description of L. monocytogenes occurrence in Brazilian food-processing facilities and foods, there is a lack of consistent data regarding listeriosis cases and outbreaks directly associated with food consumption. Listeriosis requires rapid treatment with antibiotics and most drugs suitable for Gram-positive bacteria are effective against L. monocytogenes. Only a minority of clinical antibiotic-resistant L. monocytogenes strains have been described so far; whereas many strains recovered from food-processing facilities and foods exhibited resistance to antimicrobials not suitable against listeriosis. L. monocytogenes control in food industries is a challenge, demanding proper cleaning and application of sanitization procedures to eliminate this foodborne pathogen from the food-processing environment and ensure food safety. This review focuses on presenting the L. monocytogenes distribution in food-processing environment, food contamination, and control in the food industry, as well as the consequences of listeriosis to human health, providing a comparison of the current Brazilian situation with the international scenario.

  18. Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies.

    PubMed

    Clement, Mathew; Pearson, James A; Gras, Stephanie; van den Berg, Hugo A; Lissina, Anya; Llewellyn-Lacey, Sian; Willis, Mark D; Dockree, Tamsin; McLaren, James E; Ekeruche-Makinde, Julia; Gostick, Emma; Robertson, Neil P; Rossjohn, Jamie; Burrows, Scott R; Price, David A; Wong, F Susan; Peakman, Mark; Skowera, Ania; Wooldridge, Linda

    2016-10-17

    CD8 + T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8 + T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8 + T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8 + T-cells are relatively CD8-independent. These generic differences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-specific TCRs according to the monomeric interaction affinity with cognate peptide-major histocompatibility complex class I (pMHCI). As a consequence, "blocking" anti-CD8 antibodies can suppress autoreactive CD8 + T-cell activation in a relatively selective manner. These findings provide a rational basis for the development and in vivo assessment of novel therapeutic strategies that preferentially target disease-relevant autoimmune responses within the CD8 + T-cell compartment.

  19. Spatial evolutionary epidemiology of spreading epidemics

    PubMed Central

    2016-01-01

    Most spatial models of host–parasite interactions either neglect the possibility of pathogen evolution or consider that this process is slow enough for epidemiological dynamics to reach an equilibrium on a fast timescale. Here, we propose a novel approach to jointly model the epidemiological and evolutionary dynamics of spatially structured host and pathogen populations. Starting from a multi-strain epidemiological model, we use a combination of spatial moment equations and quantitative genetics to analyse the dynamics of mean transmission and virulence in the population. A key insight of our approach is that, even in the absence of long-term evolutionary consequences, spatial structure can affect the short-term evolution of pathogens because of the build-up of spatial differentiation in mean virulence. We show that spatial differentiation is driven by a balance between epidemiological and genetic effects, and this quantity is related to the effect of kin competition discussed in previous studies of parasite evolution in spatially structured host populations. Our analysis can be used to understand and predict the transient evolutionary dynamics of pathogens and the emergence of spatial patterns of phenotypic variation. PMID:27798295

  20. Spatial evolutionary epidemiology of spreading epidemics.

    PubMed

    Lion, S; Gandon, S

    2016-10-26

    Most spatial models of host-parasite interactions either neglect the possibility of pathogen evolution or consider that this process is slow enough for epidemiological dynamics to reach an equilibrium on a fast timescale. Here, we propose a novel approach to jointly model the epidemiological and evolutionary dynamics of spatially structured host and pathogen populations. Starting from a multi-strain epidemiological model, we use a combination of spatial moment equations and quantitative genetics to analyse the dynamics of mean transmission and virulence in the population. A key insight of our approach is that, even in the absence of long-term evolutionary consequences, spatial structure can affect the short-term evolution of pathogens because of the build-up of spatial differentiation in mean virulence. We show that spatial differentiation is driven by a balance between epidemiological and genetic effects, and this quantity is related to the effect of kin competition discussed in previous studies of parasite evolution in spatially structured host populations. Our analysis can be used to understand and predict the transient evolutionary dynamics of pathogens and the emergence of spatial patterns of phenotypic variation. © 2016 The Author(s).

  1. Rapid analysis of foodborne pathogens by surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Sengupta, Atanu; Shende, Chetan; Huang, Hermes; Farquharson, Stuart; Inscore, Frank

    2012-05-01

    Foodborne diseases resulting from Campylobacter, Escherichia, Listeria, Salmonella, Shigella and Vibrio species affect as many as 76 million persons in the United States each year, resulting in 325,000 hospitalizations and 5,000 deaths. The challenge to preventing distribution and consumption of contaminated foods lies in the fact that just a few bacterial cells can rapidly multiply to millions, reaching infectious doses within a few days. Unfortunately, current methods used to detect these few cells rely on lengthy growth enrichment steps that take a similar amount of time (1 to 4 days). Consequently, there is a critical need for an analyzer that can rapidly extract and detect foodborne pathogens in 1-2 hours (not days), at 100 colony forming units per gram of food, and with a specificity that differentiates from indigenous microflora, so that false alarms are eliminated. In an effort to meet this need, we have been developing a sample system that extracts such pathogens from food, selectively binds these pathogens, and produces surface-enhanced Raman spectra (SERS). Here we present preliminary SERS measurements of Listeria and Salmonella.

  2. Exacerbated symptoms in Blastocystis sp.-infected patients treated with metronidazole: two case studies.

    PubMed

    Rajamanikam, Arutchelvan; Kumar, Suresh; Samudi, Chandramathi; Kudva, Madhav

    2018-06-05

    Blastocystis sp. is a gastrointestinal (GI) protozoan parasite reported to cause non-specific GI symptoms including diarrhea, flatulence, abdominal pain, and nausea. Complete eradication of Blastocystis sp. is rather challenging even with the drug of choice, i.e., metronidazole. Here, we report on two Blastocystis sp.-infected individuals, who presented increased parasite load and exacerbated symptoms upon treatment with the usual recommended dosage and regime of metronidazole. The two studies uniquely demonstrate for the first time a cyst count as high as fivefold more than the original cyst count before treatment and show an exacerbation of GI symptoms despite treatment. The study provides additional support in recognizing metronidazole resistance in Blastocystis sp. and its consequences towards the pathogenicity of the parasite.

  3. Are highly morphed peptide frameworks lurking silently in microbial genomes valuable as next generation antibiotic scaffolds?

    PubMed

    Walsh, Christopher T

    2017-07-01

    Antibiotics are a therapeutic class that, once deployed, select for resistant bacterial pathogens and so shorten their useful life cycles. As a consequence new versions of antibiotics are constantly needed. Among the antibiotic natural products, morphed peptide scaffolds, converting conformationally mobile, short-lived linear peptides into compact, rigidified small molecule frameworks, act on a wide range of bacterial targets. Advances in bacterial genome mining, biosynthetic gene cluster prediction and expression, and mass spectroscopic structure analysis suggests many more peptides, modified both in side chains and peptide backbones, await discovery. Such molecules may turn up new bacterial targets and be starting points for combinatorial or semisynthetic manipulations to optimize activity and pharmacology parameters.

  4. Super-shedding and the link between human infection and livestock carriage of Escherichia coli O157.

    PubMed

    Chase-Topping, Margo; Gally, David; Low, Chris; Matthews, Louise; Woolhouse, Mark

    2008-12-01

    Cattle that excrete more Escherichia coli O157 than others are known as super-shedders. Super-shedding has important consequences for the epidemiology of E. coli O157 in cattle--its main reservoir--and for the risk of human infection, particularly owing to environmental exposure. Ultimately, control measures targeted at super-shedders may prove to be highly effective. We currently have only a limited understanding of both the nature and the determinants of super-shedding. However, super-shedding has been observed to be associated with colonization at the terminal rectum and might also occur more often with certain pathogen phage types. More generally, epidemiological evidence suggests that super-shedding might be important in other bacterial and viral infections.

  5. Xp22.33p22.12 Duplication in a Patient with Intellectual Disability and Dysmorphic Facial Features

    PubMed Central

    Lintas, Carla; Picinelli, Chiara; Piras, Ignazio S.; Sacco, Roberto; Gabriele, Stefano; Verdecchia, Magda; Persico, Antonio M.

    2016-01-01

    A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage. PMID:26997944

  6. Xp22.33p22.12 Duplication in a Patient with Intellectual Disability and Dysmorphic Facial Features.

    PubMed

    Lintas, Carla; Picinelli, Chiara; Piras, Ignazio S; Sacco, Roberto; Gabriele, Stefano; Verdecchia, Magda; Persico, Antonio M

    2016-02-01

    A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage.

  7. Collateral damage: fire and Phytophthora ramorum interact to increase mortality in coast redwood

    Treesearch

    Margaret R. Metz; J. Morgan Varner; Kerri M. Frangioso; Ross K. Meentemeyer; David M. Rizzo

    2013-01-01

    Invading species can alter ecosystems by impacting the frequency, severity, and consequences of endemic disturbance regimes (Mack and D'Antonio 1998). Phytophthora ramorum, the causal agent of the emergent disease sudden oak death (SOD), is an invasive pathogen causing widespread tree mortality in coastal forests of California and Oregon. In...

  8. Powdery mildew suppresses herbivore-induced plant volatiles and interferes with parasitoid attraction in Brassica rapa

    USDA-ARS?s Scientific Manuscript database

    The co-occurrence of different antagonists on a plant can greatly affect infochemicals with ecological consequences for higher trophic levels. Here we investigated how the presence of a plant pathogen, the powdery mildew Erysiphe cruciferarum, on Brassica rapa affects 1) plant volatiles emitted in r...

  9. Genes expressed by the biological control bacterium Pseudomonas protegens Pf-5 on seed surfaces

    USDA-ARS?s Scientific Manuscript database

    Propagules of many fungal and oomycete plant pathogens can remain dormant in the soil for months or years but germinate quickly in response to seed exudates, producing germ tubes or mycelia that infect seeds. Consequently, the spermosphere is often the initial point of interaction between seed-infec...

  10. Canopy gaps decrease microbial densities and disease risk for a shade-intolerant tree species

    Treesearch

    Kurt O. Reinhart; Alejandro A. Royo; Stacie A. Kageyama; Keith. Clay

    2010-01-01

    Canopy disturbances such as windthrowevents have obvious impacts on forest structure and composition aboveground, but changes in soil microbial communities and the consequences of these changes are less understood.We characterized the densities of a soil-borne pathogenic oomycete (Pythium) and a common saprotrophic zygomycete (Mortierella...

  11. Comparison of two poultry litter qPCR assays targeting the 16S rRNA gene of Brevibacterium sp

    EPA Science Inventory

    Chicken feces are vectors of human pathogens and are also important sources of fecal pollution in environmental waters. Consequently, methods that can detect chicken fecal pollution are needed in public health and environmental monitoring studies. In this study, we compared a pre...

  12. Procurement and persistence of GFP-expressing Escherichia coli and Salmonella Typhimurium in male and female house flies exposed to cattle manure

    USDA-ARS?s Scientific Manuscript database

    Introduction: Adult house flies, Musca domestica L., are associated with animal manure and other microbe-rich substrates. Consequently, both sexes can acquire and potentially disseminate pathogenic bacteria to surrounding environments, including residential areas, via contaminated body parts and/or ...

  13. The in planta transcriptome of Ralstonia solanacearum: conserved physiological and virulence strategies during bacterial wilt of tomato.

    PubMed

    Jacobs, Jonathan M; Babujee, Lavanya; Meng, Fanhong; Milling, Annett; Allen, Caitilyn

    2012-01-01

    Plant xylem fluid is considered a nutrient-poor environment, but the bacterial wilt pathogen Ralstonia solanacearum is well adapted to it, growing to 10(8) to 10(9) CFU/g tomato stem. To better understand how R. solanacearum succeeds in this habitat, we analyzed the transcriptomes of two phylogenetically distinct R. solanacearum strains that both wilt tomato, strains UW551 (phylotype II) and GMI1000 (phylotype I). We profiled bacterial gene expression at ~6 × 10(8) CFU/ml in culture or in plant xylem during early tomato bacterial wilt pathogenesis. Despite phylogenetic differences, these two strains expressed their 3,477 common orthologous genes in generally similar patterns, with about 12% of their transcriptomes significantly altered in planta versus in rich medium. Several primary metabolic pathways were highly expressed during pathogenesis. These pathways included sucrose uptake and catabolism, and components of these pathways were encoded by genes in the scrABY cluster. A UW551 scrA mutant was significantly reduced in virulence on resistant and susceptible tomato as well as on potato and the epidemiologically important weed host Solanum dulcamara. Functional scrA contributed to pathogen competitive fitness during colonization of tomato xylem, which contained ~300 µM sucrose. scrA expression was induced by sucrose, but to a much greater degree by growth in planta. Unexpectedly, 45% of the genes directly regulated by HrpB, the transcriptional activator of the type 3 secretion system (T3SS), were upregulated in planta at high cell densities. This result modifies a regulatory model based on bacterial behavior in culture, where this key virulence factor is repressed at high cell densities. The active transcription of these genes in wilting plants suggests that T3SS has a biological role throughout the disease cycle. IMPORTANCE Ralstonia solanacearum is a widespread plant pathogen that causes bacterial wilt disease. It inflicts serious crop losses on tropical farmers, with major economic and human consequences. It is also a model for the many destructive microbes that colonize the water-conducting plant xylem tissue, which is low in nutrients and oxygen. We extracted bacteria from infected tomato plants and globally identified the biological functions that R. solanacearum expresses during plant pathogenesis. This revealed the unexpected presence of sucrose in tomato xylem fluid and the pathogen's dependence on host sucrose for virulence on tomato, potato, and the common weed bittersweet nightshade. Further, R. solanacearum was highly responsive to the plant environment, expressing several metabolic and virulence functions quite differently in the plant than in pure culture. These results reinforce the utility of studying pathogens in interaction with hosts and suggest that selecting for reduced sucrose levels could generate wilt-resistant crops.

  14. Emergence and evolution of avian H5N2 influenza viruses in chickens in Taiwan.

    PubMed

    Lee, Chang-Chun David; Zhu, Huachen; Huang, Pei-Yu; Peng, Liuxia; Chang, Yun-Cheng; Yip, Chun-Hung; Li, Yao-Tsun; Cheung, Chung-Lam; Compans, Richard; Yang, Chinglai; Smith, David K; Lam, Tommy Tsan-Yuk; King, Chwan-Chuen; Guan, Yi

    2014-05-01

    Sporadic activity by H5N2 influenza viruses has been observed in chickens in Taiwan from 2003 to 2012. The available information suggests that these viruses were generated by reassortment between a Mexican-like H5N2 virus and a local enzootic H6N1 virus. Yet the origin, prevalence, and pathogenicity of these H5N2 viruses have not been fully defined. Following the 2012 highly pathogenic avian influenza (HPAI) outbreaks, surveillance was conducted from December 2012 to July 2013 at a live-poultry wholesale market in Taipei. Our findings showed that H5N2 and H6N1 viruses cocirculated at low levels in chickens in Taiwan. Phylogenetic analyses revealed that all H5N2 viruses had hemagglutinin (HA) and neuraminidase (NA) genes derived from a 1994 Mexican-like virus, while their internal gene complexes were incorporated from the enzootic H6N1 virus lineage by multiple reassortment events. Pathogenicity studies demonstrated heterogeneous results even though all tested viruses had motifs (R-X-K/R-R) supportive of high pathogenicity. Serological surveys for common subtypes of avian viruses confirmed the prevalence of the H5N2 and H6N1 viruses in chickens and revealed an extraordinarily high seroconversion rate to an H9N2 virus, a subtype that is not found in Taiwan but is prevalent in mainland China. These findings suggest that reassortant H5N2 viruses, together with H6N1 viruses, have become established and enzootic in chickens throughout Taiwan and that a large-scale vaccination program might have been conducted locally that likely led to the introduction of the 1994 Mexican-like virus to Taiwan in 2003. H5N2 avian influenza viruses first appeared in chickens in Taiwan in 2003 and caused a series of outbreaks afterwards. Phylogenetic analyses show that the chicken H5N2 viruses have H5 and N2 genes that are closely related to those of a vaccine strain originating from Mexico in 1994, while the contemporary duck H5N2 viruses in Taiwan belong to the Eurasian gene pool. The unusually high similarity of the chicken H5N2 viruses to the Mexican vaccine strain suggests that these viruses might have been introduced to Taiwan by using inadequately inactivated or attenuated vaccines. These chicken H5N2 viruses are developing varying levels of pathogenicity that could lead to significant consequences for the local poultry industry. These findings emphasize the need for strict quality control and competent oversight in the manufacture and usage of avian influenza virus vaccines and indicate that alternatives to widespread vaccination may be desirable.

  15. Emergence and Evolution of Avian H5N2 Influenza Viruses in Chickens in Taiwan

    PubMed Central

    Lee, Chang-Chun David; Zhu, Huachen; Huang, Pei-Yu; Peng, Liuxia; Chang, Yun-Cheng; Yip, Chun-Hung; Li, Yao-Tsun; Cheung, Chung-Lam; Compans, Richard; Yang, Chinglai; Smith, David K.; Lam, Tommy Tsan-Yuk

    2014-01-01

    ABSTRACT Sporadic activity by H5N2 influenza viruses has been observed in chickens in Taiwan from 2003 to 2012. The available information suggests that these viruses were generated by reassortment between a Mexican-like H5N2 virus and a local enzootic H6N1 virus. Yet the origin, prevalence, and pathogenicity of these H5N2 viruses have not been fully defined. Following the 2012 highly pathogenic avian influenza (HPAI) outbreaks, surveillance was conducted from December 2012 to July 2013 at a live-poultry wholesale market in Taipei. Our findings showed that H5N2 and H6N1 viruses cocirculated at low levels in chickens in Taiwan. Phylogenetic analyses revealed that all H5N2 viruses had hemagglutinin (HA) and neuraminidase (NA) genes derived from a 1994 Mexican-like virus, while their internal gene complexes were incorporated from the enzootic H6N1 virus lineage by multiple reassortment events. Pathogenicity studies demonstrated heterogeneous results even though all tested viruses had motifs (R-X-K/R-R) supportive of high pathogenicity. Serological surveys for common subtypes of avian viruses confirmed the prevalence of the H5N2 and H6N1 viruses in chickens and revealed an extraordinarily high seroconversion rate to an H9N2 virus, a subtype that is not found in Taiwan but is prevalent in mainland China. These findings suggest that reassortant H5N2 viruses, together with H6N1 viruses, have become established and enzootic in chickens throughout Taiwan and that a large-scale vaccination program might have been conducted locally that likely led to the introduction of the 1994 Mexican-like virus to Taiwan in 2003. IMPORTANCE H5N2 avian influenza viruses first appeared in chickens in Taiwan in 2003 and caused a series of outbreaks afterwards. Phylogenetic analyses show that the chicken H5N2 viruses have H5 and N2 genes that are closely related to those of a vaccine strain originating from Mexico in 1994, while the contemporary duck H5N2 viruses in Taiwan belong to the Eurasian gene pool. The unusually high similarity of the chicken H5N2 viruses to the Mexican vaccine strain suggests that these viruses might have been introduced to Taiwan by using inadequately inactivated or attenuated vaccines. These chicken H5N2 viruses are developing varying levels of pathogenicity that could lead to significant consequences for the local poultry industry. These findings emphasize the need for strict quality control and competent oversight in the manufacture and usage of avian influenza virus vaccines and indicate that alternatives to widespread vaccination may be desirable. PMID:24623422

  16. Profile and Fate of Bacterial Pathogens in Sewage Treatment Plants Revealed by High-Throughput Metagenomic Approach.

    PubMed

    Li, Bing; Ju, Feng; Cai, Lin; Zhang, Tong

    2015-09-01

    The broad-spectrum profile of bacterial pathogens and their fate in sewage treatment plants (STPs) were investigated using high-throughput sequencing based metagenomic approach. This novel approach could provide a united platform to standardize bacterial pathogen detection and realize direct comparison among different samples. Totally, 113 bacterial pathogen species were detected in eight samples including influent, effluent, activated sludge (AS), biofilm, and anaerobic digestion sludge with the abundances ranging from 0.000095% to 4.89%. Among these 113 bacterial pathogens, 79 species were reported in STPs for the first time. Specially, compared to AS in bulk mixed liquor, more pathogen species and higher total abundance were detected in upper foaming layer of AS. This suggests that the foaming layer of AS might impose more threat to onsite workers and citizens in the surrounding areas of STPs because pathogens in foaming layer are easily transferred into air and cause possible infections. The high removal efficiency (98.0%) of total bacterial pathogens suggests that AS treatment process is effective to remove most bacterial pathogens. Remarkable similarities of bacterial pathogen compositions between influent and human gut indicated that bacterial pathogen profiles in influents could well reflect the average bacterial pathogen communities of urban resident guts within the STP catchment area.

  17. The RpoB H₄₈₁Y rifampicin resistance mutation and an active stringent response reduce virulence and increase resistance to innate immune responses in Staphylococcus aureus.

    PubMed

    Gao, Wei; Cameron, David R; Davies, John K; Kostoulias, Xenia; Stepnell, Justin; Tuck, Kellie L; Yeaman, Michael R; Peleg, Anton Y; Stinear, Timothy P; Howden, Benjamin P

    2013-03-15

    The occurrence of mutations in methicillin-resistant Staphylococcus aureus (MRSA) during persistent infection leads to antimicrobial resistance but may also impact host-pathogen interactions. Here, we investigate the host-pathogen consequences of 2 mutations arising in clinical MRSA during persistent infection: RpoB H₄₈₁Y, which is linked to rifampicin resistance, and RelA F₁₂₈Y, which is associated with an active stringent response. Allelic exchange experiments showed that both mutations cause global transcriptional changes, leading to upregulation of capsule production, with attenuated virulence in a murine bacteremia model and reduced susceptibility to both antimicrobial peptides and whole-blood killing. Disruption of capsule biosynthesis reversed these impacts on innate immune function. These data clearly link MRSA persistence and reduced virulence to the same mechanisms that alter antimicrobial susceptibility. Our study highlights the wider consequences of suboptimal antimicrobial use, where drug resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure.

  18. Animal health aspects of adaptation to climate change: beating the heat and parasites in a warming Europe.

    PubMed

    Skuce, P J; Morgan, E R; van Dijk, J; Mitchell, M

    2013-06-01

    Weather patterns in northern European regions have changed noticeably over the past several decades, featuring warmer, wetter weather with more extreme events. The climate is projected to continue on this trajectory for the foreseeable future, even under the most modest warming scenarios. Such changes will have a significant impact on livestock farming, both directly through effects on the animals themselves, and indirectly through changing exposure to pests and pathogens. Adaptation options aimed at taking advantage of new opportunities and/or minimising the risks of negative impacts will, in themselves, have implications for animal health and welfare. In this review, we consider the potential consequences of future intensification of animal production, challenges associated with indoor and outdoor rearing of animals and aspects of animal transportation as key examples. We investigate the direct and indirect effects of climate change on the epidemiology of important livestock pathogens, with a particular focus on parasitic infections, and the likely animal health consequences associated with selected adaptation options. Finally, we attempt to identify key gaps in our knowledge and suggest future research priorities.

  19. When environmentally persistent pathogens transform good habitat into ecological traps.

    PubMed

    Leach, Clinton B; Webb, Colleen T; Cross, Paul C

    2016-03-01

    Habitat quality plays an important role in the dynamics and stability of wildlife metapopulations. However, the benefits of high-quality habitat may be modulated by the presence of an environmentally persistent pathogen. In some cases, the presence of environmental pathogen reservoirs on high-quality habitat may lead to the creation of ecological traps, wherein host individuals preferentially colonize high-quality habitat, but are then exposed to increased infection risk and disease-induced mortality. We explored this possibility through the development of a stochastic patch occupancy model, where we varied the pathogen's virulence, transmission rate and environmental persistence as well as the distribution of habitat quality in the host metapopulation. This model suggests that for pathogens with intermediate levels of spread, high-quality habitat can serve as an ecological trap, and can be detrimental to host persistence relative to low-quality habitat. This inversion of the relative roles of high- and low-quality habitat highlights the importance of considering the interaction between spatial structure and pathogen transmission when managing wildlife populations exposed to an environmentally persistent pathogen.

  20. Hepatitis Delta Virus: Replication Strategy and Upcoming Therapeutic Options for a Neglected Human Pathogen

    PubMed Central

    Lempp, Florian A.; Urban, Stephan

    2017-01-01

    The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on a helper virus, the human Hepatitis B virus (HBV), which provides the envelope proteins required for HDV assembly. HDV affects an estimated 15–20 million out of the 240 million chronic HBV-carriers and disperses unequally in disparate geographical regions of the world. The disease it causes (chronic Hepatitis D) presents as the most severe form of viral hepatitis, leading to accelerated progression of liver dysfunction including cirrhosis and hepatocellular carcinoma and a high mortality rate. The lack of approved drugs interfering with specific steps of HDV replication poses a high burden for gaining insights into the molecular biology of the virus and, consequently, the development of specific novel medications that resiliently control HDV replication or, in the best case, functionally cure HDV infection or HBV/HDV co-infection. This review summarizes our current knowledge of HBV molecular biology, presents an update on novel cell culture and animal models to study the virus and provides updates on the clinical development of the three developmental drugs Lonafarnib, REP2139-Ca and Myrcludex B. PMID:28677645

  1. Commensal–dendritic-cell interaction specifies a unique protective skin immune signature

    PubMed Central

    Naik, Shruti; Bouladoux, Nicolas; Linehan, Jonathan L.; Han, Seong-Ji; Harrison, Oliver J.; Wilhelm, Christoph; Conlan, Sean; Himmelfarb, Sarah; Byrd, Allyson L.; Deming, Clayton; Quinones, Mariam; Brenchley, Jason M.; Kong, Heidi H.; Tussiwand, Roxanne; Murphy, Kenneth M.; Merad, Miriam; Segre, Julia A; Belkaid, Yasmine

    2015-01-01

    The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity1–4. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges5–7. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A+ CD8+ T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies. PMID:25539086

  2. Molecular Regulatory Pathways Link Sepsis With Metabolic Syndrome: Non-coding RNA Elements Underlying the Sepsis/Metabolic Cross-Talk.

    PubMed

    Meydan, Chanan; Bekenstein, Uriya; Soreq, Hermona

    2018-01-01

    Sepsis and metabolic syndrome (MetS) are both inflammation-related entities with high impact for human health and the consequences of concussions. Both represent imbalanced parasympathetic/cholinergic response to insulting triggers and variably uncontrolled inflammation that indicates shared upstream regulators, including short microRNAs (miRs) and long non-coding RNAs (lncRNAs). These may cross talk across multiple systems, leading to complex molecular and clinical outcomes. Notably, biomedical and RNA-sequencing based analyses both highlight new links between the acquired and inherited pathogenic, cardiac and inflammatory traits of sepsis/MetS. Those include the HOTAIR and MIAT lncRNAs and their targets, such as miR-122, -150, -155, -182, -197, -375, -608 and HLA-DRA. Implicating non-coding RNA regulators in sepsis and MetS may delineate novel high-value biomarkers and targets for intervention.

  3. High volume hydraulic fracturing operations: potential impacts on surface water and human health.

    PubMed

    Mrdjen, Igor; Lee, Jiyoung

    2016-08-01

    High volume, hydraulic fracturing (HVHF) processes, used to extract natural gas and oil from underground shale deposits, pose many potential hazards to the environment and human health. HVHF can negatively affect the environment by contaminating soil, water, and air matrices with potential pollutants. Due to the relatively novel nature of the process, hazards to surface waters and human health are not well known. The purpose of this article is to link the impacts of HVHF operations on surface water integrity, with human health consequences. Surface water contamination risks include: increased structural failure rates of unconventional wells, issues with wastewater treatment, and accidental discharge of contaminated fluids. Human health risks associated with exposure to surface water contaminated with HVHF chemicals include increased cancer risk and turbidity of water, leading to increased pathogen survival time. Future research should focus on modeling contamination spread throughout the environment, and minimizing occupational exposure to harmful chemicals.

  4. Disruption of Thiamine Uptake and Growth of Cells by Feline Leukemia Virus Subgroup A

    PubMed Central

    Mendoza, Ramon; Miller, A. Dusty

    2013-01-01

    Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection. PMID:23269813

  5. Disruption of thiamine uptake and growth of cells by feline leukemia virus subgroup A.

    PubMed

    Mendoza, Ramon; Miller, A Dusty; Overbaugh, Julie

    2013-03-01

    Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection.

  6. Microwaving human faecal sludge as a viable sanitation technology option for treatment and value recovery - A critical review.

    PubMed

    Afolabi, Oluwasola O D; Sohail, M

    2017-02-01

    The prolonged challenges and terrible consequences of poor sanitation, especially in developing economies, call for the exploration of new sustainable sanitation technologies. Such technologies must be: capable of effectively treating human faecal wastes without any health or environmental impacts; scalable to address rapid increases in population and urbanization; capable of meeting environmental regulations and standards for faecal management; and competitive with existing strategies. Further and importantly, despite its noxiousness and pathogenic load, the chemical composition of human faecal sludge indicates that it could be considered a potentially valuable, nutrient-rich renewable resource, rather than a problematic waste product. New approaches to faecal sludge management must consequently seek to incorporate a 'valuable resource recovery' approach, compatible with stringent treatment requirements. This review intends to advance the understanding of human faecal sludge as a sustainable organic-rich resource that is typically high in moisture (up to 97 per cent), making it a suitable candidate for dielectric heating, i.e. microwave irradiation, to promote faecal treatment, while also recovering value-added products such as ammonia liquor concentrate (suitable for fertilizers) and chars (suitable for fuel) - which can provide an economic base to sustain the technology. Additionally, microwaving human faecal sludge represents a thermally effective approach that can destroy pathogens, eradicate the foul odour associated human faecal sludge, while also preventing hazardous product formations and/or emissions, aside from other benefits such as improved dewaterability and heavy metals recovery. Key technological parameters crucial for scaling the technology as a complementary solution to the challenges of onsite sanitation are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Getting to the guts of the matter: the status and potential of 'omics' research of parasitic protists of the human gastrointestinal system.

    PubMed

    Jex, Aaron R; Koehler, Anson V; Ansell, Brendan R; Baker, Louise; Karunajeewa, Harin; Gasser, Robin B

    2013-11-01

    Parasitic protists are a major cause of diarrhoeal illnesses in humans globally. Collectively, enteric pathogens exceed all other forms of infectious disease, in terms of their estimated global prevalence and socioeconomic impact. They have a disproportionately high impact on children in impoverished communities, leading to acute (diarrhoea, vomiting, dehydration and death) and chronic disease (malabsorption, malnutrition, physical and cognitive stunting and predisposition to chronic, non-communicable disease) consequences. However, historically, investment in research and disease control measures has been disproportionately poor, leading to their current classification as neglected pathogens. A sound understanding of their biology is essential in underpinning detection, treatment and control efforts. One major tool in rapidly improving our knowledge of these parasites is the use of biological systems, including 'omic' technologies. In recent years, these tools have shown significant success when applied to enteric protists. This review summarises much of this knowledge and highlights the significant remaining knowledge gaps. A major focus of the present review was to provide a perspective on a way forward to address these gaps using advanced biotechnologies. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  8. A Drug-Sensitive Genetic Network Masks Fungi from the Immune System

    PubMed Central

    Wheeler, Robert T; Fink, Gerald R

    2006-01-01

    Fungal pathogens can be recognized by the immune system via their β-glucan, a potent proinflammatory molecule that is present at high levels but is predominantly buried beneath a mannoprotein coat and invisible to the host. To investigate the nature and significance of “masking” this molecule, we characterized the mechanism of masking and consequences of unmasking for immune recognition. We found that the underlying β-glucan in the cell wall of Candida albicans is unmasked by subinhibitory doses of the antifungal drug caspofungin, causing the exposed fungi to elicit a stronger immune response. Using a library of bakers' yeast (Saccharomyces cerevisiae) mutants, we uncovered a conserved genetic network that is required for concealing β-glucan from the immune system and limiting the host response. Perturbation of parts of this network in the pathogen C. albicans caused unmasking of its β-glucan, leading to increased β-glucan receptor-dependent elicitation of key proinflammatory cytokines from primary mouse macrophages. By creating an anti-inflammatory barrier to mask β-glucan, opportunistic fungi may promote commensal colonization and have an increased propensity for causing disease. Targeting the widely conserved gene network required for creating and maintaining this barrier may lead to novel broad-spectrum antimycotics. PMID:16652171

  9. Iron Overload Is Associated With Oxidative Stress and Nutritional Immunity During Viral Infection in Fish.

    PubMed

    Tarifeño-Saldivia, Estefanía; Aguilar, Andrea; Contreras, David; Mercado, Luis; Morales-Lange, Byron; Márquez, Katherine; Henríquez, Adolfo; Riquelme-Vidal, Camila; Boltana, Sebastian

    2018-01-01

    Iron is a trace element, essential to support life due to its inherent ability to exchange electrons with a variety of molecules. The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. During evolution, the shared requirement of micro- and macro-organisms for this important nutrient has shaped the pathogen-host relationship. Infectious pancreatic necrosis virus (IPNv) affects salmonids constituting a sanitary problem for this industry as it has an important impact on post-smolt survival. While immune modulation induced by IPNv infection has been widely characterized on Salmo salar , viral impact on iron host metabolism has not yet been elucidated. In the present work, we evaluate short-term effect of IPNv on several infected tissues from Salmo salar . We observed that IPNv displayed high tropism to headkidney, which directly correlates with a rise in oxidative stress and antiviral responses. Transcriptional profiling on headkidney showed a massive modulation of gene expression, from which biological pathways involved with iron metabolism were remarkable. Our findings suggest that IPNv infection increase oxidative stress on headkidney as a consequence of iron overload induced by a massive upregulation of genes involved in iron metabolism.

  10. 77 FR 34783 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... [Docket No. APHIS-2006-0074] RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal and Plant... regions where any subtype of highly pathogenic avian influenza (HPAI) is considered to exist. The interim... avian influenza (HPAI). On January 24, 2011, we published in the Federal Register (76 FR 4046-4056...

  11. Participation of necroptosis in the host response to acute bacterial pneumonia

    PubMed Central

    Ahn, Danielle; Prince, Alice

    2017-01-01

    Common pulmonary pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus as well as the host-adapted pathogens responsible for health care associated pneumonias such as the carbapenem-resistant Klebsiella pneumoniae and Serratia marcesens are able to activate cell death through the RIPK1/RIPK3/MLKL cascade that causes necroptosis. Necroptosis can influence the pathogenesis of pneumonia through several mechanisms. Activation of this pathway can result in the loss of specific types of immune cells, especially macrophages and in doing so contribute to host pathology through loss of their critical immunoregulatory functions. However, in other settings of infection, necroptosis promotes pathogen removal and eradication of infected cells to control excessive proinflammatory signaling. Bacterial production of pore forming toxins provides a common mechanism to activate necroptosis by diverse bacterial species, with variable consequences depending upon the specific pathogen. Included in this brief review are data demonstrating the ability of the carbapenem-resistant ST258 K. pneumoniae to activate necroptosis in the setting of pneumonia, which is counterbalanced by their suppression of CYLD expression. Exactly how necroptosis and other mechanisms of cell death are co-regulated in the response to specific pulmonary pathogens remains a topic of active investigation and may provide potential therapeutic targets in the future. PMID:28125817

  12. Participation of Necroptosis in the Host Response to Acute Bacterial Pneumonia.

    PubMed

    Ahn, Danielle; Prince, Alice

    2017-01-01

    Common pulmonary pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus, as well as the host-adapted pathogens responsible for health care-associated pneumonias, such as the carbapenem-resistant Klebsiella pneumoniae and Serratia marcecsens, are able to activate cell death through the RIPK1/RIPK3/MLKL cascade that causes necroptosis. Necroptosis can influence the pathogenesis of pneumonia through several mechanisms. Activation of this pathway can result in the loss of specific types of immune cells, especially macrophages, and, in so doing, contribute to host pathology through the loss of their critical immunoregulatory functions. However, in other settings of infection, necroptosis promotes pathogen removal and the eradication of infected cells to control excessive proinflammatory signaling. Bacterial production of pore-forming toxins provides a common mechanism to activate necroptosis by diverse bacterial species, with variable consequences depending upon the specific pathogen. Included in this brief review are data demonstrating the ability of the carbapenem-resistant ST258 K. pneumoniae to activate necroptosis in the setting of pneumonia, which is counterbalanced by their suppression of CYLD expression. Exactly how necroptosis and other mechanisms of cell death are coregulated in the response to specific pulmonary pathogens remains a topic of active investigation, and it may provide potential therapeutic targets in the future. © 2017 S. Karger AG, Basel.

  13. Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses

    PubMed Central

    Pappalardo, Morena; Juliá, Miguel; Howard, Mark J.; Rossman, Jeremy S.; Michaelis, Martin; Wass, Mark N.

    2016-01-01

    Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. A subset of these SDPs will explain the differences in human pathogenicity between Reston and the other four ebolavirus species. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. This analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission. PMID:27009368

  14. Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses.

    PubMed

    Pappalardo, Morena; Juliá, Miguel; Howard, Mark J; Rossman, Jeremy S; Michaelis, Martin; Wass, Mark N

    2016-03-24

    Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. A subset of these SDPs will explain the differences in human pathogenicity between Reston and the other four ebolavirus species. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. This analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission.

  15. The value of pathogen information in treating clinical mastitis.

    PubMed

    Cha, Elva; Smith, Rebecca L; Kristensen, Anders R; Hertl, Julia A; Schukken, Ynte H; Tauer, Loren W; Welcome, Frank L; Gröhn, Yrjö T

    2016-11-01

    The objective of this study was to determine the economic value of obtaining timely and more accurate clinical mastitis (CM) test results for optimal treatment of cows. Typically CM is first identified when the farmer observes recognisable outward signs. Further information of whether the pathogen causing CM is Gram-positive, Gram-negative or other (including no growth) can be determined by using on-farm culture methods. The most detailed level of information for mastitis diagnostics is obtainable by sending milk samples for culture to an external laboratory. Knowing the exact pathogen permits the treatment method to be specifically targeted to the causation pathogen, resulting in less discarded milk. The disadvantages are the additional waiting time to receive test results, which delays treating cows, and the cost of the culture test. Net returns per year (NR) for various levels of information were estimated using a dynamic programming model. The Value of Information (VOI) was then calculated as the difference in NR using a specific level of information as compared to more detailed information on the CM causative agent. The highest VOI was observed where the farmer assumed the pathogen causing CM was the one with the highest incidence in the herd and no pathogen specific CM information was obtained. The VOI of pathogen specific information, compared with non-optimal treatment of Staphylococcus aureus where recurrence and spread occurred due to lack of treatment efficacy, was $20.43 when the same incorrect treatment was applied to recurrent cases, and $30.52 when recurrent cases were assumed to be the next highest incidence pathogen and treated accordingly. This indicates that negative consequences associated with choosing the wrong CM treatment can make additional information cost-effective if pathogen identification is assessed at the generic information level and if the pathogen can spread to other cows if not treated appropriately.

  16. Effects of cell surface characteristics and manure-application practices on Escherichia coli populations in the subsurface: A three-farm study

    NASA Astrophysics Data System (ADS)

    Salvucci, A. E.; Elton, M.; Siler, J. D.; Zhang, W.; Richards, B. K.; Geohring, L. D.; Warnick, L. D.; Hay, A. G.; Steenhuis, T.

    2010-12-01

    The introduction of microbial pathogens into the environment from untreated manure represents a threat to water quality and human health. Thus, understanding the effect of manure management strategies is imperative to effectively mitigate the inadvertent release of pathogens, particularly in subsurface environments where they can be transported through macropores to the groundwater or through agricultural tile line to open water bodies. The production of cell-surface biomolecules is also suspected to play an important role in the environmental survival and transport of enterobacterial pathogens. This study collected Escherichia coli samples from three dairy farms with artificial tile drainage systems and active manure spreading in the Central New York region over a three-month period. Sampling targeted four potential source locations on each farm: (i) cow housing, (ii) manure storage facilities, (iii) field soil, and (iv) subsurface drainage effluent. Over 2800 E. coli isolates were recovered and consequently analyzed for the cell surface components, cellulose and curli, traits associated with increased environmental survival, altered transport and pathogenicity. The E. coli isolates from locations i-iii displayed highly variable curli and cellulose-producing communities, while isolates collected from subsurface runoff on each farm had stable curli and cellulose production communities over all sampling dates. Furthermore, the method of manure application to the fields influenced the population characteristics found in drainage effluent isolates. Incorporation of manure into the soil was correlated to isolate populations largely deficient of curli and cellulose; whereas farms that only surface-applied manure were correlated to isolate populations of high curli and cellulose production. The production of curli and cellulose has previously been shown to be a response to environmental stress on the cell. Therefore, incorporation of manure directly into the soil appears to minimize environmental stresses, like UV radiation, desiccation and temperature fluctuation, typically found on the soil surface. Our findings indicate that E. coli strains above the surface are largely diverse, until they enter subsurface environments where specific extracellular characteristics are likely advantageous for survival and/or transport.

  17. Zoonoses in pet birds: review and perspectives

    PubMed Central

    2013-01-01

    Pet birds are a not-so-well known veterinarian’s clientship fraction. Bought individually or in couples, as families often do (which is a lucrative business for pet shops or local breeders) or traded (sometimes illegally) for their very high genetic or exotic value, these birds, commonly canaries, parakeets or parrots, are regularly sold at high prices. These animals, however, are potential carriers and/or transmitters of zoonotic diseases. Some of them could have an important impact on human health, like chlamydophilosis, salmonellosis or even highly pathogenic avian influenza A H5N1. This review paper, although non exhaustive, aims at enlightening, by the description of several cases of bird-human transmission, the risks encountered by bird owners, including children. Public health consequences will be discussed and emphasis will be made on some vector-borne diseases, known to be emergent or which are underestimated, like those transmitted by the red mite Dermanyssus gallinae. Finally, biosecurity and hygiene, as well as prevention guidelines will be developed and perspectives proposed. PMID:23687940

  18. The multigenic nature of the differences in pathogenicity of H5N1 highly pathogenic avian influenza viruses in domestic ducks

    USDA-ARS?s Scientific Manuscript database

    The Eurasian H5N1 highly pathogenic avian influenza (HPAI) viruses have evolved into many genetic lineages. The divergent strains that have arisen express distinct pathobiological features and increased virulence for many bird species including domestic waterfowl. The pathogenicity of H5N1 HPAI vi...

  19. Transient virulence of emerging pathogens.

    PubMed

    Bolker, Benjamin M; Nanda, Arjun; Shah, Dharmini

    2010-05-06

    Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.

  20. Transient virulence of emerging pathogens

    PubMed Central

    Bolker, Benjamin M.; Nanda, Arjun; Shah, Dharmini

    2010-01-01

    Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution. PMID:19864267

  1. The hidden face of academic researches on classified highly pathogenic microorganisms.

    PubMed

    Devaux, Christian A

    2015-01-01

    Highly pathogenic microorganisms and toxins are manipulated in academic laboratories for fundamental research purposes, diagnostics, drugs and vaccines development. Obviously, these infectious pathogens represent a potential risk for human and/or animal health and their accidental or intentional release (biosafety and biosecurity, respectively) is a major concern of governments. In the past decade, several incidents have occurred in laboratories and reported by media causing fear and raising a sense of suspicion against biologists. Some scientists have been ordered by US government to leave their laboratory for long periods of time following the occurrence of an incident involving infectious pathogens; in other cases laboratories have been shut down and universities have been forced to pay fines and incur a long-term ban on funding after gross negligence of biosafety/biosecurity procedures. Measures of criminal sanctions have also been taken to minimize the risk that such incidents can reoccur. As United States and many other countries, France has recently strengthened its legal measures for laboratories' protection. During the past two decades, France has adopted a series of specific restriction measures to better protect scientific discoveries with a potential economic/social impact and prevent their misuse by ill-intentioned people without affecting the progress of science through fundamental research. French legal regulations concerning scientific discoveries have progressively strengthened since 2001, until the publication in November 2011 of a decree concerning the "PPST" (for "Protection du Potentiel Scientifique et Technique de la nation", the protection of sensitive scientific data). Following the same logic of protection of sensitive scientific researches, regulations were also adopted in an order published in April 2012 concerning the biology and health field. The aim was to define the legal framework that precise the conditions for authorizing microorganisms and toxins experimentation in France; these regulations apply for any operation of production, manufacturing, transportation, import, export, possession, supply, transfer, acquisition and use of highly pathogenic microorganisms and toxins, referred to as "MOT" (for "MicroOrganismes et Toxines hautement pathogènes") by the French law. Finally, laboratories conducting researches on such infectious pathogens are henceforth classified restricted area or ZRR (for "Zone à Régime Restrictif"), according an order of July 2012. In terms of economic protection, biosafety and biosecurity, these regulations represent an undeniable progress as compared to the previous condition. However, the competitiveness of research laboratories handling MOTs is likely to suffer the side effects of these severe constraints. For example research teams working on MOTs can be drastically affected both by (i) the indirect costs generated by the security measure to be applied; (ii) the working time devoted to samples recording; (iii) the establishment of traceability and reporting to national security agency ANSM, (iv) the latency period required for staff members being officially authorized to conduct experiments on MOTs; (v) the consequent reduced attractiveness for recruiting new trainees whose work would be significantly hampered by theses administrative constraints; and (vi) the limitations in the exchange of material with external laboratories and collaborators. Importantly, there is a risk that French academic researchers gradually abandon research on MOTs in favor of other projects that are less subject to legal restrictions. This would reduce the acquisition of knowledge in the field of MOTs which, in the long term, could be highly detrimental to the country by increasing its vulnerability to natural epidemics due to pathogenic microorganisms that are classified as MOTs and, by reducing its preparedness against possible bioterrorist attacks that would use such microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. 9 CFR 94.26 - Restrictions on importation of live poultry, poultry meat, and other poultry products from...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... DISEASE, HIGHLY PATHOGENIC AVIAN INFLUENZA, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR... in § 94.6(a) as free of Newcastle disease and highly pathogenic avian influenza at the time the... free of Newcastle disease and highly pathogenic avian influenza at a federally inspected slaughter...

  3. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study12

    PubMed Central

    van Vliet, Sara J; Di Giovanni, Valeria; Zhang, Ling; Richardson, Susan; van Rheenen, Patrick F

    2016-01-01

    Background: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. Objective: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in children with SAM. Design: Intestinal pathogens (n = 15), cytokines (n = 29), fecal calprotectin, and the short-chain fatty acids (SCFAs) butyrate and propionate were determined in children aged 6–59 mo (n = 79) hospitalized in Malawi for complicated SAM. The relation between variables, diarrhea, and death was assessed with partial least squares (PLS) path modeling. Results: Fatal subjects (n = 14; 18%) were younger (mean ± SD age: 17 ± 11 compared with 25 ± 11 mo; P = 0.01) with higher prevalence of diarrhea (46% compared with 18%, P = 0.03). Intestinal pathogens Shigella (36%), Giardia (33%), and Campylobacter (30%) predominated, but their presence was not associated with death or diarrhea. Calprotectin was significantly higher in children who died [median (IQR): 1360 mg/kg feces (2443–535 mg/kg feces) compared with 698 mg/kg feces (1438–244 mg/kg feces), P = 0.03]. Butyrate [median (IQR): 31 ng/mL (112–22 ng/mL) compared with 2036 ng/mL (5800–149 ng/mL), P = 0.02] and propionate [median (IQR): 167 ng/mL (831–131 ng/mL) compared with 3174 ng/mL (5819–357 ng/mL), P = 0.04] were lower in those who died. Mortality was directly related to high systemic inflammation (path coefficient = 0.49), whereas diarrhea, high calprotectin, and low SCFA production related to death indirectly via their more direct association with systemic inflammation. Conclusions: Diarrhea, high intestinal inflammation, low concentrations of fecal SCFAs, and high systemic inflammation are significantly related to mortality in SAM. However, these relations were not mediated by the presence of intestinal pathogens. These findings offer an important understanding of inflammatory changes in SAM, which may lead to improved therapies. This trial was registered at www.controlled-trials.com as ISRCTN13916953. PMID:27655441

  4. Consequences of the pathogenic T9176C mutation of human mitochondrial DNA on yeast mitochondrial ATP synthase

    PubMed Central

    Kucharczyk, Roza; Ezkurdia, Nahia; Couplan, Elodie; Procaccio, Vincent; Ackerman, Sharon H.; Blondel, Marc; di Rago, Jean-Paul

    2010-01-01

    Summary Several human neurological disorders have been associated with various mutations affecting mitochondrial enzymes involved in cellular ATP production. One of these mutations, T9176C in the mitochondrial DNA (mtDNA), changes a highly conserved leucine residue into proline at position 217 of the mitochondrially encoded Atp6p (or a) subunit of the F1FO-ATP synthase. The consequences of this mutation on the mitochondrial ATP synthase are still poorly defined. To gain insight into the primary pathogenic mechanisms induced by T9176C, we have investigated the consequences of this mutation on the ATP synthase of yeast where Atp6p is also encoded by the mtDNA. In vitro, yeast atp6-T9176C mitochondria showed a 30% decrease in the rate of ATP synthesis. When forcing the F1FO complex to work in the reverse mode, i.e. F1-catalyzed hydrolysis of ATP coupled to proton transport out of the mitochondrial matrix, the mutant showed a normal proton-pumping activity and this activity was fully sensitive to oligomycin, an inhibitor of the ATP synthase proton channel. However, under conditions of maximal ATP hydrolytic activity, using non-osmotically protected mitochondria, the mutant ATPase activity was less efficiently inhibited by oligomycin (60% inhibition versus 85% for the wild type control). BN-PAGE analyses revealed that atp6-T9176C yeast accumulated rather good levels of fully assembled ATP synthase complexes. However, a number of subcomplexes (F1, Atp9p-ring, unassembled α-F1 subunits) could be detected as well, presumably because of a decreased stability of Atp6p within the ATP synthase. Although the oxidative phosphorylation capacity was reduced in atp6-T9176C yeast, the number of ATP molecules synthesized per electron transferred to oxygen was similar compared with wild type yeast. It can therefore be inferred that the coupling efficiency within the ATP synthase was mostly unaffected and that the T9176C mutation did not increase the proton permeability of the mitochondrial inner membrane. PMID:20056103

  5. Linking sudden oak death with spatial economic value transfer

    Treesearch

    Tom Holmes; Bill Smith

    2008-01-01

    Sudden oak death (caused by Phytophthora ramorum) is currently having a dramatic impact on the flow of ecosystem services provided by trees and forests in California. Timber species in California are not thought to be at risk of mortality from this pathogen and, consequently, economic impacts accrue to non-market values of trees such as aesthetics,...

  6. Phytophthora ramorum: update On the impact and wider consequences of the epidemic in Britain

    Treesearch

    J.F. Webber

    2017-01-01

    Many new Phytophthora pathogens have arrived in the UK via the plant trade in recent decades, but arguably Phytophthora ramorum has been one of the most significant introductions to affect trees. From 2002 onwards during the early stages of the epidemic, the first impacts of P. ramorum were seen in...

  7. Loss of foundation species: consequences for the structure and dynamics of forested ecosystems

    Treesearch

    Aaron M. Ellison; Michael S. Bank; Barton D. Clinton; Elizabeth A. Colburn; Katherine Elliott; Chelcy Rae Ford; David R. Foster; Brian D. Kloeppel; Jennifer D. Knoepp; Gary M. Lovett; Jacqueline Mohan; David A. Orwig; Nicholas L. Rodenhouse; William V. Sobczak; Kristina A. Stinson; Jeffrey K. Stone; Christopher M. Swan; Jill Thompson; Betsy Von Holle; Jackson R. Webster

    2005-01-01

    In many forested ecosystems, the architecture and functional ecology of certain tree species define forest structure and their species-specific traits control ecosystem dynamics. Such foundation tree species are declining throughout the world due to introductions and outbreaks of pests and pathogens, selective removal of individual taxa, and over-harvesting. Through a...

  8. Population biology of sugar pine (Pinus lambertiana Dougl.) with reference to historical disturbances in the Lake Tahoe Basin: implications for restoration

    Treesearch

    Patricia E. Maloney; Detlev R. Vogler; Andrew J. Eckert; Camille E. Jensen; David B. Neale

    2011-01-01

    Historical logging, fire suppression, and an invasive pathogen, Cronartium ribicola, the cause of white pine blister rust (WPBR), are assumed to have dramatically affected sugar pine (Pinus lambertiana) populations in the Lake Tahoe Basin. We examined population- and genetic-level consequences of these disturbances within 10...

  9. Transcriptomic analysis reveals the potential of highly pathogenic PRRS virus to modulate immune system activation related to host-pathogen and damage associated signaling in infected porcine monocytes

    USDA-ARS?s Scientific Manuscript database

    One of the largest risks to the continued stability of the swine industry is by pathogens like porcine reproductive and respiratory syndrome virus (PRRSV) that can decimate production as it spreads among individuals. These infections can be low or highly pathogenic, and because it infects monocytic ...

  10. Risk factors for Pseudomonas aeruginosa infections consequences of inappropriate initial antimicrobial therapy: a systematic literature review meta-analysis.

    PubMed

    Merchant, Sanjay; Proudfoot, Emma M; Quadri, Hafsa N; McElroy, Heather J; Wright, William R; Gupta, Ankur; Sarpong, Eric M

    2018-02-15

    Treating infections of Gram-negative pathogens, in particular Pseudomonas aeruginosa, is a challenge for clinicians in the Asia-Pacific region due to inherent and acquired resistance to antimicrobials. This systematic review and meta-analysis provides updated information of the risk factors for P. aeruginosa infections in Asia-Pacific, and consequences (e.g., mortality, costs) of initial inappropriate antimicrobial therapy (IIAT). EMBASE and MEDLINE databases were searched for Asia-Pacific studies reporting the consequences of IIAT versus initial appropriate antimicrobial therapy (IAAT) in Gram-negative infections, and risk factors for serious P. aeruginosa infections. A meta-analysis of unadjusted mortality was performed using random-effects model. Twenty-two studies reporting mortality and 13 reporting risk factors were identified. The meta-analysis demonstrated that mortality was significantly lower in patients receiving IAAT versus IIAT, with 67% reduction observed for 28- or 30-day all-cause mortality (OR 0.33; 95% CI 0.20, 0.55; P <0.001). Risk factors for serious P. aeruginosa infection include previous exposure to antimicrobials, mechanical ventilation, and previous hospitalization. The high rates of antimicrobial resistance in Asia-Pacific, as well as increased mortality associated with IIAT and the presence of risk factors for serious infection, highlight the importance of access to newer and appropriate antimicrobials. Copyright © 2018. Published by Elsevier Ltd.

  11. Pathogen transport in groundwater systems: contrasts with traditional solute transport

    NASA Astrophysics Data System (ADS)

    Hunt, Randall J.; Johnson, William P.

    2017-06-01

    Water quality affects many aspects of water availability, from precluding use to societal perceptions of fit-for-purpose. Pathogen source and transport processes are drivers of water quality because they have been responsible for numerous outbreaks resulting in large economic losses due to illness and, in some cases, loss of life. Outbreaks result from very small exposure (e.g., less than 20 viruses) from very strong sources (e.g., trillions of viruses shed by a single infected individual). Thus, unlike solute contaminants, an acute exposure to a very small amount of contaminated water can cause immediate adverse health effects. Similarly, pathogens are larger than solutes. Thus, interactions with surfaces and settling become important even as processes important for solutes such as diffusion become less important. These differences are articulated in "Colloid Filtration Theory", a separate branch of pore-scale transport. Consequently, understanding pathogen processes requires changes in how groundwater systems are typically characterized, where the focus is on the leading edges of plumes and preferential flow paths, even if such features move only a very small fraction of the aquifer flow. Moreover, the relatively short survival times of pathogens in the subsurface require greater attention to very fast (<10 year) flow paths. By better understanding the differences between pathogen and solute transport mechanisms discussed here, a more encompassing view of water quality and source water protection is attained. With this more holistic view and theoretical understanding, better evaluations can be made regarding drinking water vulnerability and the relation between groundwater and human health.

  12. Biofilm formation by enteric pathogens and its role in plant colonization and persistence

    PubMed Central

    Yaron, Sima; Römling, Ute

    2014-01-01

    The significant increase in foodborne outbreaks caused by contaminated fresh produce, such as alfalfa sprouts, lettuce, melons, tomatoes and spinach, during the last 30 years stimulated investigation of the mechanisms of persistence of human pathogens on plants. Emerging evidence suggests that Salmonella enterica and Escherichia coli, which cause the vast majority of fresh produce outbreaks, are able to adhere to and to form biofilms on plants leading to persistence and resistance to disinfection treatments, which subsequently can cause human infections and major outbreaks. In this review, we present the current knowledge about host, bacterial and environmental factors that affect the attachment to plant tissue and the process of biofilm formation by S. enterica and E. coli, and discuss how biofilm formation assists in persistence of pathogens on the plants. Mechanisms used by S. enterica and E. coli to adhere and persist on abiotic surfaces and mammalian cells are partially similar and also used by plant pathogens and symbionts. For example, amyloid curli fimbriae, part of the extracellular matrix of biofilms, frequently contribute to adherence and are upregulated upon adherence and colonization of plant material. Also the major exopolysaccharide of the biofilm matrix, cellulose, is an adherence factor not only of S. enterica and E. coli, but also of plant symbionts and pathogens. Plants, on the other hand, respond to colonization by enteric pathogens with a variety of defence mechanisms, some of which can effectively inhibit biofilm formation. Consequently, plant compounds might be investigated for promising novel antibiofilm strategies. PMID:25351039

  13. Pathobiology of avian influenza virus infection in minor gallinaceous species: a review.

    PubMed

    Bertran, Kateri; Dolz, Roser; Majó, Natàlia

    2014-01-01

    Susceptibility to avian influenza viruses (AIVs) can vary greatly among bird species. Chickens and turkeys are major avian species that, like ducks, have been extensively studied for avian influenza. To a lesser extent, minor avian species such as quail, partridges, and pheasants have also been investigated for avian influenza. Usually, such game fowl species are highly susceptible to highly pathogenic AIVs and may consistently spread both highly pathogenic AIVs and low-pathogenic AIVs. These findings, together with the fact that game birds are considered bridge species in the poultry-wildlife interface, highlight their interest from the transmission and biosecurity points of view. Here, the general pathobiological features of low-pathogenic AIV and highly pathogenic AIV infections in this group of avian species have been covered.

  14. High Incidence of Pathogenic Streptococcus agalactiae ST485 Strain in Pregnant/Puerperal Women and Isolation of Hyper-Virulent Human CC67 Strain

    PubMed Central

    Li, Liping; Wang, Rui; Huang, Yan; Huang, Ting; Luo, Fuguang; Huang, Weiyi; Yang, Xiuying; Lei, Aiying; Chen, Ming; Gan, Xi

    2018-01-01

    Group B streptococcus (GBS) is the major pathogen causing diseases in neonates, pregnant/puerperal women, cows and fish. Recent studies have shown that GBS may be infectious across hosts and some fish GBS strain might originate from human. The purpose of this study is to investigate the genetic relationship of CC103 strains that recently emerged in cows and humans, and explore the pathogenicity of clinical GBS isolates from human to tilapia. Ninety-two pathogenic GBS isolates were identified from 19 patients with different diseases and their evolution and pathogenicity to tilapia were analyzed. The multilocus sequence typing revealed that clonal complex (CC) 103 strain was isolated from 21.74% (20/92) of patients and ST485 strain was from 14.13% (13/92) patients with multiple diseases including neonates. Genomic evolution analysis showed that both bovine and human CC103 strains alternately form independent evolutionary branches. Three CC67 isolates carried gbs2018-C gene and formed one evolutionary branch with ST61 and ST67 strains that specifically infect dairy cows. Studies of interspecies transmission to tilapia found that 21/92 (22.83%) isolates including all ST23 isolates were highly pathogenic to tilapia and demonstrated that streptococci could break through the blood-brain barrier into brain tissue. In conclusions, CC103 strains are highly prevalent among pathogenic GBS from humans and have evolved into the highly pathogenic ST485 strains specifically infecting humans. The CC67 strains isolated from cows are able to infect humans through evolutionary events of acquiring CC17-specific type C gbs2018 gene and others. Human-derived ST23 pathogenic GBS strains are highly pathogenic to tilapia. PMID:29467722

  15. Searching for resistance genes to Bursaphelenchus xylophilus using high throughput screening.

    PubMed

    Santos, Carla S; Pinheiro, Miguel; Silva, Ana I; Egas, Conceição; Vasconcelos, Marta W

    2012-11-07

    Pine wilt disease (PWD), caused by the pinewood nematode (PWN; Bursaphelenchus xylophilus), damages and kills pine trees and is causing serious economic damage worldwide. Although the ecological mechanism of infestation is well described, the plant's molecular response to the pathogen is not well known. This is due mainly to the lack of genomic information and the complexity of the disease. High throughput sequencing is now an efficient approach for detecting the expression of genes in non-model organisms, thus providing valuable information in spite of the lack of the genome sequence. In an attempt to unravel genes potentially involved in the pine defense against the pathogen, we hereby report the high throughput comparative sequence analysis of infested and non-infested stems of Pinus pinaster (very susceptible to PWN) and Pinus pinea (less susceptible to PWN). Four cDNA libraries from infested and non-infested stems of P. pinaster and P. pinea were sequenced in a full 454 GS FLX run, producing a total of 2,083,698 reads. The putative amino acid sequences encoded by the assembled transcripts were annotated according to Gene Ontology, to assign Pinus contigs into Biological Processes, Cellular Components and Molecular Functions categories. Most of the annotated transcripts corresponded to Picea genes-25.4-39.7%, whereas a smaller percentage, matched Pinus genes, 1.8-12.8%, probably a consequence of more public genomic information available for Picea than for Pinus. The comparative transcriptome analysis showed that when P. pinaster was infested with PWN, the genes malate dehydrogenase, ABA, water deficit stress related genes and PAR1 were highly expressed, while in PWN-infested P. pinea, the highly expressed genes were ricin B-related lectin, and genes belonging to the SNARE and high mobility group families. Quantitative PCR experiments confirmed the differential gene expression between the two pine species. Defense-related genes triggered by nematode infestation were detected in both P. pinaster and P. pinea transcriptomes utilizing 454 pyrosequencing technology. P. pinaster showed higher abundance of genes related to transcriptional regulation, terpenoid secondary metabolism (including some with nematicidal activity) and pathogen attack. P. pinea showed higher abundance of genes related to oxidative stress and higher levels of expression in general of stress responsive genes. This study provides essential information about the molecular defense mechanisms utilized by P. pinaster and P. pinea against PWN infestation and contributes to a better understanding of PWD.

  16. When environmentally persistent pathogens transform good habitat into ecological traps

    USGS Publications Warehouse

    Leach, Clint; Webb, Colleen T.; Cross, Paul C.

    2016-01-01

    Habitat quality plays an important role in the dynamics and stability of wildlife metapopulations. However, the benefits of high-quality habitat may be modulated by the presence of an environmentally persistent pathogen. In some cases, the presence of environmental pathogen reservoirs on high-quality habitat may lead to the creation of ecological traps, wherein host individuals preferentially colonize high-quality habitat, but are then exposed to increased infection risk and disease-induced mortality. We explored this possibility through the development of a stochastic patch occupancy model, where we varied the pathogen’s virulence, transmission rate and environmental persistence as well as the distribution of habitat quality in the host metapopulation. This model suggests that for pathogens with intermediate levels of spread, high-quality habitat can serve as an ecological trap, and can be detrimental to host persistence relative to low-quality habitat. This inversion of the relative roles of high- and low-quality habitat highlights the importance of considering the interaction between spatial structure and pathogen transmission when managing wildlife populations exposed to an environmentally persistent pathogen.

  17. Recognitional specificity and evolution in the tomato-Cladosporium fulvum pathosystem.

    PubMed

    Wulff, B B H; Chakrabarti, A; Jones, D A

    2009-10-01

    The interactions between plants and many biotrophic or hemibiotrophic pathogens are controlled by receptor proteins in the host and effector proteins delivered by the pathogen. Pathogen effectors facilitate pathogen growth through the suppression of host defenses and the manipulation of host metabolism, but recognition of a pathogen-effector protein by a host receptor enables the host to activate a suite of defense mechanisms that limit pathogen growth. In the tomato (Lycopersicon esculentum syn. Solanum lycopersicum)-Cladosporium fulvum (leaf mold fungus syn. Passalora fulva) pathosystem, the host receptors are plasma membrane-anchored, leucine-rich repeat, receptor-like proteins encoded by an array of Cf genes conferring resistance to C. fulvum. The pathogen effectors are mostly small, secreted, cysteine-rich, but otherwise largely dissimilar, extracellular proteins encoded by an array of avirulence (Avr) genes, so called because of their ability to trigger resistance and limit pathogen growth when the corresponding Cf gene is present in tomato. A number of Cf and Avr genes have been isolated, and details of the complex molecular interplay between tomato Cf proteins and C. fulvum effector proteins are beginning to emerge. Each effector appears to have a different role; probably most bind or modify different host proteins, but at least one has a passive role masking the pathogen. It is, therefore, not surprising that each effector is probably detected in a distinct and specific manner, some by direct binding, others as complexes with host proteins, and others via their modification of host proteins. The two papers accompanying this review contribute further to our understanding of the molecular specificity underlying effector perception by Cf proteins. This review, therefore, focuses on our current understanding of recognitional specificity in the tomato-C. fulvum pathosystem and highlights some of the critical questions that remain to be addressed. It also addresses the evolutionary causes and consequences of this specificity.

  18. Adaptive value of sex in microbial pathogens.

    PubMed

    Michod, Richard E; Bernstein, Harris; Nedelcu, Aurora M

    2008-05-01

    Explaining the adaptive value of sex is one of the great outstanding problems in biology. The challenge comes from the difficulty in identifying the benefits provided by sex, which must outweigh the substantial costs of sex. Here, we consider the adaptive value of sex in viruses, bacteria and fungi, and particularly the information available on the adaptive role of sex in pathogenic microorganisms. Our general theme is that the varied aspects of sex in pathogens illustrate the varied issues surrounding the evolution of sex generally. These include, the benefits of sex (in the short- and long-term), as well as the costs of sex (both to the host and to the pathogen). For the benefits of sex (that is, its adaptive value), we consider three hypotheses: (i) sex provides for effective and efficient recombinational repair of DNA damages, (ii) sex provides DNA for food, and (iii) sex produces variation and reduces genetic associations among alleles under selection. Although the evolution of sex in microbial pathogens illustrates these general issues, our paper is not a general review of theories for the evolution of sex in all organisms. Rather, we focus on the adaptive value of sex in microbial pathogens and conclude that in terms of short-term benefits, the DNA repair hypothesis has the most support and is the most generally applicable hypothesis in this group. In particular, recombinational repair of DNA damages may substantially benefit pathogens when challenged by the oxidative defenses of the host. However, in the long-term, sex may help get rid of mutations, increase the rate of adaptation of the population, and, in pathogens, may infrequently create new infective strains. An additional general issue about sex illustrated by pathogens is that some of the most interesting consequences of sex are not necessarily the reasons for which sex evolved. For example, antibiotic resistance may be transferred by bacterial sex, but this transfer is probably not the reason sex evolved in bacteria.

  19. Molecular survey of neglected bacterial pathogens reveals an abundant diversity of species and genotypes in ticks collected from animal hosts across Romania.

    PubMed

    Andersson, Martin O; Tolf, Conny; Tamba, Paula; Stefanache, Mircea; Radbea, Gabriel; Frangoulidis, Dimitrios; Tomaso, Herbert; Waldenström, Jonas; Dobler, Gerhard; Chitimia-Dobler, Lidia

    2018-03-20

    Ticks are transmitting a wide range of bacterial pathogens that cause substantial morbidity and mortality in domestic animals. The full pathogen burden transmitted by tick vectors is incompletely studied in many geographical areas, and extensive studies are required to fully understand the diversity and distribution of pathogens transmitted by ticks. We sampled 824 ticks of 11 species collected in 19 counties in Romania. Ticks were collected mainly from dogs, but also from other domestic and wild animals, and were subjected to molecular screening for pathogens. Rickettsia spp. was the most commonly detected pathogen, occurring in 10.6% (87/824) of ticks. Several species were detected: Rickettsia helvetica, R. raoultii, R. massiliae, R. monacensis, R. slovaca and R. aeschlimannii. A single occurrence of the zoonotic bacterium Bartonella vinsonii berkhoffii was detected in a tick collected from a dog. Anaplasma phagocytophilum occurred in four samples, and sequences similar to Anaplasma marginale/ovis were abundant in ticks from ruminants. In addition, molecular screening showed that ticks from dogs were carrying an Ehrlichia species identical to the HF strain as well as the enigmatic zoonotic pathogen "Candidatus Neoehrlichia mikurensis". An organism similar to E. chaffeensis or E. muris was detected in an Ixodes ricinus collected from a fox. We describe an abundant diversity of bacterial tick-borne pathogens in ticks collected from animal hosts in Romania, both on the level of species and genotypes/strains within these species. Several findings were novel for Romania, including Bartonella vinsonii subsp. berkhoffii that causes bacteremia and endocarditis in dogs. "Candidatus Neoehrlichia mikurensis" was detected in a tick collected from a dog. Previously, a single case of infection in a dog was diagnosed in Germany. The results warrant further studies on the consequences of tick-borne pathogens in domestic animals in Romania.

  20. Severity of Bovine Tuberculosis Is Associated with Co-Infection with Common Pathogens in Wild Boar

    PubMed Central

    Risco, David; Serrano, Emmanuel; Fernández-Llario, Pedro; Cuesta, Jesús M.; Gonçalves, Pilar; García-Jiménez, Waldo L.; Martínez, Remigio; Cerrato, Rosario; Velarde, Roser; Gómez, Luis; Segalés, Joaquím; Hermoso de Mendoza, Javier

    2014-01-01

    Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under controlled conditions. Furthermore, more research including other important pathogens, such as gastro-intestinal nematodes, will be necessary to complete this picture. PMID:25350002

  1. Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

    PubMed Central

    Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

    2016-01-01

    In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

  2. The spatial profiles and metabolic capabilities of microbial populations impact the growth of antibiotic-resistant mutants

    PubMed Central

    Kaushik, Karishma S.; Ratnayeke, Nalin; Katira, Parag; Gordon, Vernita D.

    2015-01-01

    Antibiotic resistance adversely affects clinical and public health on a global scale. Using the opportunistic human pathogen Pseudomonas aeruginosa, we show that increasing the number density of bacteria, on agar containing aminoglycoside antibiotics, can non-monotonically impact the survival of antibiotic-resistant mutants. Notably, at high cell densities, mutant survival is inhibited. A wide range of bacterial species can inhibit antibiotic-resistant mutants. Inhibition results from the metabolic breakdown of amino acids, which results in alkaline by-products. The consequent increase in pH acts in conjunction with aminoglycosides to mediate inhibition. Our work raises the possibility that the manipulation of microbial population structure and nutrient environment in conjunction with existing antibiotics could provide therapeutic approaches to combat antibiotic resistance. PMID:25972434

  3. High temperature and temperature variation undermine future disease susceptibility in a population of the invasive garden ant Lasius neglectus.

    PubMed

    Pamminger, Tobias; Steier, Thomas; Tragust, Simon

    2016-06-01

    Environmental temperature and temperature variation can have strong effects on the outcome of host-parasite interactions. Whilst such effects have been reported for different host systems, long-term consequences of pre-infection temperatures on host susceptibility and immunity remain understudied. Here, we show that experiencing both a biologically relevant increase in temperature and temperature variation undermines future disease susceptibility of the invasive garden ant Lasius neglectus when challenged with a pathogen under a constant temperature regime. In light of the economic and ecological importance of many social insects, our results emphasise the necessity to take the hosts' temperature history into account when studying host-parasite interactions under both natural and laboratory conditions, especially in the face of global change.

  4. High temperature and temperature variation undermine future disease susceptibility in a population of the invasive garden ant Lasius neglectus

    NASA Astrophysics Data System (ADS)

    Pamminger, Tobias; Steier, Thomas; Tragust, Simon

    2016-06-01

    Environmental temperature and temperature variation can have strong effects on the outcome of host-parasite interactions. Whilst such effects have been reported for different host systems, long-term consequences of pre-infection temperatures on host susceptibility and immunity remain understudied. Here, we show that experiencing both a biologically relevant increase in temperature and temperature variation undermines future disease susceptibility of the invasive garden ant Lasius neglectus when challenged with a pathogen under a constant temperature regime. In light of the economic and ecological importance of many social insects, our results emphasise the necessity to take the hosts' temperature history into account when studying host-parasite interactions under both natural and laboratory conditions, especially in the face of global change.

  5. Amphibian decline and extinction: what we know and what we need to learn.

    PubMed

    Collins, James P

    2010-11-01

    For over 350 million yr, thousands of amphibian species have lived on Earth. Since the 1980s, amphibians have been disappearing at an alarming rate, in many cases quite suddenly. What is causing these declines and extinctions? In the modern era (post 1500) there are 6 leading causes of biodiversity loss in general, and all of these acting alone or together are responsible for modern amphibian declines: commercial use; introduced/exotic species that compete with, prey on, and parasitize native frogs and salamanders; land use change; contaminants; climate change; and infectious disease. The first 3 causes are historical in the sense that they have been operating for hundreds of years, although the rate of change due to each accelerated greatly after about the mid-20th century. Contaminants, climate change, and emerging infectious diseases are modern causes suspected of being responsible for the so-called 'enigmatic decline' of amphibians in protected areas. Introduced/exotic pathogens, land use change, and infectious disease are the 3 causes with a clear role in amphibian decline as well as extinction; thus far, the other 3 causes are only implicated in decline and not extinction. The present work is a review of the 6 causes with a focus on pathogens and suggested areas where new research is needed. Batrachochytrium dendrobatidis (Bd) is a chytrid fungus that is an emerging infectious disease causing amphibian population decline and species extinction. Historically, pathogens have not been seen as a major cause of extinction, but Bd is an exception, which is why it is such an interesting, important pathogen to understand. The late 20th and early 21st century global biodiversity loss is characterized as a sixth extinction event. Amphibians are a striking example of these losses as they disappear at a rate that greatly exceeds historical levels. Consequently, modern amphibian decline and extinction is a lens through which we can view the larger story of biodiversity loss and its consequences.

  6. Biohazards and ecotoxicological considerations of landspreading of spent compost wastes.

    PubMed

    Rao, J R; Nelson, D; Lafferty, N; Moore, J E; Millar, B C; Xu, J; Watabe, M

    2003-01-01

    Spent mushroom compost (SMC) is a major waste of the mushroom industry with low economic value. SMC arises after mushroom production in phase II compost (pIIC), predominantly comprising straw and chicken litter as principal raw ingredients. The majority of SMC waste is disposed off by application to agricultural land. It is an attractive proposition for utilising SMC as soil inorganic fertiliser supplementation. However, there is limited data available as to the consequences of this method of disposal either in terms of microbiological loading of food-borne pathogens and those of concern to mushroom industry itself. The resulting imbalance of the natural flora of the agricultural land has not been properly audited. This study aims to initially examine SMC for prevalence of faecal bacterial pathogens including Campylobacter spp., Salmonella spp. and Listeria monocytogenes that may arise from chicken litter. At another level, it aims to ascertain the pathogenic bacteria (Pseudomonas syringae, pv phaseolicola or tolasii) and fungal populations (Trichoderma, Verticillium species) originating mainly from the straw component of the SMC, which are of concern to the mushroom industry. Lastly, the study would also qualitatively identify the diversity of bacterial populations within SMC. This was largely accomplished through employment of rDNA, PCR and direct sequencing strategies on the culturable microflora. However, for specific mushroom pathogens, nucleic acids (DNA or RNA) were directly extracted from composts before subjecting to sequence analysis. In accordance with the current legislation (ABP 02/02, Animal By Products wastes disposal EC No. 1774/2002), it is imperative to regulate the farm wastes carrying residues from animal sources including SMC before they are regarded safe for land spreading operations. The ecological microbe-microbe and plant-microbe interactions that potentially occur between the native bacterial soil flora and those added annually (approximately 10(18) cells) needs to be reviewed with caution. The above study highlights the ecological consequences involved in the disposal of SMC wastes on agricultural land and its implications for plant, animal and human health.

  7. Reassortant clade 2.3.4.4 of highly pathogenic avian influenza A (H5N6) virus, Taiwan, 2017

    USDA-ARS?s Scientific Manuscript database

    A highly pathogenic avian influenza A(H5N6) virus of clade 2.3.4.4 was detected in a domestic duck found dead in Taiwan during February 2017. The endemic situation and continued evolution of various reassortant highly pathogenic avian influenza viruses in Taiwan warrant concern about further reassor...

  8. Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States

    USDA-ARS?s Scientific Manuscript database

    A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza ...

  9. Genetic diagnosis of high-penetrance susceptibility for colorectal cancer (CRC) is achievable for a high proportion of familial CRC by exome sequencing.

    PubMed

    Chubb, Daniel; Broderick, Peter; Frampton, Matthew; Kinnersley, Ben; Sherborne, Amy; Penegar, Steven; Lloyd, Amy; Ma, Yussanne P; Dobbins, Sara E; Houlston, Richard S

    2015-02-10

    Knowledge of the contribution of high-penetrance susceptibility to familial colorectal cancer (CRC) is relevant to the counseling, treatment, and surveillance of CRC patients and families. To quantify the impact of germline mutation to familial CRC, we sequenced the mismatch repair genes (MMR) APC, MUTYH, and SMAD4/BMPR1A in 626 early-onset familial CRC cases ascertained through a population-based United Kingdom national registry. In addition, we evaluated the contribution of mutations in the exonuclease domain (exodom) of POLE and POLD1 genes that have recently been reported to confer CRC risk. Overall mutations (pathogenic, likely pathogenic) in MMR genes make the highest contribution to familial CRC (10.9%). Mutations in the other established CRC genes account for 3.3% of cases. POLE/POLD1 exodom mutations were identified in three patients with family histories consistent with dominant transmission of CRC. Collectively, mutations in the known genes account for 14.2% of familial CRC (89 of 626 cases; 95% CI = 11.5, 17.2). A genetic diagnosis is feasible in a high proportion of familial CRC. Mainstreaming such analysis in clinical practice should enable the medical management of patients and their families to be optimized. Findings suggest CRC screening of POLE and POLD1 mutation carriers should be comparable to that afforded to those at risk of HNPCC. Although the risk of CRC associated with unexplained familial CRC is in general moderate, in some families the risk is substantive and likely to be the consequence of unidentified genes, as exemplified by POLE and POLD1. Our findings have utility in the design of genetic analyses to identify such novel CRC risk genes. © 2015 by American Society of Clinical Oncology.

  10. Microorganisms and heavy metals associated with atmospheric deposition in a congested urban environment of a developing country: Sri Lanka.

    PubMed

    Weerasundara, Lakshika; Amarasekara, R W K; Magana-Arachchi, D N; Ziyath, Abdul M; Karunaratne, D G G P; Goonetilleke, Ashantha; Vithanage, Meththika

    2017-04-15

    The presence of bacteria and heavy metals in atmospheric deposition were investigated in Kandy, Sri Lanka, which is a typical city in the developing world with significant traffic congestion. Atmospheric deposition samples were analyzed for Al, Cr, Mn, Fe, Ni, Cu, Zn, Cd and Pb which are heavy metals common to urban environments. Al and Fe were found in high concentrations due to the presence of natural sources, but may also be re-suspended by vehicular traffic. Relatively high concentrations of toxic metals such as Cr and Pb in dissolved form were also found. High Zn loads can be attributed to vehicular emissions and the wide use of Zn coated roofing materials. The metal loads in wet deposition showed higher concentrations compared to dry deposition. The metal concentrations among the different sampling sites significantly differ from each other depending on the traffic conditions. Industrial activities are not significant in Kandy City. Consequently, the traffic exerts high influence on heavy metal loadings. As part of the bacterial investigations, nine species of culturable bacteria, namely; Sphingomonas sp., Pseudomonas aeruginosa, Pseudomonas monteilii, Klebsiella pneumonia, Ochrobactrum intermedium, Leclercia adecarboxylata, Exiguobacterium sp., Bacillus pumilus and Kocuria kristinae, which are opportunistic pathogens, were identified. This is the first time Pseudomonas monteilii and Ochrobactrum intermedium has been reported from a country in Asia. The culturable fraction constituted ~0.01 to 10%. Pigmented bacteria and endospore forming bacteria were copious in the atmospheric depositions due to their capability to withstand harsh environmental conditions. The presence of pathogenic bacteria and heavy metals creates potential human and ecosystem health risk. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Microbial Inhibition of Fusarium Pathogens and Biological Modification of Trichothecenes in Cereal Grains

    PubMed Central

    Wachowska, Urszula; Packa, Danuta

    2017-01-01

    Fungi of the genus Fusarium infect cereal crops during the growing season and cause head blight and other diseases. Their toxic secondary metabolites (mycotoxins) contaminate grains. Several dozen toxic compounds produced by fungal pathogens have been identified to date. Type B trichothecenes—deoxynivalenol, its acetyl derivatives and nivalenol (produced mainly by F. graminearum and F. culmorum)—are most commonly detected in cereal grains. “T-2 toxin” (produced by, among others, F. sporotrichioides) belongs to type-A trichothecenes which are more toxic than other trichothecenes. Antagonistic bacteria and fungi can affect pathogens of the genus Fusarium via different modes of action: direct (mycoparasitism or hyperparasitism), mixed-path (antibiotic secretion, production of lytic enzymes) and indirect (induction of host defense responses). Microbial modification of trichothecenes involves acetylation, deacetylation, oxidation, de-epoxidation, and epimerization, and it lowers the pathogenic potential of fungi of the genus Fusarium. Other modifing mechanisms described in the paper involve the physical adsorption of mycotoxins in bacterial cells and the conjugation of mycotoxins to glucose and other compounds in plant and fungal cells. The development of several patents supports the commercialization and wider application of microorganisms biodegrading mycotoxins in grains and, consequently, in feed additives. PMID:29261142

  12. A novel high-throughput assay to quantify the vaccine-induced inhibition of Bordetella pertussis adhesion to airway epithelia.

    PubMed

    Zanaboni, Elisa; Arato, Vanessa; Pizza, Mariagrazia; Seubert, Anja; Leuzzi, Rosanna

    2016-09-15

    Pertussis or whooping cough is an acute respiratory illness caused by the Gram-negative pathogen Bordetella pertussis. Despite high vaccination coverage whooping cough is currently re-emerging in many developed countries. Although the causes of pertussis resurgence are matter of debate, emerging evidences suggest that acellular vaccines efficiently protect against the hallmark symptoms of pertussis disease but fail to prevent colonization. This presumably impacts on increased risk of bacterial transmission and consequent spread throughout the population. These evidences suggest that improved vaccines may be required for efficient bacterial clearance in the upper respiratory tract. Consequently, there is a need for novel bioassays to evaluate at pre-clinical or clinical level the impact of different vaccines on B. pertussis colonization. We developed a high-throughput bacterial adhesion inhibition (BAI) assay based on human respiratory cell lines and on live bacteria chemically conjugated to a fluorescent dye. Employing A549 cells as model, we evaluated the impact of antibodies elicited by acellular (aP) and whole cell (wP) vaccines on B. pertussis adhesion in vitro. Moreover, we settled the method also on polarized Calu-3 cells grown at air-liquid interface (ALI), showing that this assay can be extended to more complex cell models mimicking the airway epithelium. We proved that this method is a sensitive, rapid and reproducible system to evaluate the anti-adhesive properties of vaccine-induced antibodies and can be employed to assess improved pertussis vaccines.

  13. Travel vaccination recommendations and endemic infection risks in solid organ transplantation recipients.

    PubMed

    Trubiano, Jason A; Johnson, Douglas; Sohail, Asma; Torresi, Joseph

    2016-06-01

    Solid organ transplant (SOT) recipients are often heavily immunosuppressed and consequently at risk of serious illness from vaccine preventable viral and bacterial infections or with endemic fungal and parasitic infections. We review the literature to provide guidance regarding the timing and appropriateness of vaccination and pathogen avoidance related to the immunological status of SOT recipients. A PUBMED search ([Vaccination OR vaccine] AND/OR ["specific vaccine"] AND/OR [immunology OR immune response OR cytokine OR T lymphocyte] AND transplant was performed. A review of the literature was performed in order to develop recommendations on vaccination for SOT recipients travelling to high-risk destinations. Whilst immunological failure of vaccination in SOT is primarily the result of impaired B-cell responses, the role of T-cells in vaccine failure and success remains unknown. Vaccination should be initiated at least 4 weeks prior to SOT or more than 6 months post-SOT. Avoidance of live vaccination is generally recommended, although some live vaccines may be considered in the specific situations (e.g. yellow fever). The practicing physician requires a detailed understanding of region-specific endemic pathogen risks. We provide a vaccination and endemic pathogen guide for physicians and travel clinics involved in the care of SOT recipients. In addition, recommendations based on timing of anticipated immunological recovery and available evidence regarding vaccine immunogenicity in SOT recipients are provided to help guide pre-travel consultations. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

  14. Dose-response relationships for environmentally mediated infectious disease transmission models

    PubMed Central

    Eisenberg, Joseph N. S.

    2017-01-01

    Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks, such as water treatment or surface decontamination. The shift from the classical SIR framework to one incorporating the environment requires codifying the relationship between exposure to environmental pathogens and infection, i.e. the dose–response relationship. Much of the work characterizing the functional forms of dose–response relationships has used statistical fit to experimental data. However, there has been little research examining the consequences of the choice of functional form in the context of transmission dynamics. To this end, we identify four properties of dose–response functions that should be considered when selecting a functional form: low-dose linearity, scalability, concavity, and whether it is a single-hit model. We find that i) middle- and high-dose data do not constrain the low-dose response, and different dose–response forms that are equally plausible given the data can lead to significant differences in simulated outbreak dynamics; ii) the choice of how to aggregate continuous exposure into discrete doses can impact the modeled force of infection; iii) low-dose linear, concave functions allow the basic reproduction number to control global dynamics; and iv) identifiability analysis offers a way to manage multiple sources of uncertainty and leverage environmental monitoring to make inference about infectivity. By applying an environmentally mediated infectious disease model to the 1993 Milwaukee Cryptosporidium outbreak, we demonstrate that environmental monitoring allows for inference regarding the infectivity of the pathogen and thus improves our ability to identify outbreak characteristics such as pathogen strain. PMID:28388665

  15. The Genomic Diversification of the Whole Acinetobacter Genus: Origins, Mechanisms, and Consequences

    PubMed Central

    Touchon, Marie; Cury, Jean; Yoon, Eun-Jeong; Krizova, Lenka; Cerqueira, Gustavo C.; Murphy, Cheryl; Feldgarden, Michael; Wortman, Jennifer; Clermont, Dominique; Lambert, Thierry; Grillot-Courvalin, Catherine; Nemec, Alexandr; Courvalin, Patrice; Rocha, Eduardo P.C.

    2014-01-01

    Bacterial genomics has greatly expanded our understanding of microdiversification patterns within a species, but analyses at higher taxonomical levels are necessary to understand and predict the independent rise of pathogens in a genus. We have sampled, sequenced, and assessed the diversity of genomes of validly named and tentative species of the Acinetobacter genus, a clade including major nosocomial pathogens and biotechnologically important species. We inferred a robust global phylogeny and delimited several new putative species. The genus is very ancient and extremely diverse: Genomes of highly divergent species share more orthologs than certain strains within a species. We systematically characterized elements and mechanisms driving genome diversification, such as conjugative elements, insertion sequences, and natural transformation. We found many error-prone polymerases that may play a role in resistance to toxins, antibiotics, and in the generation of genetic variation. Surprisingly, temperate phages, poorly studied in Acinetobacter, were found to account for a significant fraction of most genomes. Accordingly, many genomes encode clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems with some of the largest CRISPR-arrays found so far in bacteria. Integrons are strongly overrepresented in Acinetobacter baumannii, which correlates with its frequent resistance to antibiotics. Our data suggest that A. baumannii arose from an ancient population bottleneck followed by population expansion under strong purifying selection. The outstanding diversification of the species occurred largely by horizontal transfer, including some allelic recombination, at specific hotspots preferentially located close to the replication terminus. Our work sets a quantitative basis to understand the diversification of Acinetobacter into emerging resistant and versatile pathogens. PMID:25313016

  16. Conflicts over host manipulation between different parasites and pathogens: Investigating the ecological and medical consequences

    PubMed Central

    2016-01-01

    When parasites have different interests in regard to how their host should behave this can result in a conflict over host manipulation, i.e. parasite induced changes in host behaviour that enhance parasite fitness. Such a conflict can result in the alteration, or even complete suppression, of one parasite's host manipulation. Many parasites, and probably also symbionts and commensals, have the ability to manipulate the behaviour of their host. Non‐manipulating parasites should also have an interest in host behaviour. Given the frequency of multiple parasite infections in nature, potential conflicts of interest over host behaviour and manipulation may be common. This review summarizes the evidence on how parasites can alter other parasite's host manipulation. Host manipulation can have important ecological and medical consequences. I speculate on how a conflict over host manipulation could alter these consequences and potentially offer a new avenue of research to ameliorate harmful consequences of host manipulation. PMID:27510821

  17. Internalization of fresh produce by foodborne pathogens.

    PubMed

    Erickson, Marilyn C

    2012-01-01

    Recent studies addressing the internalization of fresh produce by foodborne pathogens arose in response to the growing number of recent and high profile outbreaks involving fresh produce. Because chemical sanitizing agents used during harvest and minimal processing are unlikely to reach enteric pathogens residing within plant tissue, it is imperative that paths for pathogen entry be recognized and minimized. Using both microscopy and microbial enumeration tools, enteric pathogens have been shown to enter plant tissues through both natural apertures (stomata, lateral junctions of roots, flowers) and damaged (wounds, cut surfaces) tissue. In studies revealing preharvest internalization via plant roots or leaf stomata, experimental conditions have primarily involved exposure of plants to high pathogen concentrations (≥ 6 log g⁻¹ soil or 6 log ml⁻¹ water), but those pathogens internalized appear to have short-term persistence. Postharvest internalization of pathogens via cut surfaces may be minimized by maintaining effective levels of sanitizing agents in waters during harvesting and minimal processing.

  18. Mechanisms of Antibiotic Resistance

    PubMed Central

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  19. The slippery difficulty of ever containing drug resistance with current practices.

    PubMed

    Fullybright, R

    2017-04-01

    It has previously been shown that the rate of drug resistance emergence in medicine is exponential, while we have been producing drugs at a much lower rate. Our ability to successfully contain resistance at any one time is function of how many drugs we have at our disposal to counter new resistances from pathogens. Here, we assess our level of preparedness through a mathematical comparison of the drug manufacture rate by the pharmaceutical industry with the resistance emergence rate in pathogens. To that effect, changes in the rates of growth of the drugs production and resistance emergence processes are computed over multiple time segments and compared. It is found that new resistance emergence rate in infectious diseases medicine remains mathematically and permanently ahead of the drugs production rate by the pharmaceutical industry. Consequently, we are not in a position to ever contain current or future strengths of resistance from pathogens. A review of current practices is called for.

  20. Pseudomonas syringae Type III Effector HopBB1 Promotes Host Transcriptional Repressor Degradation to Regulate Phytohormone Responses and Virulence.

    PubMed

    Yang, Li; Teixeira, Paulo José Pereira Lima; Biswas, Surojit; Finkel, Omri M; He, Yijian; Salas-Gonzalez, Isai; English, Marie E; Epple, Petra; Mieczkowski, Piotr; Dangl, Jeffery L

    2017-02-08

    Independently evolved pathogen effectors from three branches of life (ascomycete, eubacteria, and oomycete) converge onto the Arabidopsis TCP14 transcription factor to manipulate host defense. However, the mechanistic basis for defense control via TCP14 regulation is unknown. We demonstrate that TCP14 regulates the plant immune system by transcriptionally repressing a subset of the jasmonic acid (JA) hormone signaling outputs. A previously unstudied Pseudomonas syringae (Psy) type III effector, HopBB1, interacts with TCP14 and targets it to the SCF COI1 degradation complex by connecting it to the JA signaling repressor JAZ3. Consequently, HopBB1 de-represses the TCP14-regulated subset of JA response genes and promotes pathogen virulence. Thus, HopBB1 fine-tunes host phytohormone crosstalk by precisely manipulating part of the JA regulon to avoid pleiotropic host responses while promoting pathogen proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

    PubMed Central

    Azizi, Ali; Kumar, Ashok; Diaz-Mitoma, Francisco; Mestecky, Jiri

    2010-01-01

    The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M) cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells. PMID:21085599

  2. Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.

    PubMed

    Mielczarek, Ewelina; Blaszkowska, Joanna

    2016-08-01

    Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.

  3. Virus-Bacteria Interactions: Implications and Potential for the Applied and Agricultural Sciences.

    PubMed

    Moore, Matthew D; Jaykus, Lee-Ann

    2018-02-02

    Eukaryotic virus-bacteria interactions have recently become an emerging topic of study due to multiple significant examples related to human pathogens of clinical interest. However, such omnipresent and likely important interactions for viruses and bacteria relevant to the applied and agricultural sciences have not been reviewed or compiled. The fundamental basis of this review is that these interactions have importance and deserve more investigation, as numerous potential consequences and applications arising from their discovery are relevant to the applied sciences. The purpose of this review is to highlight and summarize eukaryotic virus-bacteria findings in the food/water, horticultural, and animal sciences. In many cases in the agricultural sciences, mechanistic understandings of the effects of virus-bacteria interactions remain unstudied, and many studies solely focus on co-infections of bacterial and viral pathogens. Given recent findings relative to human viral pathogens, further research related to virus-bacteria interactions would likely result in numerous discoveries and beneficial applications.

  4. Genomics, the origins of agriculture, and our changing microbe-scape: time to revisit some old tales and tell some new ones.

    PubMed

    Harper, Kristin N; Armelagos, George J

    2013-12-01

    Though agriculture is often viewed as one of humanity's crowning achievements, skeletal evidence indicates that dependence on domesticated plants and animals was accompanied by an increase in infectious disease. Scientists have proposed that many important infections emerged in the period following the advent of agriculture, as a result of newly dense populations and novel proximity to domestic animals that served as reservoirs for novel pathogens. Here, we review genomic evidence regarding pathogen origins, analyzing these data using the epidemiological transition framework. Genetic information has forced us to reconsider how and when many important pathogens emerged; it appears that a number of infections thought to result from contact with domesticated animals arose much earlier than agriculture was adopted. We also consider the broader effect of agriculture upon the microbiome, exploring potential consequences for human health. We end by discussing the changes in the human microbe-scape we are likely to see in the future. Copyright © 2013 Wiley Periodicals, Inc.

  5. An Escherichia coli O157-specific engineered pyocin prevents and ameliorates infection by E. coli O157:H7 in an animal model of diarrheal disease.

    PubMed

    Ritchie, Jennifer M; Greenwich, Jennifer L; Davis, Brigid M; Bronson, Roderick T; Gebhart, Dana; Williams, Steven R; Martin, David; Scholl, Dean; Waldor, Matthew K

    2011-12-01

    AvR2-V10.3 is an engineered R-type pyocin that specifically kills Escherichia coli O157, an enteric pathogen that is a major cause of food-borne diarrheal disease. New therapeutics to counteract E. coli O157 are needed, as currently available antibiotics can exacerbate the consequences of infection. We show here that orogastric administration of AvR2-V10.3 can prevent or ameliorate E. coli O157:H7-induced diarrhea and intestinal inflammation in an infant rabbit model of infection when the compound is administered either in a postexposure prophylactic regimen or after the onset of symptoms. Notably, administration of AvR2-V10.3 also reduces bacterial carriage and fecal shedding of this pathogen. Our findings support the further development of pathogen-specific R-type pyocins as a way to treat enteric infections.

  6. A High Burden of Asymptomatic Gastrointestinal Infections in Traditional Communities in Papua New Guinea.

    PubMed

    Horwood, Paul F; Soli, Kevin W; Maure, Tobias; Naito, Yuichi I; Morita, Ayako; Natsuhara, Kazumi; Tadokoro, Kiyoshi; Baba, Jun; Odani, Shingo; Tomitsuka, Eriko; Igai, Katsura; Larkins, Jo-Ann; Siba, Peter M; Pomat, William; McBryde, Emma S; Umezaki, Masahiro; Greenhill, Andrew R

    2017-12-01

    Stool samples were collected from 148 healthy adults living a traditional subsistence lifestyle in Papua New Guinea and screened for enteric pathogens using real-time RT-PCR/PCR assays. Enteric pathogens were detected in a high proportion (41%) of individuals. Clear differences were observed in the detection of pathogens between highland and lowland communities. In particular, there was a marked difference in detection rates of norovirus GII (20% and 0%, respectively) and Shigella sp. (15% and 0%, respectively). Analysis of the relationship between enteric pathogen carriage and microbial community composition of participants, using box plots to compare specific normal flora population numbers, did not suggest that gut microbial composition was directly associated with pathogen carriage. This study suggests that enteric pathogens are common in healthy individuals in Papua New Guinean highland communities, presumably acting as a reservoir of infection and thus contributing to a high burden of gastrointestinal illnesses.

  7. Genotyping-by-sequencing to re-map QTL for type II Fusarium head blight and leaf rust resistance in a wheat-tall wheatgrass introgression recombinant inbred population

    USDA-ARS?s Scientific Manuscript database

    Fusarium graminaerum (Fusarium head blight; FHB) and Puccinia recondita Roberge ex Desmaz. f. sp. tritici Eriks. & E. Henn (leaf rust; LR) are two major fungal pathogens threatening the wheat crop; consequently identifying resistance genes from various sources is always of importance to wheat breede...

  8. Six years of aerial and ground monitoring surveys for sudden oak death in California

    Treesearch

    Lisa Bell; Jeff Mai; Zachary Heath; Erik Haunreiter; Lisa M. Fischer

    2008-01-01

    Aerial surveys have been conducted since 2001 to map recent hardwood mortality and consequently target ground visits for detection of Phytophthora ramorum, the pathogen that causes sudden oak death (SOD). Each year the aerial and ground surveys monitored much of California?s forests at risk for SOD resulting in new maps of hardwood mortality,...

  9. Agroterrorism: Minimizing the Consequences of Intentionally Introduced Foreign Animal Disease

    DTIC Science & Technology

    2010-04-01

    responsibility and dedicate fewer resources to mitigate the threat. Unless they are zoonotic , animal and plant diseases do not 2 Ibid., 157. 3...of the United States and current FAD policies are inadequate. 4 Zoonotic diseases or...pathogens that can be transmitted from animals to people. Specifically, a zoonotic disease normally exists in animals can infect humans. 5 John Brogan

  10. Fecal Microbiota Transplantation Inhibits Multidrug-Resistant Gut Pathogens: Preliminary Report Performed in an Immunocompromised Host.

    PubMed

    Biliński, Jarosław; Grzesiowski, Paweł; Muszyński, Jacek; Wróblewska, Marta; Mądry, Krzysztof; Robak, Katarzyna; Dzieciątkowski, Tomasz; Wiktor-Jedrzejczak, Wiesław; Basak, Grzegorz W

    2016-06-01

    Colonization of the gastrointestinal tract with multidrug-resistant (MDR) bacteria is a consequence of gut dysbiosis. We describe the successful utilization of fecal microbiota transplantation to inhibit Klebsiella pneumoniae MBL(+) and Escherichia coli ESBL(+) gut colonization in the immunocompromised host as a novel tool in the battle against MDR microorganisms. ClinicalTrials.gov identifier NCT02461199.

  11. Landscape biology of western white pine: implications for conservation of a widely-distributed five-needle pine at its southern range limit

    Treesearch

    Patricia Maloney; Andrew Eckert; Detlev Vogler; Camille Jensen; Annette Delfino Mix; David Neale

    2016-01-01

    Throughout much of the range of western white pine, Pinus monticola Dougl., timber harvesting, fire exclusion and the presence of Cronartium ribicola J. C. Fisch., the white pine blister rust (WPBR) pathogen, have led to negative population and genetic consequences. To address these interactions, we examined population dynamics...

  12. Improved Design and Ultrasound-assisted Sanitation of Lettuce Harvesting Knives for Minimizing Escherichia coli O157:H7 Contamination

    USDA-ARS?s Scientific Manuscript database

    Laboratory studies have shown that Escherichia coli O157:H7 can be transferred to lettuce during harvesting. Knives used for lettuce coring-in-field (CIF) harvesting are likely to contact soil and consequently could serve as a vehicle for the transmission of food-borne human pathogens from contamin...

  13. Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective.

    PubMed

    Fiusa, Maiara Marx Luz; Carvalho-Filho, Marco Antonio; Annichino-Bizzacchi, Joyce M; De Paula, Erich V

    2015-05-06

    Coagulation and innate immunity have been linked together for at least 450 million years of evolution. Sepsis, one of the world's leading causes of death, is probably the condition in which this evolutionary link is more evident. However, the biological and the clinical relevance of this association have only recently gained the attention of the scientific community. During sepsis, the host response to a pathogen is invariably associated with coagulation activation. For several years, coagulation activation has been solely regarded as a mechanism of tissue damage, a concept that led to several clinical trials of anticoagulant agents for sepsis. More recently, this paradigm has been challenged by the failure of these clinical trials, and by a growing bulk of evidence supporting the concept that coagulation activation is beneficial for pathogen clearance. In this article we discuss recent basic and clinical data that point to a more balanced view of the detrimental and beneficial consequences of coagulation activation in sepsis. Reappraisal of the association between coagulation and immune activation from an evolutionary medicine perspective offers a unique opportunity to gain new insights about the pathogenesis of sepsis, paving the way to more successful approaches in both basic and clinical research in this field.

  14. Reinforcing effects of non-pathogenic bacteria and predation risk: from physiology to life history.

    PubMed

    Janssens, Lizanne; Stoks, Robby

    2014-10-01

    The important ecological role of predation risk in shaping populations, communities and ecosystems is becoming increasingly clear. In this context, synergistic effects between predation risk and other natural stressors on prey organisms are gaining attention. Although non-pathogenic bacteria can be widespread in aquatic ecosystems, their role in mediating effects of predation risk has been ignored. We here address the hypothesis that non-pathogenic bacteria may reinforce the negative effects of predation risk in larvae of the damselfly Coenagrion puella. We found synergistic effects for all three life history variables studied: mortality increased, growth reductions were magnified and bacterial load was higher when both non-lethal stressors were combined. The combined exposure to the bacterium and predation risk considerably impaired the two key antipredator mechanisms of the damselfly larvae: they no longer reduced their food intake under predation risk and showed a synergistic reduction in escape swimming speed. The reinforcing negative effects on the fitness-related traits could be explained by the observed synergistic effects on food intake, swimming muscle mass, immune function and oxidative damage. These are likely widespread consequences of energetic constraints and increased metabolic rates associated with the fight-or-flight response. We therefore hypothesize that the here documented synergistic interactions with non-pathogenic bacteria may be widespread. Our results highlight the ignored ecological role of non-pathogenic bacteria in reinforcing the negative effects of predation risk on prey organisms.

  15. The AIP Model of EMDR Therapy and Pathogenic Memories

    PubMed Central

    Hase, Michael; Balmaceda, Ute M.; Ostacoli, Luca; Liebermann, Peter; Hofmann, Arne

    2017-01-01

    Eye Movement Desensitization and Reprocessing (EMDR) therapy has been widely recognized as an efficacious treatment for post-traumatic stress disorder (PTSD). In the last years more insight has been gained regarding the efficacy of EMDR therapy in a broad field of mental disorders beyond PTSD. The cornerstone of EMDR therapy is its unique model of pathogenesis and change: the adaptive information processing (AIP) model. The AIP model developed by F. Shapiro has found support and differentiation in recent studies on the importance of memories in the pathogenesis of a range of mental disorders beside PTSD. However, theoretical publications or research on the application of the AIP model are still rare. The increasing acceptance of ideas that relate the origin of many mental disorders to the formation and consolidation of implicit dysfunctional memory lead to formation of the theory of pathogenic memories. Within the theory of pathogenic memories these implicit dysfunctional memories are considered to form basis of a variety of mental disorders. The theory of pathogenic memories seems compatible to the AIP model of EMDR therapy, which offers strategies to effectively access and transmute these memories leading to amelioration or resolution of symptoms. Merging the AIP model with the theory of pathogenic memories may initiate research. In consequence, patients suffering from such memory-based disorders may be earlier diagnosed and treated more effectively. PMID:28983265

  16. Fungi in the cystic fibrosis lung: bystanders or pathogens?

    PubMed

    Chotirmall, Sanjay H; McElvaney, Noel G

    2014-07-01

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

  17. Rapid emergence of pathogens in agro-ecosystems: global threats to agricultural sustainability and food security.

    PubMed

    McDonald, Bruce A; Stukenbrock, Eva H

    2016-12-05

    Agricultural ecosystems are composed of genetically depauperate populations of crop plants grown at a high density and over large spatial scales, with the regional composition of crop species changing little from year to year. These environments are highly conducive for the emergence and dissemination of pathogens. The uniform host populations facilitate the specialization of pathogens to particular crop cultivars and allow the build-up of large population sizes. Population genetic and genomic studies have shed light on the evolutionary mechanisms underlying speciation processes, adaptive evolution and long-distance dispersal of highly damaging pathogens in agro-ecosystems. These studies document the speed with which pathogens evolve to overcome crop resistance genes and pesticides. They also show that crop pathogens can be disseminated very quickly across and among continents through human activities. In this review, we discuss how the peculiar architecture of agro-ecosystems facilitates pathogen emergence, evolution and dispersal. We present four example pathosystems that illustrate both pathogen specialization and pathogen speciation, including different time frames for emergence and different mechanisms underlying the emergence process. Lastly, we argue for a re-design of agro-ecosystems that embraces the concept of dynamic diversity to improve their resilience to 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).

  18. Reduced Set of Virulence Genes Allows High Accuracy Prediction of Bacterial Pathogenicity in Humans

    PubMed Central

    Iraola, Gregorio; Vazquez, Gustavo; Spangenberg, Lucía; Naya, Hugo

    2012-01-01

    Although there have been great advances in understanding bacterial pathogenesis, there is still a lack of integrative information about what makes a bacterium a human pathogen. The advent of high-throughput sequencing technologies has dramatically increased the amount of completed bacterial genomes, for both known human pathogenic and non-pathogenic strains; this information is now available to investigate genetic features that determine pathogenic phenotypes in bacteria. In this work we determined presence/absence patterns of different virulence-related genes among more than finished bacterial genomes from both human pathogenic and non-pathogenic strains, belonging to different taxonomic groups (i.e: Actinobacteria, Gammaproteobacteria, Firmicutes, etc.). An accuracy of 95% using a cross-fold validation scheme with in-fold feature selection is obtained when classifying human pathogens and non-pathogens. A reduced subset of highly informative genes () is presented and applied to an external validation set. The statistical model was implemented in the BacFier v1.0 software (freely available at ), that displays not only the prediction (pathogen/non-pathogen) and an associated probability for pathogenicity, but also the presence/absence vector for the analyzed genes, so it is possible to decipher the subset of virulence genes responsible for the classification on the analyzed genome. Furthermore, we discuss the biological relevance for bacterial pathogenesis of the core set of genes, corresponding to eight functional categories, all with evident and documented association with the phenotypes of interest. Also, we analyze which functional categories of virulence genes were more distinctive for pathogenicity in each taxonomic group, which seems to be a completely new kind of information and could lead to important evolutionary conclusions. PMID:22916122

  19. Differences in pathogenicity of A/Duck/Vietnam/201/05 H5N1 highly pathogenic avian influenza virus reassortants in ducks

    USDA-ARS?s Scientific Manuscript database

    In order to understand which viral genes contribute to the high virulence of A/Dk/Vietnam/201/05 H5N1 highly pathogenic avian influenza (HPAI) virus in ducks, we used reverse genetics to generate single-gene reassortant viruses with genes from A/Ck/Indonesia/7/03, a virus that produces mild disease ...

  20. Chinese and Vietnamese strains of HP-PRRSV cause different pathogenic outcomes in United States high health swine

    USDA-ARS?s Scientific Manuscript database

    An infectious clone of a highly pathogenic PRRSV strain from Vietnam (rSRV07) was prepared, analyzed and compared to Chinese highly pathogenic PRRSV rJXwn06 and US Type 2 prototype VR-2332 in order to examine the effects of virus phenotype and genotype on growth in MARC-145 cells, as well as the imp...

  1. The pathogenesis of H7N8 low and highly pathogenic avian influenza viruses from the United States 2016 outbreak in chickens, turkeys and mallards

    USDA-ARS?s Scientific Manuscript database

    In January 2016, a combined outbreak of highly pathogenic (HP) avian influenza virus (AIV) and low pathogenicity (LP) AIV occurred in commercial turkeys in the state of Indiana, United States. Genetically, the viruses were highly similar, belonged to the North American wild bird lineage, and had not...

  2. Bats and Academics: How Do Scientists Perceive Their Object of Study?

    PubMed Central

    Boëte, Christophe; Morand, Serge

    2016-01-01

    Bats are associated with conflicting perceptions among humans, ranging from affection to disgust. If these attitudes can be associated with various factors among the general public (e.g. social norms, lack of knowledge), it is also important to understand the attitude of scientists who study bats. Such reflexive information on the researchers community itself could indeed help designing adequate mixed communication tools aimed at protecting bats and their ecosystems, as well as humans living in their vicinity that could be exposed to their pathogens. Thus, we conducted an online survey targeting researchers who spend a part of their research activity studying bats. Our aim was to determine (1) how they perceive their object of study, (2) how they perceive the representation of bats in the media and by the general population, (3) how they protect themselves against pathogen infections during their research practices, and (4) their perceptions of the causes underlying the decline in bat populations worldwide. From the 587 completed responses (response rate of 28%) having a worldwide distribution, the heterogeneity of the scientists’ perception of their own object of study was highlighted. In the majority of cases, this depended on the type of research they conducted (i.e. laboratory versus field studies) as well as their research speciality. Our study revealed a high level of personal protection equipment being utilised against pathogens during scientific practices, although the role bats play as reservoirs for a number of emerging pathogens remains poorly known. Our results also disclosed the unanimity among specialists in attributing a direct role for humans in the global decline of bat populations, mainly via environmental change, deforestation, and agriculture intensification. Overall, the present study suggests the need for better communication regarding bats and their biology, their role within the scientific community, as well as in the general public population. As a consequence, increased knowledge regarding scientists’ perceptions of bats should improve the role scientists play in influencing the perception of bats by the general public. PMID:27832185

  3. Bats and Academics: How Do Scientists Perceive Their Object of Study?

    PubMed

    Boëte, Christophe; Morand, Serge

    2016-01-01

    Bats are associated with conflicting perceptions among humans, ranging from affection to disgust. If these attitudes can be associated with various factors among the general public (e.g. social norms, lack of knowledge), it is also important to understand the attitude of scientists who study bats. Such reflexive information on the researchers community itself could indeed help designing adequate mixed communication tools aimed at protecting bats and their ecosystems, as well as humans living in their vicinity that could be exposed to their pathogens. Thus, we conducted an online survey targeting researchers who spend a part of their research activity studying bats. Our aim was to determine (1) how they perceive their object of study, (2) how they perceive the representation of bats in the media and by the general population, (3) how they protect themselves against pathogen infections during their research practices, and (4) their perceptions of the causes underlying the decline in bat populations worldwide. From the 587 completed responses (response rate of 28%) having a worldwide distribution, the heterogeneity of the scientists' perception of their own object of study was highlighted. In the majority of cases, this depended on the type of research they conducted (i.e. laboratory versus field studies) as well as their research speciality. Our study revealed a high level of personal protection equipment being utilised against pathogens during scientific practices, although the role bats play as reservoirs for a number of emerging pathogens remains poorly known. Our results also disclosed the unanimity among specialists in attributing a direct role for humans in the global decline of bat populations, mainly via environmental change, deforestation, and agriculture intensification. Overall, the present study suggests the need for better communication regarding bats and their biology, their role within the scientific community, as well as in the general public population. As a consequence, increased knowledge regarding scientists' perceptions of bats should improve the role scientists play in influencing the perception of bats by the general public.

  4. Spatial dynamics of bar-headed geese migration in the context of H5N1

    USGS Publications Warehouse

    Bourouiba, L.; Wu, Jianhong; Newman, S.; Takekawa, John Y.; Natdorj, T.; Batbayar, N.; Bishop, C.M.; Hawkes, L.A.; Butler, P.J.; Wikelski, M.

    2010-01-01

    Virulent outbreaks of highly pathogenic avian influenza (HPAI) since 2005 have raised the question about the roles of migratory and wild birds in the transmission of HPAI. Despite increased monitoring, the role of wild waterfowl as the primary source of the highly pathogenic H5N1 has not been clearly established. The impact of outbreaks of HPAI among species of wild birds which are already endangered can nevertheless have devastating consequences for the local and non-local ecology where migratory species are established. Understanding the entangled dynamics of migration and the disease dynamics will be key to prevention and control measures for humans, migratory birds and poultry. Here, we present a spatial dynamic model of seasonal migration derived from first principles and linking the local dynamics during migratory stopovers to the larger scale migratory routes. We discuss the effect of repeated epizootic at specific migratory stopovers for bar-headed geese (Anser indicus). We find that repeated deadly outbreaks of H5N1 on stopovers during the autumn migration of bar-headed geese could lead to a larger reduction in the size of the equilibrium bird population compared with that obtained after repeated outbreaks during the spring migration. However, the opposite is true during the first few years of transition to such an equilibrium. The age-maturation process of juvenile birds which are more susceptible to H5N1 reinforces this result.

  5. Antimicrobial resistance of mastitis pathogens.

    PubMed

    Oliver, Stephen P; Murinda, Shelton E

    2012-07-01

    Antibiotics are used extensively in the dairy industry to combat disease and to improve animal performance. Antibiotics such as penicillin, cephalosporin, streptomycin, and tetracycline are used for the treatment and prevention of diseases affecting dairy cows caused by a variety of gram-positive and gram-negative bacteria. Antibiotics are often administrated routinely to entire herds to prevent mastitis during the dry period. An increase in the incidence of disease in a herd generally results in increased use of antimicrobials, which in turn increases the potential for antibiotic residues in milk and the potential for increased bacterial resistance to antimicrobials. Continued use of antibiotics in the treatment and prevention of diseases of dairy cows will continue to be scrutinized. It is clear that strategies employing the prudent use of antimicrobials are needed. This clearly illustrates the importance of effective herd disease prevention and control programs. Based on studies published to date, scientific evidence does not support widespread, emerging resistance among mastitis pathogens to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in dairy cows can contribute to increased antimicrobial resistance. While antimicrobial resistance does occur, we are of the opinion that the advantages of using antibiotics for the treatment of mastitis far outweigh the disadvantages. The clinical consequences of antimicrobial resistance of dairy pathogens affecting humans appear small. Antimicrobial resistance among dairy pathogens, particularly those found in milk, is likely not a human health concern as long as the milk is pasteurized. However, there are an increasing number of people who choose to consume raw milk. Transmission of an antimicrobial-resistant mastitis pathogen and/or foodborne pathogen to humans could occur if contaminated unpasteurized milk is consumed, which is another important reason why people should not consume raw milk. Likewise, resistant bacteria contaminating meat from dairy cows should not be a significant human health concern if the meat is cooked properly. Prudent use of antibiotics in the dairy industry is important, worthwhile, and necessary. Use of antibiotics at times when animals are susceptible to new infection such as the dry period is a sound management decision and a prudent use of antibiotics on the farm. Strategies involving prudent use of antibiotics for treatment encompass identification of the pathogen causing the infection, determining the susceptibility/resistance of the pathogen to assess the most appropriate antibiotic to use for treatment, and a sufficient treatment duration to ensure effective concentrations of the antibiotic to eliminate the pathogen. As the debate on the use of antibiotics in animal agriculture continues, we need to consider the consequences of, “What would happen if antibiotics are banned for use in the dairy industry and in other food-producing animals?” The implications of this question are far reaching and include such aspects as animal welfare, health, and well-being and impacts on food quantity, quality, and food costs. This question should be an important aspect in this ongoing and controversial debate!

  6. Fungal Phytotoxins in Sustainable Weed Management.

    PubMed

    Vurro, Maurizio; Boari, Angela; Casella, Francesca; Zonno, Maria Chiara

    2018-01-01

    Fungal phytotoxins are natural secondary metabolites produced by plant pathogenic fungi during host-pathogen interactions. They have received considerable particular attention for elucidating disease etiology, and consequently to design strategies for disease control. Due to wide differences in their chemical structures, these toxic metabolites have different ecological and environmental roles and mechanisms of action. This review aims at summarizing the studies on the possible use of these metabolites as tools in biological and integrated weed management, e.g. as: novel and environmentally friendly herbicides; lead for novel compounds; sources of novel mechanisms of action. Moreover, the limiting factors for utilizing those metabolites in practice will also be briefly discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Transmission of the gut microbiota: spreading of health

    PubMed Central

    Browne, Hilary P.; Neville, B. Anne; Forster, Samuel C.; Lawley, Trevor D.

    2018-01-01

    Transmission of commensal intestinal bacteria between humans could promote health by establishing, maintaining and replenishing microbial diversity in the microbiota of an individual. Unlike pathogens, the routes of transmission for commensal bacteria remain unappreciated and poorly understood, despite the likely commonalities between both. Consequently, broad infection control measures that are designed to prevent pathogen transmission and infection, such as oversanitation and the overuse of antibiotics, may inadvertently affect human health by altering normal commensal transmission. In this Review, we discuss the mechanisms and factors that influence host-to-host transmission of the intestinal microbiota and examine how a better understanding of these processes will identify new approaches to nurture and restore transmission routes that are used by beneficial bacteria. PMID:28603278

  8. How the biodiversity sciences may aid biological tools and ecological engineering to assess the impact of climatic changes.

    PubMed

    Morand, S; Guégan, J-F

    2008-08-01

    This paper addresses how climate changes interact with other global changes caused by humans (habitat fragmentation, changes in land use, bioinvasions) to affect biodiversity. Changes in biodiversity at all levels (genetic, population and community) affect the functioning of ecosystems, in particular host-pathogen interactions, with major consequences in health ecology (emergence and re-emergence; the evolution of virulence and resistance). In this paper, the authors demonstrate that the biodiversity sciences, epidemiological theory and evolutionary ecology are indispensable in assessing the impact of climate changes, and also for modelling the evolution of host-pathogen interactions in a changing environment. The next step is to apply health ecology to the science of ecological engineering.

  9. Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus

    PubMed Central

    Chalermpalanupap, Termpanit; Weinshenker, David

    2017-01-01

    Degeneration of locus coeruleus (LC) is an underappreciated hallmark of Alzheimer's disease (AD). The LC is the main source of norepinephrine (NE) in the forebrain, and its degeneration is highly correlated with cognitive impairment and amyloid-beta (Aβ) and tangle pathology. Hyperphosphorylated tau in the LC is among the first detectable AD-like neuropathology in the brain, and while the LC/NE system impacts multiple aspects of AD (e.g., cognition, neuropathology, and neuroinflammation), the functional consequences of hyperphosphorylated tau accrual on LC neurons are not known. Recent evidence suggests that LC neurons accumulate aberrant tau species for decades before frank LC cell body degeneration occurs in AD, suggesting that a therapeutic window exists. In this review, we combine the literature on how pathogenic tau affects forebrain neurons with the known properties and degeneration patterns of LC neurons to synthesize hypotheses on hyperphosphorylated tau-induced dysfunction of LC neurons and the prion-like spread of pretangle tau from the LC to the forebrain. We also propose novel experiments using both in vitro and in vivo models to address the many questions surrounding the impact of hyperphosphorylated tau on LC neurons in AD and its role in disease progression. PMID:29038736

  10. Highly pathogenic avian influenza.

    PubMed

    Swayne, D E; Suarez, D L

    2000-08-01

    Highly pathogenic (HP) avian influenza (AI) (HPAI) is an extremely contagious, multi-organ systemic disease of poultry leading to high mortality, and caused by some H5 and H7 subtypes of type A influenza virus, family Orthomyxoviridae. However, most AI virus strains are mildly pathogenic (MP) and produce either subclinical infections or respiratory and/or reproductive diseases in a variety of domestic and wild bird species. Highly pathogenic avian influenza is a List A disease of the Office International des Epizooties, while MPAI is neither a List A nor List B disease. Eighteen outbreaks of HPAI have been documented since the identification of AI virus as the cause of fowl plague in 1955. Mildly pathogenic avian influenza viruses are maintained in wild aquatic bird reservoirs, occasionally crossing over to domestic poultry and causing outbreaks of mild disease. Highly pathogenic avian influenza viruses do not have a recognised wild bird reservoir, but can occasionally be isolated from wild birds during outbreaks in domestic poultry. Highly pathogenic avian influenza viruses have been documented to arise from MPAI viruses through mutations in the haemagglutinin surface protein. Prevention of exposure to the virus and eradication are the accepted methods for dealing with HPAI. Control programmes, which imply allowing a low incidence of infection, are not an acceptable method for managing HPAI, but have been used during some outbreaks of MPAI. The components of a strategy to deal with MPAI or HPAI include surveillance and diagnosis, biosecurity, education, quarantine and depopulation. Vaccination has been used in some control and eradication programmes for AI.

  11. Adapting High-Throughput Screening Methods and Assays for Biocontainment Laboratories

    PubMed Central

    Tigabu, Bersabeh; White, E. Lucile; Bostwick, Robert; Tower, Nichole; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W.; Noah, James W.

    2015-01-01

    Abstract High-throughput screening (HTS) has been integrated into the drug discovery process, and multiple assay formats have been widely used in many different disease areas but with limited focus on infectious agents. In recent years, there has been an increase in the number of HTS campaigns using infectious wild-type pathogens rather than surrogates or biochemical pathogen-derived targets. Concurrently, enhanced emerging pathogen surveillance and increased human mobility have resulted in an increase in the emergence and dissemination of infectious human pathogens with serious public health, economic, and social implications at global levels. Adapting the HTS drug discovery process to biocontainment laboratories to develop new drugs for these previously uncharacterized and highly pathogenic agents is now feasible, but HTS at higher biosafety levels (BSL) presents a number of unique challenges. HTS has been conducted with multiple bacterial and viral pathogens at both BSL-2 and BSL-3, and pilot screens have recently been extended to BSL-4 environments for both Nipah and Ebola viruses. These recent successful efforts demonstrate that HTS can be safely conducted at the highest levels of biological containment. This review outlines the specific issues that must be considered in the execution of an HTS drug discovery program for high-containment pathogens. We present an overview of the requirements for HTS in high-level biocontainment laboratories. PMID:25710545

  12. 9 CFR 94.26 - Restrictions on importation of live poultry, poultry meat, and other poultry products from...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... in § 94.6(a) as free of END and highly pathogenic avian influenza at the time the poultry were in the... slaughtered in a region designated in § 94.6(a) as free of END and highly pathogenic avian influenza at a... § 94.6(a) as free of END and highly pathogenic avian influenza in a federally inspected processing...

  13. 9 CFR 94.26 - Restrictions on importation of live poultry, poultry meat, and other poultry products from...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... in § 94.6(a) as free of END and highly pathogenic avian influenza at the time the poultry were in the... slaughtered in a region designated in § 94.6(a) as free of END and highly pathogenic avian influenza at a... § 94.6(a) as free of END and highly pathogenic avian influenza in a federally inspected processing...

  14. Reassortant Clade 2.3.4.4 of Highly Pathogenic Avian Influenza A(H5N6) Virus, Taiwan, 2017.

    PubMed

    Chen, Li-Hsuan; Lee, Dong-Hun; Liu, Yu-Pin; Li, Wan-Chen; Swayne, David E; Chang, Jen-Chieh; Chen, Yen-Ping; Lee, Fan; Tu, Wen-Jane; Lin, Yu-Ju

    2018-06-01

    A highly pathogenic avian influenza A(H5N6) virus of clade 2.3.4.4 was detected in a domestic duck found dead in Taiwan during February 2017. The endemic situation and continued evolution of various reassortant highly pathogenic avian influenza viruses in Taiwan warrant concern about further reassortment and a fifth wave of intercontinental spread.

  15. Pathogen transport in groundwater systems: Contrasts with traditional solute transport

    USGS Publications Warehouse

    Hunt, Randall J.; Johnson, William P.

    2017-01-01

    Water quality affects many aspects of water availability, from precluding use to societal perceptions of fit-for-purpose. Pathogen source and transport processes are drivers of water quality because they have been responsible for numerous outbreaks resulting in large economic losses due to illness and, in some cases, loss of life. Outbreaks result from very small exposure (e.g., less than 20 viruses) from very strong sources (e.g., trillions of viruses shed by a single infected individual). Thus, unlike solute contaminants, an acute exposure to a very small amount of contaminated water can cause immediate adverse health effects. Similarly, pathogens are larger than solutes. Thus, interactions with surfaces and settling become important even as processes important for solutes such as diffusion become less important. These differences are articulated in “Colloid Filtration Theory”, a separate branch of pore-scale transport. Consequently, understanding pathogen processes requires changes in how groundwater systems are typically characterized, where the focus is on the leading edges of plumes and preferential flow paths, even if such features move only a very small fraction of the aquifer flow. Moreover, the relatively short survival times of pathogens in the subsurface require greater attention to very fast (<10 year) flow paths. By better understanding the differences between pathogen and solute transport mechanisms discussed here, a more encompassing view of water quality and source water protection is attained. With this more holistic view and theoretical understanding, better evaluations can be made regarding drinking water vulnerability and the relation between groundwater and human health.

  16. Effects of an invasive forest pathogen on abundance of ticks and their vertebrate hosts in a California Lyme disease focus.

    PubMed

    Swei, Andrea; Ostfeld, Richard S; Lane, Robert S; Briggs, Cheryl J

    2011-05-01

    Invasive species, including pathogens, can have important effects on local ecosystems, including indirect consequences on native species. This study focuses on the effects of an invasive plant pathogen on a vertebrate community and Ixodes pacificus, the vector of the Lyme disease pathogen (Borrelia burgdorferi) in California. Phytophthora ramorum, the causative agent of sudden oak death, is a non-native pathogen killing trees in California and Oregon. We conducted a multi-year study using a gradient of SOD-caused disturbance to assess the impact on the dusky-footed woodrat (Neotoma fuscipes) and the deer mouse (Peromyscus maniculatus), two reservoir hosts of B. burgdorferi, as well as the impact on the Columbian black-tailed deer (Odocoileus hemionus columbianus) and the western fence lizard (Sceloporus occidentalis), both of which are important hosts for I. pacificus but are not pathogen reservoirs. Abundances of P. maniculatus and S. occidentalis were positively correlated with greater SOD disturbance, whereas N. fuscipes abundance was negatively correlated. We did not find a change in space use by O. hemionus. Our data show that SOD has a positive impact on the density of nymphal ticks, which is expected to increase the risk of human exposure to Lyme disease all else being equal. A positive correlation between SOD disturbance and the density of nymphal ticks was expected given increased abundances of two important hosts: deer mice and western fence lizards. However, further research is needed to integrate the direct effects of SOD on ticks, for example via altered abiotic conditions with host-mediated indirect effects.

  17. 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.

  18. Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions

    PubMed Central

    2018-01-01

    SUMMARY Transcriptomics, the analysis of genome-wide RNA expression, is a common approach to investigate host and pathogen processes in infectious diseases. Technical and bioinformatic advances have permitted increasingly thorough analyses of the association of RNA expression with fundamental biology, immunity, pathogenesis, diagnosis, and prognosis. Transcriptomic approaches can now be used to realize a previously unattainable goal, the simultaneous study of RNA expression in host and pathogen, in order to better understand their interactions. This exciting prospect is not without challenges, especially as focus moves from interactions in vitro under tightly controlled conditions to tissue- and systems-level interactions in animal models and natural and experimental infections in humans. Here we review the contribution of transcriptomic studies to the understanding of malaria, a parasitic disease which has exerted a major influence on human evolution and continues to cause a huge global burden of disease. We consider malaria a paradigm for the transcriptomic assessment of systemic host-pathogen interactions in humans, because much of the direct host-pathogen interaction occurs within the blood, a readily sampled compartment of the body. We illustrate lessons learned from transcriptomic studies of malaria and how these lessons may guide studies of host-pathogen interactions in other infectious diseases. We propose that the potential of transcriptomic studies to improve the understanding of malaria as a disease remains partly untapped because of limitations in study design rather than as a consequence of technological constraints. Further advances will require the integration of transcriptomic data with analytical approaches from other scientific disciplines, including epidemiology and mathematical modeling. PMID:29695497

  19. Carnivore Attractant or Plant Elicitor? Multifunctional Roles of Methyl Salicylate Lures in Tomato Defense.

    PubMed

    Rowen, Elizabeth; Gutensohn, Michael; Dudareva, Natalia; Kaplan, Ian

    2017-06-01

    Synthetic plant volatile lures attract natural enemies, but may have non-target effects due to the multifunctional nature of volatile signals. For example, methyl salicylate (MeSA) is used to attract predators, yet also serves as a signaling hormone involved in plant pathogen defense. We investigated the consequences of deploying MeSA lures to attract predators for tomato (Solanum lycopersicum) defense against herbivores. To understand the spatial distribution of the lure's effect, we exposed tomatoes in the field to MeSA along a linear distance gradient and induced defenses by simulating feeding by hornworm caterpillars in a fully crossed factorial design (+/- MeSA, +/- herbivory). Subsequently, we analyzed activity of several defensive proteins (protease inhibitors, polyphenol oxidase, peroxidase), development of hornworm larvae (Manduca sexta), growth of fungal pathogens (Cladosporium and Alternaria), and attractiveness to herbivores and predators. Overall, MeSA-exposed plants were more resistant to both insects and pathogens. Secondary pathogen infection was reduced by 25% in MeSA exposed plants, possibly due to elevated polyphenol oxidase activity. Interestingly, we found that lures affected plant pathogen defenses equivalently across all distances (up to 4 m away) indicating that horizontal diffusion of a synthetic volatile may be greater than previously assumed. While thrips avoided colonizing hornworm- damaged tomato plants, this induced resistance was not observed upon pre-exposure to MeSA, suggesting that MeSA suppresses the repellant effect induced by herbivory. Thus, using MeSA lures in biological control may inadvertently protect crops from pathogens, but has mixed effects on plant resistance to insect herbivores.

  20. Microbial Quality, Safety, and Pathogen Detection by Using Quantitative PCR of Raw Salad Vegetables Sold in Dhanbad City, India.

    PubMed

    Mritunjay, Sujeet K; Kumar, Vipin

    2017-01-01

    Consumption of ready-to-eat fresh vegetables has increased worldwide, with a consequent increase in outbreaks caused by foodborne pathogens. In the Indian subcontinent, raw fresh vegetables are usually consumed without washing or other decontamination procedures, thereby leading to new food safety threats. In this study, the microbiological quality and pathogenic profile of raw salad vegetables was evaluated through standard protocols. In total, 480 samples (60 each of eight different salad vegetables) of cucumber, tomato, carrot, coriander, cabbage, beetroot, radish, and spinach were collected from different locations in Dhanbad, a city famous for its coal fields and often called the "Coal Capital of India." The samples were analyzed for total plate count, total coliforms, Escherichia coli , E. coli O157:H7, Listeria monocytogenes , and Salmonella spp. Incidences of pathogens were detected through quantitative PCR subsequent to isolation. Results showed that 46.7% (for total plate counts) and 30% (for total coliforms) of samples were unacceptable for consumption per the Food Safety and Standards Authority of India. Pathogenic microorganisms were detected in 3.7% of total samples. E. coli O157:H7 was detected in three samples of spinach (2) and beetroot ( 1 ); L. monocytogenes was detected in 14 samples of spinach ( 8 ), tomato ( 3 ), cucumber ( 2 ), and radish ( 1 ); and Salmonella spp. were detected in 16 samples of spinach ( 7 ), tomato ( 3 ), beetroot ( 2 ), cucumber ( 2 ), carrot ( 1 ), and radish ( 1 ). Pathogens were not detected in any of the cabbage and coriander samples.

  1. Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions.

    PubMed

    Lee, Hyun Jae; Georgiadou, Athina; Otto, Thomas D; Levin, Michael; Coin, Lachlan J; Conway, David J; Cunnington, Aubrey J

    2018-06-01

    Transcriptomics, the analysis of genome-wide RNA expression, is a common approach to investigate host and pathogen processes in infectious diseases. Technical and bioinformatic advances have permitted increasingly thorough analyses of the association of RNA expression with fundamental biology, immunity, pathogenesis, diagnosis, and prognosis. Transcriptomic approaches can now be used to realize a previously unattainable goal, the simultaneous study of RNA expression in host and pathogen, in order to better understand their interactions. This exciting prospect is not without challenges, especially as focus moves from interactions in vitro under tightly controlled conditions to tissue- and systems-level interactions in animal models and natural and experimental infections in humans. Here we review the contribution of transcriptomic studies to the understanding of malaria, a parasitic disease which has exerted a major influence on human evolution and continues to cause a huge global burden of disease. We consider malaria a paradigm for the transcriptomic assessment of systemic host-pathogen interactions in humans, because much of the direct host-pathogen interaction occurs within the blood, a readily sampled compartment of the body. We illustrate lessons learned from transcriptomic studies of malaria and how these lessons may guide studies of host-pathogen interactions in other infectious diseases. We propose that the potential of transcriptomic studies to improve the understanding of malaria as a disease remains partly untapped because of limitations in study design rather than as a consequence of technological constraints. Further advances will require the integration of transcriptomic data with analytical approaches from other scientific disciplines, including epidemiology and mathematical modeling. Copyright © 2018 Lee et al.

  2. Development of a high- versus low-pathogenicity model of the free-living amoeba Naegleria fowleri.

    PubMed

    Burri, Denise C; Gottstein, Bruno; Zumkehr, Béatrice; Hemphill, Andrew; Schürch, Nadia; Wittwer, Matthias; Müller, Norbert

    2012-10-01

    Species in the genus Naegleria are free-living amoebae of the soil and warm fresh water. Although around 30 species have been recognized, Naegleria fowleri is the only one that causes primary amoebic meningoencephalitis (PAM) in humans. PAM is an acute and fast progressing disease affecting the central nervous system. Most of the patients die within 1-2 weeks of exposure to the infectious water source. The fact that N. fowleri causes such fast progressing and highly lethal infections has opened many questions regarding the relevant pathogenicity factors of the amoeba. In order to investigate the pathogenesis of N. fowleri under defined experimental conditions, we developed a novel high- versus low-pathogenicity model for this pathogen. We showed that the composition of the axenic growth media influenced growth behaviour and morphology, as well as in vitro cytotoxicity and in vivo pathogenicity of N. fowleri. Trophozoites maintained in Nelson's medium were highly pathogenic for mice, demonstrated rapid in vitro proliferation, characteristic expression of surface membrane vesicles and a small cell diameter, and killed target mouse fibroblasts by both contact-dependent and -independent destruction. In contrast, N. fowleri cultured in PYNFH medium exhibited a low pathogenicity, slower growth, increased cell size and contact-dependent target cell destruction. However, cultivation of the amoeba in PYNFH medium supplemented with liver hydrolysate (LH) resulted in trophozoites that were highly pathogenic in mice, and demonstrated an intermediate proliferation rate in vitro, diminished cell diameter and contact-dependent target cell destruction. Thus, in this model, the presence of LH resulted in increased proliferation of trophozoites in vitro and enhanced pathogenicity of N. fowleri in mice. However, neither in vitro cytotoxicity mechanisms nor the presence of membrane vesicles on the surface correlated with the pathologic potential of the amoeba. This indicated that the pathogenicity of N. fowleri remains a complex interaction between as-yet-unidentified cellular mechanisms.

  3. Triggering through NOD-2 Differentiates Bone Marrow Precursors to Dendritic Cells with Potent Bactericidal activity

    PubMed Central

    Khan, Nargis; Aqdas, Mohammad; Vidyarthi, Aurobind; Negi, Shikha; Pahari, Susanta; Agnihotri, Tapan; Agrewala, Javed N.

    2016-01-01

    Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naïve T cells. The role of pattern recognition receptors like Toll-Like Receptors and Nod-Like Receptors expressed on DCs is well-defined in the recognition of the pathogens. However, nothing is precisely studied regarding the impact of NOD-2 signaling during the differentiation of DCs. Consequently, we explored the role of NOD-2 signaling in the differentiation of DCs and therefore their capability to activate innate and adaptive immunity. Intriguingly, we observed that NOD-2 stimulated DCs (nDCs) acquired highly activated and matured phenotype and exhibited substantially greater bactericidal activity by robust production of nitric oxide. The mechanism involved in improving the functionality of nDCs was dependent on IFN-αβ signaling, leading to the activation of STAT pathways. Furthermore, we also observed that STAT-1 and STAT-4 dependent maturation and activation of DCs was under the feedback mechanism of SOCS-1 and SOCS-3 proteins. nDCs acquired enhanced potential to activate chiefly Th1 and Th17 immunity. Taken together, these results suggest that nDCs can be exploited as an immunotherapeutic agent in bolstering host immunity and imparting protection against the pathogens. PMID:27265209

  4. A taxonomic review of viruses infecting crustaceans with an emphasis on wild hosts.

    PubMed

    Bateman, K S; Stentiford, G D

    2017-07-01

    Numerous infections by viral pathogens have been described from wild and cultured crustacean hosts, yet relatively few of these pathogens have been formally characterised and classified. To date viruses have generally been tentatively assigned to families based upon morphological and developmental characteristics and their location of infection within the host cell. Often nucleotide sequence information is unavailable. Some of these viral infections have caused well-documented devastating consequences on the global crustacean farming industry whilst their effects on wild populations remain largely unstudied. This paper provides an up to date review of all known viruses described infecting crustacean hosts. Full characterisation and harmonisation of these descriptions utilising specifications proposed by the International Committee on Taxonomy of Viruses (ICTV) is required to synonymise numerous examples of differential naming or abbreviation of naming, of the same virus in some cases. Development and application of techniques such as viral purification and high throughput sequencing of viral genomes will assist with these full descriptions and, provide appropriate diagnostic targets for surveillance of known and novel relatives. This review also highlights the importance of comparative study with viruses infecting insects and other arthropods to assist this process. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  5. Vegetable Contamination by the Fecal Bacteria of Poultry Manure: Case Study of Gardening Sites in Southern Benin

    PubMed Central

    Atidégla, Séraphin C.; Huat, Joël; Agbossou, Euloge K.; Saint-Macary, Hervé; Glèlè Kakai, Romain

    2016-01-01

    A study was conducted in southern Benin to assess the contamination of vegetables by fecal coliforms, Escherichia coli, and fecal streptococci as one consequence of the intensification of vegetable cropping through fertilization with poultry manure. For this purpose, on-farm trials were conducted in 2009 and 2010 at Yodo-Condji and Ayi-Guinnou with three replications and four fertilization treatments including poultry manure and three vegetable crops (leafy eggplant, tomato, and carrot). Sampling, laboratory analyses, and counts of fecal bacteria in the samples were performed in different cropping seasons. Whatever the fertilization treatment, the logs of mean fecal bacteria count per g of fresh vegetables were variable but higher than AFNOR criteria. The counts ranged from 8 to 10 fecal coliforms, from 5 to 8 fecal streptococci, and from 2 to 6 Escherichia coli, whereas AFNOR criteria are, respectively, 0, 1, and 0. The long traditional use of poultry manure and its use during the study helped obtain this high population of fecal pathogens. Results confirmed that the contamination of vegetables by fecal bacteria is mainly due to the use of poultry manure. The use of properly composted poultry manure with innovative cropping techniques should help reduce the number and incidence of pathogens. PMID:27069914

  6. Case study: design and implementation of training for scientists deploying to Ebola diagnostic field laboratories in Sierra Leone: October 2014 to February 2016

    PubMed Central

    Lewis, Suzanna M.; Lansley, Amber; Fraser, Sara; Shieber, Clare; Shah, Sonal; Semper, Amanda; Bailey, Daniel; Busuttil, Jason; Evans, Liz; Carroll, Miles W.; Silman, Nigel J.; Brooks, Tim; Shallcross, Jane A.

    2017-01-01

    As part of the UK response to the 2013–2016 Ebola virus disease (EVD) epidemic in West Africa, Public Health England (PHE) were tasked with establishing three field Ebola virus (EBOV) diagnostic laboratories in Sierra Leone by the UK Department for International Development (DFID). These provided diagnostic support to the Ebola Treatment Centre (ETC) facilities located in Kerry Town, Makeni and Port Loko. The Novel and Dangerous Pathogens (NADP) Training group at PHE, Porton Down, designed and implemented a pre-deployment Ebola diagnostic laboratory training programme for UK volunteer scientists being deployed to the PHE EVD laboratories. Here, we describe the training, workflow and capabilities of these field laboratories for use in response to disease epidemics and in epidemiological surveillance. We discuss the training outcomes, the laboratory outputs, lessons learned and the legacy value of the support provided. We hope this information will assist in the recruitment and training of staff for future responses and in the design and implementation of rapid deployment diagnostic field laboratories for future outbreaks of high consequence pathogens. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’. PMID:28396470

  7. Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency.

    PubMed

    Almalki, Abdulraheem; Alston, Charlotte L; Parker, Alasdair; Simonic, Ingrid; Mehta, Sarju G; He, Langping; Reza, Mojgan; Oliveira, Jorge M A; Lightowlers, Robert N; McFarland, Robert; Taylor, Robert W; Chrzanowska-Lightowlers, Zofia M A

    2014-01-01

    Mitochondrial aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in protein synthesis since they charge tRNAs with their cognate amino acids. Mutations in the genes encoding mitochondrial aaRSs have been associated with a wide spectrum of human mitochondrial diseases. Here we report the identification of pathogenic mutations (a partial genomic deletion and a highly conserved p. Asp325Tyr missense variant) in FARS2, the gene encoding mitochondrial phenylalanyl-tRNA synthetase, in a patient with early-onset epilepsy and isolated complex IV deficiency in muscle. The biochemical defect was expressed in myoblasts but not in fibroblasts and associated with decreased steady state levels of COXI and COXII protein and reduced steady state levels of the mt-tRNA(Phe) transcript. Functional analysis of the recombinant mutant p. Asp325Tyr FARS2 protein showed an inability to bind ATP and consequently undetectable aminoacylation activity using either bacterial tRNA or human mt-tRNA(Phe) as substrates. Lentiviral transduction of cells with wildtype FARS2 restored complex IV protein levels, confirming that the p.Asp325Tyr mutation is pathogenic, causing respiratory chain deficiency and neurological deficits on account of defective aminoacylation of mt-tRNA(Phe). © 2013. Published by Elsevier B.V. All rights reserved.

  8. Understanding the association of Escherichia coli with diverse macroalgae in the lagoon of Venice

    NASA Astrophysics Data System (ADS)

    Quero, Grazia M.; Fasolato, Luca; Vignaroli, Carla; Luna, Gian Marco

    2015-06-01

    Recent studies provided evidence that the macroalga Cladopohora in lakes hosts associated Escherichia coli, with consequences on the environmental and human health. We expanded these investigations to other macroalgae (Ulva spp., Sargassum muticum and Undaria pinnatifida) widespread in the lagoon of Venice (Italy). Attached E. coli were abundant, accounting up to 3,250 CFU gram-1 of alga. Macroalgal-associated isolates belonged to all E. coli phylogroups, including pathogenic ones, and to Escherichia cryptic clades. Attached E. coli showed potential to grow even at in situ temperature on macroalgal extracts as only source of carbon and nutrients, and ability to produce biofilm in vitro. The genotypic diversity of the attached isolates was high, with significant differences between algae and the overlying water. Our evidences suggest that attached populations consist of both resident and transient strains, likely resulting from the heterogeneous input of fecal bacteria from the city. We report that cosmopolitan and invasive macroalgae may serve as source of E. coli, including pathogenic genotypes, and that this habitat can potentially support their growth. Considering the global diffusion of the macroalgae here studied, this phenomenon is likely occurring in other coastal cities worldwide and deserves further investigations from either the sanitary and ecological perspectives.

  9. Understanding the association of Escherichia coli with diverse macroalgae in the lagoon of Venice

    PubMed Central

    Quero, Grazia M.; Fasolato, Luca; Vignaroli, Carla; Luna, Gian Marco

    2015-01-01

    Recent studies provided evidence that the macroalga Cladopohora in lakes hosts associated Escherichia coli, with consequences on the environmental and human health. We expanded these investigations to other macroalgae (Ulva spp., Sargassum muticum and Undaria pinnatifida) widespread in the lagoon of Venice (Italy). Attached E. coli were abundant, accounting up to 3,250 CFU gram−1 of alga. Macroalgal-associated isolates belonged to all E. coli phylogroups, including pathogenic ones, and to Escherichia cryptic clades. Attached E. coli showed potential to grow even at in situ temperature on macroalgal extracts as only source of carbon and nutrients, and ability to produce biofilm in vitro. The genotypic diversity of the attached isolates was high, with significant differences between algae and the overlying water. Our evidences suggest that attached populations consist of both resident and transient strains, likely resulting from the heterogeneous input of fecal bacteria from the city. We report that cosmopolitan and invasive macroalgae may serve as source of E. coli, including pathogenic genotypes, and that this habitat can potentially support their growth. Considering the global diffusion of the macroalgae here studied, this phenomenon is likely occurring in other coastal cities worldwide and deserves further investigations from either the sanitary and ecological perspectives. PMID:26043415

  10. The role of MAPK signal transduction pathways in the response to oxidative stress in the fungal pathogen Candida albicans: implications in virulence.

    PubMed

    de Dios, Carmen Herrero; Román, Elvira; Monge, Rebeca Alonso; Pla, Jesús

    2010-12-01

    In recent years, Mitogen-Activated Protein Kinase (MAPK) pathways have emerged as major regulators of cellular physiology. In the fungal pathogen Candida albicans, three different MAPK pathways have been characterized in the last years. The HOG pathway is mainly a stress response pathway that is activated in response to osmotic and oxidative stress and also participates regulating other pathways. The SVG pathway (or mediated by the Cek1 MAPK) is involved in cell wall formation under vegetative and filamentous growth, while the Mkc1-mediated pathway is involved in cell wall integrity. Oxidative stress is one of the types of stress that every fungal cell has to face during colonization of the host, where the cell encounters both hypoxia niches (i.e. gut) and high concentrations of reactive oxygen species (upon challenge with immune cells). Two pathways have been shown to be activated in response to oxidative stress: the HOG pathway and the MKC1-mediated pathway while the third, the Cek1 pathway is deactivated. The timing, kinetics, stimuli and functional responses generated upon oxidative stress differ among them; however, they have essential functional consequences that severely influence pathogenesis. MAPK pathways are, therefore, valuable targets to be explored in antifungal research.

  11. Understanding the association of Escherichia coli with diverse macroalgae in the lagoon of Venice.

    PubMed

    Quero, Grazia M; Fasolato, Luca; Vignaroli, Carla; Luna, Gian Marco

    2015-06-04

    Recent studies provided evidence that the macroalga Cladopohora in lakes hosts associated Escherichia coli, with consequences on the environmental and human health. We expanded these investigations to other macroalgae (Ulva spp., Sargassum muticum and Undaria pinnatifida) widespread in the lagoon of Venice (Italy). Attached E. coli were abundant, accounting up to 3,250 CFU gram(-1) of alga. Macroalgal-associated isolates belonged to all E. coli phylogroups, including pathogenic ones, and to Escherichia cryptic clades. Attached E. coli showed potential to grow even at in situ temperature on macroalgal extracts as only source of carbon and nutrients, and ability to produce biofilm in vitro. The genotypic diversity of the attached isolates was high, with significant differences between algae and the overlying water. Our evidences suggest that attached populations consist of both resident and transient strains, likely resulting from the heterogeneous input of fecal bacteria from the city. We report that cosmopolitan and invasive macroalgae may serve as source of E. coli, including pathogenic genotypes, and that this habitat can potentially support their growth. Considering the global diffusion of the macroalgae here studied, this phenomenon is likely occurring in other coastal cities worldwide and deserves further investigations from either the sanitary and ecological perspectives.

  12. Immunology of Yersinia pestis Infection.

    PubMed

    Bi, Yujing

    2016-01-01

    As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial "noninflammatory" phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called "proinflammatory" phase. In contrast, the host also utilizes its immune system to eliminate the invading bacteria. Neutrophil and macrophage are the first defense against Yersinia pestis invading through phagocytosis and killing. Other innate immune cells also play different roles, such as dendritic cells which help to generate more T helper cells. After several days post infection, the adaptive immune response begins to provide organism-specific protection and has a long-lasting immunological memory. Thus, with the cooperation and collaboration of innate and acquired immunity, the bacterium may be eliminated from the host. The research of Yersinia pestis and host immune systems provides an important topic to understand pathogen-host interaction and consequently develop effective countermeasures.

  13. Qualitative and quantitative detection of T7 bacteriophages using paper based sandwich ELISA.

    PubMed

    Khan, Mohidus Samad; Pande, Tripti; van de Ven, Theo G M

    2015-08-01

    Viruses cause many infectious diseases and consequently epidemic health threats. Paper based diagnostics and filters can offer attractive options for detecting and deactivating pathogens. However, due to their infectious characteristics, virus detection using paper diagnostics is more challenging compared to the detection of bacteria, enzymes, DNA or antigens. The major objective of this study was to prepare reliable, degradable and low cost paper diagnostics to detect viruses, without using sophisticated optical or microfluidic analytical instruments. T7 bacteriophage was used as a model virus. A paper based sandwich ELISA technique was developed to detect and quantify the T7 phages in solution. The paper based sandwich ELISA detected T7 phage concentrations as low as 100 pfu/mL to as high as 10(9) pfu/mL. The compatibility of paper based sandwich ELISA with the conventional titre count was tested using T7 phage solutions of unknown concentrations. The paper based sandwich ELISA technique is faster and economical compared to the traditional detection techniques. Therefore, with proper calibration and right reagents, and by following the biosafety regulations, the paper based technique can be said to be compatible and economical to the sophisticated laboratory diagnostic techniques applied to detect pathogenic viruses and other microorganisms. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. An Intracellular Peptidyl-Prolyl cis/trans Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease.

    PubMed

    Wiemels, Richard E; Cech, Stephanie M; Meyer, Nikki M; Burke, Caleb A; Weiss, Andy; Parks, Anastacia R; Shaw, Lindsey N; Carroll, Ronan K

    2017-01-01

    Staphylococcus aureus is an important human pathogen that relies on a large repertoire of secreted and cell wall-associated proteins for pathogenesis. Consequently, the ability of the organism to cause disease is absolutely dependent on its ability to synthesize and successfully secrete these proteins. In this study, we investigate the role of peptidyl-prolyl cis/trans isomerases (PPIases) on the activity of the S. aureus secreted virulence factor nuclease (Nuc). We identify a staphylococcal cyclophilin-type PPIase (PpiB) that is required for optimal activity of Nuc. Disruption of ppiB results in decreased nuclease activity in culture supernatants; however, the levels of Nuc protein are not altered, suggesting that the decrease in activity results from misfolding of Nuc in the absence of PpiB. We go on to demonstrate that PpiB exhibits PPIase activity in vitro, is localized to the bacterial cytosol, and directly interacts with Nuc in vitro to accelerate the rate of Nuc refolding. Finally, we demonstrate an additional role for PpiB in S. aureus hemolysis and demonstrate that the S. aureus parvulin-type PPIase PrsA also plays a role in the activity of secreted virulence factors. The deletion of prsA leads to a decrease in secreted protease and phospholipase activity, similar to that observed in other Gram-positive pathogens. Together, these results demonstrate, for the first time to our knowledge, that PPIases play an important role in the secretion of virulence factors in S. aureus IMPORTANCE: Staphylococcus aureus is a highly dangerous bacterial pathogen capable of causing a variety of infections throughout the human body. The ability of S. aureus to cause disease is largely due to an extensive repertoire of secreted and cell wall-associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the secretory (Sec) system in a denatured state. Consequently, once outside the cell, they must refold into their active form. This step often requires the assistance of bacterial folding proteins, such as PPIases. In this work, we investigate the role of PPIases in S. aureus and uncover a cyclophilin-type enzyme that assists in the folding/refolding of staphylococcal nuclease. Copyright © 2016 American Society for Microbiology.

  15. Amino Acid Substitutions in PB1 of Avian Influenza Viruses Influence Pathogenicity and Transmissibility in Chickens

    PubMed Central

    Suzuki, Yasushi; Uchida, Yuko; Tanikawa, Taichiro; Maeda, Naohiro; Takemae, Nobuhiro

    2014-01-01

    ABSTRACT Amino acid substitutions were introduced into avian influenza virus PB1 in order to characterize the interaction between polymerase activity and pathogenicity. Previously, we used recombinant viruses containing the hemagglutinin (HA) and neuraminidase (NA) genes from the highly pathogenic avian influenza virus (HPAIV) H5N1 strain and other internal genes from two low-pathogenicity avian influenza viruses isolated from chicken and wild-bird hosts (LP and WB, respectively) to demonstrate that the pathogenicity of highly pathogenic avian influenza viruses (HPAIVs) of subtype H5N1 in chickens is regulated by the PB1 gene (Y. Uchida et al., J. Virol. 86:2686–2695, 2012, doi:http://dx.doi.org/10.1128/JVI.06374-11). In the present study, we introduced a C38Y substitution into WB PB1 and demonstrated that this substitution increased both polymerase activity in DF-1 cells in vitro and the pathogenicity of the recombinant viruses in chickens. The V14A substitution in LP PB1 reduced polymerase activity but did not affect pathogenicity in chickens. Interestingly, the V14A substitution reduced viral shedding and transmissibility. These studies demonstrate that increased polymerase activity correlates directly with enhanced pathogenicity, while decreased polymerase activity does not always correlate with pathogenicity and requires further analysis. IMPORTANCE We identified 2 novel amino acid substitutions in the avian influenza virus PB1 gene that affect the characteristics of highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype, such as viral replication and polymerase activity in vitro and pathogenicity and transmissibly in chickens. An amino acid substitution at residue 38 in PB1 directly affected pathogenicity in chickens and was associated with changes in polymerase activity in vitro. A substitution at residue 14 reduced polymerase activity in vitro, while its effects on pathogenicity and transmissibility depended on the constellation of internal genes. PMID:25031333

  16. THE USE OF PLANTS TO PROTECT PLANTS AND FOOD AGAINST FUNGAL PATHOGENS: A REVIEW.

    PubMed

    Shuping, D S S; Eloff, J N

    2017-01-01

    Plant fungal pathogens play a crucial role in the profitability, quality and quantity of plant production. These phytopathogens are persistent in avoiding plant defences causing diseases and quality losses around the world that amount to billions of US dollars annually. To control the scourge of plant fungal diseases, farmers have used fungicides to manage the damage of plant pathogenic fungi. Drawbacks such as development of resistance and environmental toxicity associated with these chemicals have motivated researchers and cultivators to investigate other possibilities. Several databases were accessed to determine work done on protecting plants against plant fungal pathogens with plant extracts using search terms "plant fungal pathogen", "plant extracts" and "phytopathogens". Proposals are made on the best extractants and bioassay techniques to be used. In addition to chemical fungicides, biological agents have been used to deal with plant fungal diseases. There are many examples where plant extracts or plant derived compounds have been used as commercial deterrents of fungi on a large scale in agricultural and horticultural setups. One advantage of this approach is that plant extracts usually contain more than one antifungal compound. Consequently the development of resistance of pathogens may be lower if the different compounds affect a different metabolic process. Plants cultivated using plants extracts may also be marketed as organically produced. Many papers have been published on effective antimicrobial compounds present in plant extracts focusing on applications in human health. More research is required to develop suitable, sustainable, effective, cheaper botanical products that can be used to help overcome the scourge of plant fungal diseases. Scientists who have worked only on using plants to control human and animal fungal pathogens should consider the advantages of focusing on plant fungal pathogens. This approach could not only potentially increase food security for rural farmers, lead to commercial rewards, but it is also much easier to test the efficacy in greenhouse or field experiments. Even if extracts are toxic it may still be useful in the floriculture industry.

  17. The enemy within: phloem-limited pathogens

    USDA-ARS?s Scientific Manuscript database

    The growing impact of phloem-limited pathogens on high-value crops has led to a renewed interest in understanding how they cause disease. Although these pathogens cause substantial crop losses, many are poorly characterized. In this review, we present examples of phloem-limited pathogens that includ...

  18. Xylella genomics and bacterial pathogenicity to plants.

    PubMed

    Dow, J M; Daniels, M J

    2000-12-01

    Xylella fastidiosa, a pathogen of citrus, is the first plant pathogenic bacterium for which the complete genome sequence has been published. Inspection of the sequence reveals high relatedness to many genes of other pathogens, notably Xanthomonas campestris. Based on this, we suggest that Xylella possesses certain easily testable properties that contribute to pathogenicity. We also present some general considerations for deriving information on pathogenicity from bacterial genomics. Copyright 2000 John Wiley & Sons, Ltd.

  19. Machine learning for the meta-analyses of microbial pathogens' volatile signatures.

    PubMed

    Palma, Susana I C J; Traguedo, Ana P; Porteira, Ana R; Frias, Maria J; Gamboa, Hugo; Roque, Ana C A

    2018-02-20

    Non-invasive and fast diagnostic tools based on volatolomics hold great promise in the control of infectious diseases. However, the tools to identify microbial volatile organic compounds (VOCs) discriminating between human pathogens are still missing. Artificial intelligence is increasingly recognised as an essential tool in health sciences. Machine learning algorithms based in support vector machines and features selection tools were here applied to find sets of microbial VOCs with pathogen-discrimination power. Studies reporting VOCs emitted by human microbial pathogens published between 1977 and 2016 were used as source data. A set of 18 VOCs is sufficient to predict the identity of 11 microbial pathogens with high accuracy (77%), and precision (62-100%). There is one set of VOCs associated with each of the 11 pathogens which can predict the presence of that pathogen in a sample with high accuracy and precision (86-90%). The implemented pathogen classification methodology supports future database updates to include new pathogen-VOC data, which will enrich the classifiers. The sets of VOCs identified potentiate the improvement of the selectivity of non-invasive infection diagnostics using artificial olfaction devices.

  20. Pathogen prevalence, group bias, and collectivism in the standard cross-cultural sample.

    PubMed

    Cashdan, Elizabeth; Steele, Matthew

    2013-03-01

    It has been argued that people in areas with high pathogen loads will be more likely to avoid outsiders, to be biased in favor of in-groups, and to hold collectivist and conformist values. Cross-national studies have supported these predictions. In this paper we provide new pathogen codes for the 186 cultures of the Standard Cross-Cultural Sample and use them, together with existing pathogen and ethnographic data, to try to replicate these cross-national findings. In support of the theory, we found that cultures in high pathogen areas were more likely to socialize children toward collectivist values (obedience rather than self-reliance). There was some evidence that pathogens were associated with reduced adult dispersal. However, we found no evidence of an association between pathogens and our measures of group bias (in-group loyalty and xenophobia) or intergroup contact.

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