Surface properties of Entamoeba: increased rates of human erythrocyte phagocytosis in pathogenic strains

PubMed Central

1978-01-01

The assertion that ingestion of human erythrocytes is restricted to invasive strains of Entamoeba histolytica has not been evaluated previously by comparative studies. In this report we describe the in vitro ingestion of human erythrocytes by pathogenic and nonpathogenic Entamoeba. Microscopic evaluation of erythrophagocytosis by eight different Entamoeba grown in culture revealed that strains of E. histolytica isolated from cases of human dysentery show a much higher rate of erythrocyte ingestion than nonpathogenic strains. However, all strains are able to phagocytize erythrocytes. The extremely high rate of phagocytic activity shown by pathogenic E. histolytica could be one of the properties related to the pathogenicity of this parasitic protozoan. PMID:722237

Pathogenicity of Human ST23 Streptococcus agalactiae to Fish and Genomic Comparison of Pathogenic and Non-pathogenic Isolates.

PubMed

Wang, Rui; Li, Liping; Huang, Yin; Huang, Ting; Tang, Jiayou; Xie, Ting; Lei, Aiying; Luo, Fuguang; Li, Jian; Huang, Yan; Shi, Yunliang; Wang, Dongying; Chen, Ming; Mi, Qiang; Huang, Weiyi

2017-01-01

Streptococcus agalactiae , or Group B Streptococcus (GBS), is a major pathogen causing neonatal sepsis and meningitis, bovine mastitis, and fish meningoencephalitis. CC23, including its namesake ST23, is not only the predominant GBS strain derived from human and cattle, but also can infect a variety of homeothermic and poikilothermic species. However, it has never been characterized in fish. This study aimed to determine the pathogenicity of ST23 GBS to fish and explore the mechanisms causing the difference in the pathogenicity of ST23 GBS based on the genome analysis. Infection of tilapia with 10 human-derived ST23 GBS isolates caused tissue damage and the distribution of pathogens within tissues. The mortality rate of infection was ranged from 76 to 100%, and it was shown that the mortality rate caused by only three human isolates had statistically significant difference compared with fish-derived ST7 strain ( P < 0.05), whereas the mortality caused by other seven human isolates did not show significant difference compared with fish-derived ST7 strain. The genome comparison and prophage analysis showed that the major genome difference between virulent and non-virulent ST23 GBS was attributed to the different prophage sequences. The prophage in the P1 region contained about 43% GC and encoded 28-39 proteins, which can mediate the acquisition of YafQ/DinJ structure for GBS by phage recombination. YafQ/DinJ belongs to one of the bacterial toxin-antitoxin (TA) systems and allows cells to cope with stress. The ST23 GBS strains carrying this prophage were not pathogenic to tilapia, but the strains without the prophage or carrying the pophage that had gene mutation or deletion, especially the deletion of YafQ/DinJ structure, were highly pathogenic to tilapia. In conclusion, human ST23 GBS is highly pathogenic to fish, which may be related to the phage recombination.

Pathogenicity of Human ST23 Streptococcus agalactiae to Fish and Genomic Comparison of Pathogenic and Non-pathogenic Isolates

PubMed Central

Wang, Rui; Li, Liping; Huang, Yin; Huang, Ting; Tang, Jiayou; Xie, Ting; Lei, Aiying; Luo, Fuguang; Li, Jian; Huang, Yan; Shi, Yunliang; Wang, Dongying; Chen, Ming; Mi, Qiang; Huang, Weiyi

2017-01-01

Streptococcus agalactiae, or Group B Streptococcus (GBS), is a major pathogen causing neonatal sepsis and meningitis, bovine mastitis, and fish meningoencephalitis. CC23, including its namesake ST23, is not only the predominant GBS strain derived from human and cattle, but also can infect a variety of homeothermic and poikilothermic species. However, it has never been characterized in fish. This study aimed to determine the pathogenicity of ST23 GBS to fish and explore the mechanisms causing the difference in the pathogenicity of ST23 GBS based on the genome analysis. Infection of tilapia with 10 human-derived ST23 GBS isolates caused tissue damage and the distribution of pathogens within tissues. The mortality rate of infection was ranged from 76 to 100%, and it was shown that the mortality rate caused by only three human isolates had statistically significant difference compared with fish-derived ST7 strain (P < 0.05), whereas the mortality caused by other seven human isolates did not show significant difference compared with fish-derived ST7 strain. The genome comparison and prophage analysis showed that the major genome difference between virulent and non-virulent ST23 GBS was attributed to the different prophage sequences. The prophage in the P1 region contained about 43% GC and encoded 28–39 proteins, which can mediate the acquisition of YafQ/DinJ structure for GBS by phage recombination. YafQ/DinJ belongs to one of the bacterial toxin–antitoxin (TA) systems and allows cells to cope with stress. The ST23 GBS strains carrying this prophage were not pathogenic to tilapia, but the strains without the prophage or carrying the pophage that had gene mutation or deletion, especially the deletion of YafQ/DinJ structure, were highly pathogenic to tilapia. In conclusion, human ST23 GBS is highly pathogenic to fish, which may be related to the phage recombination. PMID:29056932

Ancient pathogen DNA in archaeological samples detected with a Microbial Detection Array.

PubMed

Devault, Alison M; McLoughlin, Kevin; Jaing, Crystal; Gardner, Shea; Porter, Teresita M; Enk, Jacob M; Thissen, James; Allen, Jonathan; Borucki, Monica; DeWitte, Sharon N; Dhody, Anna N; Poinar, Hendrik N

2014-03-06

Ancient human remains of paleopathological interest typically contain highly degraded DNA in which pathogenic taxa are often minority components, making sequence-based metagenomic characterization costly. Microarrays may hold a potential solution to these challenges, offering a rapid, affordable, and highly informative snapshot of microbial diversity in complex samples without the lengthy analysis and/or high cost associated with high-throughput sequencing. Their versatility is well established for modern clinical specimens, but they have yet to be applied to ancient remains. Here we report bacterial profiles of archaeological and historical human remains using the Lawrence Livermore Microbial Detection Array (LLMDA). The array successfully identified previously-verified bacterial human pathogens, including Vibrio cholerae (cholera) in a 19th century intestinal specimen and Yersinia pestis ("Black Death" plague) in a medieval tooth, which represented only minute fractions (0.03% and 0.08% alignable high-throughput shotgun sequencing reads) of their respective DNA content. This demonstrates that the LLMDA can identify primary and/or co-infecting bacterial pathogens in ancient samples, thereby serving as a rapid and inexpensive paleopathological screening tool to study health across both space and time.

Ticks and Tick-Borne Pathogens of the Caribbean: Current Understanding and Future Directions for More Comprehensive Surveillance.

PubMed

Gondard, Mathilde; Cabezas-Cruz, Alejandro; Charles, Roxanne A; Vayssier-Taussat, Muriel; Albina, Emmanuel; Moutailler, Sara

2017-01-01

Ticks are obligate hematophagous arthropods of significant importance to human and veterinary medicine. They transmit a vast array of pathogens, including bacteria, viruses, protozoa, and helminths. Most epidemiological data on ticks and tick-borne pathogens (TBPs) in the West Indies are limited to common livestock pathogens such as Ehrlichia ruminantium, Babesia spp. (i.e., B. bovis and B. bigemina ), and Anaplasma marginale , and less information is available on companion animal pathogens. Of note, human tick-borne diseases (TBDs) remain almost completely uncharacterized in the West Indies. Information on TBP presence in wildlife is also missing. Herein, we provide a comprehensive review of the ticks and TBPs affecting human and animal health in the Caribbean, and introduce the challenges associated with understanding TBD epidemiology and implementing successful TBD management in this region. In particular, we stress the need for innovative and versatile surveillance tools using high-throughput pathogen detection (e.g., high-throughput real-time microfluidic PCR). The use of such tools in large epidemiological surveys will likely improve TBD prevention and control programs in the Caribbean.

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.

Correlation between Tick Density and Pathogen Endemicity, New Hampshire

PubMed Central

Walk, Seth T.; Xu, Guang; Stull, Jason W.

2009-01-01

To assess the endemicity of tick-borne pathogens in New Hampshire, we surveyed adult tick vectors. Pathogens were more prevalent in areas of high tick density, suggesting a correlation between tick establishment and pathogen endemicity. Infection rates in ticks correlated with disease frequency in humans. PMID:19331738

Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China.

PubMed

Ke, Changwen; Mok, Chris Ka Pun; Zhu, Wenfei; Zhou, Haibo; He, Jianfeng; Guan, Wenda; Wu, Jie; Song, Wenjun; Wang, Dayan; Liu, Jiexiong; Lin, Qinhan; Chu, Daniel Ka Wing; Yang, Lei; Zhong, Nanshan; Yang, Zifeng; Shu, Yuelong; Peiris, Joseph Sriyal Malik

2017-07-01

The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient's adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread.

Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-α administered to the buccal mucosa.

PubMed

Strayer, David R; Carter, William A; Stouch, Bruce C; Stittelaar, Koert J; Thoolen, Robert J M M; Osterhaus, Albert D M E; Mitchell, William M

2014-10-01

Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection®). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses. Copyright © 2014. Published by Elsevier B.V.

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.

Westward Spread of Highly Pathogenic Avian Influenza A(H7N9) Virus among Humans, China.

PubMed

Yang, Qiqi; Shi, Wei; Zhang, Lei; Xu, Yi; Xu, Jing; Li, Shen; Zhang, Junjun; Hu, Kan; Ma, Chaofeng; Zhao, Xiang; Li, Xiyan; Liu, Feng; Tong, Xin; Zhang, Guogang; Yu, Pengbo; Pybus, Oliver G; Tian, Huaiyu

2018-06-01

We report infection of humans with highly pathogenic avian influenza A(H7N9) virus in Shaanxi, China, in May 2017. We obtained complete genomes for samples from 5 patients and from live poultry markets or farms in 4 cities. Results indicate that H7N9 is spreading westward from southern and eastern China.

Occurrence of human pathogenic Clostridium botulinum among healthy dairy animals: an emerging public health hazard.

PubMed

Abdel-Moein, Khaled A; Hamza, Dalia A

2016-01-01

The current study was conducted to investigate the occurrence of human pathogenic Clostridium botulinum in the feces of dairy animals. Fecal samples were collected from 203 apparently healthy dairy animals (50 cattle, 50 buffaloes, 52 sheep, 51 goats). Samples were cultured to recover C. botulinum while human pathogenic C. botulinum strains were identified after screening of all C. botulinum isolates for the presence of genes that encode toxins type A, B, E, F. The overall prevalence of C. botulinum was 18.7% whereas human pathogenic C. botulinum strains (only type A) were isolated from six animals at the rates of 2, 2, 5.8, and 2% for cattle, buffaloes, sheep, and goats, respectively. High fecal carriage rates of C. botulinum among apparently healthy dairy animals especially type A alarm both veterinary and public health communities for a potential role which may be played by dairy animals in the epidemiology of such pathogen.

Pathogens and host immunity in the ancient human oral cavity

PubMed Central

Warinner, Christina; Matias Rodrigues, João F.; Vyas, Rounak; Trachsel, Christian; Shved, Natallia; Grossmann, Jonas; Radini, Anita; Hancock, Y.; Tito, Raul Y.; Fiddyment, Sarah; Speller, Camilla; Hendy, Jessica; Charlton, Sophy; Luder, Hans Ulrich; Salazar-García, Domingo C.; Eppler, Elisabeth; Seiler, Roger; Hansen, Lars; Samaniego Castruita, José Alfredo; Barkow-Oesterreicher, Simon; Teoh, Kai Yik; Kelstrup, Christian; Olsen, Jesper V.; Nanni, Paolo; Kawai, Toshihisa; Willerslev, Eske; von Mering, Christian; Lewis, Cecil M.; Collins, Matthew J.; Gilbert, M. Thomas P.; Rühli, Frank; Cappellini, Enrico

2014-01-01

Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize: (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) the first evidence of ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, “red-complex” pathogens, and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity, and diet, thereby extending the direct investigation of common diseases into the human evolutionary past. PMID:24562188

Developing a Salivary Antibody Multiplex Immunoassay to Measure Human Exposure to Environmental Pathogens

EPA Science Inventory

The etiology and impacts of human exposure to environmental pathogens are of major concern worldwide and, thus, the ability to assess exposure and infections using cost effective, high-throughput approaches would be indispensable. The principal objective of this work is to devel...

Lectins in human pathogenic fungi.

PubMed

Gallegos, Belém; Martínez, Ruth; Pérez, Laura; Del Socorro Pina, María; Perez, Eduardo; Hernández, Pedro

2014-01-01

Lectins are carbohydrate-binding proteins widely distributed in nature. They constitute a highly diverse group of proteins consisting of many different protein families that are, in general, structurally unrelated. In the last few years, mushroom and other fungal lectins have attracted wide attention due to their antitumour, antiproliferative and immunomodulatory activities. The present mini-review provides concise information about recent developments in understanding lectins from human pathogenic fungi. A bibliographic search was performed in the Science Direct and PubMed databases, using the following keywords "lectin", "fungi", "human" and "pathogenic". Lectins present in fungi have been classified; however, the role played by lectins derived from human pathogenic fungi in infectious processes remains uncertain; thus, this is a scientific field requiring more research. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines

PubMed Central

Kim, Shin-Hee; Samal, Siba K.

2016-01-01

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens. PMID:27384578

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.

PubMed

Kim, Shin-Hee; Samal, Siba K

2016-07-04

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.

NATURAL ATYPICAL LISTERIA INNOCUA STRAINS WITH LISTERIA MONOCYTOGENES PATHOGENICITY ISLAND 1 GENES

EPA Science Inventory

The detection of the human foodborne pathogen, Listeria monocytogenes, in food, environmental samples and clinical specimens associated with cases of listeriosis, a rare but high mortality-rate disease, requires distinguishing the pathogen from other Listeria species. Speciation...

The highly pathogenic H7N3 avian influenza strain from July 2012 in Mexico acquired an extended cleavage site through recombination with host 28S rRNA.

PubMed

Maurer-Stroh, Sebastian; Lee, Raphael T C; Gunalan, Vithiagaran; Eisenhaber, Frank

2013-05-01

A characteristic difference between highly and non-highly pathogenic avian influenza strains is the presence of an extended, often multibasic, cleavage motif insertion in the hemagglutinin protein. Such motif is found in H7N3 strains from chicken farm outbreaks in 2012 in Mexico. Through phylogenetic, sequence and structural analysis, we try to shed light on the role, prevalence, likelihood of appearance and origin of the inserted cleavage motifs in these H7N3 avian influenza strains. The H7N3 avian influenza strain which caused outbreaks in chicken farms in June/July 2012 in Mexico has a new extended cleavage site which is the likely reason for its high pathogenicity in these birds. This cleavage site appears to have been naturally acquired and was not present in the closest low pathogenic precursors. Structural modeling shows that insertion of a productive cleavage site is quite flexible to accept insertions of different length and with sequences from different possible origins. Different from recent cleavage site insertions, the origin of the insert here is not from the viral genome but from host 28S ribosomal RNA (rRNA) instead. This is a novelty for a natural acquisition as a similar insertion has so far only been observed in a laboratory strain before. Given the abundance of viral and host RNA in infected cells, the acquisition of a pathogenicity-enhancing extended cleavage site through a similar route by other low-pathogenic avian strains in future does not seem unlikely. Important for surveillance of these H7N3 strains, the structural sites known to enhance mammalian airborne transmission are dominated by the characteristic avian residues and the risk of human to human transmission should currently be low but should be monitored for future changes accordingly. This highly pathogenic H7N3 avian influenza strain acquired a novel extended cleavage site which likely originated from recombination with 28S rRNA from the avian host. Notably, this new virus can infect humans but currently lacks critical host receptor adaptations that would facilitate human to human transmission.

Natural selection and infectious disease in human populations

PubMed Central

Karlsson, Elinor K.; Kwiatkowski, Dominic P.; Sabeti, Pardis C.

2015-01-01

The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology. PMID:24776769

SPECIES-SPECIFIC DETECTION OF THREE HUMAN-PATHOGENIC MICROSPORIDIAL SPECIES FROM THE GENUS ENCEPHALITOZOON VIA FLUOROGENIC 5' NUCLEASE PCR ASSAYS

EPA Science Inventory

This describes fluorogenic 5' nuclease PCR assays suitable for rapid, sensitive, quantitative, high-throughput detection of the human-pathogenic microsporidial species Encephalitozoon hellem, E. cunicli and E. intestinalis. The assays utilize species-specific primer sets and a g...

Characterization of multiple antibiotic resistance of culturable microorganisms and metagenomic analysis of total microbial diversity of marine fish sold in retail shops in Mumbai, India.

PubMed

Naik, Onkar A; Shashidhar, Ravindranath; Rath, Devashish; Bandekar, Jayant R; Rath, Archana

2018-03-01

Marine fish species were analyzed for culturable and total metagenomic microbial diversity, antibiotic resistance (AR) pattern, and horizontal gene transfer in culturable microorganisms. We observed a high AR microbial load of 3 to 4 log CFU g -1 . Many fish pathogens like Providencia, Staphylococcus, Klebsiella pneumoniae, Enterobacter, Vagococcus, and Aeromonas veronii were isolated. Photobacterium and Vibrio were two major fish and human pathogens which were identified in the fish metagenome. Other pathogens that were identified were Shewanella, Acinetobacter, Psychrobacter, and Flavobacterium. Most of these pathogens were resistant to multiple antibiotics such as erythromycin, kanamycin, neomycin, streptomycin, penicillin, cefotaxime, bacitracin, rifampicin, trimethoprim, ciprofloxacin, and doxycycline with a high multiple antibiotic resistance index of 0.54-0.77. The fish microflora showed high prevalence of AR genes like bla TEM , Class I integron, tetA, aph(3')-IIIa, ermB, aadA, and sul1. Nineteen of 26 AR isolates harbored Class I integrons showing high co-resistance to trimethoprim, kanamycin, doxycycline, and cefotaxime. Mobile R-plasmids from 6 of the 12 AR pathogens were transferred to recipient E. coli after conjugation. The transconjugants harbored the same R-plasmid carrying bla CTX-M , dfr1, tetA, bla TEM , and cat genes. This study confirms that fish is a potential carrier of AR pathogens which can enter the human gut via food chain. To the best of our knowledge, this is the first study in the Indian subcontinent reporting a direct evidence of spread of AR pathogens to humans from specific marine fish consumption.

Impacts of climate change on indirect human exposure to pathogens and chemicals from agriculture.

PubMed

Boxall, Alistair B A; Hardy, Anthony; Beulke, Sabine; Boucard, Tatiana; Burgin, Laura; Falloon, Peter D; Haygarth, Philip M; Hutchinson, Thomas; Kovats, R Sari; Leonardi, Giovanni; Levy, Leonard S; Nichols, Gordon; Parsons, Simon A; Potts, Laura; Stone, David; Topp, Edward; Turley, David B; Walsh, Kerry; Wellington, Elizabeth M H; Williams, Richard J

2009-04-01

Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. In this review, we used expert input and considered literature on climate change; health effects resulting from exposure to pathogens and chemicals arising from agriculture; inputs of chemicals and pathogens to agricultural systems; and human exposure pathways for pathogens and chemicals in agricultural systems. We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes.

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

Inadequately Treated Wastewater as a Source of Human Enteric Viruses in the Environment

PubMed Central

Okoh, Anthony I.; Sibanda, Thulani; Gusha, Siyabulela S.

2010-01-01

Human enteric viruses are causative agents in both developed and developing countries of many non-bacterial gastrointestinal tract infections, respiratory tract infections, conjunctivitis, hepatitis and other more serious infections with high morbidity and mortality in immunocompromised individuals such as meningitis, encephalitis and paralysis. Human enteric viruses infect and replicate in the gastrointestinal tract of their hosts and are released in large quantities in the stools of infected individuals. The discharge of inadequately treated sewage effluents is the most common source of enteric viral pathogens in aquatic environments. Due to the lack of correlation between the inactivation rates of bacterial indicators and viral pathogens, human adenoviruses have been proposed as a suitable index for the effective indication of viral contaminants in aquatic environments. This paper reviews the major genera of pathogenic human enteric viruses, their pathogenicity and epidemiology, as well as the role of wastewater effluents in their transmission. PMID:20644692

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

PubMed

Casadevall, Arturo

2012-01-01

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

Comparisons of Highly Virulent H5N1 Influenza A Viruses Isolated from Humans and Chickens from Hong Kong

PubMed Central

Suarez, David L.; Perdue, Michael L.; Cox, Nancy; Rowe, Thomas; Bender, Catherine; Huang, Jing; Swayne, David E.

1998-01-01

Genes of an influenza A (H5N1) virus from a human in Hong Kong isolated in May 1997 were sequenced and found to be all avian-like (K. Subbarao et al., Science 279:393–395, 1998). Gene sequences of this human isolate were compared to those of a highly pathogenic chicken H5N1 influenza virus isolated from Hong Kong in April 1997. Sequence comparisons of all eight RNA segments from the two viruses show greater than 99% sequence identity between them. However, neither isolate’s gene sequence was closely (>95% sequence identity) related to any other gene sequences found in the GenBank database. Phylogenetic analysis demonstrated that the nucleotide sequences of at least four of the eight RNA segments clustered with Eurasian origin avian influenza viruses. The hemagglutinin gene phylogenetic analysis also included the sequences from an additional three human and two chicken H5N1 virus isolates from Hong Kong, and the isolates separated into two closely related groups. However, no single amino acid change separated the chicken origin and human origin isolates, but they all contained multiple basic amino acids at the hemagglutinin cleavage site, which is associated with a highly pathogenic phenotype in poultry. In experimental intravenous inoculation studies with chickens, all seven viruses were highly pathogenic, killing most birds within 24 h. All infected chickens had virtually identical pathologic lesions, including moderate to severe diffuse edema and interstitial pneumonitis. Viral nucleoprotein was most frequently demonstrated in vascular endothelium, macrophages, heterophils, and cardiac myocytes. Asphyxiation from pulmonary edema and generalized cardiovascular collapse were the most likely pathogenic mechanisms responsible for illness and death. In summary, a small number of changes in hemagglutinin gene sequences defined two closely related subgroups, with both subgroups having human and chicken members, among the seven viruses examined from Hong Kong, and all seven viruses were highly pathogenic in chickens and caused similar lesions in experimental inoculations. PMID:9658115

Mining virulence genes using metagenomics.

PubMed

Belda-Ferre, Pedro; Cabrera-Rubio, Raúl; Moya, Andrés; Mira, Alex

2011-01-01

When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.

Viral replication rate regulates clinical outcome and CD8 T cell responses during highly pathogenic H5N1 influenza virus infection in mice.

PubMed

Hatta, Yasuko; Hershberger, Karen; Shinya, Kyoko; Proll, Sean C; Dubielzig, Richard R; Hatta, Masato; Katze, Michael G; Kawaoka, Yoshihiro; Suresh, M

2010-10-07

Since the first recorded infection of humans with H5N1 viruses of avian origin in 1997, sporadic human infections continue to occur with a staggering mortality rate of >60%. Although sustained human-to-human transmission has not occurred yet, there is a growing concern that these H5N1 viruses might acquire this trait and raise the specter of a pandemic. Despite progress in deciphering viral determinants of pathogenicity, we still lack crucial information on virus/immune system interactions pertaining to severe disease and high mortality associated with human H5N1 influenza virus infections. Using two human isolates of H5N1 viruses that differ in their pathogenicity in mice, we have defined mechanistic links among the rate of viral replication, mortality, CD8 T cell responses, and immunopathology. The extreme pathogenicity of H5N1 viruses was directly linked to the ability of the virus to replicate rapidly, and swiftly attain high steady-state titers in the lungs within 48 hours after infection. The remarkably high replication rate of the highly pathogenic H5N1 virus did not prevent the induction of IFN-β or activation of CD8 T cells, but the CD8 T cell response was ineffective in controlling viral replication in the lungs and CD8 T cell deficiency did not affect viral titers or mortality. Additionally, BIM deficiency ameliorated lung pathology and inhibited T cell apoptosis without affecting survival of mice. Therefore, rapidly replicating, highly lethal H5N1 viruses could simply outpace and overwhelm the adaptive immune responses, and kill the host by direct cytopathic effects. However, therapeutic suppression of early viral replication and the associated enhancement of CD8 T cell responses improved the survival of mice following a lethal H5N1 infection. These findings suggest that suppression of early H5N1 virus replication is key to the programming of an effective host response, which has implications in treatment of this infection in humans.

Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China

PubMed Central

Ke, Changwen; Mok, Chris Ka Pun; Zhu, Wenfei; Zhou, Haibo; He, Jianfeng; Guan, Wenda; Wu, Jie; Song, Wenjun; Wang, Dayan; Liu, Jiexiong; Lin, Qinhan; Chu, Daniel Ka Wing; Yang, Lei; Zhong, Nanshan; Peiris, Joseph Sriyal Malik

2017-01-01

The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient’s adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread. PMID:28580899

Prevalence of plant beneficial and human pathogenic bacteria isolated from salad vegetables in India.

PubMed

Nithya, Angamuthu; Babu, Subramanian

2017-03-14

The study aimed at enumerating, identifying and categorizing the endophytic cultivable bacterial community in selected salad vegetables (carrot, cucumber, tomato and onion). Vegetable samples were collected from markets of two vegetable hot spot growing areas, during two different crop harvest seasons. Crude and diluted vegetable extracts were plated and the population of endophytic bacteria was assessed based on morphologically distinguishable colonies. The bacterial isolates were identified by growth in selective media, biochemical tests and 16S rRNA gene sequencing. The endophytic population was found to be comparably higher in cucumber and tomato in both of the sampling locations, whereas lower in carrot and onion. Bacterial isolates belonged to 5 classes covering 46 distinct species belonging to 19 genera. Human opportunistic pathogens were predominant in carrot and onion, whereas plant beneficial bacteria dominated in cucumber and tomato. Out of the 104 isolates, 16.25% are human pathogens and 26.5% are human opportunistic pathogens. Existence of a high population of plant beneficial bacteria was found to have suppressed the population of plant and human pathogens. There is a greater potential to study the native endophytic plant beneficial bacteria for developing them as biocontrol agents against human pathogens that are harboured by plants.

Pathogenesis, Transmissibility, and Tropism of a Highly Pathogenic Avian Influenza A(H7N7) Virus Associated With Human Conjunctivitis in Italy, 2013.

PubMed

Belser, Jessica A; Creager, Hannah M; Zeng, Hui; Maines, Taronna R; Tumpey, Terrence M

2017-09-15

H7 subtype influenza viruses represent a persistent public health threat because of their continued detection in poultry and ability to cause human infection. An outbreak of highly pathogenic avian influenza H7N7 virus in Italy during 2013 resulted in 3 cases of human conjunctivitis. We determined the pathogenicity and transmissibility of influenza A/Italy/3/2013 virus in mouse and ferret models and examined the replication kinetics of this virus in several human epithelial cell types. The moderate virulence observed in mammalian models and the capacity for transmission in a direct contact model underscore the need for continued study of H7 subtype viruses. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Novel Reassortant H5N6 Influenza A Virus from the Lao People’s Democratic Republic Is Highly Pathogenic in Chickens

PubMed Central

Layton, Daniel S.; Phommachanh, Phouvong; Harper, Jennifer; Payne, Jean; Evans, Ryan M.; Valdeter, Stacey; Walker, Som; Harvey, Gemma; Shan, Songhua; Bruce, Matthew P.; Rootes, Christina L.; Gough, Tamara J.; Rohringer, Andreas; Peck, Grantley R.; Fardy, Sarah J.; Karpala, Adam J.; Johnson, Dayna; Wang, Jianning; Douangngeun, Bounlom; Morrissy, Christopher; Wong, Frank Y. K.; Bean, Andrew G. D.; Bingham, John; Williams, David T.

2016-01-01

Avian influenza viruses of H5 subtype can cause highly pathogenic disease in poultry. In March 2014, a new reassortant H5N6 subtype highly pathogenic avian influenza virus emerged in Lao People’s Democratic Republic. We have assessed the pathogenicity, pathobiology and immunological responses associated with this virus in chickens. Infection caused moderate to advanced disease in 6 of 6 chickens within 48 h of mucosal inoculation. High virus titers were observed in blood and tissues (kidney, spleen, liver, duodenum, heart, brain and lung) taken at euthanasia. Viral antigen was detected in endothelium, neurons, myocardium, lymphoid tissues and other cell types. Pro-inflammatory cytokines were elevated compared to non-infected birds. Our study confirmed that this new H5N6 reassortant is highly pathogenic, causing disease in chickens similar to that of Asian H5N1 viruses, and demonstrated the ability of such clade 2.3.4-origin H5 viruses to reassort with non-N1 subtype viruses while maintaining a fit and infectious phenotype. Recent detection of influenza H5N6 poultry infections in Lao PDR, China and Viet Nam, as well as six fatal human infections in China, demonstrate that these emergent highly pathogenic H5N6 viruses may be widely established in several countries and represent an emerging threat to poultry and human populations. PMID:27631618

Novel Reassortant H5N6 Influenza A Virus from the Lao People's Democratic Republic Is Highly Pathogenic in Chickens.

PubMed

Butler, Jeffrey; Stewart, Cameron R; Layton, Daniel S; Phommachanh, Phouvong; Harper, Jennifer; Payne, Jean; Evans, Ryan M; Valdeter, Stacey; Walker, Som; Harvey, Gemma; Shan, Songhua; Bruce, Matthew P; Rootes, Christina L; Gough, Tamara J; Rohringer, Andreas; Peck, Grantley R; Fardy, Sarah J; Karpala, Adam J; Johnson, Dayna; Wang, Jianning; Douangngeun, Bounlom; Morrissy, Christopher; Wong, Frank Y K; Bean, Andrew G D; Bingham, John; Williams, David T

2016-01-01

Avian influenza viruses of H5 subtype can cause highly pathogenic disease in poultry. In March 2014, a new reassortant H5N6 subtype highly pathogenic avian influenza virus emerged in Lao People's Democratic Republic. We have assessed the pathogenicity, pathobiology and immunological responses associated with this virus in chickens. Infection caused moderate to advanced disease in 6 of 6 chickens within 48 h of mucosal inoculation. High virus titers were observed in blood and tissues (kidney, spleen, liver, duodenum, heart, brain and lung) taken at euthanasia. Viral antigen was detected in endothelium, neurons, myocardium, lymphoid tissues and other cell types. Pro-inflammatory cytokines were elevated compared to non-infected birds. Our study confirmed that this new H5N6 reassortant is highly pathogenic, causing disease in chickens similar to that of Asian H5N1 viruses, and demonstrated the ability of such clade 2.3.4-origin H5 viruses to reassort with non-N1 subtype viruses while maintaining a fit and infectious phenotype. Recent detection of influenza H5N6 poultry infections in Lao PDR, China and Viet Nam, as well as six fatal human infections in China, demonstrate that these emergent highly pathogenic H5N6 viruses may be widely established in several countries and represent an emerging threat to poultry and human populations.

Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)

USDA-ARS?s Scientific Manuscript database

There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a surrogate for humans in influenza pathogenicity a...

Impacts of Climate Change on Indirect Human Exposure to Pathogens and Chemicals from Agriculture

PubMed Central

Boxall, Alistair B.A.; Hardy, Anthony; Beulke, Sabine; Boucard, Tatiana; Burgin, Laura; Falloon, Peter D.; Haygarth, Philip M.; Hutchinson, Thomas; Kovats, R. Sari; Leonardi, Giovanni; Levy, Leonard S.; Nichols, Gordon; Parsons, Simon A.; Potts, Laura; Stone, David; Topp, Edward; Turley, David B.; Walsh, Kerry; Wellington, Elizabeth M.H.; Williams, Richard J.

2009-01-01

Objective Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources In this review, we used expert input and considered literature on climate change; health effects resulting from exposure to pathogens and chemicals arising from agriculture; inputs of chemicals and pathogens to agricultural systems; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes. PMID:19440487

Universal Detection and Identification of Avian Influenza Virus by Use of Resequencing Microarrays▿ †

PubMed Central

Lin, Baochuan; Malanoski, Anthony P.; Wang, Zheng; Blaney, Kate M.; Long, Nina C.; Meador, Carolyn E.; Metzgar, David; Myers, Christopher A.; Yingst, Samuel L.; Monteville, Marshall R.; Saad, Magdi D.; Schnur, Joel M.; Tibbetts, Clark; Stenger, David A.

2009-01-01

Zoonotic microbes have historically been, and continue to emerge as, threats to human health. The recent outbreaks of highly pathogenic avian influenza virus in bird populations and the appearance of some human infections have increased the concern of a possible new influenza pandemic, which highlights the need for broad-spectrum detection methods for rapidly identifying the spread or outbreak of all variants of avian influenza virus. In this study, we demonstrate that high-density resequencing pathogen microarrays (RPM) can be such a tool. The results from 37 influenza virus isolates show that the RPM platform is an effective means for detecting and subtyping influenza virus, while simultaneously providing sequence information for strain resolution, pathogenicity, and drug resistance without additional analysis. This study establishes that the RPM platform is a broad-spectrum pathogen detection and surveillance tool for monitoring the circulation of prevalent influenza viruses in the poultry industry and in wild birds or incidental exposures and infections in humans. PMID:19279171

European bats as carriers of viruses with zoonotic potential.

PubMed

Kohl, Claudia; Kurth, Andreas

2014-08-13

Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats.

Development, upscaling and validation of the purification process for human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII produced in a human cell-line.

PubMed

Winge, Stefan; Yderland, Louise; Kannicht, Christoph; Hermans, Pim; Adema, Simon; Schmidt, Torben; Gilljam, Gustav; Linhult, Martin; Tiemeyer, Maya; Belyanskaya, Larisa; Walter, Olaf

2015-11-01

Human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII (rFVIII), is the first rFVIII produced in a human cell-line approved by the European Medicines Agency. To describe the development, upscaling and process validation for industrial-scale human-cl rhFVIII purification. The purification process involves one centrifugation, two filtration, five chromatography columns and two dedicated pathogen clearance steps (solvent/detergent treatment and 20 nm nanofiltration). The key purification step uses an affinity resin (VIIISelect) with high specificity for FVIII, removing essentially all host-cell proteins with >80% product recovery. The production-scale multi-step purification process efficiently removes process- and product-related impurities and results in a high-purity rhFVIII product, with an overall yield of ∼50%. Specific activity of the final product was >9000 IU/mg, and the ratio between active FVIII and total FVIII protein present was >0.9. The entire production process is free of animal-derived products. Leaching of potential harmful compounds from chromatography resins and all pathogens tested were below the limit of quantification in the final product. Human-cl rhFVIII can be produced at 500 L bioreactor scale, maintaining high purity and recoveries. The innovative purification process ensures a high-purity and high-quality human-cl rhFVIII product with a high pathogen safety margin. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Genomic Evidence for the Evolution of Streptococcus equi: Host Restriction, Increased Virulence, and Genetic Exchange with Human Pathogens

PubMed Central

Paillot, Romain; Steward, Karen F.; Webb, Katy; Ainslie, Fern; Jourdan, Thibaud; Bason, Nathalie C.; Holroyd, Nancy E.; Mungall, Karen; Quail, Michael A.; Sanders, Mandy; Simmonds, Mark; Willey, David; Brooks, Karen; Aanensen, David M.; Spratt, Brian G.; Jolley, Keith A.; Maiden, Martin C. J.; Kehoe, Michael; Chanter, Neil; Bentley, Stephen D.; Robinson, Carl; Maskell, Duncan J.; Parkhill, Julian; Waller, Andrew S.

2009-01-01

The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A2 toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci. PMID:19325880

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

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.

Highly pathogenic avian influenza A(H5N8) outbreaks: protection and management of exposed people in Europe, 2014/15 and 2016

PubMed Central

Adlhoch, Cornelia; Brown, Ian H.; Angelova, Svetla G.; Bálint, Ádám; Bouwstra, Ruth; Buda, Silke; Castrucci, Maria R.; Dabrera, Gavin; Dán, Ádám; Grund, Christian; Harder, Timm; van der Hoek, Wim; Krisztalovics, Katalin; Parry-Ford, Frances; Popescu, Rodica; Wallensten, Anders; Zdravkova, Anna; Zohari, Siamak; Tsolova, Svetla; Penttinen, Pasi

2016-01-01

Introduction of highly pathogenic avian influenza (HPAI) virus A(H5N8) into Europe prompted animal and human health experts to implement protective measures to prevent transmission to humans. We describe the situation in 2016 and list public health measures and recommendations in place. We summarise critical interfaces identified during the A(H5N1) and A(H5N8) outbreaks in 2014/15. Rapid exchange of information between the animal and human health sectors is critical for a timely, effective and efficient response. PMID:27983512

Preliminary Epidemiology of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017.

PubMed

Zhou, Lei; Tan, Yi; Kang, Min; Liu, Fuqiang; Ren, Ruiqi; Wang, Yali; Chen, Tao; Yang, Yiping; Li, Chao; Wu, Jie; Zhang, Hengjiao; Li, Dan; Greene, Carolyn M; Zhou, Suizan; Iuliano, A Danielle; Havers, Fiona; Ni, Daxin; Wang, Dayan; Feng, Zijian; Uyeki, Timothy M; Li, Qun

2017-08-01

We compared the characteristics of cases of highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) A(H7N9) virus infections in China. HPAI A(H7N9) case-patients were more likely to have had exposure to sick and dead poultry in rural areas and were hospitalized earlier than were LPAI A(H7N9) case-patients.

Rapid acquisition of polymorphic virulence markers during adaptation of highly pathogenic avian influenza H5N8 virus in the mouse.

PubMed

Choi, Won-Suk; Baek, Yun Hee; Kwon, Jin Jung; Jeong, Ju Hwan; Park, Su-Jin; Kim, Young-Il; Yoon, Sun-Woo; Hwang, Jungwon; Kim, Myung Hee; Kim, Chul-Joong; Webby, Richard J; Choi, Young Ki; Song, Min-Suk

2017-01-17

Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD 50 , up to 0.5 log10 PFU/mL) within 5 passages. Sequence analysis revealed the acquisition of several virulence markers, including the novel marker P708S in PB1 gene. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; thus, rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential.

Rapid acquisition of polymorphic virulence markers during adaptation of highly pathogenic avian influenza H5N8 virus in the mouse

PubMed Central

Choi, Won-Suk; Baek, Yun Hee; Kwon, Jin Jung; Jeong, Ju Hwan; Park, Su-Jin; Kim, Young-il; Yoon, Sun-Woo; Hwang, Jungwon; Kim, Myung Hee; Kim, Chul-Joong; Webby, Richard J.; Choi, Young Ki; Song, Min-Suk

2017-01-01

Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD50, up to 0.5 log10 PFU/mL) within 5 passages. Sequence analysis revealed the acquisition of several virulence markers, including the novel marker P708S in PB1 gene. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; thus, rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential. PMID:28094780

Multidrug-resistant pathogenic Escherichia coli isolated from wild birds in a veterinary hospital.

PubMed

Borges, C A; Beraldo, L G; Maluta, R P; Cardozo, M V; Barboza, K B; Guastalli, E A L; Kariyawasam, S; DebRoy, C; Ávila, F A

2017-02-01

Wild birds are carriers of Escherichia coli. However, little is known about their role as reservoirs for extra-intestinal pathogenic E. coli (ExPEC). In this work we investigated E. coli strains carrying virulence genes related to human and animal ExPEC isolated from free-living wild birds treated in a veterinary hospital. Multidrug resistance was found in 47.4% of the strains, but none of them were extended-spectrum beta-lactamase producers. Not only the virulence genes, but also the serogroups (e.g. O1 and O2) detected in the isolates of E. coli have already been implicated in human and bird diseases. The sequence types detected were also found in wild, companion and food animals, environmental and human clinical isolates in different countries. Furthermore, from the 19 isolates, 17 (89.5%) showed a degree of pathogenicity on an in vivo infection model. The isolates showed high heterogeneity by pulsed-field gel electrophoresis indicating that E. coli from these birds are clonally diverse. Overall, the results showed that wild birds can be reservoirs and/or vectors of highly pathogenic and multidrug-resistant E. coli that have the potential to cause disease in humans and poultry.

Growth rate, transmission mode and virulence in human pathogens.

PubMed

Leggett, Helen C; Cornwallis, Charlie K; Buckling, Angus; West, Stuart A

2017-05-05

The harm that pathogens cause to hosts during infection, termed virulence, varies across species from negligible to a high likelihood of rapid death. Classic theory for the evolution of virulence is based on a trade-off between pathogen growth, transmission and host survival, which predicts that higher within-host growth causes increased transmission and higher virulence. However, using data from 61 human pathogens, we found the opposite correlation to the expected positive correlation between pathogen growth rate and virulence. We found that (i) slower growing pathogens are significantly more virulent than faster growing pathogens, (ii) inhaled pathogens and pathogens that infect via skin wounds are significantly more virulent than pathogens that are ingested, but (iii) there is no correlation between symptoms of infection that aid transmission (such as diarrhoea and coughing) and virulence. Overall, our results emphasize how virulence can be influenced by mechanistic life-history details, especially transmission mode, that determine how parasites infect and exploit their hosts.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'. © 2017 The Authors.

Human infection with highly pathogenic H5N1 influenza virus.

PubMed

Gambotto, Andrea; Barratt-Boyes, Simon M; de Jong, Menno D; Neumann, Gabriele; Kawaoka, Yoshihiro

2008-04-26

Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this Seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarise the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.

Pathogenesis, Transmissibility, and Ocular Tropism of a Highly Pathogenic Avian Influenza A (H7N3) Virus Associated with Human Conjunctivitis

PubMed Central

Belser, Jessica A.; Davis, C. Todd; Balish, Amanda; Edwards, Lindsay E.; Zeng, Hui; Maines, Taronna R.; Gustin, Kortney M.; Martínez, Irma López; Fasce, Rodrigo; Cox, Nancy J.; Katz, Jacqueline M.

2013-01-01

H7 subtype influenza A viruses, responsible for numerous outbreaks in land-based poultry in Europe and the Americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. The emergence of a highly pathogenic avian influenza H7N3 virus in poultry throughout the state of Jalisco, Mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus (A/Mexico/InDRE7218/2012 [MX/7218]) and related avian H7 subtype viruses in mouse and ferret models. Several high- and low-pathogenicity H7N3 and H7N9 viruses replicated efficiently in the respiratory tract of mice without prior adaptation following intranasal inoculation, but only MX/7218 virus caused lethal disease in this species. H7N3 and H7N9 viruses were also detected in the mouse eye following ocular inoculation. Virus from both H7N3 and H7N9 subtypes replicated efficiently in the upper and lower respiratory tracts of ferrets; however, only MX/7218 virus infection caused clinical signs and symptoms and was capable of transmission to naive ferrets in a direct-contact model. Similar to other highly pathogenic H7 viruses, MX/7218 replicated to high titers in human bronchial epithelial cells, yet it downregulated numerous genes related to NF-κB-mediated signaling transduction. These findings indicate that the recently isolated North American lineage H7 subtype virus associated with human conjunctivitis is capable of causing severe disease in mice and spreading to naive-contact ferrets, while concurrently retaining the ability to replicate within ocular tissue and allowing the eye to serve as a portal of entry. PMID:23487452

Propagation of Human Enteropathogens in Constructed Horizontal Wetlands Used for Tertiary Wastewater Treatment ▿

PubMed Central

Graczyk, Thaddeus K.; Lucy, Frances E.; Tamang, Leena; Mashinski, Yessika; Broaders, Michael A.; Connolly, Michelle; Cheng, Hui-Wen A.

2009-01-01

Constructed subsurface flow (SSF) and free-surface flow (FSF) wetlands are being increasingly implemented worldwide into wastewater treatments in response to the growing need for microbiologically safe reclaimed waters, which is driven by an exponential increase in the human population and limited water resources. Wastewater samples from four SSF and FSF wetlands in northwestern Ireland were tested qualitatively and quantitatively for Cryptosporidium spp., Giardia duodenalis, and human-pathogenic microsporidia, with assessment of their viability. Overall, seven species of human enteropathogens were detected in wetland influents, vegetated areas, and effluents: Cryptosporidium parvum, C. hominis, C. meleagridis, C. muris, G. duodenalis, Encephalitozoon hellem, and Enterocytozoon bieneusi. SSF wetland had the highest pathogen removal rate (i.e., Cryptosporidium, 97.4%; G. duodenalis, 95.4%); however, most of these values for FSF were in the negative area (mean, −84.0%), meaning that more pathogens were discharged by FSF wetlands than were delivered to wetlands with incoming wastewater. We demonstrate here that (i) the composition of human enteropathogens in wastewater entering and leaving SSF and FSF wetlands is highly complex and dynamic, (ii) the removal and inactivation of human-pathogenic microorganisms were significantly higher at the SSF wetland, (iii) FSF wetlands may not always provide sufficient remediation for human enteropathogens, (iv) wildlife can contribute a substantial load of human zoonotic pathogens to wetlands, (v) most of the pathogens discharged by wetlands were viable, (vi) large volumes of wetland effluents can contribute to contamination of surface waters used for recreation and drinking water abstraction and therefore represent a serious public health threat, and (vii) even with the best pathogen removal rates achieved by SSF wetland, the reduction of pathogens was not enough for a safety reuse of the reclaimed water. To our knowledge, this is the first report of C. meleagridis from Ireland. PMID:19411413

Understanding Virulence in the Brucellae and Francisellae: Towards Efficacious Treatments for Two Potential Biothreat Agents

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

Rasley, A; Parsons, D A; El-Etr, S

2009-12-30

Francisella tularensis, Yersinia pestis and Brucellae species are highly infectious pathogens classified as select agents by the Centers for Disease Control and Prevention (CDC) with the potential for use in bioterrorism attacks. These organisms are known to be facultative intracellular pathogens that preferentially infect human monocytes. As such, understanding how the host responds to infection with these organisms is paramount in detecting and combating human disease. We have compared the ability of fully virulent strains of each pathogen and their non-pathogenic near neighbors to enter and survive inside the human monocytic cell line THP-1 and have quantified the cellular responsemore » to infection with the goal of identifying both unique and common host response patterns. We expanded the scope of these studies to include experiments with pathogenic and non-pathogenic strains of Y. pestis, the causative agent of plague. Nonpathogenic strains of each organism were impaired in their ability to survive intracellularly compared with their pathogenic counterparts. Furthermore, infection of THP-1 cells with pathogenic strains of Y. pestis and F. tularensis resulted in marked increases in the secretion of the inflammatory chemokines IL-8, RANTES, and MIP-1{beta}. In contrast, B. melitensis infection failed to elicit any significant increases in a panel of cytokines tested. These differences may underscore distinct strategies in pathogenic mechanisms employed by these pathogens.« less

Disparate Proteome Responses of Pathogenic and Non-pathogenic Aspergilli to Human Serum Measured by Activity-Based Protein Profiling (ABPP)

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

Wiedner, Susan D.; Ansong, Charles; Webb-Robertson, Bobbie-Jo M.

2013-07-01

Aspergillus fumigatus is the primary pathogen causing the devastating pulmonary disease Invasive Aspergillosis in immunocompromised individuals. Genomic analysis shows high synteny between A. fumigatus and closely related rarely pathogenic Neosartorya fischeri and Aspergillus clavatus genomes. To investigate the presence of unique or highly inducible protein reactivity in the pathogen, we applied activity-based protein profiling to compare protein reactivity of all three fungi over time in minimal media growth and in response to human serum. We found 350 probe-reactive proteins exclusive to A. fumigatus, including known virulence associated proteins, and 13 proteins associated with stress response exclusive to A. fumigatus culturemore » in serum. Though the fungi are highly orthologous, A. fumigatus has significantly more activity across varied biological process. Only 50% of expected orthologs of measured A. fumigatus reactive proteins were observed in N. fischeri and A. clavatus. Human serum induced processes uniquely or significantly represented in A. fumigatus include actin organization and assembly, transport, and fatty acid, cell membrane, and cell wall synthesis. Additionally, signaling proteins regulating vegetative growth, conidiation, and cell wall integrity, required for appropriate cellular response to external stimuli, had higher reactivity over time in A. fumigatus and N. fisheri, but not in A. clavatus. Together, we show that measured proteins and physiological processes identified solely or significantly over-represented in A. fumigatus reveal a unique adaptive response to human protein not found in closely related, but rarely aspergilli. These unique protein reactivity responses may reveal how A. fumigatus initiates pulmonary invasion leading to Invasive Aspergillosis.« less

Testing of human specimens for the presence of highly pathogenic zoonotic avian influenza virus A(H5N1) in Poland in 2006-2008 - justified or unnecessary steps?

PubMed

Romanowska, Magdalena; Nowak, Iwona; Brydak, Lidia; Wojtyla, Andrzej

2009-01-01

Since 1997, human infections with highly pathogenic zoonotic avian influenza viruses have shown that the risk of influenza pandemic is significant. In Europe, infections caused by the highly pathogenic avian influenza A(H7N7) virus were confirmed in the human population in 2003 in the Netherlands. Moreover, outbreaks of A(H5N1) infections were observed in wild and farm birds in different European regions, including Poland in 2006-2008. This study presents 16 patients in Poland from whom clinical specimens were collected and tested for A(H5N1) highly pathogenic avian influenza. This article shows the results of laboratory tests and discusses the legitimacy of the collection and testing of the specimens. All patients were negative for A(H5N1) infection. Nevertheless, only two patients met clinical and epidemiological criteria from the avian influenza case definition. The conclusion is that there is still a strong necessity for increasing the awareness of medical and laboratory staff, as well as the awareness of some occupational groups about human infections with avian influenza viruses, including the importance of seasonal influenza vaccination. It should also be emphasized that in the case of patients suspected of being infected with avian influenza, the information about clinical symptoms is insufficient and must be accompanied by a wide epidemiological investigation.

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

PubMed Central

Criss, Alison K.; Seifert, H. Steven

2012-01-01

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

Poultry as reservoir for extraintestinal pathogenic Escherichia coli O45:K1:H7-B2-ST95 in humans.

PubMed

Mora, Azucena; Viso, Susana; López, Cecilia; Alonso, María Pilar; García-Garrote, Fernando; Dabhi, Ghizlane; Mamani, Rosalía; Herrera, Alexandra; Marzoa, Juan; Blanco, Miguel; Blanco, Jesús E; Moulin-Schouleur, Maryvonne; Schouler, Catherine; Blanco, Jorge

2013-12-27

Escherichia coli strains O45:K1:H7 are implicated in severe human infections such as meningitis. Since an increasing prevalence of serogroup O45 among avian pathogenic (APEC) and human extraintestinal pathogenic (ExPEC) E. coli strains isolated in Spain have been noticed, the aims of the present study were to investigate similarities between poultry and human O45 isolates, and to investigate the evolutionary relationship of ST95 types. The genetic relatedness and virulence gene profiles of 55 O45 APEC obtained from an avian colibacillosis collection (1991-2011) and 19 human O45 ExPEC from a human septicemic/uropathogenic (UPEC) E. coli collection (1989-2010) were determined by multilocus sequence typing (MLST), pulsed-field-gel-electrophoresis (PFGE), ECOR phylogrouping, and PCR-based genotyping. Two main clonal groups were established. The most prevalent and highly pathogenic O45:K1:H7-B2-ST95 shows a successful persistence since the 90s to the present, with parallel evolution both in human and poultry, on the basis of their PFGE and virulence gene profile similarities (9 human strains and 15 avian strains showed ≥85% PFGE identity). Comparison of this group with other ST95 closely related members (O1:K1:H7 and O18:K1:H7 isolates from our collections) shows pathogenic specialization through conserved virulence genotypes. The other prevalent O45 clonal group characterized in this study, the O45:HNM/H19-D-ST371/ST2676 was only detected in APEC strains suggesting host specificity. In conclusion, poultry could be acting as a reservoir of O45:K1:H7-B2-ST95 and other pathogenic ST95 serotypes in humans. Further studies would be necessary to clarify if pathogenic mechanisms used by ST95 strains are the same in avian and human hosts. Copyright © 2013 Elsevier B.V. All rights reserved.

Microbiological Safety of Animal Wastes Processed by Physical Heat Treatment: An Alternative To Eliminate Human Pathogens in Biological Soil Amendments as Recommended by the Food Safety Modernization Act.

PubMed

Chen, Zhao; Jiang, Xiuping

2017-03-01

Animal wastes have high nutritional value as biological soil amendments of animal origin for plant cultivation in sustainable agriculture; however, they can be sources of some human pathogens. Although composting is an effective way to reduce pathogen levels in animal wastes, pathogens may still survive under certain conditions and persist in the composted products, which potentially could lead to fresh produce contamination. According to the U.S. Food and Drug Administration Food Safety Modernization Act, alternative treatments are recommended for reducing or eliminating human pathogens in raw animal manure. Physical heat treatments can be considered an effective method to inactivate pathogens in animal wastes. However, microbial inactivation in animal wastes can be affected by many factors, such as composition of animal wastes, type and physiological stage of the tested microorganism, and heat source. Following some current processing guidelines for physical heat treatments may not be adequate for completely eliminating pathogens from animal wastes. Therefore, this article primarily reviews the microbiological safety and economic value of physically heat-treated animal wastes as biological soil amendments.

Highly pathogenic avian influenza A(H5N8) outbreaks: protection and management of exposed people in Europe, 2014/15 and 2016.

PubMed

Adlhoch, Cornelia; Brown, Ian H; Angelova, Svetla G; Bálint, Ádám; Bouwstra, Ruth; Buda, Silke; Castrucci, Maria R; Dabrera, Gavin; Dán, Ádám; Grund, Christian; Harder, Timm; van der Hoek, Wim; Krisztalovics, Katalin; Parry-Ford, Frances; Popescu, Rodica; Wallensten, Anders; Zdravkova, Anna; Zohari, Siamak; Tsolova, Svetla; Penttinen, Pasi

2016-12-08

Introduction of highly pathogenic avian influenza (HPAI) virus A(H5N8) into Europe prompted animal and human health experts to implement protective measures to prevent transmission to humans. We describe the situation in 2016 and list public health measures and recommendations in place. We summarise critical interfaces identified during the A(H5N1) and A(H5N8) outbreaks in 2014/15. Rapid exchange of information between the animal and human health sectors is critical for a timely, effective and efficient response. This article is copyright of ECDC, 2016.

[A case of human infection with highly pathogenic avian influenza A (H7N9) virus through poultry processing without protection measure].

PubMed

Ma, Y; Zhang, Z B; Cao, L; Lu, J Y; Li, K B; Su, W Z; Li, T G; Yang, Z C; Wang, M

2018-06-10

Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.

Detecting the emergence of novel, zoonotic viruses pathogenic to humans.

PubMed

Rosenberg, Ronald

2015-03-01

RNA viruses, with their high potential for mutation and epidemic spread, are the most common class of pathogens found as new causes of human illness. Despite great advances made in diagnostic technology since the 1950s, the annual rate at which novel virulent viruses have been found has remained at 2-3. Most emerging viruses are zoonoses; they have jumped from mammal or bird hosts to humans. An analysis of virus discovery indicates that the small number of novel viruses discovered annually is an artifact of inadequate surveillance in tropical and subtropical countries, where even established endemic pathogens are often misdiagnosed. Many of the emerging viruses of the future are already infecting humans but remain to be uncovered by a strategy of disease surveillance in selected populations.

Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

PubMed

Garamszegi, Sara; Franzosa, Eric A; Xia, Yu

2013-01-01

A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are otherwise hidden in the traditional binary network, highlighting the power and necessity of high-resolution approaches in host-pathogen systems biology.

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.

Taking forward a 'One Health' approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential.

PubMed

Zumla, Alimuddin; Dar, Osman; Kock, Richard; Muturi, Matthew; Ntoumi, Francine; Kaleebu, Pontiano; Eusebio, Macete; Mfinanga, Sayoki; Bates, Matthew; Mwaba, Peter; Ansumana, Rashid; Khan, Mishal; Alagaili, Abdulaziz N; Cotten, Matthew; Azhar, Esam I; Maeurer, Markus; Ippolito, Giuseppe; Petersen, Eskild

2016-06-01

The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a 'One Health' approach to control such zoonotic pathogens with epidemic potential. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Role of India's wildlife in the emergence and re-emergence of zoonotic pathogens, risk factors and public health implications.

PubMed

Singh, B B; Gajadhar, A A

2014-10-01

Evolving land use practices have led to an increase in interactions at the human/wildlife interface. The presence and poor knowledge of zoonotic pathogens in India's wildlife and the occurrence of enormous human populations interfacing with, and critically linked to, forest ecosystems warrant attention. Factors such as diverse migratory bird populations, climate change, expanding human population and shrinking wildlife habitats play a significant role in the emergence and re-emergence of zoonotic pathogens from India's wildlife. The introduction of a novel Kyasanur forest disease virus (family flaviviridae) into human populations in 1957 and subsequent occurrence of seasonal outbreaks illustrate the key role that India's wild animals play in the emergence and reemergence of zoonotic pathogens. Other high priority zoonotic diseases of wildlife origin which could affect both livestock and humans include influenza, Nipah, Japanese encephalitis, rabies, plague, leptospirosis, anthrax and leishmaniasis. Continuous monitoring of India's extensively diverse and dispersed wildlife is challenging, but their use as indicators should facilitate efficient and rapid disease-outbreak response across the region and occasionally the globe. Defining and prioritizing research on zoonotic pathogens in wildlife are essential, particularly in a multidisciplinary one-world one-health approach which includes human and veterinary medical studies at the wildlife-livestock-human interfaces. This review indicates that wild animals play an important role in the emergence and re-emergence of zoonotic pathogens and provides brief summaries of the zoonotic diseases that have occurred in wild animals in India. Copyright © 2014 Elsevier B.V. All rights reserved.

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

High pressure inactivation of human norovirus virus-like particles: evidence that the capsid of human norovirus is highly pressure resistant

USDA-ARS?s Scientific Manuscript database

Human norovirus (NoV) is the leading cause of non-bacterial acute gastroenteritis epidemics worldwide. High pressure processing (HPP) has been considered a promising non-thermal processing technology to inactivate food- and water-borne viral pathogens. Due to the lack of an effective cell culture fo...

The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases.

PubMed

Rabaa, Maia A; Tue, Ngo Tri; Phuc, Tran My; Carrique-Mas, Juan; Saylors, Karen; Cotten, Matthew; Bryant, Juliet E; Nghia, Ho Dang Trung; Cuong, Nguyen Van; Pham, Hong Anh; Berto, Alessandra; Phat, Voong Vinh; Dung, Tran Thi Ngoc; Bao, Long Hoang; Hoa, Ngo Thi; Wertheim, Heiman; Nadjm, Behzad; Monagin, Corina; van Doorn, H Rogier; Rahman, Motiur; Tra, My Phan Vu; Campbell, James I; Boni, Maciej F; Tam, Pham Thi Thanh; van der Hoek, Lia; Simmonds, Peter; Rambaut, Andrew; Toan, Tran Khanh; Van Vinh Chau, Nguyen; Hien, Tran Tinh; Wolfe, Nathan; Farrar, Jeremy J; Thwaites, Guy; Kellam, Paul; Woolhouse, Mark E J; Baker, Stephen

2015-12-01

The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence.

Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A(H5N1) viruses in ferrets

USDA-ARS?s Scientific Manuscript database

Sporadic avian to human transmission of highly pathogenic avian influenza (HPAI) A (H5N1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. Following the spread and sustained circulation of clade 2 viruses across multiple continents, num...

Airborne transmission of H5N1 high pathogenicity avian influenza viruses during simulated home slaughter

USDA-ARS?s Scientific Manuscript database

Most H5N1 human infections have occurred following exposure to H5N1 high pathogenicity avian influenza (HPAI) virus-infected poultry, especially when poultry are home slaughtered or slaughtered in live poultry markets. Previous studies have demonstrated that slaughter of clade 1 isolate A/Vietnam/1...

Evolution of highly pathogenic avian influenza H5N1 viruses in Egypt indicating progressive adaptation

USDA-ARS?s Scientific Manuscript database

Highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was first diagnosed in poultry in Egypt in 2006, and since then the disease became enzootic in poultry throughout the country affecting the poultry industry and village poultry as well as infecting humans. Vaccination has been used ...

Survey for selected pathogens in wild pigs (Sus scrofa) from Guam, Marianna Islands, USA

USDA-ARS?s Scientific Manuscript database

Pigs (Sus scrofa) were introduced to the United States Territory of Guam in the late 1600’s and are now feral, widespread and present in high densities on parts of the island. Feral pigs are reservoirs for pathogens of concern to domestic animals and humans. Although there are no data on pathogen ex...

Lab-on-a-chip modules for detection of highly pathogenic bacteria: from sample preparation to detection

NASA Astrophysics Data System (ADS)

Julich, S.; Kopinč, R.; Hlawatsch, N.; Moche, C.; Lapanje, A.; Gärtner, C.; Tomaso, H.

2014-05-01

Lab-on-a-chip systems are innovative tools for the detection and identification of microbial pathogens in human and veterinary medicine. The major advantages are small sample volume and a compact design. Several fluidic modules have been developed to transform analytical procedures into miniaturized scale including sampling, sample preparation, target enrichment, and detection procedures. We present evaluation data for single modules that will be integrated in a chip system for the detection of pathogens. A microfluidic chip for purification of nucleic acids was established for cell lysis using magnetic beads. This assay was evaluated with spiked environmental aerosol and swab samples. Bacillus thuringiensis was used as simulant for Bacillus anthracis, which is closely related but non-pathogenic for humans. Stationary PCR and a flow-through PCR chip module were investigated for specific detection of six highly pathogenic bacteria. The conventional PCR assays could be transferred into miniaturized scale using the same temperature/time profile. We could demonstrate that the microfluidic chip modules are suitable for the respective purposes and are promising tools for the detection of bacterial pathogens. Future developments will focus on the integration of these separate modules to an entire lab-on-a-chip system.

Signatures of Pleiotropy, Economy and Convergent Evolution in a Domain-Resolved Map of Human–Virus Protein–Protein Interaction Networks

PubMed Central

Garamszegi, Sara; Franzosa, Eric A.; Xia, Yu

2013-01-01

A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are otherwise hidden in the traditional binary network, highlighting the power and necessity of high-resolution approaches in host-pathogen systems biology. PMID:24339775

Immunoglobulin gene usage in the human anti-pathogen response.

PubMed

Newkirk, M M; Rioux, J D

1995-09-01

The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)

Image-based Analysis to Study Plant Infection with Human Pathogens

PubMed Central

Schikora, Marek; Schikora, Adam

2014-01-01

Our growing awareness that contaminated plants, fresh fruits and vegetables are responsible for a significant proportion of food poisoning with pathogenic microorganisms indorses the demand to understand the interactions between plants and human pathogens. Today we understand that those pathogens do not merely survive on or within plants, they actively infect plant organisms by suppressing their immune system. Studies on the infection process and disease development used mainly physiological, genetic, and molecular approaches, and image-based analysis provides yet another method for this toolbox. Employed as an observational tool, it bears the potential for objective and high throughput approaches, and together with other methods it will be very likely a part of data fusion approaches in the near future. PMID:25505501

Comparative Review of Antimicrobial Resistance in Humans and Nonhuman Primates.

PubMed

Kim, Jeffrey; Coble, Dondrae J; Salyards, Gregory W; Habing, Gregory G

2018-04-02

Antimicrobial resistance (AMR) presents serious threats to human and animal health. Although AMR of pathogens is often evaluated independently between humans and animals, comparative analysis of AMR between humans and animals is necessary for zoonotic pathogens. Major surveillance systems monitor AMR of zoonotic pathogens in humans and food animals, but comprehensive AMR data in veterinary medicine is not diligently monitored for most animal species with which humans commonly contact, including NHP. The objective of this review is to provide a complete report of the prevalences of AMR among zoonotic bacteria that present the greatest threats to NHP, occupational, and public health. High prevalences of AMR exist among Shigella, Campylobacter, and Yersinia, including resistance to antimicrobials important to public health, such as macrolides. Despite improvements in regulations, standards, policies, practices, and zoonotic awareness, occupational exposures to and illnesses due to zoonotic pathogens continue to be reported and, given the documented prevalences of AMR, constitute an occupational and public health risk. However, published literature is sparse, thus indicating the need for veterinarians to proactively monitor AMR in dangerous zoonotic bacteria, to enable veterinarians to make more informed decisions to maximize antimicrobial therapy and minimize occupational risk.

Comparative Review of Antimicrobial Resistance in Humans and Nonhuman Primates.

PubMed

Kim, Jeffrey; Coble, Dondrae J; Salyards, Gregory W; Habing, Gregory G

2019-03-01

Antimicrobial resistance (AMR) presents serious threats to human and animal health. Although AMR of pathogens is often evaluated independently between humans and animals, comparative analysis of AMR between humans and animals is necessary for zoonotic pathogens. Major surveillance systems monitor AMR of zoonotic pathogens in humans and food animals, but comprehensive AMR data in veterinary medicine is not diligently monitored for most animal species with which humans commonly contact, including NHP. The objective of this review is to provide a complete report of the prevalences of AMR among zoonotic bacteria that present the greatest threats to NHP, occupational, and public health. High prevalences of AMR exist among Shigella, Campylobacter, and Yersinia, including resistance to antimicrobials important to public health, such as macrolides. Despite improvements in regulations, standards, policies, practices, and zoonotic awareness, occupational exposures to and illnesses due to zoonotic pathogens continue to be reported and, given the documented prevalences of AMR, constitute an occupational and public health risk. However, published literature is sparse, thus indicating the need for veterinarians to proactively monitor AMR in dangerous zoonotic bacteria, to enable veterinarians to make more informed decisions to maximize antimicrobial therapy and minimize occupational risk.

Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings.

PubMed

Pan, Ming; Gao, Rongbao; Lv, Qiang; Huang, Shunhe; Zhou, Zhonghui; Yang, Lei; Li, Xiaodan; Zhao, Xiang; Zou, Xiaohui; Tong, Wenbin; Mao, Suling; Zou, Shumei; Bo, Hong; Zhu, Xiaoping; Liu, Lei; Yuan, Heng; Zhang, Minghong; Wang, Daqing; Li, Zumao; Zhao, Wei; Ma, Maoli; Li, Yaqiang; Li, Tianshu; Yang, Huiping; Xu, Jianan; Zhou, Lijun; Zhou, Xingyu; Tang, Wei; Song, Ying; Chen, Tao; Bai, Tian; Zhou, Jianfang; Wang, Dayan; Wu, Guizhen; Li, Dexin; Feng, Zijian; Gao, George F; Wang, Yu; He, Shusen; Shu, Yuelong

2016-01-01

Severe infection with avian influenza A (H5N6) virus in humans was identified first in 2014 in China. Before that, it was unknown or unclear if the disease or the pathogen affected people. This study illustrates the virological and clinical findings of a fatal H5N6 virus infection in a human patient. We obtained and analyzed the clinical, epidemiological, and virological data from the patient. Reverse transcription polymerase chain reaction (RT-PCR), viral culture, and sequencing were conducted for determination of the causative pathogen. The patient, who presented with fever, severe pneumonia, leucopenia, and lymphopenia, developed septic shock and acute respiratory distress syndrome (ARDS), and died on day 10 after illness onset. A novel reassortant avian-origin influenza A (H5N6) virus was isolated from the throat swab or trachea aspirate of the patient. The virus was reassorted with the HA gene of clade 2.3.4.4 H5, the internal genes of clade 2.3.2.1 H5, and the NA gene of the H6N6 avian virus. The cleavage site of the HA gene contained multiple basic amino acids, indicating that the novel H5N6 virus was highly pathogenic in chicken. A novel, highly pathogenic avian influenza H5N6 virus with a backbone of H5N1 virus acquired from the NA gene from the H6N6 virus has been identified. It caused human infection resulting in severe respiratory disease. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen Pneumocystis.

PubMed

Cissé, Ousmane H; Ma, Liang; Wei Huang, Da; Khil, Pavel P; Dekker, John P; Kutty, Geetha; Bishop, Lisa; Liu, Yueqin; Deng, Xilong; Hauser, Philippe M; Pagni, Marco; Hirsch, Vanessa; Lempicki, Richard A; Stajich, Jason E; Cuomo, Christina A; Kovacs, Joseph A

2018-05-08

Pneumocystis species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable in vitro Human Pneumocystis infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of Pneumocystis infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that Pneumocystis species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of Pneumocystis populations during their spread across mammals. IMPORTANCE Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. Pneumocystis , a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, Pneumocystis can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different Pneumocystis species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that Pneumocystis may have undergone recent host shifts. The results demonstrate that Pneumocystis strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.

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.

Genomic identification of potential targets unique to Candida albicans for the discovery of antifungal agents.

PubMed

Tripathi, Himanshu; Luqman, Suaib; Meena, Abha; Khan, Feroz

2014-01-01

Despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen Candida albicans are up to 40%. Studies suggest that drug resistance in the three most common species of human fungal pathogens viz., C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and Cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in the target enzymes or high expression of drug transporter genes. Drug resistance in human fungal pathogens has led to an imperative need for the identification of new targets unique to fungal pathogens. In the present study, we have used a comparative genomics approach to find out potential target proteins unique to C. albicans, an opportunistic fungus responsible for severe infection in immune-compromised human. Interestingly, many target proteins of existing antifungal agents showed orthologs in human cells. To identify unique proteins, we have compared proteome of C. albicans [SC5314] i.e., 14,633 total proteins retrieved from the RefSeq database of NCBI, USA with proteome of human and non-pathogenic yeast Saccharomyces cerevisiae. Results showed that 4,568 proteins were identified unique to C. albicans as compared to those of human and later when these unique proteins were compared with S. cerevisiae proteome, finally 2,161 proteins were identified as unique proteins and after removing repeats total 1,618 unique proteins (42 functionally known, 1,566 hypothetical and 10 unknown) were selected as potential antifungal drug targets unique to C. albicans.

Reoccurrence of H5Nx clade 2.3.4.4 highly pathogenic avian influenza viruses in wild birds during 2016

USDA-ARS?s Scientific Manuscript database

The Asian-origin H5N1 A/goose/Guangdong/1/1996 (Gs/GD) lineage of high pathogenicity avian influenza viruses (HPAIV) has become widespread across four continents, affecting poultry, wild birds and humans. H5N1 HPAIV has evolved into multiple hemagglutinin (HA) genetic clades and reassorting with dif...

Impact of highly pathogenic avian influenza virus strain on generation and transmission of bioaerosols during simulated slaughter of infected chickens and ducks

USDA-ARS?s Scientific Manuscript database

Human infections with H5N1 highly pathogenic avian influenza (HPAI) virus occur following exposure to H5N1 virus-infected poultry, often during home slaughter or live-poultry market slaughter processes. Using bioaerosol samplers, we demonstrated that infectious H5N1 airborne particles were produced ...

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

PubMed Central

Eppinger, Mark; Cebula, Thomas A

2015-01-01

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

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.

Assessment and impact of microbial fecal pollution and human enteric pathogens in a coastal community.

PubMed

Lipp, E K; Farrah, S A; Rose, J B

2001-04-01

The goals of this study were to assess watersheds impacted by high densities of OSDS (onsite sewage disposal systems) for evidence of fecal contamination and evaluate the occurrence of human pathogens in coastal waters off west Florida. Eleven stations (representing six watersheds) were intensively sampled for microbial indicators of fecal pollution (fecal coliform bacteria, enterococci, Clostridium perfringens and coliphage) and the human enteric pathogens, Cryptosporidium, Giardia, and enteroviruses during the summer rainy season (May-September 1996). Levels of all indicators ranged between < 5 and > 4000 CFU/100 ml. Cryptosporidium and Giardia were detected infrequently (6.8% and 2.3% of samples tested positive, respectively). Conversely, infectious enteroviruses were detected at low levels in 5 of the 6 watersheds sampled. Using cluster analysis, sites were grouped into two categories, high and low risks, based on combined levels of indicators. These results suggest that stations of highest pollution risk were located within areas of high OSDS densities. Furthermore, data indicate a subsurface transport of contaminated water to surface waters. The high prevalence of enteroviruses throughout the study area suggests a chronic pollution problem and potential risk to recreational swimmers in and around Sarasota Bay.

Reptiles as Reservoirs of Bacterial Infections: Real Threat or Methodological Bias?

PubMed

Zancolli, Giulia; Mahsberg, Dieter; Sickel, Wiebke; Keller, Alexander

2015-10-01

Bacterial infections secondary to snakebites and human pathogens (e.g., Salmonella) have been linked to the oral microbiota of snakes and pet reptiles. Based on culture-dependent studies, it is speculated that snakes' oral microbiota reflects the fecal flora of their ingested preys. However, cultured-based techniques have been shown to be limited as they fail to identify unculturable microorganisms which represent the vast majority of the microbial diversity. Here, we used culture-independent high-throughput sequencing to identify reptile-associated pathogens and to characterize the oral microbial community of five snakes, one gecko, and two terrapins. Few potential human pathogens were detected at extremely low frequencies. Moreover, bacterial taxa represented in the snake's oral cavity bore little resemblance to their preys' fecal microbiota. Overall, we found distinct, highly diverse microbial communities with consistent, species-specific patterns contrary to previous culture-based studies. Our study does not support the widely held assumption that reptiles' oral cavity acts as pathogen reservoir and provides important insights for future research.

Pathogens in drinking water: Are there any new ones

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

Reasoner, D.J.

1993-01-01

Since 1976 three newly recognized human pathogens have become familiar to the drinking water industry as waterborne disease agents. These are: the legionnaires disease agent, Legionella pneumophila and related species; and two protozoan pathogens, Giardia lamblia and Cryptosporidium parvum, both of which form highly disinfectant resistant cysts that are shed in the feces of infected individuals. The question frequently arises - are there other emerging waterborne pathogens that may pose a human health problem that the drinking water industry will have to deal with. The paper will review the current state of knowledge of the occurrence and incidence of pathogensmore » and opportunistic pathogens other than Legionella, Giardia and Cryptosporidium in treated and untreated drinking water. Bacterial agents that will be reviewed include Aeromonas, Pseudomonas, Campylobacter, Mycobacterium, Yersinia and Plesiomonas. Aspects of detection of these agents including detection methods and feasibility of monitoring will be addressed.« less

Tracking the establishment of local endemic populations of an emergent enteric pathogen

PubMed Central

Holt, Kathryn E.; Thieu Nga, Tran Vu; Thanh, Duy Pham; Vinh, Ha; Kim, Dong Wook; Vu Tra, My Phan; Campbell, James I.; Hoang, Nguyen Van Minh; Vinh, Nguyen Thanh; Minh, Pham Van; Thuy, Cao Thu; Nga, Tran Thi Thu; Thompson, Corinne; Dung, Tran Thi Ngoc; Nhu, Nguyen Thi Khanh; Vinh, Phat Voong; Tuyet, Pham Thi Ngoc; Phuc, Hoang Le; Lien, Nguyen Thi Nam; Phu, Bui Duc; Ai, Nguyen Thi Thuy; Tien, Nguyen Manh; Dong, Nguyen; Parry, Christopher M.; Hien, Tran Tinh; Farrar, Jeremy J.; Parkhill, Julian; Dougan, Gordon; Thomson, Nicholas R.; Baker, Stephen

2013-01-01

Shigella sonnei is a human-adapted pathogen that is emerging globally as the dominant agent of bacterial dysentery. To investigate local establishment, we sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data show that S. sonnei was introduced into Vietnam in the 1980s and has undergone localized clonal expansion, punctuated by genomic fixation events through periodic selective sweeps. We uncover geographical spread, spatially restricted frontier populations, and convergent evolution through local gene pool sampling. This work provides a unique, high-resolution insight into the microevolution of a pioneering human pathogen during its establishment in a new host population. PMID:24082120

Avian influenza viruses in humans.

PubMed

Malik Peiris, J S

2009-04-01

Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.

Productivity, biodiversity, and pathogens influence the global hunter-gatherer population density.

PubMed

Tallavaara, Miikka; Eronen, Jussi T; Luoto, Miska

2018-02-06

The environmental drivers of species distributions and abundances are at the core of ecological research. However, the effects of these drivers on human abundance are not well-known. Here, we report how net primary productivity, biodiversity, and pathogen stress affect human population density using global ethnographic hunter-gatherer data. Our results show that productivity has significant effects on population density globally. The most important direct drivers, however, depend on environmental conditions: biodiversity influences population density exclusively in low-productivity regions, whereas pathogen stress does so in high-productivity regions. Our results also indicate that subtropical and temperate forest biomes provide the highest carrying capacity for hunter-gatherer populations. These findings document that environmental factors play a key role in shaping global population density patterns of preagricultural humans.

Opportunistic pathogens enriched in showerhead biofilms

PubMed Central

Feazel, Leah M.; Baumgartner, Laura K.; Peterson, Kristen L.; Frank, Daniel N.; Harris, J. Kirk; Pace, Norman R.

2009-01-01

The environments we humans encounter daily are sources of exposure to diverse microbial communities, some of potential concern to human health. In this study, we used culture-independent technology to investigate the microbial composition of biofilms inside showerheads as ecological assemblages in the human indoor environment. Showers are an important interface for human interaction with microbes through inhalation of aerosols, and showerhead waters have been implicated in disease. Although opportunistic pathogens commonly are cultured from shower facilities, there is little knowledge of either their prevalence or the nature of other microorganisms that may be delivered during shower usage. To determine the composition of showerhead biofilms and waters, we analyzed rRNA gene sequences from 45 showerhead sites around the United States. We find that variable and complex, but specific, microbial assemblages occur inside showerheads. Particularly striking was the finding that sequences representative of non-tuberculous mycobacteria (NTM) and other opportunistic human pathogens are enriched to high levels in many showerhead biofilms, >100-fold above background water contents. We conclude that showerheads may present a significant potential exposure to aerosolized microbes, including documented opportunistic pathogens. The health risk associated with showerhead microbiota needs investigation in persons with compromised immune or pulmonary systems. PMID:19805310

Pathogen-driven selection in the human genome.

PubMed

Cagliani, Rachele; Sironi, Manuela

2013-01-01

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

A HIGHLY SELECTIVE PCR PROTOCOL FOR DETECTING 16S RRNA GENES OF THE GENUS PSEUDOMONAS (SENSU STRICTO) IN ENVIRONMENTAL SAMPLES

EPA Science Inventory

Pseudomonas species are plant, animal, and human pathogens; exhibit plant pathogen-suppressing properties useful in biological control; or express metabolic versatilities valued in biotechnology and bioremediation. Specific detection of Pseudomonas species in the environment may ...

Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals

PubMed Central

Kaplan, Bryan S.; Russier, Marion; Jeevan, Trushar; Marathe, Bindumadhav; Govorkova, Elena A.; Russell, Charles J.; Kim-Torchetti, Mia; Choi, Young Ki; Brown, Ian; Saito, Takehiko; Stallknecht, David E.; Krauss, Scott

2016-01-01

ABSTRACT Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses. PMID:27303732

Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals.

PubMed

Kaplan, Bryan S; Russier, Marion; Jeevan, Trushar; Marathe, Bindumadhav; Govorkova, Elena A; Russell, Charles J; Kim-Torchetti, Mia; Choi, Young Ki; Brown, Ian; Saito, Takehiko; Stallknecht, David E; Krauss, Scott; Webby, Richard J

2016-01-01

Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses.

What’s the risk? Identifying potential human pathogens within grey-headed flying foxes faeces

PubMed Central

Galbraith, Penelope; Coutts, Scott; Prosser, Toby; Boyce, John; McCarthy, David T.

2018-01-01

Pteropus poliocephalus (grey-headed flying foxes) are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%), Pasteurellaceae (19.9% ± 25.7%) and Moraxellaceae (9.4% ± 11.8%) dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals. PMID:29360880

[Animals as a potential source of human fungal infections].

PubMed

Dworecka-Kaszak, Bozena

2008-01-01

Changing environment is a reason, that many saprotrophic fungi became opportunists and in the end also maybe a pathogenic. Host specific adaptation is not so strong among fungi, so there are many common fungal pathogens for people and for animals. Animals suffering from dermatomycosis are well recognize as source of human superficial mycoses. Breeding of different exotic animals such as parrots, various Reptiles and Amphibians, miniature Rodents and keeping them as a pets in the peoples houses, have become more and more popular in the recent years. This article is shortly presenting which animals maybe a potential source of fungal infections for humans. Looking for the other mycoses as systemic mycoses, especially candidiasis or aspergilosis there are no data, which allow excluding sick animals as a source of infection for human, even if those deep mycoses have endogenic reactivation mechanism. Immunocompromised people are in high-risk group when they take care of animals. Another important source of potentially pathogenic, mostly air-born fungi may be animal use in experimental laboratory work. During the experiments is possible that laboratory workers maybe hurt and these animals and their environment, food and house boxes could be the possible source of microorganisms, pathogenic for humans or other animals. Unusual way to inoculate these potentially pathogens into the skin of laboratory personnel may cause granulomatous, local lesions on their hands.

Listeria: A foodborne pathogen that knows how to survive.

PubMed

Gandhi, Megha; Chikindas, Michael L

2007-01-01

The foodborne pathogen Listeria is the causative agent of listeriosis, a severe disease with high hospitalization and case fatality rates. Listeria monocytogenes can survive and grow over a wide range of environmental conditions such as refrigeration temperatures, low pH and high salt concentration. This allows the pathogen to overcome food preservation and safety barriers, and pose a potential risk to human health. This review focuses on the key issues such as survival of the pathogen in adverse environments, and the important adaptation and survival mechanisms such as biofilm formation, quorum sensing and antimicrobial resistance. Studies on the development of technologies to prevent and control L. monocytogenes contamination in foods and food processing facilities are also discussed.

Aerially transmitted human fungal pathogens: what can we learn from metagenomics and comparative genomics?

PubMed

Aliouat-Denis, Cécile-Marie; Chabé, Magali; Delhaes, Laurence; Dei-Cas, Eduardo

2014-01-01

In the last few decades, aerially transmitted human fungal pathogens have been increasingly recognized to impact the clinical course of chronic pulmonary diseases, such as asthma, cystic fibrosis or chronic obstructive pulmonary disease. Thanks to recent development of culture-free high-throughput sequencing methods, the metagenomic approaches are now appropriate to detect, identify and even quantify prokaryotic or eukaryotic microorganism communities inhabiting human respiratory tract and to access the complexity of even low-burden microbe communities that are likely to play a role in chronic pulmonary diseases. In this review, we explore how metagenomics and comparative genomics studies can alleviate fungal culture bottlenecks, improve our knowledge about fungal biology, lift the veil on cross-talks between host lung and fungal microbiota, and gain insights into the pathogenic impact of these aerially transmitted fungi that affect human beings. We reviewed metagenomic studies and comparative genomic analyses of carefully chosen microorganisms, and confirmed the usefulness of such approaches to better delineate biology and pathogenesis of aerially transmitted human fungal pathogens. Efforts to generate and efficiently analyze the enormous amount of data produced by such novel approaches have to be pursued, and will potentially provide the patients suffering from chronic pulmonary diseases with a better management. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

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

PubMed Central

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

2011-01-01

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

Time for T? Immunoinformatics addresses vaccine design for neglected tropical and emerging infectious diseases

PubMed Central

Terry, Frances E; Moise, Leonard; Martin, Rebecca F; Torres, Melissa; Pilotte, Nils; Williams, Steven A; De Groot, Anne S

2015-01-01

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere. PMID:25193104

Control of viremia and maintenance of intestinal CD4(+) memory T cells in SHIV(162P3) infected macaques after pathogenic SIV(MAC251) challenge.

PubMed

Pahar, Bapi; Lackner, Andrew A; Piatak, Michael; Lifson, Jeffrey D; Wang, Xiaolei; Das, Arpita; Ling, Binhua; Montefiori, David C; Veazey, Ronald S

2009-05-10

Recent HIV vaccine failures have prompted calls for more preclinical vaccine testing in non-human primates. However, similar to HIV infection of humans, developing a vaccine that protects macaques from infection following pathogenic SIV(MAC251) challenge has proven difficult, and current vaccine candidates at best, only reduce viral loads after infection. Here we demonstrate that prior infection with a chimeric simian-human immunodeficiency virus (SHIV) containing an HIV envelope gene confers protection against intravenous infection with the heterologous, highly pathogenic SIV(MAC251) in rhesus macaques. Although definitive immune correlates of protection were not identified, preservation and/or restoration of intestinal CD4(+) memory T cells were associated with protection from challenge and control of viremia. These results suggest that protection against pathogenic lentiviral infection or disease progression is indeed possible, and may correlate with preservation of mucosal CD4(+) T cells.

Epidemiological role of birds in the transmission and maintenance of zoonoses.

PubMed

Contreras, A; Gómez-Martín, A; Paterna, A; Tatay-Dualde, J; Prats-Van Der Ham, M; Corrales, J C; De La Fe, C; Sánchez, A

2016-12-01

The risk of zoonoses spreading from birds to humans is lower, quantitatively speaking, than the risk of transmission between other host groups, because the two taxonomic groups share fewer pathogens. Nevertheless, birds have a number of epidemiological characteristics that make them extremely important hosts in the transmission and maintenance of zoonoses, including their susceptibility to pathogens that are extremely hazardous to humans (such as highly pathogenic avian influenza virus, West Nile virus and Chlamydia psittaci) and their ability to travel long distances, especially in the case of migratory birds. The fact that the human diet includes poultry products (meat, eggs and their by-products) also means that most human cases of foodborne zoonoses are infections of avian origin. Lastly, close contact between humans and pet birds or urban birds leads to interactions of public health concern. This article sets out to describe the main factors that determine the role of birds in the epidemiology of zoonotic infections. © OIE (World Organisation for Animal Health), 2016.

Novel Mycobacterium tuberculosis complex pathogen, M. mungi.

PubMed

Alexander, Kathleen A; Laver, Pete N; Michel, Anita L; Williams, Mark; van Helden, Paul D; Warren, Robin M; Gey van Pittius, Nicolaas C

2010-08-01

Seven outbreaks involving increasing numbers of banded mongoose troops and high death rates have been documented. We identified a Mycobacterium tuberculosis complex pathogen, M. mungi sp. nov., as the causative agent among banded mongooses that live near humans in Chobe District, Botswana. Host spectrum and transmission dynamics remain unknown.

Impacts of exotic forest pathogens on Mediterranean ecosystems: Four case studies

Treesearch

Matteo Garbelotto; Marco Pautasso

2011-01-01

Mediterranean ecosystems are hotspots of biodiversity. Because of a coincidence of high species richness and human presence, Mediterranean biodiversity is particularly threatened by processes such as habitat degradation, fragmentation and loss, pollution, climate change and introduction of invasive species. Invasive tree pathogens are among the problematic exotic...

Structural, functional and immunogenic insights on Cu,Zn Superoxide Dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

USDA-ARS?s Scientific Manuscript database

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 he...

Multiple introductions of highly pathogenic avian influenza H5N1 viruses into Bangladesh

PubMed Central

Marinova-Petkova, Atanaska; Feeroz, Mohammed M; Rabiul Alam, SM; Kamrul Hasan, M; Akhtar, Sharmin; Jones-Engel, Lisa; Walker, David; McClenaghan, Laura; Rubrum, Adam; Franks, John; Seiler, Patrick; Jeevan, Trushar; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G

2014-01-01

Highly pathogenic H5N1 and low pathogenic H9N2 influenza viruses are endemic to poultry markets in Bangladesh and have cocirculated since 2008. H9N2 influenza viruses circulated constantly in the poultry markets, whereas highly pathogenic H5N1 viruses occurred sporadically, with peaks of activity in cooler months. Thirty highly pathogenic H5N1 influenza viruses isolated from poultry were characterized by antigenic, molecular, and phylogenetic analyses. Highly pathogenic H5N1 influenza viruses from clades 2.2.2 and 2.3.2.1 were isolated from live bird markets only. Phylogenetic analysis of the 30 H5N1 isolates revealed multiple introductions of H5N1 influenza viruses in Bangladesh. There was no reassortment between the local H9N2 influenza viruses and H5N1 genotype, despite their prolonged cocirculation. However, we detected two reassortant H5N1 viruses, carrying the M gene from the Chinese H9N2 lineage, which briefly circulated in the Bangladesh poultry markets and then disappeared. On the other hand, interclade reassortment occurred within H5N1 lineages and played a role in the genesis of the currently dominant H5N1 viruses in Bangladesh. Few ‘human-like' mutations in H5N1 may account for the limited number of human cases. Antigenically, clade 2.3.2.1 H5N1 viruses in Bangladesh have evolved since their introduction and are currently mainly homogenous, and show evidence of recent antigenic drift. Although reassortants containing H9N2 genes were detected in live poultry markets in Bangladesh, these reassortants failed to supplant the dominant H5N1 lineage. PMID:26038508

Molecular Detection and Characterization of Tick-borne Pathogens in Dogs and Ticks from Nigeria

PubMed Central

Kamani, Joshua; Baneth, Gad; Mumcuoglu, Kosta Y.; Waziri, Ndadilnasiya E.; Eyal, Osnat; Guthmann, Yifat; Harrus, Shimon

2013-01-01

Background Only limited information is currently available on the prevalence of vector borne and zoonotic pathogens in dogs and ticks in Nigeria. The aim of this study was to use molecular techniques to detect and characterize vector borne pathogens in dogs and ticks from Nigeria. Methodology/Principal Findings Blood samples and ticks (Rhipicephalus sanguineus, Rhipicephalus turanicus and Heamaphysalis leachi) collected from 181 dogs from Nigeria were molecularly screened for human and animal vector-borne pathogens by PCR and sequencing. DNA of Hepatozoon canis (41.4%), Ehrlichia canis (12.7%), Rickettsia spp. (8.8%), Babesia rossi (6.6%), Anaplasma platys (6.6%), Babesia vogeli (0.6%) and Theileria sp. (0.6%) was detected in the blood samples. DNA of E. canis (23.7%), H. canis (21.1%), Rickettsia spp. (10.5%), Candidatus Neoehrlichia mikurensis (5.3%) and A. platys (1.9%) was detected in 258 ticks collected from 42 of the 181 dogs. Co- infections with two pathogens were present in 37% of the dogs examined and one dog was co-infected with 3 pathogens. DNA of Rickettsia conorii israelensis was detected in one dog and Rhipicephalus sanguineus tick. DNA of another human pathogen, Candidatus N. mikurensis was detected in Rhipicephalus sanguineus and Heamaphysalis leachi ticks, and is the first description of Candidatus N. mikurensis in Africa. The Theileria sp. DNA detected in a local dog in this study had 98% sequence identity to Theileria ovis from sheep. Conclusions/Significance The results of this study indicate that human and animal pathogens are abundant in dogs and their ticks in Nigeria and portray the potential high risk of human exposure to infection with these agents. PMID:23505591

Human Herpes Simplex Virus Type 1 in Confiscated Gorilla

PubMed Central

Oxford, Kristie L.; Gardner-Roberts, David; Kinani, Jean-Felix; Spelman, Lucy; Barry, Peter A.; Cranfield, Michael R.; Lowenstine, Linda J.

2014-01-01

In 2007, we detected human herpes simplex virus type 1, which caused stomatitis, in a juvenile confiscated eastern lowland gorilla (Gorilla beringei graueri) that had a high degree of direct contact with human caretakers. Our findings confirm that pathogens can transfer between nonhuman primate hosts and humans. PMID:25341185

Human herpes simplex virus type 1 in confiscated gorilla.

PubMed

Gilardi, Kirsten V K; Oxford, Kristie L; Gardner-Roberts, David; Kinani, Jean-Felix; Spelman, Lucy; Barry, Peter A; Cranfield, Michael R; Lowenstine, Linda J

2014-11-01

In 2007, we detected human herpes simplex virus type 1, which caused stomatitis, in a juvenile confiscated eastern lowland gorilla (Gorilla beringei graueri) that had a high degree of direct contact with human caretakers. Our findings confirm that pathogens can transfer between nonhuman primate hosts and humans.

Biological characterization of highly pathogenic avian influenza H5N1 viruses that infected humans in Egypt in 2014-2015.

PubMed

El-Shesheny, Rabeh; Mostafa, Ahmed; Kandeil, Ahmed; Mahmoud, Sara H; Bagato, Ola; Naguib, Amel; Refaey, Samir El; Webby, Richard J; Ali, Mohamed A; Kayali, Ghazi

2017-03-01

Highly pathogenic avian influenza (HPAI) H5N1 influenza viruses emerged as a human pathogen in 1997 with expected potential to undergo sustained human-to-human transmission and pandemic viral spread. HPAI H5N1 is endemic in Egyptian poultry and has caused sporadic human infection. The first outbreak in early 2006 was caused by clade 2.2 viruses that rapidly evolved genetically and antigenically. A sharp increase in the number of human cases was reported in Egypt in the 2014/2015 season. In this study, we analyzed and characterized three isolates of HPAI H5N1 viruses isolated from infected humans in Egypt in 2014/2015. Phylogenetic analysis demonstrated that the nucleotide sequences of eight segments of the three isolates were clustered with those of members of clade 2.2.1.2. We also found that the human isolates from 2014/2015 had a slight, non-significant difference in their affinity for human-like sialic acid receptors. In contrast, they showed significant differences in their replication kinetics in MDCK, MDCK-SIAT, and A549 cells as well as in embryonated chicken eggs. An antiviral bioassay study revealed that all of the isolates were susceptible to amantadine. Therefore, further investigation and monitoring is required to correlate the genetic and/or antigenic changes of the emerging HPAI H5N1 viruses with possible alteration in their characteristics and their potential to become a further threat to public health.

[Study of pathogenicity of Nipah virus and its vaccine development].

PubMed

Yoneda, Misako

2014-01-01

Nipah virus (NiV), a paramyxovirus, was first discovered in Malaysia in 1998 in an outbreak of infection in pigs and humans, and incurred a high fatality rate in humans. We established a system that enabled the rescue of replicating NiVs from a cloned DNA. Using the system, we analyzed the functions of accessory proteins in infected cells and the implications in in vivo pathogenicity. Further, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins, which appeared to be an appropriate to NiV vaccine candidate for use in humans.

Detection of Waterborne Protozoa, Viruses, and Bacteria in Groundwater and Other Water Samples in the Kathmandu Valley, Nepal

NASA Astrophysics Data System (ADS)

Haramoto, E.

2018-03-01

In this study, the prevalence of various waterborne pathogens in water samples collected in the Kathmandu Valley, Nepal, and the applicability of Escherichia coli as an indicator of pathogen contamination in groundwater were assessed. Fifty-three water samples, including shallow groundwater and river water, were analyzed to examine the presence of protozoan (oo)cysts via fluorescence microscopy and that of viral and bacterial genomes via quantitative PCR. At least one of the seven types of pathogens tested (i.e., Cryptosporidium, Giardia, human adenoviruses, noroviruses of genogroups I and II, group A rotaviruses, and Vibrio cholerae) was detected in 68% (15/22) of the shallow dug well water samples; groundwater in the shallow dug wells was more contaminated compared with that in shallow tube wells (8/15, 53%). River water and sewage samples were contaminated with extremely high concentrations of multiple pathogens, whereas a tap water sample supplied by a water tanker tested positive for human adenoviruses and V. cholerae. The detection of host-specific Bacteroidales genetic markers revealed the effects of human and animal feces on groundwater contamination. The tested pathogens were sometimes detected even in E. coli-negative groundwater samples, indicative of the limitations of using E. coli as an indicator for waterborne pathogens in groundwater.

Identification of Rare PB2-D701N Mutation from a Patient with Severe Influenza: Contribution of the PB2-D701N Mutation to the Pathogenicity of Human Influenza.

PubMed

Nieto, Amelia; Pozo, Francisco; Vidal-García, Matxalen; Omeñaca, Manuel; Casas, Inmaculada; Falcón, Ana

2017-01-01

Several amino acid changes have been previously implicated in adaptation of avian influenza viruses to human hosts, among them the D701N change in the PB2 polymerase subunit that also is the main determinant of avian virus pathogenesis in animal models. However, previous studies using recombinant viruses did not provide conclusive information of the contribution of this PB2 residue to pathogenicity in human influenza virus strains. We identified this mutation in an A(H1N1)pdm09-like human influenza virus isolated from an infected patient with pneumonia and acute respiratory failure, admitted to the intensive care unit. An exhaustive search has revealed PB2-D701 as a highly conserved position in all available H1N1 human virus sequences in NCBI database, showing a very low prevalence of PB2-D701N change. Presence of PB2-701N amino acid correlates with severe or fatal outcome in those scarce cases with known disease outcome of the infection. In these patients, the residue PB2-701N may contribute to pathogenicity as it was previously reported in humans infected with avian viruses. This study helps to clarify a debate that has arisen regarding the role of PB2-D701N in human influenza virus pathogenicity.

Identification of Rare PB2-D701N Mutation from a Patient with Severe Influenza: Contribution of the PB2-D701N Mutation to the Pathogenicity of Human Influenza

PubMed Central

Nieto, Amelia; Pozo, Francisco; Vidal-García, Matxalen; Omeñaca, Manuel; Casas, Inmaculada; Falcón, Ana

2017-01-01

Several amino acid changes have been previously implicated in adaptation of avian influenza viruses to human hosts, among them the D701N change in the PB2 polymerase subunit that also is the main determinant of avian virus pathogenesis in animal models. However, previous studies using recombinant viruses did not provide conclusive information of the contribution of this PB2 residue to pathogenicity in human influenza virus strains. We identified this mutation in an A(H1N1)pdm09-like human influenza virus isolated from an infected patient with pneumonia and acute respiratory failure, admitted to the intensive care unit. An exhaustive search has revealed PB2-D701 as a highly conserved position in all available H1N1 human virus sequences in NCBI database, showing a very low prevalence of PB2-D701N change. Presence of PB2-701N amino acid correlates with severe or fatal outcome in those scarce cases with known disease outcome of the infection. In these patients, the residue PB2-701N may contribute to pathogenicity as it was previously reported in humans infected with avian viruses. This study helps to clarify a debate that has arisen regarding the role of PB2-D701N in human influenza virus pathogenicity. PMID:28421062

Variable high pressure processing sensitivities for GII human noroviruses

USDA-ARS?s Scientific Manuscript database

Human norovirus (HuNoV) is the leading cause of foodborne diseases worldwide. High pressure processing (HPP) is one of the most promising non-thermal technologies for decontamination of viral pathogens in foods. However, the survival of HuNoVs by HPP is poorly understood because these viruses cann...

High pressure treatment of human norovirus-like particles: factors affecting destruction efficacy

USDA-ARS?s Scientific Manuscript database

Human norovirus (HuNoV) is the leading cause of foodborne diseases worldwide. High pressure processing (HPP) is considered a promising non-thermal technology to inactivate viral pathogens in foods. However, the effectiveness of HPP on inactivating HuNoV remains poorly understood because it cannot be...

[Tularaemia - an overview of the current knowledge].

PubMed

Lukásová, Eva; Cermák, Pavel; Smelá, Gabriela; Jedlicková, Anna

2010-02-01

Francisella tularensis belongs to the family Francisellaceae. It is the aetiological agent of a zoonosis called tularaemia, spread throughout the northern hemisphere. Currently, several subspecies of F. tularensis may be distinguished with various pathogenicity and geographical distribution. In human medicine, only sporadic infections or local epidemics are reported. Given the fact that F. tularensis is highly pathogenic for humans and is easily spread by aerosol, water or food, it may be exploited as a biological weapon. It belongs to fastidious strains requiring specially prepared culture media.

Novel Highly Pathogenic Avian Influenza A(H5N6) Virus in the Netherlands, December 2017.

PubMed

Beerens, Nancy; Koch, Guus; Heutink, Rene; Harders, Frank; Vries, D P Edwin; Ho, Cynthia; Bossers, Alex; Elbers, Armin

2018-04-17

A novel highly pathogenic avian influenza A(H5N6) virus affecting wild birds and commercial poultry was detected in the Netherlands in December 2017. Phylogenetic analysis demonstrated that the virus is a reassortant of H5N8 clade 2.3.4.4 viruses and not related to the Asian H5N6 viruses that caused human infections.

Rodents on pig and chicken farms - a potential threat to human and animal health.

PubMed

Backhans, Annette; Fellström, Claes

2012-01-01

Rodents can cause major problems through spreading various diseases to animals and humans. The two main species of rodents most commonly found on farms around the world are the house mouse (Mus musculus) and the brown rat (Rattus norvegicus). Both species are omnivorous and can breed year-round under favourable conditions. This review describes the occurrence of pathogens in rodents on specialist pig and chicken farms, which are usually closed units with a high level of bio-security. However, wild rodents may be difficult to exclude completely, even from these sites, and can pose a risk of introducing and spreading pathogens. This article reviews current knowledge regarding rodents as a hazard for spreading disease on farms. Most literature available regards zoonotic pathogens, while the literature regarding pathogens that cause disease in farm animals is more limited.

Can Plant Viruses Cross the Kingdom Border and Be Pathogenic to Humans?

PubMed Central

Balique, Fanny; Lecoq, Hervé; Raoult, Didier; Colson, Philippe

2015-01-01

Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans. PMID:25903834

Evolution of Influenza A Virus by Mutation and Re-Assortment

PubMed Central

Shao, Wenhan; Li, Xinxin; Goraya, Mohsan Ullah; Wang, Song; Chen, Ji-Long

2017-01-01

Influenza A virus (IAV), a highly infectious respiratory pathogen, has continued to be a significant threat to global public health. To complete their life cycle, influenza viruses have evolved multiple strategies to interact with a host. A large number of studies have revealed that the evolution of influenza A virus is mainly mediated through the mutation of the virus itself and the re-assortment of viral genomes derived from various strains. The evolution of influenza A virus through these mechanisms causes worldwide annual epidemics and occasional pandemics. Importantly, influenza A virus can evolve from an animal infected pathogen to a human infected pathogen. The highly pathogenic influenza virus has resulted in stupendous economic losses due to its morbidity and mortality both in human and animals. Influenza viruses fall into a category of viruses that can cause zoonotic infection with stable adaptation to human, leading to sustained horizontal transmission. The rapid mutations of influenza A virus result in the loss of vaccine optimal efficacy, and challenge the complete eradication of the virus. In this review, we highlight the current understanding of influenza A virus evolution caused by the mutation and re-assortment of viral genomes. In addition, we discuss the specific mechanisms by which the virus evolves. PMID:28783091

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

PubMed

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

2015-10-15

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

A molecular arms race between host innate antiviral response and emerging human coronaviruses.

PubMed

Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

2016-02-01

Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

Patient-derived avian influenza A (H5N6) virus is highly pathogenic in mice but can be effectively treated by anti-influenza polyclonal antibodies.

PubMed

Pan, Weiqi; Xie, Haojun; Li, Xiaobo; Guan, Wenda; Chen, Peihai; Zhang, Beiwu; Zhang, Mincong; Dong, Ji; Wang, Qian; Li, Zhixia; Li, Shufen; Yang, Zifeng; Li, Chufang; Zhong, Nanshan; Huang, Jicheng; Chen, Ling

2018-06-13

Highly pathogenic avian influenza A (H5N6) virus has been circulating in poultry since 2013 and causes sporadic infections and fatalities in humans. Due to the re-occurrence and continuous evolution of this virus subtype, there is an urgent need to better understand the pathogenicity of the H5N6 virus and to identify effective preventative and therapeutic strategies. We established a mouse model to evaluate the virulence of H5N6 A/Guangzhou/39715/2014 (H5N6/GZ14), which was isolated from an infected patient. BALB/c mice were inoculated intranasally with H5N6/GZ14 and monitored for morbidity, mortality, cytokine production, lung injury, viral replication, and viral dissemination to other organs. H5N6/GZ14 is highly pathogenic and can kill 50% of mice at a very low infectious dose of 5 plaque-forming units (pfu). Infection with H5N6/GZ14 showed rapid disease progression, viral replication to high titers in the lung, a strongly induced pro-inflammatory cytokine response, and severe lung injury. Moreover, infectious H5N6/GZ14 could be detected in the heart and brain of the infected mice. We also demonstrated that anti-influenza polyclonal antibodies generated by immunizing rhesus macaques could protect mice from lethal infection. Our results provide insights into the pathogenicity of the H5N6 human isolate.

Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens

PubMed Central

Martínez, Isidoro; Oliveros, Juan C.; Cuesta, Isabel; de la Barrera, Jorge; Ausina, Vicente; Casals, Cristina; de Lorenzo, Alba; García, Ernesto; García-Fojeda, Belén; Garmendia, Junkal; González-Nicolau, Mar; Lacoma, Alicia; Menéndez, Margarita; Moranta, David; Nieto, Amelia; Ortín, Juan; Pérez-González, Alicia; Prat, Cristina; Ramos-Sevillano, Elisa; Regueiro, Verónica; Rodriguez-Frandsen, Ariel; Solís, Dolores; Yuste, José; Bengoechea, José A.; Melero, José A.

2017-01-01

Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here. PMID:28298903

[Human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy].

PubMed

Riehm, Julia M; Löscher, Thomas

2015-07-01

Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. In the last 1500 years and during three dreaded pandemics, millions of people became victims of Justinian's plague, the Black Death, or modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and American countries. Due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. In fact, plague is currently classified as a "re-emerging disease". Infection may occur after the bite of an infected flea, but also after oral ingestion or inhalation of the pathogen. The clinical presentations comprise the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Most human cases can successfully be treated with antibiotics. However, the high transmission rate and lethality of pneumonic plague require international and mandatory case notification and quarantine of patients. Rapid diagnosis, therapy and barrier nursing are not only crucial for the individual patient but also for the prevention of further spread of the pathogen or of epidemics. Therefore, WHO emergency schedules demand the isolation of cases, identification and surveillance of contacts as well as control of zoonotic reservoir animals and vectors. These sanctions and effective antibiotic treatment usually allow a rapid containment of outbreaks. However, multiple antibiotic resistant strains of Y. pestis have been isolated from patients in the past. So far, no outbreaks with such strains have been reported.

Prevalence of Avian-Pathogenic Escherichia coli Strain O1 Genomic Islands among Extraintestinal and Commensal E. coli Isolates

PubMed Central

Johnson, Timothy J.; Wannemuehler, Yvonne; Kariyawasam, Subhashinie; Johnson, James R.; Logue, Catherine M.

2012-01-01

Escherichia coli strains that cause disease outside the intestine are known as extraintestinal pathogenic E. coli (ExPEC) and include pathogens of humans and animals. Previously, the genome of avian-pathogenic E. coli (APEC) O1:K1:H7 strain O1, from ST95, was sequenced and compared to those of several other E. coli strains, identifying 43 genomic islands. Here, the genomic islands of APEC O1 were compared to those of other sequenced E. coli strains, and the distribution of 81 genes belonging to 12 APEC O1 genomic islands among 828 human and avian ExPEC and commensal E. coli isolates was determined. Multiple islands were highly prevalent among isolates belonging to the O1 and O18 serogroups within phylogenetic group B2, which are implicated in human neonatal meningitis. Because of the extensive genomic similarities between APEC O1 and other human ExPEC strains belonging to the ST95 phylogenetic lineage, its ability to cause disease in a rat model of sepsis and meningitis was assessed. Unlike other ST95 lineage strains, APEC O1 was unable to cause bacteremia or meningitis in the neonatal rat model and was significantly less virulent than uropathogenic E. coli (UPEC) CFT073 in a mouse sepsis model, despite carrying multiple neonatal meningitis E. coli (NMEC) virulence factors and belonging to the ST95 phylogenetic lineage. These results suggest that host adaptation or genome modifications have occurred either in APEC O1 or in highly virulent ExPEC isolates, resulting in differences in pathogenicity. Overall, the genomic islands examined provide targets for further discrimination of the different ExPEC subpathotypes, serogroups, phylogenetic types, and sequence types. PMID:22467781

Prevalence of avian-pathogenic Escherichia coli strain O1 genomic islands among extraintestinal and commensal E. coli isolates.

PubMed

Johnson, Timothy J; Wannemuehler, Yvonne; Kariyawasam, Subhashinie; Johnson, James R; Logue, Catherine M; Nolan, Lisa K

2012-06-01

Escherichia coli strains that cause disease outside the intestine are known as extraintestinal pathogenic E. coli (ExPEC) and include pathogens of humans and animals. Previously, the genome of avian-pathogenic E. coli (APEC) O1:K1:H7 strain O1, from ST95, was sequenced and compared to those of several other E. coli strains, identifying 43 genomic islands. Here, the genomic islands of APEC O1 were compared to those of other sequenced E. coli strains, and the distribution of 81 genes belonging to 12 APEC O1 genomic islands among 828 human and avian ExPEC and commensal E. coli isolates was determined. Multiple islands were highly prevalent among isolates belonging to the O1 and O18 serogroups within phylogenetic group B2, which are implicated in human neonatal meningitis. Because of the extensive genomic similarities between APEC O1 and other human ExPEC strains belonging to the ST95 phylogenetic lineage, its ability to cause disease in a rat model of sepsis and meningitis was assessed. Unlike other ST95 lineage strains, APEC O1 was unable to cause bacteremia or meningitis in the neonatal rat model and was significantly less virulent than uropathogenic E. coli (UPEC) CFT073 in a mouse sepsis model, despite carrying multiple neonatal meningitis E. coli (NMEC) virulence factors and belonging to the ST95 phylogenetic lineage. These results suggest that host adaptation or genome modifications have occurred either in APEC O1 or in highly virulent ExPEC isolates, resulting in differences in pathogenicity. Overall, the genomic islands examined provide targets for further discrimination of the different ExPEC subpathotypes, serogroups, phylogenetic types, and sequence types.

2.1 Natural History of Highly Pathogenic Avian Influenza H5N1

PubMed Central

Sonnberg, Stephanie; Webby, Richard J.; Webster, Robert G.

2013-01-01

The ecology of highly pathogenic avian influenza (HPAI) H5N1 has significantly changed from sporadic outbreaks in terrestrial poultry to persistent circulation in terrestrial and aquatic poultry and potentially in wild waterfowl. A novel genotype of HPAI H5N1 arose in 1996 in southern China and through ongoing mutation, reassortment, and natural selection, has diverged into distinct lineages and expanded into multiple reservoir hosts. The evolution of Goose/Guangdong-lineage highly pathogenic H5N1 viruses is ongoing: while stable interactions exist with some reservoir hosts, these viruses are continuing to evolve and adapt to others, and pose an un-calculable risk to sporadic hosts, including humans. PMID:23735535

Antifungal activity of different neem leaf extracts and the nimonol against some important human pathogens

PubMed Central

Mahmoud, D.A.; Hassanein, N.M.; Youssef, K.A.; Abou Zeid, M.A.

2011-01-01

This study was conducted to evaluate the effect of aqueous, ethanolic and ethyl acetate extracts from neem leaves on growth of some human pathogens (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Candida albicans and Microsporum gypseum) in vitro. Different concentrations (5, 10, 15 and 20%) prepared from these extracts inhibited the growth of the test pathogens and the effect gradually increased with concentration. The 20% ethyl acetate extract gave the strongest inhibition compared with the activity obtained by the same concentration of the other extracts. High Performance Liquid Chromatography (HPLC) analysis of ethyl acetate extract showed the presence of a main component (nimonol) which was purified and chemically confirmed by Nuclear Magnetic Resonance (NMR) spectroscopic analysis. The 20% ethyl acetate extract lost a part of its antifungal effect after pooling out the nimonol and this loss in activity was variable on test pathogens. The purified nimonol as a separate compound did not show any antifungal activity when assayed against all the six fungal pathogens. PMID:24031718

Pathogen Transmission from Humans to Great Apes is a Growing Threat to Primate Conservation.

PubMed

Dunay, Emily; Apakupakul, Kathleen; Leard, Stephen; Palmer, Jamie L; Deem, Sharon L

2018-01-23

All six great ape species are listed as endangered or critically endangered by the IUCN and experiencing decreasing population trends. One of the threats to these non-human primates is the transmission of pathogens from humans. We conducted a literature review on occurrences of pathogen transmission from humans to great apes to highlight this often underappreciated issue. In total, we found 33 individual occurrences of probable or confirmed pathogen transmission from humans to great apes: 23 involved both pathogen and disease transmission, 7 pathogen transmission only, 2 positive antibody titers to zoonotic pathogens, and 1 pathogen transmission with probable disease. Great ape populations were categorized into captive, semi-free-living, and free-living conditions. The majority of occurrences involved chimpanzees (Pan troglodytes) (n = 23) or mountain gorillas (Gorilla beringei beringei) (n = 8). These findings have implications for conservation efforts and management of endangered great ape populations. Future efforts should focus on monitoring and addressing zoonotic pathogen and disease transmission between humans, great ape species, and other taxa to ensure the health of humans, wild and domestic animals, and the ecosystems we share.

Detection of Zoonotic Pathogens and Characterization of Novel Viruses Carried by Commensal Rattus norvegicus in New York City

PubMed Central

Bhat, Meera; Firth, Matthew A.; Williams, Simon H.; Frye, Matthew J.; Simmonds, Peter; Conte, Juliette M.; Ng, James; Garcia, Joel; Bhuva, Nishit P.; Lee, Bohyun; Che, Xiaoyu; Quan, Phenix-Lan; Lipkin, W. Ian

2014-01-01

ABSTRACT Norway rats (Rattus norvegicus) are globally distributed and concentrate in urban environments, where they live and feed in closer proximity to human populations than most other mammals. Despite the potential role of rats as reservoirs of zoonotic diseases, the microbial diversity present in urban rat populations remains unexplored. In this study, we used targeted molecular assays to detect known bacterial, viral, and protozoan human pathogens and unbiased high-throughput sequencing to identify novel viruses related to agents of human disease in commensal Norway rats in New York City. We found that these rats are infected with bacterial pathogens known to cause acute or mild gastroenteritis in people, including atypical enteropathogenic Escherichia coli, Clostridium difficile, and Salmonella enterica, as well as infectious agents that have been associated with undifferentiated febrile illnesses, including Bartonella spp., Streptobacillus moniliformis, Leptospira interrogans, and Seoul hantavirus. We also identified a wide range of known and novel viruses from groups that contain important human pathogens, including sapoviruses, cardioviruses, kobuviruses, parechoviruses, rotaviruses, and hepaciviruses. The two novel hepaciviruses discovered in this study replicate in the liver of Norway rats and may have utility in establishing a small animal model of human hepatitis C virus infection. The results of this study demonstrate the diversity of microbes carried by commensal rodent species and highlight the need for improved pathogen surveillance and disease monitoring in urban environments. PMID:25316698

Reconstructing the emergence of a lethal infectious disease of wildlife supports a key role for spread through translocations by humans

PubMed Central

Cunningham, Andrew A.; Langton, Tom E. S.

2016-01-01

There have been few reconstructions of wildlife disease emergences, despite their extensive impact on biodiversity and human health. This is in large part attributable to the lack of structured and robust spatio-temporal datasets. We overcame logistical problems of obtaining suitable information by using data from a citizen science project and formulating spatio-temporal models of the spread of a wildlife pathogen (genus Ranavirus, infecting amphibians). We evaluated three main hypotheses for the rapid increase in disease reports in the UK: that outbreaks were being reported more frequently, that climate change had altered the interaction between hosts and a previously widespread pathogen, and that disease was emerging due to spatial spread of a novel pathogen. Our analysis characterized localized spread from nearby ponds, consistent with amphibian dispersal, but also revealed a highly significant trend for elevated rates of additional outbreaks in localities with higher human population density—pointing to human activities in also spreading the virus. Phylogenetic analyses of pathogen genomes support the inference of at least two independent introductions into the UK. Together these results point strongly to humans repeatedly translocating ranaviruses into the UK from other countries and between UK ponds, and therefore suggest potential control measures. PMID:27683363

Pathogenic Vibrio species isolated from estuarine environments (Ceará, Brazil) - antimicrobial resistance and virulence potential profiles.

PubMed

Menezes, Francisca G R DE; Rodriguez, Marina T T; Carvalho, Fátima C T DE; Rebouças, Rosa H; Costa, Renata A; Sousa, Oscarina V DE; Hofer, Ernesto; Vieira, Regine H S F

2017-01-01

Detection of virulent strains associated with aquatic environment is a current concern for the management and control of human and animal health. Thus, Vibrio diversity was investigated in four estuaries from state of Ceará (Pacoti, Choró, Pirangi and Jaguaribe) followed by antimicrobial susceptibility to different antimicrobials used in aquaculture and detection of main virulence factors to human health. Isolation and identification were performed on TCBS agar (selective medium) and dichotomous key based on biochemical characteristics, respectively. Nineteen strains of genus Vibrio were catalogued. Vibrio parahaemolyticus (Choró River) and V. alginolyticus (Pacoti River) were the most abundant species in the four estuaries. All strains were submitted to disk diffusion technique (15 antimicrobials were tested). Resistance was found to: penicillin (82%), ampicillin (54%), cephalotin (7%), aztreonan (1%), gentamicin, cefotaxime and ceftriaxone (0.5%). Five pathogenic strains were chosen to verification of virulence factors. Four estuaries showed a high abundance of species. High number of tested positive strains for virulence is concerning, since some of those strains are associated to human diseases, while others are known pathogens of aquatic organisms.

Toward a Genome-Wide Systems Biology Analysis of Host-Pathogen Interactions in Group A Streptococcus

PubMed Central

Musser, James M.; DeLeo, Frank R.

2005-01-01

Genome-wide analysis of microbial pathogens and molecular pathogenesis processes has become an area of considerable activity in the last 5 years. These studies have been made possible by several advances, including completion of the human genome sequence, publication of genome sequences for many human pathogens, development of microarray technology and high-throughput proteomics, and maturation of bioinformatics. Despite these advances, relatively little effort has been expended in the bacterial pathogenesis arena to develop and use integrated research platforms in a systems biology approach to enhance our understanding of disease processes. This review discusses progress made in exploiting an integrated genome-wide research platform to gain new knowledge about how the human bacterial pathogen group A Streptococcus causes disease. Results of these studies have provided many new avenues for basic pathogenesis research and translational research focused on development of an efficacious human vaccine and novel therapeutics. One goal in summarizing this line of study is to bring exciting new findings to the attention of the investigative pathology community. In addition, we hope the review will stimulate investigators to consider using analogous approaches for analysis of the molecular pathogenesis of other microbes. PMID:16314461

Control of human pathogenic Yersinia enterocolitica in minced meat: Comparative analysis of different interventions using a risk assessment approach.

PubMed

Van Damme, I; De Zutter, L; Jacxsens, L; Nauta, M J

2017-06-01

This study aimed to evaluate the effect of different processing scenarios along the farm-to-fork chain on the contamination of minced pork with human pathogenic Y. enterocolitica. A modular process risk model (MPRM) was used to perform the assessment of the concentrations of pathogenic Y. enterocolitica in minced meat produced in industrial meat processing plants. The model described the production of minced pork starting from the contamination of pig carcasses with pathogenic Y. enterocolitica just before chilling. The endpoints of the assessment were (i) the proportion of 0.5 kg minced meat packages that contained pathogenic Y. enterocolitica and (ii) the proportion of 0.5 kg minced meat packages that contained more than 10³ pathogenic Y. enterocolitica at the end of storage, just before consumption of raw pork or preparation. Comparing alternative scenarios to the baseline model showed that the initial contamination and different decontamination procedures of carcasses have an important effect on the proportion of highly contaminated minced meat packages at the end of storage. The addition of pork cheeks and minimal quantities of tonsillar tissue into minced meat also had a large effect on the endpoint estimate. Finally, storage time and temperature at consumer level strongly influenced the number of highly contaminated packages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of the Internal Genes of Influenza A (H7N9) Virus Contributing to High Pathogenicity in Mice

PubMed Central

Bi, Yuhai; Xie, Qing; Zhang, Shuang; Li, Yun; Xiao, Haixia; Jin, Tao; Zheng, Weinan; Li, Jing; Jia, Xiaojuan; Sun, Lei; Liu, Jinhua; Qin, Chuan

2014-01-01

ABSTRACT The recently identified H7N9 influenza A virus has caused severe economic losses and worldwide public concern. Genetic analysis indicates that its six internal genes all originated from H9N2 viruses. However, the H7N9 virus is more highly pathogenic in humans than H9N2, which suggests that the internal genes of H7N9 have mutated. To analyze which H7N9 virus internal genes contribute to its high pathogenicity, a series of reassortants was generated by reverse genetics, with each virus containing a single internal gene of the typical A/Anhui/1/2013 (H7N9) (AH-H7N9) virus in the genetic background of the A/chicken/Shandong/lx1023/2007 (H9N2) virus. The replication ability, polymerase activity, and pathogenicity of these viruses were then evaluated in vitro and in vivo. These recombinants displayed high genetic compatibility, and the H7N9-derived PB2, M, and NP genes were identified as the virulence genes for the reassortants in mice. Further investigation confirmed that the PB2 K627 residue is critical for the high pathogenicity of the H7N9 virus and the reassortant containing the H7N9-derived PB2 segment (H9N2-AH/PB2). Notably, the H7N9-derived PB2 gene displayed greater compatibility with the H9N2 genome than that of H7N9, endowing the H9N2-AH/PB2 reassortant with greater viability and virulence than the parental H7N9 virus. In addition, the H7N9 virus, with the exception of the H9N2 reassortants, could effectively replicate in human A549 cells. Our results indicate that PB2, M, and NP are the key virulence genes, together with the surface hemagglutinin (HA) and neuraminidase (NA) proteins, contributing to the high infectivity of the H7N9 virus in humans. IMPORTANCE To date, the novel H7N9 influenza A virus has caused 437 human infections, with approximately 30% mortality. Previous work has primarily focused on the two viral surface proteins, HA and NA, but the contribution of the six internal genes to the high pathogenicity of H7N9 has not been systematically studied. Here, the H9N2 virus was used as a genetic backbone to evaluate the virulence genes of H7N9 virus in vitro and in vivo. Our data indicate that the PB2, M, and NP genes play important roles in viral infection in mice and, together with HA and NA, contribute to the high infectivity of the H7N9 virus in humans. PMID:25320305

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).

Interrelationships of food safety and plant pathology: the life cycle of human pathogens on plants.

PubMed

Barak, Jeri D; Schroeder, Brenda K

2012-01-01

Bacterial food-borne pathogens use plants as vectors between animal hosts, all the while following the life cycle script of plant-associated bacteria. Similar to phytobacteria, Salmonella, pathogenic Escherichia coli, and cross-domain pathogens have a foothold in agricultural production areas. The commonality of environmental contamination translates to contact with plants. Because of the chronic absence of kill steps against human pathogens for fresh produce, arrival on plants leads to persistence and the risk of human illness. Significant research progress is revealing mechanisms used by human pathogens to colonize plants and important biological interactions between and among bacteria in planta. These findings articulate the difficulty of eliminating or reducing the pathogen from plants. The plant itself may be an untapped key to clean produce. This review highlights the life of human pathogens outside an animal host, focusing on the role of plants, and illustrates areas that are ripe for future investigation.

Reliable detection of Bacillus anthracis, Francisella tularensis and Yersinia pestis by using multiplex qPCR including internal controls for nucleic acid extraction and amplification.

PubMed

Janse, Ingmar; Hamidjaja, Raditijo A; Bok, Jasper M; van Rotterdam, Bart J

2010-12-08

Several pathogens could seriously affect public health if not recognized timely. To reduce the impact of such highly pathogenic micro-organisms, rapid and accurate diagnostic tools are needed for their detection in various samples, including environmental samples. Multiplex real-time PCRs were designed for rapid and reliable detection of three major pathogens that have the potential to cause high morbidity and mortality in humans: B. anthracis, F. tularensis and Y. pestis. The developed assays detect three pathogen-specific targets, including at least one chromosomal target, and one target from B. thuringiensis which is used as an internal control for nucleic acid extraction from refractory spores as well as successful DNA amplification. Validation of the PCRs showed a high analytical sensitivity, specificity and coverage of diverse pathogen strains. The multiplex qPCR assays that were developed allow the rapid detection of 3 pathogen-specific targets simultaneously, without compromising sensitivity. The application of B. thuringiensis spores as internal controls further reduces false negative results. This ensures highly reliable detection, while template consumption and laboratory effort are kept at a minimum.

Reliable detection of Bacillus anthracis, Francisella tularensis and Yersinia pestis by using multiplex qPCR including internal controls for nucleic acid extraction and amplification

PubMed Central

2010-01-01

Background Several pathogens could seriously affect public health if not recognized timely. To reduce the impact of such highly pathogenic micro-organisms, rapid and accurate diagnostic tools are needed for their detection in various samples, including environmental samples. Results Multiplex real-time PCRs were designed for rapid and reliable detection of three major pathogens that have the potential to cause high morbidity and mortality in humans: B. anthracis, F. tularensis and Y. pestis. The developed assays detect three pathogen-specific targets, including at least one chromosomal target, and one target from B. thuringiensis which is used as an internal control for nucleic acid extraction from refractory spores as well as successful DNA amplification. Validation of the PCRs showed a high analytical sensitivity, specificity and coverage of diverse pathogen strains. Conclusions The multiplex qPCR assays that were developed allow the rapid detection of 3 pathogen-specific targets simultaneously, without compromising sensitivity. The application of B. thuringiensis spores as internal controls further reduces false negative results. This ensures highly reliable detection, while template consumption and laboratory effort are kept at a minimum PMID:21143837

The Arginine Decarboxylase Pathways of Host and Pathogen Interact to Impact Inflammatory Pathways in the Lung

PubMed Central

Dalluge, Joseph J.; Welchlin, Cole W.; Hughes, John; Han, Wei; Blackwell, Timothy S.; Laguna, Theresa A.; Williams, Bryan J.

2014-01-01

The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic. PMID:25350753

The arginine decarboxylase pathways of host and pathogen interact to impact inflammatory pathways in the lung.

PubMed

Paulson, Nick B; Gilbertsen, Adam J; Dalluge, Joseph J; Welchlin, Cole W; Hughes, John; Han, Wei; Blackwell, Timothy S; Laguna, Theresa A; Williams, Bryan J

2014-01-01

The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic.

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

PubMed Central

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

2015-01-01

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

Proteomic screening of variola virus reveals a unique NF-kappaB inhibitor that is highly conserved among pathogenic orthopoxviruses.

PubMed

Mohamed, Mohamed R; Rahman, Masmudur M; Lanchbury, Jerry S; Shattuck, Donna; Neff, Chris; Dufford, Max; van Buuren, Nick; Fagan, Katharine; Barry, Michele; Smith, Scott; Damon, Inger; McFadden, Grant

2009-06-02

Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. Here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cDNA libraries. Several protein-protein interactions were identified, including an interaction between variola G1R, an ankryin/F-box containing protein, and human nuclear factor kappa-B1 (NF-kappaB1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-kappaB1/p105. Orthologs of G1R are present in a variety of pathogenic orthopoxviruses, but not in vaccinia virus, and expression of any one of these viral proteins blocks NF-kappaB signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses.

Control of viremia and maintenance of intestinal CD4+ memory T cells in SHIV162P3 infected macaques after pathogenic SIVMAC251 challenge

PubMed Central

Pahar, Bapi; Lackner, Andrew A.; Piatak, Michael; Lifson, Jeffrey D.; Wang, Xiaolei; Das, Arpita; Ling, Binhua; Montefiori, David C.; Veazey, Ronald S.

2009-01-01

Recent HIV vaccine failures have prompted calls for more preclinical vaccine testing in nonhuman primates. However, similar to HIV infection of humans, developing a vaccine that protects macaques from infection following pathogenic SIVMAC251 challenge has proven difficult, and current vaccine candidates at best, only reduce viral loads after infection. Here we demonstrate that prior infection with a chimeric simian-human immunodeficiency virus (SHIV) containing an HIV envelope gene confers protection against intravenous infection with the heterologous, highly pathogenic SIVMAC251 in rhesus macaques. Although definitive immune correlates of protection were not identified, preservation and/or restoration of intestinal CD4+ memory T cells were associated with protection from challenge and control of viremia. These results suggest that protection against pathogenic lentiviral infection or disease progression is indeed possible, and may correlate with preservation of mucosal CD4+ T cells. PMID:19298994

Rodent-associated Bartonella Febrile Illness, Southwestern United States

PubMed Central

Iralu, Jonathan; Bai, Ying; Crook, Larry; Tempest, Bruce; Simpson, Gary; McKenzie, Taylor

2006-01-01

Serum specimens from 114 patients hospitalized with a febrile illness were tested with an indirect immunofluorescence assay (IFA) using Bartonella antigens prepared from 6 species of sigmodontine rodents and 3 known human Bartonella pathogens: B. henselae, B. quintana, and B. elizabethae. Acute- and convalescent-phase serum samples from 5 of these patients showed seroconversion with an IFA titer >512 to rodent-associated Bartonella antigens. The highest titer was against antigen derived from the white-throated woodrat (Neotoma albigula), although this rodent is not necessarily implicated as the source of infection. Three of the 5 who seroconverted showed no cross-reaction to the 3 Bartonella human pathogens. Common clinical characteristics were fever, chills, myalgias, leukopenia, thrombocytopenia, and transaminasemia. Although antibodies to Bartonella are cross-reactive, high-titer seroconversions to rodent-associated Bartonella antigens in adults with common clinical characteristics should stimulate the search for additional Bartonella human pathogens. PMID:16836824

Geographic variation in the relationship between human Lyme disease incidence and density of infected host-seeking Ixodes scapularis nymphs in the Eastern United States.

PubMed

Pepin, Kim M; Eisen, Rebecca J; Mead, Paul S; Piesman, Joseph; Fish, Durland; Hoen, Anne G; Barbour, Alan G; Hamer, Sarah; Diuk-Wasser, Maria A

2012-06-01

Prevention and control of Lyme disease is difficult because of the complex biology of the pathogen's (Borrelia burgdorferi) vector (Ixodes scapularis) and multiple reservoir hosts with varying degrees of competence. Cost-effective implementation of tick- and host-targeted control methods requires an understanding of the relationship between pathogen prevalence in nymphs, nymph abundance, and incidence of human cases of Lyme disease. We quantified the relationship between estimated acarological risk and human incidence using county-level human case data and nymphal prevalence data from field-derived estimates in 36 eastern states. The estimated density of infected nymphs (mDIN) was significantly correlated with human incidence (r = 0.69). The relationship was strongest in high-prevalence areas, but it varied by region and state, partly because of the distribution of B. burgdorferi genotypes. More information is needed in several high-prevalence states before DIN can be used for cost-effectiveness analyses.

An Egyptian HPAI H5N1 isolate from clade 2.2.1.2 is highly pathogenic in an experimentally infected domestic duck breed (Sudani duck).

PubMed

Samir, M; Hamed, M; Abdallah, F; Kinh Nguyen, V; Hernandez-Vargas, E A; Seehusen, F; Baumgärtner, W; Hussein, A; Ali, A A H; Pessler, F

2018-06-01

The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause major problems in poultry and can, although rarely, cause human infection. Being enzootic in domestic poultry, Egyptian isolates are continuously evolving, and novel clades vary in their pathogenicity in avian hosts. Considering the importance of domestic ducks as natural hosts of HPAI H5N1 viruses and their likelihood of physical contact with other avian hosts and humans, it is of utmost importance to characterize the pathogenicity of newly emerged HPAI strains in the domestic duck. The most recently identified Egyptian clade 2.2.1.2 HPAI H5N1 viruses have been isolated from naturally infected pigeons, turkeys and humans. However, essentially nothing is known about their pathogenicity in domestic ducks. We therefore characterized the pathogenicity of an Egyptian HPAI H5N1 isolate A/chicken/Faquos/amn12/2011 (clade 2.2.1.2) in Sudani duck, a domestic duck breed commonly reared in Egypt. While viral transcription (HA mRNA) was highest in lung, heart and kidney peaking between 40 and 48 hpi, lower levels were detected in brain. Weight loss of infected ducks started at 16 hpi and persisted until 120 hpi. The first severe clinical signs were noted by 32 hpi and peaked in severity at 72 and 96 hpi. Haematological analyses showed a decline in total leucocytes, granulocytes, platelets and granulocyte/lymphocyte ratio, but lymphocytosis. Upon necropsy, lesions were obvious in heart, liver, spleen and pancreas and consisted mainly of necrosis and petechial haemorrhage. Histologically, lungs were the most severely affected organs, whereas brain only showed mild neuronal degeneration and gliosis at 48 hpi despite obvious neurological clinical signs. Taken together, our results provide first evidence that this HPAI H5N1 isolate (clade 2.2.1.2) is highly pathogenic to Sudani ducks and highlight the importance of this breed as potential reservoir and disseminator of HPAI strains from this clade. © 2018 Blackwell Verlag GmbH.

The genome sequence of avian pathogenic Escherichia coli strain O1:K1:H7 shares strong similarities with human extraintestinal pathogenic E. coli genomes.

PubMed

Johnson, Timothy J; Kariyawasam, Subhashinie; Wannemuehler, Yvonne; Mangiamele, Paul; Johnson, Sara J; Doetkott, Curt; Skyberg, Jerod A; Lynne, Aaron M; Johnson, James R; Nolan, Lisa K

2007-04-01

Escherichia coli strains that cause disease outside the intestine are known as extraintestinal pathogenic E. coli (ExPEC) and include human uropathogenic E. coli (UPEC) and avian pathogenic E. coli (APEC). Regardless of host of origin, ExPEC strains share many traits. It has been suggested that these commonalities may enable APEC to cause disease in humans. Here, we begin to test the hypothesis that certain APEC strains possess potential to cause human urinary tract infection through virulence genotyping of 1,000 APEC and UPEC strains, generation of the first complete genomic sequence of an APEC (APEC O1:K1:H7) strain, and comparison of this genome to all available human ExPEC genomic sequences. The genomes of APEC O1 and three human UPEC strains were found to be remarkably similar, with only 4.5% of APEC O1's genome not found in other sequenced ExPEC genomes. Also, use of multilocus sequence typing showed that some of the sequenced human ExPEC strains were more like APEC O1 than other human ExPEC strains. This work provides evidence that at least some human and avian ExPEC strains are highly similar to one another, and it supports the possibility that a food-borne link between some APEC and UPEC strains exists. Future studies are necessary to assess the ability of APEC to overcome the hurdles necessary for such a food-borne transmission, and epidemiological studies are required to confirm that such a phenomenon actually occurs.

Phyto-synthesis of silver nanoscale particles using Morinda citrifolia L. and its inhibitory activity against human pathogens.

PubMed

Sathishkumar, Gnanasekar; Gobinath, Chandrakasan; Karpagam, Karuppiah; Hemamalini, Vedagiri; Premkumar, Kumpati; Sivaramakrishnan, Sivaperumal

2012-06-15

Leaf extract of Morinda citrifolia L. was assessed for the synthesis of silver nanoscale particles under different temperature and reaction time. Synthesized nanoscale (MCAgNPs) particles were confirmed by analysing the excitation of surface plasmon resonance (SPR) using UV-visible spectrophotometer at 420 nm. Further SEM, HRTEM analysis confirmed the range of particle size between 10 and 60 nm and SEAD pattern authorizes the face centered cubic (fcc) crystalline nature of the MCAgNPs. Fourier transform infrared spectrum (FTIR) of synthesized MCAgNPs confirms the presence of high amount of phenolic compounds in the plant extract which may possibly influence the reduction process and stabilization of nanoparticles. Further, inhibitory activity of MCAgNPs and plant extract were tested against human pathogens like Eschericia coli, Pseudomonas aeroginosa, Klebsiella pneumoniae, Enterobacter aerogenes, Bacillus cereus and Enterococci sp. The results indicated that the MCAgNPs showed moderate inhibitory actions against human pathogens than crude plant extract, demonstrating its antimicrobial value against pathogenic diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

Mapping population and pathogen movements

PubMed Central

Tatem, Andrew J.

2014-01-01

For most of human history, populations have been relatively isolated from each other, and only recently has there been extensive contact between peoples, flora and fauna from both old and new worlds. The reach, volume and speed of modern travel are unprecedented, with human mobility increasing in high income countries by over 1000-fold since 1800. This growth is putting people at risk from the emergence of new strains of familiar diseases, and from completely new diseases, while ever more cases of the movement of both disease vectors and the diseases they carry are being seen. Pathogens and their vectors can now move further, faster and in greater numbers than ever before. Equally however, we now have access to the most detailed and comprehensive datasets on human mobility and pathogen distributions ever assembled, in order to combat these threats. This short review paper provides an overview of these datasets, with a particular focus on low income regions, and covers briefly approaches used to combine them to help us understand and control some of the negative effects of population and pathogen movements. PMID:24480992

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

The most important parasites in Serbia involving the foodborne route of transmission

NASA Astrophysics Data System (ADS)

Petrović, J. M.; Prodanov-Radulović, J. Z.; Vasilev, S. D.

2017-09-01

Food can be an important route for transmission of parasites to humans. Compared to other foodborne pathogens in Serbia, foodborne (or potentially foodborne) parasites do not get the attention they undoubtedly deserve. The aim of this article is to give an overview of the most important parasitic pathogens that can be transmitted by food, and that cause disease in humans: Echinococcus, Trichinella, Taenia solium and Toxoplasma gondii. For each of these pathogens, the severity of human diseases they cause, incidence, mortality and case fatality rate among humans in Serbia as well as their prevalence in animal species in Serbia are described. Some of the described foodborne parasites can induce severe disease symptoms in humans associated with high case fatality rates, while others can cause massive outbreaks. All of the aforementioned parasites occur throughout Serbia and cause both severe public health problems and substantial economic losses in livestock production. In conclusion, the control measures of foodborne parasites certainly need to include education of farmers and improvement of veterinary sanitary measures in animal farming and animal waste control.

Best Practices for Preventing Vector-Borne Diseases in Dogs and Humans.

PubMed

Dantas-Torres, Filipe; Otranto, Domenico

2016-01-01

Vector-borne diseases constitute a diversified group of illnesses, which are caused by a multitude of pathogens transmitted by arthropod vectors, such as mosquitoes, fleas, ticks, and sand flies. Proper management of these diseases is important from both human and veterinary medicine standpoints, given that many of these pathogens are transmissible to humans and dogs, which often live in close contact. In this review, we summarize the most important vector-borne diseases of dogs and humans and the best practices for their prevention. The control of these diseases would ultimately improve animal and human health and wellbeing, particularly in developing countries in the tropics, where the risk of these diseases is high and access to health care is poor. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-01-01

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

A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System

PubMed Central

Coudray-Meunier, Coralie; Fraisse, Audrey; Martin-Latil, Sandra; Delannoy, Sabine; Fach, Patrick; Perelle, Sylvie

2016-01-01

Human enteric viruses are recognized as the main causes of food- and waterborne diseases worldwide. Sensitive and quantitative detection of human enteric viruses is typically achieved through quantitative RT-PCR (RT-qPCR). A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The performance of high-throughput PCR methods was investigated for detecting 19 human pathogenic viruses and two main process controls used in food virology. The conventional real-time PCR system was compared to the RT-dPCR and RT-qPCR array. Based on the number of genome copies calculated by spectrophotometry, sensitivity was found to be slightly better with RT-qPCR than with RT-dPCR for 14 viruses by a factor range of from 0.3 to 1.6 log10. Conversely, sensitivity was better with RT-dPCR than with RT-qPCR for seven viruses by a factor range of from 0.10 to 1.40 log10. Interestingly, the number of genome copies determined by RT-dPCR was always from 1 to 2 log10 lower than the expected copy number calculated by RT-qPCR standard curve. The sensitivity of the RT-qPCR and RT-qPCR array assays was found to be similar for two viruses, and better with RT-qPCR than with RT-qPCR array for eighteen viruses by a factor range of from 0.7 to 3.0 log10. Conversely, sensitivity was only 0.30 log10 better with the RT-qPCR array than with conventional RT-qPCR assays for norovirus GIV detection. Finally, the RT-qPCR array and RT-dPCR assays were successfully used together to screen clinical samples and quantify pathogenic viruses. Additionally, this method made it possible to identify co-infection in clinical samples. In conclusion, given the rapidity and potential for large numbers of viral targets, this nanofluidic RT-qPCR assay should have a major impact on human pathogenic virus surveillance and outbreak investigations and is likely to be of benefit to public health. PMID:26824897

Genesis and Dissemination of Highly Pathogenic H5N6 Avian Influenza Viruses

PubMed Central

Yang, Lei; Zhu, Wenfei; Li, Xiaodan; Bo, Hong; Zhang, Ye; Zou, Shumei; Gao, Rongbao; Dong, Jie; Zhao, Xiang; Chen, Wenbing; Dong, Libo; Zou, Xiaohui; Xing, Yongcai

2016-01-01

ABSTRACT Clade 2.3.4.4 highly pathogenic avian influenza viruses (H5Nx) have spread from Asia to other parts of the world. Since 2014, human infections with clade 2.3.4.4 highly pathogenic avian influenza H5N6 viruses have been continuously reported in China. To investigate the genesis of the virus, we analyzed 123 H5 or N6 environmental viruses sampled from live-poultry markets or farms from 2012 to 2015 in Mainland China. Our results indicated that clade 2.3.4.4 H5N2/N6/N8 viruses shared the same hemagglutinin gene as originated in early 2009. From 2012 to 2015, the genesis of highly pathogenic avian influenza H5N6 viruses occurred via two independent pathways. Three major reassortant H5N6 viruses (reassortants A, B, and C) were generated. Internal genes of reassortant A and B viruses and reassortant C viruses derived from clade 2.3.2.1c H5N1 and H9N2 viruses, respectively. Many mammalian adaption mutations and antigenic variations were detected among the three reassortant viruses. Considering their wide circulation and dynamic reassortment in poultry, we highly recommend close monitoring of the viruses in poultry and humans. IMPORTANCE Since 2014, clade 2.3.4.4 highly pathogenic avian influenza (H5Nx) viruses have caused many outbreaks in both wild and domestic birds globally. Severe human cases with novel H5N6 viruses in this group were also reported in China in 2014 and 2015. To investigate the genesis of the genetic diversity of these H5N6 viruses, we sequenced 123 H5 or N6 environmental viruses sampled from 2012 to 2015 in China. Sequence analysis indicated that three major reassortants of these H5N6 viruses had been generated by two independent evolutionary pathways. The H5N6 reassortant viruses had been detected in most provinces of southern China and neighboring countries. Considering the mammalian adaption mutations and antigenic variation detected, the spread of these viruses should be monitored carefully due to their pandemic potential. PMID:28003485

Task 1.5 Genomic Shift and Drift Trends of Emerging Pathogens

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

Borucki, M

2010-01-05

The Lawrence Livermore National Laboratory (LLNL) Bioinformatics group has recently taken on a role in DTRA's Transformation Medical Technologies Initiative (TMTI). The high-level goal of TMTI is to accelerate the development of broad-spectrum countermeasures. To achieve those goals, TMTI has a near term need to conduct analyses of genomic shift and drift trends of emerging pathogens, with a focused eye on select agent pathogens, as well as antibiotic and virulence markers. Most emerging human pathogens are zoonotic viruses with a genome composed of RNA. The high mutation rate of the replication enzymes of RNA viruses contributes to sequence drift andmore » provides one mechanism for these viruses to adapt to diverse hosts (interspecies transmission events) and cause new human and zoonotic diseases. Additionally, new viral pathogens frequently emerge due to genetic shift (recombination and segment reassortment) which allows for dramatic genotypic and phenotypic changes to occur rapidly. Bacterial pathogens also evolve via genetic drift and shift, although sequence drift generally occurs at a much slower rate for bacteria as compared to RNA viruses. However, genetic shift such as lateral gene transfer and inter- and intragenomic recombination enables bacteria to rapidly acquire new mechanisms of survival and antibiotic resistance. New technologies such as rapid whole genome sequencing of bacterial genomes, ultra-deep sequencing of RNA virus populations, metagenomic studies of environments rich in antibiotic resistance genes, and the use of microarrays for the detection and characterization of emerging pathogens provide mechanisms to address the challenges posed by the rapid emergence of pathogens. Bioinformatic algorithms that enable efficient analysis of the massive amounts of data generated by these technologies as well computational modeling of protein structures and evolutionary processes need to be developed to allow the technology to fulfill its potential.« less

Human Genomic Loci Important in Common Infectious Diseases: Role of High-Throughput Sequencing and Genome-Wide Association Studies

PubMed Central

Sserwadda, Ivan; Amujal, Marion; Namatovu, Norah

2018-01-01

HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers. PMID:29755620

Contamination of produce with human pathogens: sources and solutions

USDA-ARS?s Scientific Manuscript database

Outbreaks of foodborne illnesses associated with the presence of human pathogens have led to increased concern about the prevalence of pathogens in the environment and the vulnerability of fresh produce to contamination by these pathogens. As the FDA strives to mandate treatments to reduce pathogen...

Whole genome sequencing of the fish pathogen Francisella noatunensis subsp. orientalis Toba04 gives novel insights into Francisella evolution and pathogenecity

PubMed Central

2012-01-01

Background Francisella is a genus of gram-negative bacterium highly virulent in fishes and human where F. tularensis is causing the serious disease tularaemia in human. Recently Francisella species have been reported to cause mortality in aquaculture species like Atlantic cod and tilapia. We have completed the sequencing and draft assembly of the Francisella noatunensis subsp. orientalisToba04 strain isolated from farmed Tilapia. Compared to other available Francisella genomes, it is most similar to the genome of Francisella philomiragia subsp. philomiragia, a free-living bacterium not virulent to human. Results The genome is rearranged compared to the available Francisella genomes even though we found no IS-elements in the genome. Nearly 16% percent of the predicted ORFs are pseudogenes. Computational pathway analysis indicates that a number of the metabolic pathways are disrupted due to pseudogenes. Comparing the novel genome with other available Francisella genomes, we found around 2.5% of unique genes present in Francisella noatunensis subsp. orientalis Toba04 and a list of genes uniquely present in the human-pathogenic Francisella subspecies. Most of these genes might have transferred from bacterial species through horizontal gene transfer. Comparative analysis between human and fish pathogen also provide insights into genes responsible for pathogenecity. Our analysis of pseudogenes indicates that the evolution of Francisella subspecies’s pseudogenes from Tilapia is old with large number of pseudogenes having more than one inactivating mutation. Conclusions The fish pathogen has lost non-essential genes some time ago. Evolutionary analysis of the Francisella genomes, strongly suggests that human and fish pathogenic Francisella species have evolved independently from free-living metabolically competent Francisella species. These findings will contribute to understanding the evolution of Francisella species and pathogenesis. PMID:23131096

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

PubMed

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

2013-01-01

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

Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model

PubMed Central

Weidensdorfer, Marko; Chae, Ju Ik; Makobe, Celestine; Stahl, Julia; Averhoff, Beate; Müller, Volker; Schürmann, Christoph; Brandes, Ralf P.; Wilharm, Gottfried; Ballhorn, Wibke; Christ, Sara; Linke, Dirk; Fischer, Doris; Göttig, Stephan

2015-01-01

Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore, ex vivo infection of human organs might represent an attractive method to overcome these limitations. We infected whole human umbilical cords ex vivo with Bartonella henselae or Acinetobacter baumannii under dynamic flow conditions mimicking the in vivo infection situation of human endothelium. For this purpose, methods for quantifying endothelium-adherent wild-type and trimeric autotransporter adhesin (TAA)-deficient bacteria were set up. Data revealed that (i) A. baumannii binds in a TAA-dependent manner to endothelial cells, (ii) this organ infection model led to highly reproducible adherence rates, and furthermore, (iii) this model allowed to dissect the biological function of TAAs in the natural course of human infections. These findings indicate that infection models using ex vivo human tissue samples (“organ microbiology”) might be a valuable tool in analyzing bacterial pathogenicity with the capacity to replace animal infection models at least partially. PMID:26712205

[Occupational exposure induced human transmissible highly pathogenic H5N1 avian influenza in one patient].

PubMed

Zhou, Hong-sheng; Liu, Jing-hu; Wang, Xiu-quan; Guo, Jiang-hua; Song, Xiao-lin

2007-03-01

To describe the clinical manifestations and lung imaging characteristics of the human transmissible highly pathogenic H5N1 avian influenza. The clinical manifestations and lung imaging characteristics of human transmissible highly pathogenic H5N1 avian influenza in one patient were reviewed and analyzed. The patient had the clear history of occupational exposure. The fever and symptoms of influenza were prominent at onset and associated with the symptoms of the digestive tract. The laboratory findings comprised the significant decrease of the white blood cell count and the lymphocyte number and the impairment of the liver function and the myocardial enzymes. The disease progressed rapidly and multiple organs including lung, heart, liver and kidneys were involved. It was ineffective to administer anti-fungal, anti-virus and anti-inflammation medicines. It was in vain to use mechanical ventilation and pneumothorax intubation and closed drainage as well as the support therapy. In the X-ray film, the lesions progressed quickly and changed diversely with absorption and development at the same time. The nasal and throat swabs and the gargle specimen were detected with RT-PCR and real time PCR by Chinese Center for Disease Control and Prevention. The results showed that both the specific HA and NA genes of the avian influenza virus H5N1 subtype were positive and in the same time a strain of avian influenza virus A/jiangxi/1/2005H5N1) was separated and obtained from the nasal and throat swabs. The autopsy showed that diffuse injury of alveolus in lungs, DIC and multiple organ injury. The human transmissible highly pathogenic H5N1 avian influenza is a lethal disease. The disease progresses rapidly with the absorption and development at the same time in the lungs and unfortunately there are no effective therapeutic measures. The prevention of the contagious disease for the occupationally exposed population should be emphasized.

Assessment of sources of human pathogens and fecal contamination in a Florida freshwater lake.

PubMed

Staley, Christopher; Reckhow, Kenneth H; Lukasik, Jerzy; Harwood, Valerie J

2012-11-01

We investigated the potential for a variety of environmental reservoirs to harbor or contribute fecal indicator bacteria (FIB), DNA markers of human fecal contamination, and human pathogens to a freshwater lake. We hypothesized that submerged aquatic vegetation (SAV), sediments, and stormwater act as reservoirs and/or provide inputs of FIB and human pathogens to this inland water. Analysis included microbial source tracking (MST) markers of sewage contamination (Enterococcus faecium esp gene, human-associated Bacteroides HF183, and human polyomaviruses), pathogens (Salmonella, Cryptosporidium, Giardia, and enteric viruses), and FIB (fecal coliforms, Escherichia coli, and enterococci). Bayesian analysis was used to assess relationships among microbial and physicochemical variables. FIB in the water were correlated with concentrations in SAV and sediment. Furthermore, the correlation of antecedent rainfall and major rain events with FIB concentrations and detection of human markers and pathogens points toward multiple reservoirs for microbial contaminants in this system. Although pathogens and human-source markers were detected in 55% and 21% of samples, respectively, markers rarely coincided with pathogen detection. Bayesian analysis revealed that low concentrations (<45 CFU × 100 ml(-1)) of fecal coliforms were associated with 93% probability that pathogens would not be detected; furthermore the Bayes net model showed associations between elevated temperature and rainfall with fecal coliform and enterococci concentrations, but not E. coli. These data indicate that many under-studied matrices (e.g. SAV, sediment, stormwater) are important reservoirs for FIB and potentially human pathogens and demonstrate the usefulness of Bayes net analysis for water quality assessment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tick-borne pathogens and associated co-infections in ticks collected from domestic animals in central China.

PubMed

Chen, Zhuo; Liu, Qin; Liu, Ji-Qi; Xu, Bian-Li; Lv, Shan; Xia, Shang; Zhou, Xiao-Nong

2014-05-22

Ticks can transmit a number of pathogens to humans and domestic animals. Tick borne diseases (TBDs), which may lead to organ failure and death have been recently reported in China. 98.75% of the total cases (>1000) in Henan provinces have been reported in Xinyang city. Therefore, the aims of this study were to investigate the fauna of ticks and detect the potential pathogens in ticks in Xinyang, the region of central China. Ticks were collected from 10 villages of Xinyang from April to December 2012, from domestic animals including sheep, cattle and dogs. Then identification of ticks and detection of tick-borne pathogens, including Babesia spp., Theileria spp., Anaplasma spp., Ehrlichia spp., Rickettsia spp., tick-borne encephalitis virus (TBEV), Borrelia burgdorferi sensu lato, Leishmania infantum, were undertaken by using polymerase chain reaction assay (PCR) and sequence analysis. Moreover, the co-infection patterns of various pathogens were compared among locations where ticks were collected. A total of 308 ticks were collected. Two species of Ixodidae were found, namely Haemaphysalis longicornis (96.75%) and Rhipicephalus microplus (3.25%). Five genera of pathogens, namely Theileria spp. (3.25%), Anaplasma spp. (2.92%), Babesia spp. (1.95%), Ehrlichia spp. (2.92%) and Rickettsia spp. (0.65%), were detected in 7 villages. Co-infections by two pathogens were diagnosed in 11.11% of all infected ticks. Both human and animal pathogens were abundant in ticks in the study areas. Humans and animals in these regions were at a high risk of exposure to piroplasmosis, since piroplasm had the highest rates of infection and co-infection in positive ticks.

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

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.

Highly Pathogenic Avian Influenza A(H5N1) Viruses at the Animal-Human Interface in Vietnam, 2003-2010.

PubMed

Creanga, Adrian; Hang, Nguyen Le Khanh; Cuong, Vuong Duc; Nguyen, Ha T; Phuong, Hoang Vu Mai; Thanh, Le Thi; Thach, Nguyen Co; Hien, Pham Thi; Tung, Nguyen; Jang, Yunho; Balish, Amanda; Dang, Nguyen Hoang; Duong, Mai Thuy; Huong, Ngo Thu; Hoa, Do Ngoc; Tho, Nguyen Dang; Klimov, Alexander; Kapella, Bryan K; Gubareva, Larisa; Kile, James C; Hien, Nguyen Tran; Mai, Le Quynh; Davis, C Todd

2017-09-15

Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Pan-genome analysis of human gastric pathogen H. pylori: comparative genomics and pathogenomics approaches to identify regions associated with pathogenicity and prediction of potential core therapeutic targets.

PubMed

Ali, Amjad; Naz, Anam; Soares, Siomar C; Bakhtiar, Marriam; Tiwari, Sandeep; Hassan, Syed S; Hanan, Fazal; Ramos, Rommel; Pereira, Ulisses; Barh, Debmalya; Figueiredo, Henrique César Pereira; Ussery, David W; Miyoshi, Anderson; Silva, Artur; Azevedo, Vasco

2015-01-01

Helicobacter pylori is a human gastric pathogen implicated as the major cause of peptic ulcer and second leading cause of gastric cancer (~70%) around the world. Conversely, an increased resistance to antibiotics and hindrances in the development of vaccines against H. pylori are observed. Pan-genome analyses of the global representative H. pylori isolates consisting of 39 complete genomes are presented in this paper. Phylogenetic analyses have revealed close relationships among geographically diverse strains of H. pylori. The conservation among these genomes was further analyzed by pan-genome approach; the predicted conserved gene families (1,193) constitute ~77% of the average H. pylori genome and 45% of the global gene repertoire of the species. Reverse vaccinology strategies have been adopted to identify and narrow down the potential core-immunogenic candidates. Total of 28 nonhost homolog proteins were characterized as universal therapeutic targets against H. pylori based on their functional annotation and protein-protein interaction. Finally, pathogenomics and genome plasticity analysis revealed 3 highly conserved and 2 highly variable putative pathogenicity islands in all of the H. pylori genomes been analyzed.

Capacity building efforts and perceptions for wildlife surveillance to detect zoonotic pathogens: comparing stakeholder perspectives.

PubMed

Schwind, Jessica S; Goldstein, Tracey; Thomas, Kate; Mazet, Jonna A K; Smith, Woutrina A

2014-07-04

The capacity to conduct zoonotic pathogen surveillance in wildlife is critical for the recognition and identification of emerging health threats. The PREDICT project, a component of United States Agency for International Development's Emerging Pandemic Threats program, has introduced capacity building efforts to increase zoonotic pathogen surveillance in wildlife in global 'hot spot' regions where zoonotic disease emergence is likely to occur. Understanding priorities, challenges, and opportunities from the perspectives of the stakeholders is a key component of any successful capacity building program. A survey was administered to wildlife officials and to PREDICT-implementing in-country project scientists in 16 participating countries in order to identify similarities and differences in perspectives between the groups regarding capacity needs for zoonotic pathogen surveillance in wildlife. Both stakeholder groups identified some human-animal interfaces (i.e. areas of high contact between wildlife and humans with the potential risk for disease transmission), such as hunting and markets, as important for ongoing targeting of wildlife surveillance. Similarly, findings regarding challenges across stakeholder groups showed some agreement in that a lack of sustainable funding across regions was the greatest challenge for conducting wildlife surveillance for zoonotic pathogens (wildlife officials: 96% and project scientists: 81%). However, the opportunity for improving zoonotic pathogen surveillance capacity identified most frequently by wildlife officials as important was increasing communication or coordination among agencies, sectors, or regions (100% of wildlife officials), whereas the most frequent opportunities identified as important by project scientists were increasing human capacity, increasing laboratory capacity, and the growing interest or awareness regarding wildlife disease or surveillance programs (all identified by 69% of project scientists). A One Health approach to capacity building applied at local and global scales will have the greatest impact on improving zoonotic pathogen surveillance in wildlife. This approach will involve increasing communication and cooperation across ministries and sectors so that experts and stakeholders work together to identify and mitigate surveillance gaps. Over time, this transdisciplinary approach to capacity building will help overcome existing challenges and promote efficient targeting of high risk interfaces for zoonotic pathogen transmission.

Genetic diversity in Treponema pallidum: implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

PubMed Central

Šmajs, David; Norris, Steven J.; Weinstock, George M.

2013-01-01

Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, T. paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections. PMID:22198325

Mosquitoes on a plane: Disinsection will not stop the spread of vector-borne pathogens, a simulation study

PubMed Central

Mier-y-Teran-Romero, Luis; Tatem, Andrew J.

2017-01-01

Mosquito-borne diseases are increasingly being recognized as global threats, with increased air travel accelerating their occurrence in travelers and their spread to new locations. Since the early days of aviation, concern over the possible transportation of infected mosquitoes has led to recommendations to disinsect aircraft. Despite rare reports of mosquitoes, most likely transported on aircraft, infecting people far from endemics areas, it is unclear how important the role of incidentally transported mosquitoes is compared to the role of traveling humans. We used data for Plasmodium falciparum and dengue viruses to estimate the probability of introduction of these pathogens by mosquitoes and by humans via aircraft under ideal conditions. The probability of introduction of either pathogen by mosquitoes is low due to few mosquitoes being found on aircraft, low infection prevalence among mosquitoes, and high mortality. Even without disinsection, introduction via infected human travelers was far more likely than introduction by infected mosquitoes; more than 1000 times more likely for P. falciparum and more than 200 times more likely for dengue viruses. Even in the absence of disinsection and under the most favorable conditions, introduction of mosquito-borne pathogens via air travel is far more likely to occur as a result of an infected human travelling rather than the incidental transportation of infected mosquitoes. Thus, while disinsection may serve a role in preventing the spread of vector species and other invasive insects, it is unlikely to impact the spread of mosquito-borne pathogens. PMID:28672006

Genome-wide phylogenetic analysis of the pathogenic potential of Vibrio furnissii

PubMed Central

Lux, Thomas M.; Lee, Rob; Love, John

2014-01-01

We recently reported the genome sequence of a free-living strain of Vibrio furnissii (NCTC 11218) harvested from an estuarine environment. V. furnissii is a widespread, free-living proteobacterium and emerging pathogen that can cause acute gastroenteritis in humans and lethal zoonoses in aquatic invertebrates, including farmed crustaceans and molluscs. Here we present the analyses to assess the potential pathogenic impact of V. furnissii. We compared the complete genome of V. furnissii with 8 other emerging and pathogenic Vibrio species. We selected and analyzed more deeply 10 genomic regions based upon unique or common features, and used 3 of these regions to construct a phylogenetic tree. Thus, we positioned V. furnissii more accurately than before and revealed a closer relationship between V. furnissii and V. cholerae than previously thought. However, V. furnissii lacks several important features normally associated with virulence in the human pathogens V. cholera and V. vulnificus. A striking feature of the V. furnissii genome is the hugely increased Super Integron, compared to the other Vibrio. Analyses of predicted genomic islands resulted in the discovery of a protein sequence that is present only in Vibrio associated with diseases in aquatic animals. We also discovered evidence of high levels horizontal gene transfer in V. furnissii. V. furnissii seems therefore to have a dynamic and fluid genome that could quickly adapt to environmental perturbation or increase its pathogenicity. Taken together, these analyses confirm the potential of V. furnissii as an emerging marine and possible human pathogen, especially in the developing, tropical, coastal regions that are most at risk from climate change. PMID:25191313

Genome-wide phylogenetic analysis of the pathogenic potential of Vibrio furnissii.

PubMed

Lux, Thomas M; Lee, Rob; Love, John

2014-01-01

We recently reported the genome sequence of a free-living strain of Vibrio furnissii (NCTC 11218) harvested from an estuarine environment. V. furnissii is a widespread, free-living proteobacterium and emerging pathogen that can cause acute gastroenteritis in humans and lethal zoonoses in aquatic invertebrates, including farmed crustaceans and molluscs. Here we present the analyses to assess the potential pathogenic impact of V. furnissii. We compared the complete genome of V. furnissii with 8 other emerging and pathogenic Vibrio species. We selected and analyzed more deeply 10 genomic regions based upon unique or common features, and used 3 of these regions to construct a phylogenetic tree. Thus, we positioned V. furnissii more accurately than before and revealed a closer relationship between V. furnissii and V. cholerae than previously thought. However, V. furnissii lacks several important features normally associated with virulence in the human pathogens V. cholera and V. vulnificus. A striking feature of the V. furnissii genome is the hugely increased Super Integron, compared to the other Vibrio. Analyses of predicted genomic islands resulted in the discovery of a protein sequence that is present only in Vibrio associated with diseases in aquatic animals. We also discovered evidence of high levels horizontal gene transfer in V. furnissii. V. furnissii seems therefore to have a dynamic and fluid genome that could quickly adapt to environmental perturbation or increase its pathogenicity. Taken together, these analyses confirm the potential of V. furnissii as an emerging marine and possible human pathogen, especially in the developing, tropical, coastal regions that are most at risk from climate change.

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.

PubMed

Hilgenfeld, Rolf; Peiris, Malik

2013-10-01

This article introduces a series of invited papers in Antiviral Research marking the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus that emerged in southern China in late 2002. Until that time, coronaviruses had not been recognized as agents causing severe disease in humans, hence, the emergence of the SARS-CoV came as a complete surprise. Research during the past ten years has revealed the existence of a diverse pool of coronaviruses circulating among various bat species and other animals, suggesting that further introductions of highly pathogenic coronaviruses into the human population are not merely probable, but inevitable. The recent emergence of another coronavirus causing severe disease, Middle East respiratory syndrome (MERS), in humans, has made it clear that coronaviruses pose a major threat to human health, and that more research is urgently needed to elucidate their replication mechanisms, identify potential drug targets, and develop effective countermeasures. In this series, experts in many different aspects of coronavirus replication and disease will provide authoritative, up-to-date reviews of the following topics: - clinical management and infection control of SARS; - reservoir hosts of coronaviruses; - receptor recognition and cross-species transmission of SARS-CoV; - SARS-CoV evasion of innate immune responses; - structures and functions of individual coronaviral proteins; - anti-coronavirus drug discovery and development; and - the public health legacy of the SARS outbreak. Each article will be identified in the last line of its abstract as belonging to the series "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses." Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-01-01

Rapidly evolving pathogens cause a diverse array of diseases and epidemics that threaten crop yield, food security as well as human, animal and ecosystem health. To combat infection greater comparative knowledge is required on the pathogenic process in multiple species. The Pathogen-Host Interactions database (PHI-base) catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and protist pathogens. Mutant phenotypes are associated with gene information. The included pathogens infect a wide range of hosts including humans, animals, plants, insects, fish and other fungi. The current version, PHI-base 3.6, available at http://www.phi-base.org, stores information on 2875 genes, 4102 interactions, 110 host species, 160 pathogenic species (103 plant, 3 fungal and 54 animal infecting species) and 181 diseases drawn from 1243 references. Phenotypic and gene function information has been obtained by manual curation of the peer-reviewed literature. A controlled vocabulary consisting of nine high-level phenotype terms permits comparisons and data analysis across the taxonomic space. PHI-base phenotypes were mapped via their associated gene information to reference genomes available in Ensembl Genomes. Virulence genes and hotspots can be visualized directly in genome browsers. Future plans for PHI-base include development of tools facilitating community-led curation and inclusion of the corresponding host target(s). © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Molecular assessment of bacterial pathogens - a contribution to drinking water safety.

PubMed

Brettar, Ingrid; Höfle, Manfred G

2008-06-01

Human bacterial pathogens are considered as an increasing threat to drinking water supplies worldwide because of the growing demand of high-quality drinking water and the decreasing quality and quantity of available raw water. Moreover, a negative impact of climate change on freshwater resources is expected. Recent advances in molecular detection technologies for bacterial pathogens in drinking water bear the promise in improving the safety of drinking water supplies by precise detection and identification of the pathogens. More importantly, the array of molecular approaches allows understanding details of infection routes of waterborne diseases, the effects of changes in drinking water treatment, and management of freshwater resources.

Streptococcus suis infection

PubMed Central

Feng, Youjun; Zhang, Huimin; Wu, Zuowei; Wang, Shihua; Cao, Min; Hu, Dan; Wang, Changjun

2014-01-01

Streptococcus suis (S. suis) is a family of pathogenic gram-positive bacterial strains that represents a primary health problem in the swine industry worldwide. S. suis is also an emerging zoonotic pathogen that causes severe human infections clinically featuring with varied diseases/syndromes (such as meningitis, septicemia, and arthritis). Over the past few decades, continued efforts have made significant progress toward better understanding this zoonotic infectious entity, contributing in part to the elucidation of the molecular mechanism underlying its high pathogenicity. This review is aimed at presenting an updated overview of this pathogen from the perspective of molecular epidemiology, clinical diagnosis and typing, virulence mechanism, and protective antigens contributing to its zoonosis. PMID:24667807

Reduced experimental infectivity and transmissibility of intercontinental H5 (H5N8 and H5N2) compared to Eurasian H5N1 highly pathogenic avian influenza viruses for chickens, turkeys, and Japanese quail

USDA-ARS?s Scientific Manuscript database

H5N1 high pathogenicity avian influenza (HPAI) virus (HPAIV) emerged in 1996 in Guangdong China and has since spread to infect and cause deaths in wild birds, poultry and humans in over 63 countries in Asia, Europe and Africa; and more recently a reassortant H5N8 clade 2.3.4.4 HPAI virus has spread ...

Environmental Transport of Emerging Human-Pathogenic Cryptosporidium Species and Subtypes through Combined Sewer Overflow and Wastewater

PubMed Central

Huang, Chengchen; Hu, Yue; Wang, Lin; Wang, Yuanfei; Li, Na; Guo, Yaqiong; Xiao, Lihua

2017-01-01

ABSTRACT The environmental transport of Cryptosporidium spp. through combined sewer overflow (CSO) and the occurrence of several emerging human-pathogenic Cryptosporidium species in developing countries remain unclear. In this study, we collected 40 CSO samples and 40 raw wastewater samples from Shanghai, China, and examined them by PCR and DNA sequencing for Cryptosporidium species (targeting the small subunit rRNA gene) and Giardia duodenalis (targeting the triosephosphate isomerase, β-giardin, and glutamate dehydrogenase genes) and Enterocytozoon bieneusi (targeting the ribosomal internal transcribed spacer) genotypes. Human-pathogenic Cryptosporidium species were further subtyped by sequence analysis of the 60-kDa glycoprotein gene, with additional multilocus sequence typing on the emerging zoonotic pathogen Cryptosporidium ubiquitum. Cryptosporidium spp., G. duodenalis, and E. bieneusi were detected in 12 and 15, 33 and 32, and 37 and 40 CSO and wastewater samples, respectively, including 10 Cryptosporidium species, 3 G. duodenalis assemblages, and 8 E. bieneusi genotypes. In addition to Cryptosporidium hominis and Cryptosporidium parvum, two new pathogens identified in industrialized nations, C. ubiquitum and Cryptosporidium viatorum, were frequently detected. The two novel C. ubiquitum subtype families identified appeared to be genetic recombinants of known subtype families. Similarly, the dominant group 1 E. bieneusi genotypes and G. duodenalis subassemblage AII are known human pathogens. The similar distribution of human-pathogenic Cryptosporidium species and E. bieneusi and G. duodenalis genotypes between wastewater and CSO samples reaffirms that storm overflow is potentially a significant contamination source of pathogens in surface water. The frequent identification of C. ubiquitum and C. viatorum in urban wastewater suggests that these newly identified human pathogens may be endemic in China. IMPORTANCE Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are major waterborne pathogens. Their transport into surface water through combined sewer overflow, which remains largely untreated in developing countries, has not been examined. In addition, the identification of these pathogens to genotypes and subtypes in urban storm overflow and wastewater is necessary for rapid and accurate assessment of pathogen transmission in humans and transport in the environment. Data from this study suggest that, like untreated urban wastewater, combined sewer overflow is commonly contaminated with human-pathogenic Cryptosporidium, G. duodenalis, and E. bieneusi genotypes and subtypes, and urban storm overflow potentially plays a significant role in the contamination of drinking source water and recreational water with human pathogens. They also indicate that Cryptosporidium ubiquitum and Cryptosporidium viatorum, two newly identified human pathogens, may be common in China, and genetic recombination can lead to the emergence of novel C. ubiquitum subtype families. PMID:28600310

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

76 FR 30176 - Expedited Review for New Animal Drug Applications for Human Pathogen Reduction Claims; Withdrawal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2001-D-0066] (Formerly Docket No. 2001D-0107) Expedited Review for New Animal Drug Applications for Human Pathogen... Review for New Animal Drug Applications for Human Pathogen Reduction Claims.'' The guidance predates the...

H5N1 influenza viruses: outbreaks and biological properties

PubMed Central

Neumann, Gabriele; Chen, Hualan; Gao, George F; Shu, Yuelong; Kawaoka, Yoshihiro

2010-01-01

All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Hong Kong that transmitted to humans, resulting in the first documented cases of human death by avian influenza virus infection. A new outbreak started in July 2003 in poultry in Vietnam, Indonesia, and Thailand, and highly pathogenic avian H5N1 influenza viruses have since spread throughout Asia and into Europe and Africa. These viruses continue to infect humans with a high mortality rate and cause worldwide concern of a looming pandemic. Moreover, H5N1 virus outbreaks have had devastating effects on the poultry industries throughout Asia. Since H5N1 virus outbreaks appear to originate from Southern China, we here examine H5N1 influenza viruses in China, with an emphasis on their biological properties. PMID:19884910

Food and human gut as reservoirs of transferable antibiotic resistance encoding genes

PubMed Central

Rolain, Jean-Marc

2013-01-01

The increase and spread of antibiotic resistance (AR) over the past decade in human pathogens has become a worldwide health concern. Recent genomic and metagenomic studies in humans, animals, in food and in the environment have led to the discovery of a huge reservoir of AR genes called the resistome that could be mobilized and transferred from these sources to human pathogens. AR is a natural phenomenon developed by bacteria to protect antibiotic-producing bacteria from their own products and also to increase their survival in highly competitive microbial environments. Although antibiotics are used extensively in humans and animals, there is also considerable usage of antibiotics in agriculture, especially in animal feeds and aquaculture. The aim of this review is to give an overview of the sources of AR and the use of antibiotics in these reservoirs as selectors for emergence of AR bacteria in humans via the food chain. PMID:23805136

Cross talk between animal and human influenza viruses.

PubMed

Ozawa, Makoto; Kawaoka, Yoshihiro

2013-01-01

Although outbreaks of highly pathogenic avian influenza in wild and domestic birds have been posing the threat of a new influenza pandemic for the past decade, the first pandemic of the twenty-first century came from swine viruses. This fact emphasizes the complexity of influenza viral ecology and the difficulty of predicting influenza viral dynamics. Complete control of influenza viruses seems impossible. However, we must minimize the impact of animal and human influenza outbreaks by learning lessons from past experiences and recognizing the current status. Here, we review the most recent influenza virology data in the veterinary field, including aspects of zoonotic agents and recent studies that assess the pandemic potential of H5N1 highly pathogenic avian influenza viruses.

Crosstalk between animal and human influenza viruses

PubMed Central

Ozawa, Makoto; Kawaoka, Yoshihiro

2017-01-01

Although outbreaks of highly pathogenic avian influenza in wild and domestic birds have been posing the threat of a new influenza pandemic for the last decade, the first pandemic of the 21st century came from swine viruses. This fact emphasizes the complexity of influenza viral ecology and the difficulty of predicting influenza viral dynamics. Complete control of influenza viruses seems impossible. However, we must minimize the impact of animal and human influenza outbreaks by learning lessons from past experiences and recognizing the current status. Here, we review the most recent influenza virology data in the veterinary field, including aspects of zoonotic agents and recent studies that assessed the pandemic potential of H5N1 highly pathogenic avian influenza viruses. PMID:25387011

Comparison of fecal indicators with pathogenic bacteria and rotavirus in groundwater.

PubMed

Ferguson, Andrew S; Layton, Alice C; Mailloux, Brian J; Culligan, Patricia J; Williams, Daniel E; Smartt, Abby E; Sayler, Gary S; Feighery, John; McKay, Larry D; Knappett, Peter S K; Alexandrova, Ekaterina; Arbit, Talia; Emch, Michael; Escamilla, Veronica; Ahmed, Kazi Matin; Alam, Md Jahangir; Streatfield, P Kim; Yunus, Mohammad; van Geen, Alexander

2012-08-01

Groundwater is routinely analyzed for fecal indicators but direct comparisons of fecal indicators to the presence of bacterial and viral pathogens are rare. This study was conducted in rural Bangladesh where the human population density is high, sanitation is poor, and groundwater pumped from shallow tubewells is often contaminated with fecal bacteria. Five indicator microorganisms (E. coli, total coliform, F+RNA coliphage, Bacteroides and human-associated Bacteroides) and various environmental parameters were compared to the direct detection of waterborne pathogens by quantitative PCR in groundwater pumped from 50 tubewells. Rotavirus was detected in groundwater filtrate from the largest proportion of tubewells (40%), followed by Shigella (10%), Vibrio (10%), and pathogenic E. coli (8%). Spearman rank correlations and sensitivity-specificity calculations indicate that some, but not all, combinations of indicators and environmental parameters can predict the presence of pathogens. Culture-dependent fecal indicator bacteria measured on a single date did not predict total bacterial pathogens, but annually averaged monthly measurements of culturable E. coli did improve prediction for total bacterial pathogens. A qPCR-based E. coli assay was the best indicator for the bacterial pathogens. F+RNA coliphage were neither correlated nor sufficiently sensitive towards rotavirus, but were predictive of bacterial pathogens. Since groundwater cannot be excluded as a significant source of diarrheal disease in Bangladesh and neighboring countries with similar characteristics, the need to develop more effective methods for screening tubewells with respect to microbial contamination is necessary. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparison of fecal indicators with pathogenic bacteria and rotavirus in groundwater

PubMed Central

Ferguson, Andrew S.; Layton, Alice C.; Mailloux, Brian J; Culligan, Patricia J.; Williams, Daniel E.; Smartt, Abby E.; Sayler, Gary S.; Feighery, John; McKay, Larry; Knappett, Peter S.K.; Alexandrova, Ekaterina; Arbit, Talia; Emch, Michael; Escamilla, Veronica; Ahmed, Kazi Matin; Alam, Md. Jahangir; Streatfield, P. Kim; Yunus, Mohammad; van Geen, Alexander

2012-01-01

Groundwater is routinely analyzed for fecal indicators but direct comparisons of fecal indicators to the presence of bacterial and viral pathogens are rare. This study was conducted in rural Bangladesh where the human population density is high, sanitation is poor, and groundwater pumped from shallow tubewells is often contaminated with fecal bacteria. Five indicator microorganisms (E. coli, total coliform, F+RNA coliphage, Bacteroides and human-associated Bacteroides) and various environmental parameters were compared to the direct detection of waterborne pathogens by quantitative PCR in groundwater pumped from 50 tubewells. Rotavirus was detected in groundwater filtrate from the largest proportion of tubewells (40%), followed by Shigella (10%), Vibrio (10%), and pathogenic E. coli (8%). Spearman rank correlations and sensitivity-specificity calculations indicate that some, but not all, combinations of indicators and environmental parameters can predict the presence of pathogens. Culture-dependent fecal indicator bacteria measured on a single date did not predict total bacterial pathogens, but annually averaged monthly measurements of culturable E. coli did improve prediction for total bacterial pathogens. A qPCR-based E. coli assay was the best indicator for the bacterial pathogens. F+RNA coliphage were neither correlated nor sufficiently sensitive towards rotavirus, but were predictive of bacterial pathogens. Since groundwater cannot be excluded as a significant source of diarrheal disease in Bangladesh and neighboring countries with similar characteristics, the need to develop more effective methods for screening tubewells with respect to microbial contamination is necessary. PMID:22705866

Human infection with a highly pathogenic avian influenza A (H5N6) virus in Yunnan province, China.

PubMed

Xu, Wen; Li, Hong; Jiang, Li

2016-01-01

Highly pathogenic avian influenza A H5N6 virus has caused four human infections in China. This study reports the preliminary findings of the first known human case of H5N6 in Yunnan province. The patient initially developed symptoms of sore throat and coughing on 27 January 2015. The disease rapidly progressed to severe pneumonia, multiple organ dysfunctions and acute respiratory distress syndrome and the patient died on 6 February. Virological analysis determined that the virus belonged to H5 clade 2.3.4.4 and it has obtained partial ability for mammalian adaptation and amantadine resistance. Environmental investigation found H5 in 63% of the samples including poultry faeces, tissues, cage surface swabs and sewage from local live poultry markets by real-time RT-PCR. These findings suggest that the expanding and enhancing of surveillance in both avian and humans are necessary to monitor the evolution of H5 influenza virus and to facilitate early detection of suspected cases.

Listeria monocytogenes presence during fermentation, drying and storage of Petrovská klobása sausage

NASA Astrophysics Data System (ADS)

Janković, V.; Mitrović, R.; Lakićević, B.; Velebit, B.; Baltić, T.

2017-09-01

The majority of human listeriosis cases appear to be caused by consumption of ready-to-eat (RTE) foods contaminated at the time of consumption with high levels of Listeria monocytogenes. Although strategies to prevent growth of L. monocytogenes in RTE products are critical for reducing the incidence of human listeriosis, this pathogen is highly difficult to control in fermented sausage processing environments due to its high tolerance to low pH and high salt concentration. The aims of the present study were to investigate the occurrence, presence and elimination of L. monocytogenes in Petrovská klobása sausage during processing, fermentation, drying and storage. L. monocytogenes, which was detected at the beginning of the production cycle, disappeared before day 30. The pathogen decline was much faster in those sausages which were dried in controlled, industrial conditions than in those dried applying the traditional, household technique.

Aeromonas hydrophila and Aeromonas veronii Predominate among Potentially Pathogenic Ciprofloxacin- and Tetracycline-Resistant Aeromonas Isolates from Lake Erie

PubMed Central

Shinko, Jasmine; Augustyniak, Alexander; Gee, Christopher; Andraso, Greg

2014-01-01

Members of the genus Aeromonas are ubiquitous in nature and have increasingly been implicated in numerous diseases of humans and other animal taxa. Although some species of aeromonads are human pathogens, their presence, density, and relative abundance are rarely considered in assessing water quality. The objectives of this study were to identify Aeromonas species within Lake Erie, determine their antibiotic resistance patterns, and assess their potential pathogenicity. Aeromonas strains were isolated from Lake Erie water by use of Aeromonas selective agar with and without tetracycline and ciprofloxacin. All isolates were analyzed for hemolytic ability and cytotoxicity against human epithelial cells and were identified to the species level by using 16S rRNA gene restriction fragment length polymorphisms and phylogenetic analysis based on gyrB gene sequences. A molecular virulence profile was identified for each isolate, using multiplex PCR analysis of six virulence genes. We demonstrated that Aeromonas comprised 16% of all culturable bacteria from Lake Erie. Among 119 Aeromonas isolates, six species were identified, though only two species (Aeromonas hydrophila and A. veronii) predominated among tetracycline- and ciprofloxacin-resistant isolates. Additionally, both of these species demonstrated pathogenic phenotypes in vitro. Virulence gene profiles demonstrated a high prevalence of aerolysin and serine protease genes among A. hydrophila and A. veronii isolates, a genetic profile which corresponded with pathogenic phenotypes. Together, our findings demonstrate increased antibiotic resistance among potentially pathogenic strains of aeromonads, illustrating an emerging potential health concern. PMID:24242249

No evidence of transmission of H5N1 highly pathogenic avian influenza to humans after unprotected contact with infected wild swans.

PubMed

Wallensten, A; Salter, M; Bennett, S; Brown, I; Hoschler, K; Oliver, I

2010-02-01

Highly pathogenic avian influenza (HPAI) subtype H5N1 remains a public health threat as long as it circulates in wild and domestic birds. Information on the transmissibility of H5N1 HPAI from wild birds is needed for evidence-based public health advice. We investigated if transmission of H5N1 HPAI had taken place in people that had unprotected contact with infected wild mute swans during an incident at the Abbotsbury Swannery in Dorset, England. Thirteen people who had been exposed to infected swans were contacted and actively followed up for symptoms. Serology was taken after 30 days. We did not find evidence of transmission of H5N1 HPAI to humans during the incident. The incident provided a rare opportunity to study the transmissibility of the virus from wild birds to humans.

Prevalence and diversity of human pathogenic rickettsiae in urban versus rural habitats, Hungary.

PubMed

Szekeres, Sándor; Docters van Leeuwen, Arieke; Rigó, Krisztina; Jablonszky, Mónika; Majoros, Gábor; Sprong, Hein; Földvári, Gábor

2016-02-01

Tick-borne rickettsioses belong to the important emerging infectious diseases worldwide. We investigated the potential human exposure to rickettsiae by determining their presence in questing ticks collected in an urban park of Budapest and a popular hunting and recreational forest area in southern Hungary. Differences were found in the infectious risk between the two habitats. Rickettsia monacensis and Rickettsia helvetica were identified with sequencing in questing Ixodes ricinus, the only ticks species collected in the city park. Female I. ricinus had a particularly high prevalence of R. helvetica (45%). Tick community was more diverse in the rural habitat with Dermacentor reticulatus ticks having especially high percentage (58%) of Rickettsia raoultii infection. We conclude that despite the distinct eco-epidemiological traits, the risk (hazard and exposure) of acquiring human pathogenic rickettsial infections in both the urban and the rural study sites exists.

A Review of the Current Status of Relevant Zoonotic Pathogens in Wild Swine (Sus scrofa) Populations: Changes Modulating the Risk of Transmission to Humans.

PubMed

Ruiz-Fons, F

2017-02-01

Many wild swine populations in different parts of the World have experienced an unprecedented demographic explosion that may result in increased exposure of humans to wild swine zoonotic pathogens. Interactions between humans and wild swine leading to pathogen transmission could come from different ways, being hunters and game professionals the most exposed to acquiring infections from wild swine. However, increasing human settlements in semi-natural areas, outdoor activities, socio-economic changes and food habits may increase the rate of exposure to wild swine zoonotic pathogens and to potentially emerging pathogens from wild swine. Frequent and increasing contact rate between humans and wild swine points to an increasing chance of zoonotic pathogens arising from wild swine to be transmitted to humans. Whether this frequent contact could lead to new zoonotic pathogens emerging from wild swine to cause human epidemics or emerging disease outbreaks is difficult to predict, and assessment should be based on thorough epidemiologic surveillance. Additionally, several gaps in knowledge on wild swine global population dynamics trends and wild swine-zoonotic pathogen interactions should be addressed to correctly assess the potential role of wild swine in the emergence of diseases in humans. In this work, viruses such as hepatitis E virus, Japanese encephalitis virus, Influenza virus and Nipah virus, and bacteria such as Salmonella spp., Shiga toxin-producing Escherichia coli, Campylobacter spp. and Leptospira spp. have been identified as the most prone to be transmitted from wild swine to humans on the basis of geographic spread in wild swine populations worldwide, pathogen circulation rates in wild swine populations, wild swine population trends in endemic areas, susceptibility of humans to infection, transmissibility from wild swine to humans and existing evidence of wild swine-human transmission events. © 2015 Blackwell Verlag GmbH.

Relatively low prevalence of Babesia microti and Anaplasma phagocytophilum in Ixodes scapularis ticks collected in the Lehigh Valley region of eastern Pennsylvania.

PubMed

Edwards, Marten J; Barbalato, Laura A; Makkapati, Amulya; Pham, Katerina D; Bugbee, Louise M

2015-09-01

Several human pathogens are transmitted by the blacklegged tick, Ixodes scapularis. These include the spirochetes that cause Lyme disease (Borrelia burgdorferi) which is endemic to the Lehigh Valley region of eastern Pennsylvania. Emerging and currently rare tick-borne diseases have been of increasing concern in this region, including tick-borne relapsing fever (caused by Borrelia miyamotoi), human granulocytic anaplasmosis (caused by Anaplasma phagocytophilum), and human babesiosis (caused by Babesia microti). Real-time PCR assays and in some instances, conventional PCR followed by DNA sequencing, were used to screen 423 DNA samples that were prepared from questing adult and nymph stage I. scapularis ticks for infection with four tick-borne human pathogens. B. burgdorferi was detected in 23.2% of the sampled ticks, while B. miyamotoi, B. microti and a human variant of A. phagocytophilum were detected in less than 0.5% of the ticks. Our results are consistent with those expected in a region where Lyme disease is prevalent and human cases of tick-borne relapsing fever, babesiosis and human granulocytic anaplasmosis are not currently widespread. It is expected that this study will serve as a baseline for future studies of tick-borne pathogens in an area that is in close proximity to regions of high endemicity for Lyme disease, human granulocytic anaplasmosis and human babesiosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Biofilms in Water, Its role and impact in human disease transmission

DTIC Science & Technology

2008-01-01

increasing realization of the importance of the world’s oceans as a source of potentially pathogenic microorganisms. Human bacterial pathogens...colorimetric microtitre model for the detection of Staphylococcus aureus biofilms. Lett Appl Microbiol 2008, 46:249-254. A new microplate model for...Polz M: Diversity, sources, and detection of human bacterial pathogens in the marine environment. In Oceans and Health: Pathogens in the Marine

Application of photostable quantum dots for indirect immunofluorescent detection of specific bacterial serotypes on small marine animals

NASA Astrophysics Data System (ADS)

Decho, Alan W.; Beckman, Erin M.; Chandler, G. Thomas; Kawaguchi, Tomohiro

2008-06-01

An indirect immunofluorescence approach was developed using semiconductor quantum dot nanocrystals to label and detect a specific bacterial serotype of the bacterial human pathogen Vibrio parahaemolyticus, attached to small marine animals (i.e. benthic harpacticoid copepods), which are suspected pathogen carriers. This photostable labeling method using nanotechnology will potentially allow specific serotypes of other bacterial pathogens to be detected with high sensitivity in a range of systems, and can be easily applied for sensitive detection to other Vibrio species such as Vibrio cholerae.

Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

PubMed

Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M

2016-05-10

Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in infection that was reduced at later time points. A similar expression pattern was observed in the parasites. Our analyses provide specific insights into the interplay between human macrophages and Leishmania parasites and constitute an important general resource for the study of how pathogens evade host defenses and modulate the functions of the cell to survive intracellularly. Copyright © 2016 Fernandes et al.

West Nile Virus Epidemics in North America Are Driven by Shifts in Mosquito Feeding Behavior

PubMed Central

Kramer, Laura D; Jones, Matthew J; Marra, Peter P; Daszak, Peter

2006-01-01

West Nile virus (WNV) has caused repeated large-scale human epidemics in North America since it was first detected in 1999 and is now the dominant vector-borne disease in this continent. Understanding the factors that determine the intensity of the spillover of this zoonotic pathogen from birds to humans (via mosquitoes) is a prerequisite for predicting and preventing human epidemics. We integrated mosquito feeding behavior with data on the population dynamics and WNV epidemiology of mosquitoes, birds, and humans. We show that Culex pipiens, the dominant enzootic (bird-to-bird) and bridge (bird-to-human) vector of WNV in urbanized areas in the northeast and north-central United States, shifted its feeding preferences from birds to humans by 7-fold during late summer and early fall, coinciding with the dispersal of its preferred host (American robins, Turdus migratorius) and the rise in human WNV infections. We also show that feeding shifts in Cx. tarsalis amplify human WNV epidemics in Colorado and California and occur during periods of robin dispersal and migration. Our results provide a direct explanation for the timing and intensity of human WNV epidemics. Shifts in feeding from competent avian hosts early in an epidemic to incompetent humans after mosquito infection prevalences are high result in synergistic effects that greatly amplify the number of human infections of this and other pathogens. Our results underscore the dramatic effects of vector behavior in driving the transmission of zoonotic pathogens to humans. PMID:16494532

What is the risk for exposure to vector-borne pathogens in United States national parks?

PubMed

Eisen, Lars; Wong, David; Shelus, Victoria; Eisen, Rebecca J

2013-03-01

United States national parks attract > 275 million visitors annually and collectively present risk of exposure for staff and visitors to a wide range of arthropod vector species (most notably fleas, mosquitoes, and ticks) and their associated bacterial, protozoan, or viral pathogens. We assessed the current state of knowledge for risk of exposure to vector-borne pathogens in national parks through a review of relevant literature, including internal National Park Service documents and organismal databases. We conclude that, because of lack of systematic surveillance for vector-borne pathogens in national parks, the risk of pathogen exposure for staff and visitors is unclear. Existing data for vectors within national parks were not based on systematic collections and rarely include evaluation for pathogen infection. Extrapolation of human-based surveillance data from neighboring communities likely provides inaccurate estimates for national parks because landscape differences impact transmission of vector-borne pathogens and human-vector contact rates likely differ inside versus outside the parks because of differences in activities or behaviors. Vector-based pathogen surveillance holds promise to define when and where within national parks the risk of exposure to infected vectors is elevated. A pilot effort, including 5-10 strategic national parks, would greatly improve our understanding of the scope and magnitude of vector-borne pathogen transmission in these high-use public settings. Such efforts also will support messaging to promote personal protection measures and inform park visitors and staff of their responsibility for personal protection, which the National Park Service preservation mission dictates as the core strategy to reduce exposure to vector-borne pathogens in national parks.

High Prevalence of Intermediate Leptospira spp. DNA in Febrile Humans from Urban and Rural Ecuador.

PubMed

Chiriboga, Jorge; Barragan, Verónica; Arroyo, Gabriela; Sosa, Andrea; Birdsell, Dawn N; España, Karool; Mora, Ana; Espín, Emilia; Mejía, María Eugenia; Morales, Melba; Pinargote, Carmina; Gonzalez, Manuel; Hartskeerl, Rudy; Keim, Paul; Bretas, Gustavo; Eisenberg, Joseph N S; Trueba, Gabriel

2015-12-01

Leptospira spp., which comprise 3 clusters (pathogenic, saprophytic, and intermediate) that vary in pathogenicity, infect >1 million persons worldwide each year. The disease burden of the intermediate leptospires is unclear. To increase knowledge of this cluster, we used new molecular approaches to characterize Leptospira spp. in 464 samples from febrile patients in rural, semiurban, and urban communities in Ecuador; in 20 samples from nonfebrile persons in the rural community; and in 206 samples from animals in the semiurban community. We observed a higher percentage of leptospiral DNA-positive samples from febrile persons in rural (64%) versus urban (21%) and semiurban (25%) communities; no leptospires were detected in nonfebrile persons. The percentage of intermediate cluster strains in humans (96%) was higher than that of pathogenic cluster strains (4%); strains in animal samples belonged to intermediate (49%) and pathogenic (51%) clusters. Intermediate cluster strains may be causing a substantial amount of fever in coastal Ecuador.

High Prevalence of Intermediate Leptospira spp. DNA in Febrile Humans from Urban and Rural Ecuador

PubMed Central

Chiriboga, Jorge; Barragan, Verónica; Arroyo, Gabriela; Sosa, Andrea; Birdsell, Dawn N.; España, Karool; Mora, Ana; Espín, Emilia; Mejía, María Eugenia; Morales, Melba; Pinargote, Carmina; Gonzalez, Manuel; Hartskeerl, Rudy; Keim, Paul; Bretas, Gustavo; Eisenberg, Joseph N.S.

2015-01-01

Leptospira spp., which comprise 3 clusters (pathogenic, saprophytic, and intermediate) that vary in pathogenicity, infect >1 million persons worldwide each year. The disease burden of the intermediate leptospires is unclear. To increase knowledge of this cluster, we used new molecular approaches to characterize Leptospira spp. in 464 samples from febrile patients in rural, semiurban, and urban communities in Ecuador; in 20 samples from nonfebrile persons in the rural community; and in 206 samples from animals in the semiurban community. We observed a higher percentage of leptospiral DNA–positive samples from febrile persons in rural (64%) versus urban (21%) and semiurban (25%) communities; no leptospires were detected in nonfebrile persons. The percentage of intermediate cluster strains in humans (96%) was higher than that of pathogenic cluster strains (4%); strains in animal samples belonged to intermediate (49%) and pathogenic (51%) clusters. Intermediate cluster strains may be causing a substantial amount of fever in coastal Ecuador. PMID:26583534

Metapopulation Dynamics Enable Persistence of Influenza A, Including A/H5N1, in Poultry

PubMed Central

Hosseini, Parviez Rana; Fuller, Trevon; Harrigan, Ryan; Zhao, Delong; Arriola, Carmen Sofia; Gonzalez, Armandoe; Miller, Matthew Joshua; Xiao, Xiangming; Smith, Tom B.; Jones, Jamie Holland; Daszak, Peter

2013-01-01

Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified. PMID:24312455

[Highly contagious diseases with human-to-human transmission].

PubMed

Rybka, Aleš; Szanyi, Juraj; Kapla, Jaroslav; Plíšek, Stanislav

2012-12-01

Highly contagious diseases are caused by various biological agents that pose a risk to individuals and may have a potential for public health impact. They result in high mortality and morbidity rates, might cause public panic and therefore require special measures. The pathogens that can be easily disseminated or transmitted from person to person are the riskiest for clinicians (Ebola virus, Marburg virus, Lassa virus, Crimean-Congo hemorrhagic fever virus, Variola major, SARS virus and Yersinia pestis). Human-to-human transmission has not been confirmed for the other biological agents and therefore they pose a very low risk for population.

Exploitation of microbial forensics and nanotechnology for the monitoring of emerging pathogens.

PubMed

Bokhari, Habib

2018-03-07

Emerging infectious diseases remain among the leading causes of global mortality. Traditional laboratory diagnostic approaches designed to detect and track infectious disease agents provide a framework for surveillance of bio threats. However, surveillance and outbreak investigations using such time-consuming approaches for early detection of pathogens remain the major pitfall. Hence, reasonable real-time surveillance systems to anticipate threats to public health and environment are critical for identifying specific aetiologies and preventing the global spread of infectious disease. The current review discusses the growing need for monitoring and surveillance of pathogens with the same zeal and approach as adopted by microbial forensics laboratories, and further strengthening it by integrating with the innovative nanotechnology for rapid detection of microbial pathogens. Such innovative diagnostics platforms will help to track pathogens from high risk areas and environment by pre-emptive approach that will minimize damages. The various scenarios with the examples are discussed where the high risk associated human pathogens in particular were successfully detected using various nanotechnology approaches with potential future prospects in the field of microbial forensics.

Adaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice.

PubMed

Otte, A; Sauter, M; Daxer, M A; McHardy, A C; Klingel, K; Gabriel, G

2015-07-01

During the 2009 H1N1 influenza pandemic, infection attack rates were particularly high among young individuals who suffered from pneumonia with occasional death. Moreover, previously reported determinants of mammalian adaptation and pathogenicity were not present in 2009 pandemic H1N1 influenza A viruses. Thus, it was proposed that unknown viral factors might have contributed to disease severity in humans. In this study, we performed a comparative analysis of two clinical 2009 pandemic H1N1 strains that belong to the very early and later phases of the pandemic. We identified mutations in the viral hemagglutinin (HA) and the nucleoprotein (NP) that occurred during pandemic progression and mediate increased virulence in mice. Lethal disease outcome correlated with elevated viral replication in the alveolar epithelium, increased proinflammatory cytokine and chemokine responses, pneumonia, and lymphopenia in mice. These findings show that viral mutations that have occurred during pandemic circulation among humans are associated with severe disease in mice. In this study, novel determinants of 2009 pandemic H1N1 influenza pathogenicity were identified in the viral hemagglutinin (HA) and the nucleoprotein (NP) genes. In contrast to highly pathogenic avian influenza viruses, increased virulence in mice did not correlate with enhanced polymerase activity but with reduced activity. Lethal 2009 pandemic H1N1 infection in mice correlated with lymphopenia and severe pneumonia. These studies suggest that molecular mechanisms that mediate 2009 pandemic H1N1 influenza pathogenicity are distinct from those that mediate avian influenza virus pathogenicity in mice. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Differential Contribution of PB1-F2 to the Virulence of Highly Pathogenic H5N1 Influenza A Virus in Mammalian and Avian Species

PubMed Central

Schmolke, Mirco; Manicassamy, Balaji; Pena, Lindomar; Sutton, Troy; Hai, Rong; Varga, Zsuzsanna T.; Hale, Benjamin G.; Steel, John; Pérez, Daniel R.; García-Sastre, Adolfo

2011-01-01

Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20th century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism. PMID:21852950

Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species.

PubMed

Schmolke, Mirco; Manicassamy, Balaji; Pena, Lindomar; Sutton, Troy; Hai, Rong; Varga, Zsuzsanna T; Hale, Benjamin G; Steel, John; Pérez, Daniel R; García-Sastre, Adolfo

2011-08-01

Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20(th) century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism.

Presence of Pathogens and Indicator Microbes at a Non-Point Source Subtropical Recreational Marine Beach ▿ †

PubMed Central

Abdelzaher, Amir M.; Wright, Mary E.; Ortega, Cristina; Solo-Gabriele, Helena M.; Miller, Gary; Elmir, Samir; Newman, Xihui; Shih, Peter; Bonilla, J. Alfredo; Bonilla, Tonya D.; Palmer, Carol J.; Scott, Troy; Lukasik, Jerzy; Harwood, Valerie J.; McQuaig, Shannon; Sinigalliano, Chris; Gidley, Maribeth; Plano, Lisa R. W.; Zhu, Xiaofang; Wang, John D.; Fleming, Lora E.

2010-01-01

Swimming in ocean water, including ocean water at beaches not impacted by known point sources of pollution, is an increasing health concern. This study was an initial evaluation of the presence of indicator microbes and pathogens and the association among the indicator microbes, pathogens, and environmental conditions at a subtropical, recreational marine beach in south Florida impacted by non-point sources of pollution. Twelve water and eight sand samples were collected during four sampling events at high or low tide under elevated or reduced solar insolation conditions. The analyses performed included analyses of fecal indicator bacteria (FIB) (fecal coliforms, Escherichia coli, enterococci, and Clostridium perfringens), human-associated microbial source tracking (MST) markers (human polyomaviruses [HPyVs] and Enterococcus faecium esp gene), and pathogens (Vibrio vulnificus, Staphylococcus aureus, enterovirus, norovirus, hepatitis A virus, Cryptosporidium spp., and Giardia spp.). The enterococcus concentrations in water and sand determined by quantitative PCR were greater than the concentrations determined by membrane filtration measurement. The FIB concentrations in water were below the recreational water quality standards for three of the four sampling events, when pathogens and MST markers were also generally undetectable. The FIB levels exceeded regulatory guidelines during one event, and this was accompanied by detection of HPyVs and pathogens, including detection of the autochthonous bacterium V. vulnificus in sand and water, detection of the allochthonous protozoans Giardia spp. in water, and detection of Cryptosporidium spp. in sand samples. The elevated microbial levels were detected at high tide and under low-solar-insolation conditions. Additional sampling should be conducted to further explore the relationships between tidal and solar insolation conditions and between indicator microbes and pathogens in subtropical recreational marine waters impacted by non-point source pollution. PMID:19966020

Hair sheep blood, citrated or defibrinated, fulfills all requirements of blood agar for diagnostic microbiology laboratory tests.

PubMed

Yeh, Ellen; Pinsky, Benjamin A; Banaei, Niaz; Baron, Ellen Jo

2009-07-03

Blood agar is used for the identification and antibiotic susceptibility testing of many bacterial pathogens. In the developing world, microbiologists use human blood agar because of the high cost and inhospitable conditions for raising wool sheep or horses to supply blood. Many pathogens either fail to grow entirely or exhibit morphologies and hemolytic patterns on human blood agar that confound colony recognition. Furthermore, human blood can be hazardous to handle due to HIV and hepatitis. This study investigated whether blood from hair sheep, a hardy, low-maintenance variety of sheep adapted for hot climates, was suitable for routine clinical microbiology studies. Hair sheep blood obtained by jugular venipuncture was anticoagulated by either manual defibrination or collection in human blood bank bags containing citrate-phosphate-dextrose. Trypticase soy 5% blood agar was made from both forms of hair sheep blood and commercial defibrinated wool sheep blood. Growth characteristics, colony morphologies, and hemolytic patterns of selected human pathogens, including several streptococcal species, were evaluated. Specialized identification tests, including CAMP test, reverse CAMP test, and satellite colony formation with Haemophilus influenzae and Abiotrophia defectiva were also performed. Mueller-Hinton blood agar plates prepared from the three blood types were compared in antibiotic susceptibility tests by disk diffusion and E-test. The results of all studies showed that blood agar prepared from citrated hair sheep blood is suitable for microbiological tests used in routine identification and susceptibility profiling of human pathogens. The validation of citrated hair sheep blood eliminates the labor-intensive and equipment-requiring process of manual defibrination. Use of hair sheep blood, in lieu of human blood currently used by many developing world laboratories and as an alternative to cost-prohibitive commercial sheep blood, offers the opportunity to dramatically improve the safety and accuracy of laboratory diagnosis of pathogenic bacteria in resource-poor countries.

Complete genome sequence of the Campylobacter cuniculorum type strain LMG 24588

USDA-ARS?s Scientific Manuscript database

Campylobacter cuniculorum has been isolated from rabbits (Oryctolagus cuniculus). Although C. cuniculorum is highly prevalent in rabbits farmed for human consumption, the pathogenicity of this organism in humans is still unknown. This study describes the whole-genome sequence of the C. cuniculorum t...

Zoonotic bacterial meningitis in human adults.

PubMed

van Samkar, Anusha; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

2016-09-13

To describe the epidemiology, etiology, clinical characteristics, treatment, outcome, and prevention of zoonotic bacterial meningitis in human adults. We identified 16 zoonotic bacteria causing meningitis in adults. Zoonotic bacterial meningitis is uncommon compared to bacterial meningitis caused by human pathogens, and the incidence has a strong regional distribution. Zoonotic bacterial meningitis is mainly associated with animal contact, consumption of animal products, and an immunocompromised state of the patient. In a high proportion of zoonotic bacterial meningitis cases, CSF analysis showed only a mildly elevated leukocyte count. The recommended antibiotic therapy differs per pathogen, and the overall mortality is low. Zoonotic bacterial meningitis is uncommon but is associated with specific complications. The suspicion should be raised in patients with bacterial meningitis who have recreational or professional contact with animals and in patients living in regions endemic for specific zoonotic pathogens. An immunocompromised state is associated with a worse prognosis. Identification of risk factors and underlying disease is necessary to improve treatment. © 2016 American Academy of Neurology.

Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus

PubMed Central

Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

2014-01-01

The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome. PMID:26038499

Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus.

PubMed

Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

2014-10-01

The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome.

Trade-offs between acquired and innate immune defenses in humans

PubMed Central

McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

2016-01-01

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

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

Detection of Pathogen Exposure in African Buffalo Using Non-Specific Markers of Inflammation

PubMed Central

Glidden, Caroline K.; Beechler, Brianna; Buss, Peter Erik; Charleston, Bryan; de Klerk-Lorist, Lin-Mari; Maree, Francois Frederick; Muller, Timothy; Pérez-Martin, Eva; Scott, Katherine Anne; van Schalkwyk, Ockert Louis; Jolles, Anna

2018-01-01

Detecting exposure to new or emerging pathogens is a critical challenge to protecting human, domestic animal, and wildlife health. Yet, current techniques to detect infections typically target known pathogens of humans or economically important animals. In the face of the current surge in infectious disease emergence, non-specific disease surveillance tools are urgently needed. Tracking common host immune responses indicative of recent infection may have potential as a non-specific diagnostic approach for disease surveillance. The challenge to immunologists is to identify the most promising markers, which ideally should be highly conserved across pathogens and host species, become upregulated rapidly and consistently in response to pathogen invasion, and remain elevated beyond clearance of infection. This study combined an infection experiment and a longitudinal observational study to evaluate the utility of non-specific markers of inflammation [NSMI; two acute phase proteins (haptoglobin and serum amyloid A), two pro-inflammatory cytokines (IFNγ and TNF-α)] as indicators of pathogen exposure in a wild mammalian species, African buffalo (Syncerus caffer). Specifically, in the experimental study, we asked (1) How quickly do buffalo mount NSMI responses upon challenge with an endemic pathogen, foot-and-mouth disease virus; (2) for how long do NSMI remain elevated after viral clearance and; (3) how pronounced is the difference between peak NSMI concentration and baseline NSMI concentration? In the longitudinal study, we asked (4) Are elevated NSMI associated with recent exposure to a suite of bacterial and viral respiratory pathogens in a wild population? Among the four NSMI that we tested, haptoglobin showed the strongest potential as a surveillance marker in African buffalo: concentrations quickly and consistently reached high levels in response to experimental infection, remaining elevated for almost a month. Moreover, elevated haptoglobin was indicative of recent exposure to two respiratory pathogens assessed in the longitudinal study. We hope this work motivates studies investigating suites of NSMI as indicators for pathogen exposure in a broader range of both pathogen and host species, potentially transforming how we track disease burden in natural populations. PMID:29375568

Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi

PubMed Central

2011-01-01

Background Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans. Results 97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales (Coccidioides species) and the mould Aspergillus fumigatus. The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species. Conclusions Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens. PMID:21247460

Pathogen inactivation of human serum facilitates its clinical use for islet cell culture and subsequent transplantation.

PubMed

Ståhle, Magnus U; Brandhorst, Daniel; Korsgren, Olle; Knutson, Folke

2011-01-01

Serum is regarded as an essential supplement to promote survival and growth of cells during culture. However, the potential risk of transmitting diseases disqualifies the use of serum for clinical cell therapy in most countries. Hence, most clinical cell therapy programs have replaced human serum with human serum albumin, which can result in inferior quality of released cell products. Photochemical treatment of different blood products utilizing Intercept® technology has been shown to inactivate a broad variety of pathogens of RNA and DNA origin. The present study assesses the feasibility of using pathogen-inactivated, blood group-compatible serum for use in human pancreatic islet culture. Isolated human islets were cultured at 37°C for 3-4 days in CMRL 1066 supplemented with 10% of either pathogen-inactivated or nontreated human serum. Islet quality assessment included glucose-stimulated insulin release (perifusion), ADP/ATP ratio, cytokine expression, and posttransplant function in diabetic nude mice. No differences were found between islets cultured in pathogen-inactivated or control serum regarding stimulated insulin release, intracellular insulin content, and ADP/ATP ratio. Whether media was supplemented with treated or nontreated serum, islet expression of IL-6, IL-8, MCP-1, or tissue factor was not affected. The final diabetes-reversal rate of mice receiving islets cultured in pathogen-inactivated or nontreated serum was 78% and 87%, respectively (NS). As reported here, pathogen-inactivated human serum does not affect viability or functional integrity of cultured human islets. The implementation of this technology for RNA- and DNA-based pathogen inactivation should enable reintroduction of human serum for clinical cell therapy.

Live Bird Markets of Bangladesh: H9N2 Viruses and the Near Absence of Highly Pathogenic H5N1 Influenza

PubMed Central

Negovetich, Nicholas J.; Feeroz, Mohammed M.; Jones-Engel, Lisa; Walker, David; Alam, S. M. Rabiul; Hasan, Kamrul; Seiler, Patrick; Ferguson, Angie; Friedman, Kim; Barman, Subrata; Franks, John; Turner, Jasmine; Krauss, Scott; Webby, Richard J.; Webster, Robert G.

2011-01-01

Avian influenza surveillance in Bangladesh has been passive, relying on poultry farmers to report suspected outbreaks of highly pathogenic H5N1 influenza. Here, the results of an active surveillance effort focusing on the live-bird markets are presented. Prevalence of influenza infection in the birds of the live bird markets is 23.0%, which is similar to that in poultry markets in other countries. Nearly all of the isolates (94%) were of the non-pathogenic H9N2 subtype, but viruses of the H1N2, H1N3, H3N6, H4N2, H5N1, and H10N7 subtypes were also observed. The highly pathogenic H5N1-subtype virus was observed at extremely low prevalence in the surveillance samples (0.08%), and we suggest that the current risk of infection for humans in the retail poultry markets in Bangladesh is negligible. However, the high prevalence of the H9 subtype and its potential for interaction with the highly pathogenic H5N1-subtype, i.e., reassortment and attenuation of host morbidity, highlight the importance of active surveillance of the poultry markets. PMID:21541296

Highly Pathogenic H5N1 Influenza A Virus Strains Provoke Heterogeneous IFN-α/β Responses That Distinctively Affect Viral Propagation in Human Cells

PubMed Central

Matthaei, Markus; Budt, Matthias; Wolff, Thorsten

2013-01-01

The fatal transmissions of highly pathogenic avian influenza A viruses (IAV) of the H5N1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. While type I interferons (IFN-α/β) are well described to contribute to the species barrier of many zoonotic viruses, current data to the role of these antiviral cytokines during human H5N1 IAV infections is limited and contradictory. We hypothesized an important role for the IFN system in limiting productive infection of avian H5N1 strains in human cells. Hence, we examined IFN-α/β gene activation by different avian and human H5N1 isolates, if the IFN-α/β response restricts H5N1 growth and whether the different strains were equally capable to regulate the IFN-α/β system via their IFN-antagonistic NS1 proteins. Two human H5N1 isolates and a seasonal H3N2 strain propagated efficiently in human respiratory cells and induced little IFN-β, whereas three purely avian H5N1 strains were attenuated for replication and provoked higher IFN secretion. Replication of avian viruses was significantly enhanced on interferon-deficient cells, and exogenous IFN potently limited the growth of all strains in human cells. Moreover, IFN-α/β activation by all strains depended on retinoic acid-inducible gene I excluding principal differences in receptor activation between the different viruses. Interestingly, all H5N1 NS1 proteins suppressed IFN-α/β induction comparably well to the NS1 of seasonal IAV. Thus, our study shows that H5N1 strains are heterogeneous in their capacity to activate human cells in an NS1-independent manner. Our findings also suggest that H5N1 viruses need to acquire adaptive changes to circumvent strong IFN-α/β activation in human host cells. Since no single amino acid polymorphism could be associated with a respective high- or low induction phenotype we propose that the necessary adaptations to overcome the human IFN-α/β barrier involve mutations in multiple H5N1 genes. PMID:23451066

A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts.

PubMed

Gerwien, Franziska; Safyan, Abu; Wisgott, Stephanie; Hille, Fabrice; Kaemmer, Philipp; Linde, Jörg; Brunke, Sascha; Kasper, Lydia; Hube, Bernhard

2016-10-18

Iron is an essential micronutrient for both pathogens and their hosts, which restrict iron availability during infections in an effort to prevent microbial growth. Successful human pathogens like the yeast Candida glabrata have thus developed effective iron acquisition strategies. Their regulation has been investigated well for some pathogenic fungi and in the model organism Saccharomyces cerevisiae, which employs an evolutionarily derived system. Here, we show that C. glabrata uses a regulation network largely consisting of components of the S. cerevisiae regulon but also of elements of other pathogenic fungi. Specifically, similarly to baker's yeast, Aft1 is the main positive regulator under iron starvation conditions, while Cth2 degrades mRNAs encoding iron-requiring enzymes. However, unlike the case with S. cerevisiae, a Sef1 ortholog is required for full growth under iron limitation conditions, making C. glabrata an evolutionary intermediate to SEF1-dependent fungal pathogens. Therefore, C. glabrata has evolved an iron homeostasis system which seems to be unique within the pathogenic fungi. The fungus Candida glabrata represents an evolutionarily close relative of the well-studied and benign baker's yeast and model organism Saccharomyces cerevisiae On the other hand, C. glabrata is an important opportunistic human pathogen causing both superficial and systemic infections. The ability to acquire trace metals, in particular, iron, and to tightly regulate this process during infection is considered an important virulence attribute of a variety of pathogens. Importantly, S. cerevisiae uses a highly derivative regulatory system distinct from those of other fungi. Until now, the regulatory mechanism of iron homeostasis in C. glabrata has been mostly unknown. Our study revealed a hybrid iron regulation network that is unique to C. glabrata and is placed at an evolutionary midpoint between those of S. cerevisiae and related fungal pathogens. We thereby show that, in the host, even a successful human pathogen can rely largely on a strategy normally found in nonpathogenic fungi from a terrestrial environment. Copyright © 2016 Gerwien et al.

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.

Airborne pathogens from dairy manure aerial irrigation and the human health risk

USGS Publications Warehouse

Borchardt, Mark A.; Burch, Tucker R

2016-01-01

Dairy manure, like the fecal excrement from any domesticated or wild animal, can contain pathogens capable of infecting humans and causing illness or even death. Pathogens in dairy manure can be broadly divided into categories of taxonomy or infectiousness. Dividing by taxonomy there are three pathogen groups in dairy manure: viruses (e.g., bovine rotavirus), bacteria (e.g., Salmonella species), and protozoa (e.g., Cryptosporidium parvum). There are two categories of infectiousness for pathogens found in animals: those that are zoonotic and those that are not. A zoonotic pathogen is one that can infect both human and animal hosts. Some zoonotic pathogens found in dairy manure cause illness in both hosts (e.g., Salmonella) while other zoonotic pathogens, like Escherichia coli O157:H7, (enterohemorrhagic E. coli (EHEC)) cause illness only in humans. As a general rule, the gastrointestinal viruses found in dairy manure are not zoonotic. While there are exceptions (e.g., rare reports of bovine rotavirus infecting children), for the most part the viruses in dairy manure are not a human health concern. The primary concerns are the zoonotic bacteria and protozoa in dairy manure.

Detection of human pathogenic Fusarium species in hospital and communal sink biofilms by using a highly specific monoclonal antibody.

PubMed

Al-Maqtoofi, Marwan; Thornton, Christopher R

2016-11-01

The fungus Fusarium is well known as a plant pathogen, but has recently emerged as an opportunistic pathogen of humans. Habitats providing direct human exposure to infectious propagules are largely unknown, but there is growing evidence that plumbing systems are sources of human pathogenic strains in the Fusarium solani species complex (FSSC) and Fusarium oxysporum species complex (FOSC), the most common groups infecting humans. Here, a newly developed Fusarium-specific monoclonal antibody (mAb ED7) was used to track FSSC and FOSC strains in sink drain biofilms by detecting its target antigen, an extracellular 200 kDa carbohydrate, in saline swabs. The antigen was detectable in 52% of swab samples collected from sinks across a University campus and a tertiary care hospital. The mAb was 100% accurate in detecting FSSC, FOSC, and F. dimerum species complex (FDSC) strains that were present, as mixed fungal communities, in 83% of sink drain biofilms. Specificity of the ELISA was confirmed by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2 rRNA-encoding regions of culturable yeasts and molds that were recovered using mycological culture, while translation elongation factor (TEF)-1α analysis of Fusarium isolates included FSSC 1-a, FOSC 33, and FDSC ET-gr, the most common clinical pathotypes in each group. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Hemocytes from Pediculus humanus humanus are hosts for human bacterial pathogens

PubMed Central

Coulaud, Pierre-Julien; Lepolard, Catherine; Bechah, Yassina; Berenger, Jean-Michel; Raoult, Didier; Ghigo, Eric

2015-01-01

Pediculus humanus humanus is an human ectoparasite which represents a serious public health threat because it is vector for pathogenic bacteria. It is important to understand and identify where bacteria reside in human body lice to define new strategies to counterstroke the capacity of vectorization of the bacterial pathogens by body lice. It is known that phagocytes from vertebrates can be hosts or reservoirs for several microbes. Therefore, we wondered if Pediculus humanus humanus phagocytes could hide pathogens. In this study, we characterized the phagocytes from Pediculus humanus humanus and evaluated their contribution as hosts for human pathogens such as Rickettsia prowazekii, Bartonella Quintana, and Acinetobacter baumannii. PMID:25688336

Human Monoclonal Antibodies Against a Plethora of Viral Pathogens From Single Combinatorial Libraries

NASA Astrophysics Data System (ADS)

Williamson, R. Anthony; Burioni, Roberto; Sanna, Pietro P.; Partridge, Lynda J.; Barbas, Carlos F., III; Burton, Dennis R.

1993-05-01

Conventional antibody generation usually requires active immunization with antigen immediately prior to the preparation procedure. Combinatorial antibody library technology offers the possibility of cloning a range of antibody specificities at a single point in time and then accessing these specificities at will. Here we show that human monoclonal antibody Fab fragments against a plethora of infectious agents can be readily derived from a single library. Further examination of a number of libraries shows that whenever antibody against a pathogen can be detected in the serum of the donor, then specific antibodies can be derived from the corresponding library. We describe the generation of human Fab fragments against herpes simplex virus types 1 and 2, human cytomegalovirus, varicella zoster virus, rubella, human immunodeficiency virus type 1, and respiratory syncytial virus. The antibodies are shown to be highly specific and a number are effective in neutralizing virus in vitro.

[Mosquitoes as vectors for exotic pathogens in Germany].

PubMed

Becker, N; Krüger, A; Kuhn, C; Plenge-Bönig, A; Thomas, S M; Schmidt-Chanasit, J; Tannich, E

2014-05-01

As a result of intensified globalization of international trade and of substantial travel activities, mosquito-borne exotic pathogens are becoming an increasing threat for Europe. In Germany some 50 different mosquito species are known, several of which have vector competence for pathogens. During the last few years a number of zoonotic arboviruses that are pathogenic for humans have been isolated from mosquitoes in Germany including Usutu, Sindbis and Batai viruses. In addition, filarial worms, such as Dirofilaria repens have been repeatedly detected in mosquitoes from the federal state of Brandenburg. Other pathogens, in particular West Nile virus, are expected to emerge sooner or later in Germany as the virus is already circulating in neighboring countries, e.g. France, Austria and the Czech Republic. In upcoming years the risk for arbovirus transmission might increase in Germany due to increased occurrence of new so-called "invasive" mosquito species, such as the Asian bush mosquito Ochlerotatus japonicus or the Asian tiger mosquito Aedes albopictus. These invasive species are characterized by high vector competence for a broad range of pathogens and a preference for human blood meals. For risk assessment, a number of mosquito and pathogen surveillance projects have been initiated in Germany during the last few years; however, mosquito control strategies and plans of action have to be developed and put into place to allow early and efficient action against possible vector-borne epidemics.

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.

Effects of Simulated Microgravity on a Host-Pathogen System

NASA Technical Reports Server (NTRS)

Gilbert, Rachel; Lo, Rachel; Bhattacharya, Sharmila

2017-01-01

While it has been shown that decades of astronauts and cosmonauts can suffer from illnesses both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. However, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use a ground-based simulated microgravity environment to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to counteract immune dysfunction in future space exploration.

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

PubMed Central

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

2012-01-01

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

Antigenic Variation and Immune Escape in the MTBC

PubMed Central

2017-01-01

Microbes that infect other organisms encounter host immune responses, and must overcome or evade innate and adaptive immune responses to successfully establish infection. Highly successful microbial pathogens, including M. tuberculosis, are able to evade adaptive immune responses (mediated by antibodies and/or T lymphocytes) and thereby establish long-term chronic infection. One mechanism that diverse pathogens use to evade adaptive immunity is antigenic variation, in which structural variants emerge that alter recognition by established immune responses and allow those pathogens to persist and/or to infect previously-immune hosts. Despite the wide use of antigenic variation by diverse pathogens, this mechanism appears to be infrequent in M. tuberculosis, as indicated by findings that known and predicted human T cell epitopes in this organism are highly conserved, although there are exceptions. These findings have implications for diagnostic tests that are based on measuring host immune responses, and for vaccine design and development. PMID:29116635

Antimicrobial Resistance Percentages of Salmonella and Shigella in Seafood Imported to Jordan: Higher Percentages and More Diverse Profiles in Shigella.

PubMed

Obaidat, Mohammad M; Bani Salman, Alaa E

2017-03-01

This study determined the prevalence and antimicrobial resistance of human-specific ( Shigella spp.) and zoonotic ( Salmonella enterica ) foodborne pathogens in internationally traded seafood. Sixty-four Salmonella and 61 Shigella isolates were obtained from 330 imported fresh fish samples from Egypt, Yemen, and India. The pathogens were isolated on selective media, confirmed by PCR, and tested for antimicrobial resistance. Approximately 79 and 98% of the Salmonella and Shigella isolates, respectively, exhibited resistance to at least one antimicrobial, and 8 and 49% exhibited multidrug resistance (resistance to three or more antimicrobial classes). Generally, Salmonella exhibited high resistance to amoxicillin-clavulanic acid, cephalothin, streptomycin, and ampicillin; very low resistance to kanamycin, tetracycline, gentamicin, chloramphenicol, nalidixic acid, sulfamethoxazole-trimethoprim, and ciprofloxacin; and no resistance to ceftriaxone. Meanwhile, Shigella spp. exhibited high resistance to tetracycline, amoxicillin-clavulanic acid, cephalothin, streptomycin, and ampicillin; low resistance to kanamycin, nalidixic acid, sulfamethoxazole-trimethoprim, and ceftriaxone; and very low resistance to gentamicin and ciprofloxacin. Salmonella isolates exhibited 14 resistance profiles, Shigella isolates 42. This study is novel in showing that a human-specific pathogen has higher antimicrobial resistance percentages and more diverse profiles than a zoonotic pathogen. Thus, the impact of antimicrobial use in humans is as significant as, if not more significant than, it is in animals in spreading antibiotic resistance through food. This study also demonstrates that locally derived antimicrobial resistance can spread and pose a public health risk worldwide through seafood trade and that high resistance would make a possible outbreak difficult to control. So, capacity building and monitoring harvest water areas are encouraged in fish producing countries.

TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.

PubMed

Marchesan, Julie; Jiao, Yizu; Schaff, Riley A; Hao, Jie; Morelli, Thiago; Kinney, Janet S; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J; Inohara, Naohiro; Giannobile, William V

2016-06-01

Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TLR4, NOD1 and NOD2 Mediate Immune Recognition of Putative Newly-Identified Periodontal Pathogens

PubMed Central

Schaff, Riley A.; Hao, Jie; Morelli, Thiago; Kinney, Janet S.; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J.; Inohara, Naohiro; Giannobile, William V.

2015-01-01

SUMMARY Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. While the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, 6 being classical pathogens and 4 putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone marrow–derived macrophages (BMDM) from wild-type (WT) and toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. C. concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney (HEK) cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2-stimulatory activity. These studies allowed us to provide important evidence on newly-identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). PMID:26177212

Wildlife Trade and Human Health in Lao PDR: An Assessment of the Zoonotic Disease Risk in Markets.

PubMed

Greatorex, Zoe F; Olson, Sarah H; Singhalath, Sinpakone; Silithammavong, Soubanh; Khammavong, Kongsy; Fine, Amanda E; Weisman, Wendy; Douangngeun, Bounlom; Theppangna, Watthana; Keatts, Lucy; Gilbert, Martin; Karesh, William B; Hansel, Troy; Zimicki, Susan; O'Rourke, Kathleen; Joly, Damien O; Mazet, Jonna A K

2016-01-01

Although the majority of emerging infectious diseases can be linked to wildlife sources, most pathogen spillover events to people could likely be avoided if transmission was better understood and practices adjusted to mitigate risk. Wildlife trade can facilitate zoonotic disease transmission and represents a threat to human health and economies in Asia, highlighted by the 2003 SARS coronavirus outbreak, where a Chinese wildlife market facilitated pathogen transmission. Additionally, wildlife trade poses a serious threat to biodiversity. Therefore, the combined impacts of Asian wildlife trade, sometimes termed bush meat trade, on public health and biodiversity need assessing. From 2010 to 2013, observational data were collected in Lao PDR from markets selling wildlife, including information on volume, form, species and price of wildlife; market biosafety and visitor origin. The potential for traded wildlife to host zoonotic diseases that pose a serious threat to human health was then evaluated at seven markets identified as having high volumes of trade. At the seven markets, during 21 observational surveys, 1,937 alive or fresh dead mammals (approximately 1,009 kg) were observed for sale, including mammals from 12 taxonomic families previously documented to be capable of hosting 36 zoonotic pathogens. In these seven markets, the combination of high wildlife volumes, high risk taxa for zoonoses and poor biosafety increases the potential for pathogen presence and transmission. To examine the potential conservation impact of trade in markets, we assessed the status of 33,752 animals observed during 375 visits to 93 markets, under the Lao PDR Wildlife and Aquatic Law. We observed 6,452 animals listed by Lao PDR as near extinct or threatened with extinction. The combined risks of wildlife trade in Lao PDR to human health and biodiversity highlight the need for a multi-sector approach to effectively protect public health, economic interests and biodiversity.

Wildlife Trade and Human Health in Lao PDR: An Assessment of the Zoonotic Disease Risk in Markets

PubMed Central

Singhalath, Sinpakone; Silithammavong, Soubanh; Khammavong, Kongsy; Fine, Amanda E.; Weisman, Wendy; Douangngeun, Bounlom; Theppangna, Watthana; Keatts, Lucy; Gilbert, Martin; Karesh, William B.; Hansel, Troy; Zimicki, Susan; O’Rourke, Kathleen; Joly, Damien O.; Mazet, Jonna A. K.

2016-01-01

Although the majority of emerging infectious diseases can be linked to wildlife sources, most pathogen spillover events to people could likely be avoided if transmission was better understood and practices adjusted to mitigate risk. Wildlife trade can facilitate zoonotic disease transmission and represents a threat to human health and economies in Asia, highlighted by the 2003 SARS coronavirus outbreak, where a Chinese wildlife market facilitated pathogen transmission. Additionally, wildlife trade poses a serious threat to biodiversity. Therefore, the combined impacts of Asian wildlife trade, sometimes termed bush meat trade, on public health and biodiversity need assessing. From 2010 to 2013, observational data were collected in Lao PDR from markets selling wildlife, including information on volume, form, species and price of wildlife; market biosafety and visitor origin. The potential for traded wildlife to host zoonotic diseases that pose a serious threat to human health was then evaluated at seven markets identified as having high volumes of trade. At the seven markets, during 21 observational surveys, 1,937 alive or fresh dead mammals (approximately 1,009 kg) were observed for sale, including mammals from 12 taxonomic families previously documented to be capable of hosting 36 zoonotic pathogens. In these seven markets, the combination of high wildlife volumes, high risk taxa for zoonoses and poor biosafety increases the potential for pathogen presence and transmission. To examine the potential conservation impact of trade in markets, we assessed the status of 33,752 animals observed during 375 visits to 93 markets, under the Lao PDR Wildlife and Aquatic Law. We observed 6,452 animals listed by Lao PDR as near extinct or threatened with extinction. The combined risks of wildlife trade in Lao PDR to human health and biodiversity highlight the need for a multi-sector approach to effectively protect public health, economic interests and biodiversity. PMID:27008628

High prevalence of Toxoplasma gondii infection in Ethiopian cats in Addis Ababa, coinfection, and a review of toxoplasmosis in humans and other animals in Ethiopia

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline Immunodeficiency Virus (FIV), and Feline Leukemia Virus (FeLv) are related to Human Immunodeficiency Virus, and Human T-lymphotrophic Virus, respectively, and these viruses are immunosuppressive. In the present study, the p...

A human pathogenic bacterial infection model using the two-spotted cricket, Gryllus bimaculatus.

PubMed

Kochi, Yuto; Miyashita, Atsushi; Tsuchiya, Kohsuke; Mitsuyama, Masao; Sekimizu, Kazuhisa; Kaito, Chikara

2016-08-01

Invertebrate animal species that can withstand temperatures as high as 37°C, the human body temperature, are limited. In the present study, we utilized the two-spotted cricket, Gryllus bimaculatus, which lives in tropical and subtropical regions, as an animal model of human pathogenic bacterial infection. Injection of Pseudomonas aeruginosa or Staphylococcus aureus into the hemolymph killed crickets. Injected P. aeruginosa or S. aureus proliferated in the hemolymph until the cricket died. The ability of these pathogenic bacteria to kill the crickets was blocked by the administration of antibiotics. S. aureus gene-knockout mutants of virulence factors, including cvfA, agr and srtA, exhibited decreased killing ability compared with the parent strain. The dose at which 50% of crickets were killed by P. aeruginosa or S. aureus was not decreased at 37°C compared with that at 27°C. Injection of Listeria monocytogenes, which upregulates toxin expression at 37°C, killed crickets, and the dose at which 50% of crickets were killed was decreased at 37°C compared with that at 27°C. These findings suggest that the two-spotted cricket is a useful model animal for evaluating the virulence properties of various human pathogenic bacteria at variable temperature including 37°C. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Enterococci in the environment

USGS Publications Warehouse

Byappanahalli, Muruleedhara N.; Nevers, Meredith B.; Korajkic, Asja; Staley, Zachery R.; Harwood, Valerie J.

2012-01-01

Enterococci are common, commensal members of gut communities in mammals and birds, yet they are also opportunistic pathogens that cause millions of human and animal infections annually. Because they are shed in human and animal feces, are readily culturable, and predict human health risks from exposure to polluted recreational waters, they are used as surrogates for waterborne pathogens and as fecal indicator bacteria (FIB) in research and in water quality testing throughout the world. Evidence from several decades of research demonstrates, however, that enterococci may be present in high densities in the absence of obvious fecal sources and that environmental reservoirs of these FIB are important sources and sinks, with the potential to impact water quality. This review focuses on the distribution and microbial ecology of enterococci in environmental (secondary) habitats, including the effect of environmental stressors; an outline of their known and apparent sources, sinks, and fluxes; and an overview of the use of enterococci as FIB. Finally, the significance of emerging methodologies, such as microbial source tracking (MST) and empirical predictive models, as tools in water quality monitoring is addressed. The mounting evidence for widespread extraenteric sources and reservoirs of enterococci demonstrates the versatility of the genus Enterococcus and argues for the necessity of a better understanding of their ecology in natural environments, as well as their roles as opportunistic pathogens and indicators of human pathogens.

Enterococci in the Environment

PubMed Central

Byappanahalli, Muruleedhara N.; Nevers, Meredith B.; Korajkic, Asja; Staley, Zachery R.

2012-01-01

Summary: Enterococci are common, commensal members of gut communities in mammals and birds, yet they are also opportunistic pathogens that cause millions of human and animal infections annually. Because they are shed in human and animal feces, are readily culturable, and predict human health risks from exposure to polluted recreational waters, they are used as surrogates for waterborne pathogens and as fecal indicator bacteria (FIB) in research and in water quality testing throughout the world. Evidence from several decades of research demonstrates, however, that enterococci may be present in high densities in the absence of obvious fecal sources and that environmental reservoirs of these FIB are important sources and sinks, with the potential to impact water quality. This review focuses on the distribution and microbial ecology of enterococci in environmental (secondary) habitats, including the effect of environmental stressors; an outline of their known and apparent sources, sinks, and fluxes; and an overview of the use of enterococci as FIB. Finally, the significance of emerging methodologies, such as microbial source tracking (MST) and empirical predictive models, as tools in water quality monitoring is addressed. The mounting evidence for widespread extraenteric sources and reservoirs of enterococci demonstrates the versatility of the genus Enterococcus and argues for the necessity of a better understanding of their ecology in natural environments, as well as their roles as opportunistic pathogens and indicators of human pathogens. PMID:23204362

Host target modification as a strategy to counter pathogen hijacking of the jasmonate hormone receptor

DOE PAGES

Zhang, Li; Yao, Jian; Withers, John; ...

2015-11-02

In the past decade, characterization of the host targets of pathogen virulence factors took a center stage in the study of pathogenesis and disease susceptibility in plants and humans. However, the impressive knowledge of host targets has not been broadly exploited to inhibit pathogen infection. In this paper, we show that host target modification could be a promising new approach to “protect” the disease-vulnerable components of plants. In particular, recent studies have identified the plant hormone jasmonate (JA) receptor as one of the common targets of virulence factors from highly evolved biotrophic/hemibiotrophic pathogens. Strains of the bacterial pathogen Pseudomonas syringae,more » for example, produce proteinaceous effectors, as well as a JA-mimicking toxin, coronatine (COR), to activate JA signaling as a mechanism to promote disease susceptibility. Guided by the crystal structure of the JA receptor and evolutionary clues, we succeeded in modifying the JA receptor to allow for sufficient endogenous JA signaling but greatly reduced sensitivity to COR. Transgenic Arabidopsis expressing this modified receptor not only are fertile and maintain a high level of insect defense, but also gain the ability to resist COR-producing pathogens Pseudomonas syringae pv. tomato and P. syringae pv. maculicola. Finally, our results provide a proof-of-concept demonstration that host target modification can be a promising new approach to prevent the virulence action of highly evolved pathogens.« less

A New Family of Capsule Polymerases Generates Teichoic Acid-Like Capsule Polymers in Gram-Negative Pathogens.

PubMed

Litschko, Christa; Oldrini, Davide; Budde, Insa; Berger, Monika; Meens, Jochen; Gerardy-Schahn, Rita; Berti, Francesco; Schubert, Mario; Fiebig, Timm

2018-05-29

Group 2 capsule polymers represent crucial virulence factors of Gram-negative pathogenic bacteria. They are synthesized by enzymes called capsule polymerases. In this report, we describe a new family of polymerases that combine glycosyltransferase and hexose- and polyol-phosphate transferase activity to generate complex poly(oligosaccharide phosphate) and poly(glycosylpolyol phosphate) polymers, the latter of which display similarity to wall teichoic acid (WTA), a cell wall component of Gram-positive bacteria. Using modeling and multiple-sequence alignment, we showed homology between the predicted polymerase domains and WTA type I biosynthesis enzymes, creating a link between Gram-negative and Gram-positive cell wall biosynthesis processes. The polymerases of the new family are highly abundant and found in a variety of capsule-expressing pathogens such as Neisseria meningitidis , Actinobacillus pleuropneumoniae , Haemophilus influenzae , Bibersteinia trehalosi , and Escherichia coli with both human and animal hosts. Five representative candidates were purified, their activities were confirmed using nuclear magnetic resonance (NMR) spectroscopy, and their predicted folds were validated by site-directed mutagenesis. IMPORTANCE Bacterial capsules play an important role in the interaction between a pathogen and the immune system of its host. During the last decade, capsule polymerases have become attractive tools for the production of capsule polymers applied as antigens in glycoconjugate vaccine formulations. Conventional production of glycoconjugate vaccines requires the cultivation of the pathogen and thus the highest biosafety standards, leading to tremendous costs. With regard to animal husbandry, where vaccines could avoid the extensive use of antibiotics, conventional production is not sufficiently cost-effective. In contrast, enzymatic synthesis of capsule polymers is pathogen-free and fast, offers high stereo- and regioselectivity, and works with high efficacy. The new capsule polymerase family described here vastly increases the toolbox of enzymes available for biotechnology purposes. Representatives are abundantly found in human pathogens but also in animal pathogens, paving the way for the exploitation of polymerases for the development of a new generation of vaccines for animal husbandry. Copyright © 2018 Litschko et al.

Pathogen survival trajectories: an eco-environmental approach to the modeling of human campylobacteriosis ecology.

PubMed Central

Skelly, Chris; Weinstein, Phil

2003-01-01

Campylobacteriosis, like many human diseases, has its own ecology in which the propagation of human infection and disease depends on pathogen survival and finding new hosts in order to replicate and sustain the pathogen population. The complexity of this process, a process common to other enteric pathogens, has hampered control efforts. Many unknowns remain, resulting in a poorly understood disease ecology. To provide structure to these unknowns and help direct further research and intervention, we propose an eco-environmental modeling approach for campylobacteriosis. This modeling approach follows the pathogen population as it moves through the environments that define the physical structure of its ecology. In this paper, we term the ecologic processes and environments through which these populations move "pathogen survival trajectories." Although such a modeling approach could have veterinary applications, our emphasis is on human campylobacteriosis and focuses on human exposures to Campylobacter through feces, food, and aquatic environments. The pathogen survival trajectories that lead to human exposure include ecologic filters that limit population size, e.g., cooking food to kill Campylobacter. Environmental factors that influence the size of the pathogen reservoirs include temperature, nutrient availability, and moisture availability during the period of time the pathogen population is moving through the environment between infected and susceptible hosts. We anticipate that the modeling approach proposed here will work symbiotically with traditional epidemiologic and microbiologic research to help guide and evaluate the acquisition of new knowledge about the ecology, eventual intervention, and control of campylobacteriosis. PMID:12515674

3-Bromopyruvate: a novel antifungal agent against the human pathogen Cryptococcus neoformans.

PubMed

Dyląg, Mariusz; Lis, Paweł; Niedźwiecka, Katarzyna; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

2013-05-03

We have investigated the antifungal activity of the pyruvic acid analogue: 3-bromopyruvate (3-BP). Growth inhibition by 3-BP of 110 strains of yeast-like and filamentous fungi was tested by standard spot tests or microdilution method. The human pathogen Cryptococcus neoformans exhibited a low Minimal Inhibitory Concentration (MIC) of 0.12-0.15 mM 3-BP. The high toxicity of 3-BP toward C. neoformans correlated with high intracellular accumulation of 3-BP and also with low levels of intracellular ATP and glutathione. Weak cytotoxicity towards mammalian cells and lack of resistance conferred by the PDR (Pleiotropic Drug Resistance) network in the yeast Saccharomyces cerevisiae, are other properties of 3-BP that makes it a novel promising anticryptococcal drug. Copyright © 2013 Elsevier Inc. All rights reserved.

(Highly pathogenic) avian influenza as a zoonotic agent.

PubMed

Kalthoff, Donata; Globig, Anja; Beer, Martin

2010-01-27

Zoonotic agents challenging the world every year afresh are influenza A viruses. In the past, human pandemics caused by influenza A viruses had been occurring periodically. Wild aquatic birds are carriers of the full variety of influenza virus A subtypes, and thus, most probably constitute the natural reservoir of all influenza A viruses. Whereas avian influenza viruses in their natural avian reservoir are generally of low pathogenicity (LPAIV), some have gained virulence by mutation after transmission and adaptation to susceptible gallinaceous poultry. Those so-called highly pathogenic avian influenza viruses (HPAIV) then cause mass die-offs in susceptible birds and lead to tremendous economical losses when poultry is affected. Besides a number of avian influenza virus subtypes that have sporadically infected mammals, the HPAIV H5N1 Asia shows strong zoonotic characteristics and it was transmitted from birds to different mammalian species including humans. Theoretically, pandemic viruses might derive directly from avian influenza viruses or arise after genetic reassortment between viruses of avian and mammalian origin. So far, HPAIV H5N1 already meets two conditions for a pandemic virus: as a new subtype it has been hitherto unseen in the human population and it has infected at least 438 people, and caused severe illness and high lethality in 262 humans to date (August 2009). The acquisition of efficient human-to-human transmission would complete the emergence of a new pandemic virus. Therefore, fighting H5N1 at its source is the prerequisite to reduce pandemic risks posed by this virus. Other influenza viruses regarded as pandemic candidates derive from subtypes H2, H7, and H9 all of which have infected humans in the past. Here, we will give a comprehensive overview on avian influenza viruses in concern to their zoonotic potential. Copyright 2009 Elsevier B.V. All rights reserved.

A Robust Framework for Microbial Archaeology

PubMed Central

Warinner, Christina; Herbig, Alexander; Mann, Allison; Yates, James A. Fellows; Weiβ, Clemens L.; Burbano, Hernán A.; Orlando, Ludovic; Krause, Johannes

2017-01-01

Microbial archaeology is flourishing in the era of high-throughput sequencing, revealing the agents behind devastating historical plagues, identifying the cryptic movements of pathogens in prehistory, and reconstructing the ancestral microbiota of humans. Here, we introduce the fundamental concepts and theoretical framework of the discipline, then discuss applied methodologies for pathogen identification and microbiome characterization from archaeological samples. We give special attention to the process of identifying, validating, and authenticating ancient microbes using high-throughput DNA sequencing data. Finally, we outline standards and precautions to guide future research in the field. PMID:28460196

Epidemiology of the Ebola Virus: Facts and Hypotheses.

PubMed

Portela Câmara F

1998-12-01

Marburg and Ebola viruses are emerging pathogens recognized since 1967, and in 1976, when they were first identified. These viruses are the only members of the Filoviridae family. They cause severe, frequently fatal, hemorrhagic fever. Each genus includes some serotypes with the distinctive characteristics to cause high mortality rate during outbreaks. The Ebola-Zaire subtype is the most lethal variant. The epidemiology of human pathogenic filovirus is reviewed in this paper considering the most relevant facts. Primary human cases arise probably through close contact with infected primates. This point may be the key to preventing the introduction of these viruses in human populations. Once introduced in humans, the infection may spread through close contact with infected individuals or their body fluids, particularly in hospital environments. A main feature of filovirus outbreaks is the occurrence of cycles of secondary infection.

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.

Identification of Tick-Borne Pathogens in Ticks Feeding on Humans in Turkey

PubMed Central

Orkun, Ömer; Karaer, Zafer; Çakmak, Ayşe; Nalbantoğlu, Serpil

2014-01-01

Background The importance of tick-borne diseases is increasing all over the world, including Turkey. The tick-borne disease outbreaks reported in recent years and the abundance of tick species and the existence of suitable habitats increase the importance of studies related to the epidemiology of ticks and tick-borne pathogens in Turkey. The aim of this study was to investigate the presence of and to determine the infection rates of some tick-borne pathogens, including Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in the ticks removed from humans in different parts of Ankara. Methodology/Principal Findings A total of 169 ticks belonging to the genus Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus were collected by removing from humans in different parts of Ankara. Ticks were molecularly screened for Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae by PCR and sequencing analysis. We detected 4 Babesia spp.; B. crassa, B. major, B. occultans and B. rossi, one Borrelia spp.; B. burgdorferi sensu stricto and 3 spotted fever group rickettsiae; R. aeschlimannii, R. slovaca and R. hoogstraalii in the tick specimens analyzed. This is the report showing the presence of B. rossi in a region that is out of Africa and in the host species Ha. parva. In addition, B. crassa, for which limited information is available on its distribution and vector species, and B. occultans, for which no conclusive information is available on its presence in Turkey, were identified in Ha. parva and H. marginatum, respectively. Two human pathogenic rickettsia species (R. aeschlimannii and R. slovaca) were detected with a high prevalence in ticks. Additionally, B. burgdorferi sensu stricto was detected in unusual tick species (H. marginatum, H. excavatum, Hyalomma spp. (nymph) and Ha. parva). Conclusions/Significance This study investigates both the distribution of several tick-borne pathogens affecting humans and animals, and the presence of new tick-borne pathogens in Turkey. More epidemiological studies are warranted for B. rossi, which is very pathogenic for dogs, because the presented results suggest that B. rossi might have a wide distribution in Turkey. Furthermore, we recommend that tick-borne pathogens, especially R. aeschlimannii, R. slovaca, and B. burgdorferi sensu stricto, should be taken into consideration in patients who had a tick bite in Turkey. PMID:25101999

Identification of tick-borne pathogens in ticks feeding on humans in Turkey.

PubMed

Orkun, Ömer; Karaer, Zafer; Çakmak, Ayşe; Nalbantoğlu, Serpil

2014-08-01

The importance of tick-borne diseases is increasing all over the world, including Turkey. The tick-borne disease outbreaks reported in recent years and the abundance of tick species and the existence of suitable habitats increase the importance of studies related to the epidemiology of ticks and tick-borne pathogens in Turkey. The aim of this study was to investigate the presence of and to determine the infection rates of some tick-borne pathogens, including Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in the ticks removed from humans in different parts of Ankara. A total of 169 ticks belonging to the genus Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus were collected by removing from humans in different parts of Ankara. Ticks were molecularly screened for Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae by PCR and sequencing analysis. We detected 4 Babesia spp.; B. crassa, B. major, B. occultans and B. rossi, one Borrelia spp.; B. burgdorferi sensu stricto and 3 spotted fever group rickettsiae; R. aeschlimannii, R. slovaca and R. hoogstraalii in the tick specimens analyzed. This is the report showing the presence of B. rossi in a region that is out of Africa and in the host species Ha. parva. In addition, B. crassa, for which limited information is available on its distribution and vector species, and B. occultans, for which no conclusive information is available on its presence in Turkey, were identified in Ha. parva and H. marginatum, respectively. Two human pathogenic rickettsia species (R. aeschlimannii and R. slovaca) were detected with a high prevalence in ticks. Additionally, B. burgdorferi sensu stricto was detected in unusual tick species (H. marginatum, H. excavatum, Hyalomma spp. (nymph) and Ha. parva). This study investigates both the distribution of several tick-borne pathogens affecting humans and animals, and the presence of new tick-borne pathogens in Turkey. More epidemiological studies are warranted for B. rossi, which is very pathogenic for dogs, because the presented results suggest that B. rossi might have a wide distribution in Turkey. Furthermore, we recommend that tick-borne pathogens, especially R. aeschlimannii, R. slovaca, and B. burgdorferi sensu stricto, should be taken into consideration in patients who had a tick bite in Turkey.

Quantitative Microbial Risk Assessment and Infectious Disease Transmission Modeling of Waterborne Enteric Pathogens.

PubMed

Brouwer, Andrew F; Masters, Nina B; Eisenberg, Joseph N S

2018-04-20

Waterborne enteric pathogens remain a global health threat. Increasingly, quantitative microbial risk assessment (QMRA) and infectious disease transmission modeling (IDTM) are used to assess waterborne pathogen risks and evaluate mitigation. These modeling efforts, however, have largely been conducted independently for different purposes and in different settings. In this review, we examine the settings where each modeling strategy is employed. QMRA research has focused on food contamination and recreational water in high-income countries (HICs) and drinking water and wastewater in low- and middle-income countries (LMICs). IDTM research has focused on large outbreaks (predominately LMICs) and vaccine-preventable diseases (LMICs and HICs). Human ecology determines the niches that pathogens exploit, leading researchers to focus on different risk assessment research strategies in different settings. To enhance risk modeling, QMRA and IDTM approaches should be integrated to include dynamics of pathogens in the environment and pathogen transmission through populations.

76 FR 30705 - Problem Formulation for Human Health Risk Assessments of Pathogens in Land-Applied Biosolids

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9311-4] Problem Formulation for Human Health Risk Assessments of Pathogens in Land-Applied Biosolids AGENCY: Environmental Protection Agency (EPA). ACTION: Notice... Formulation for Human Health Risk Assessments of Pathogens in Land-Applied Biosolids'' EPA/600/R-08/035F...

New York City House Mice (Mus musculus) as Potential Reservoirs for Pathogenic Bacteria and Antimicrobial Resistance Determinants.

PubMed

Williams, Simon H; Che, Xiaoyu; Paulick, Ashley; Guo, Cheng; Lee, Bohyun; Muller, Dorothy; Uhlemann, Anne-Catrin; Lowy, Franklin D; Corrigan, Robert M; Lipkin, W Ian

2018-04-17

House mice ( Mus musculus ) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella , Salmonella , Clostridium difficile , and diarrheagenic Escherichia coli Furthermore, genes mediating antimicrobial resistance to fluoroquinolones ( qnrB ) and β-lactam drugs ( bla SHV and bla ACT/MIR ) were widely distributed. Culture and molecular strain typing of C. difficile revealed that mice harbor ribotypes associated with human disease, and screening of kidney samples demonstrated genetic evidence of pathogenic Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment. IMPORTANCE Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes. Copyright © 2018 Williams et al.

Computational Identification and Comparative Analysis of Secreted and Transmembrane Proteins in Six Burkholderia Species.

PubMed

Nguyen, Thao Thi; Lee, Hyun-Hee; Park, Jungwook; Park, Inmyoung; Seo, Young-Su

2017-04-01

As a step towards discovering novel pathogenesis-related proteins, we performed a genome scale computational identification and characterization of secreted and transmembrane (TM) proteins, which are mainly responsible for bacteria-host interactions and interactions with other bacteria, in the genomes of six representative Burkholderia species. The species comprised plant pathogens ( B. glumae BGR1, B. gladioli BSR3), human pathogens ( B. pseudomallei K96243, B. cepacia LO6), and plant-growth promoting endophytes ( Burkholderia sp. KJ006, B. phytofirmans PsJN). The proportions of putative classically secreted proteins (CSPs) and TM proteins among the species were relatively high, up to approximately 20%. Lower proportions of putative type 3 non-classically secreted proteins (T3NCSPs) (~10%) and unclassified non-classically secreted proteins (NCSPs) (~5%) were observed. The numbers of TM proteins among the three clusters (plant pathogens, human pathogens, and endophytes) were different, while the distribution of these proteins according to the number of TM domains was conserved in which TM proteins possessing 1, 2, 4, or 12 TM domains were the dominant groups in all species. In addition, we observed conservation in the protein size distribution of the secreted protein groups among the species. There were species-specific differences in the functional characteristics of these proteins in the various groups of CSPs, T3NCSPs, and unclassified NCSPs. Furthermore, we assigned the complete sets of the conserved and unique NCSP candidates of the collected Burkholderia species using sequence similarity searching. This study could provide new insights into the relationship among plant-pathogenic, human-pathogenic, and endophytic bacteria.

Is your lunch salad safe to eat? Occurrence of bacterial pathogens and potential for pathogen growth in pre-packed ready-to-eat mixed-ingredient salads.

PubMed

Söderqvist, Karin

2017-01-01

As part of a trend toward healthy convenience foods, ready-to-eat (RTE) mixed-ingredient salads have become popular products among consumers. A mixed-ingredient salad contains combinations of raw ( e.g . leafy vegetables and tomatoes) and processed ( e.g . chicken, salmon, ham, pasta and couscous) ingredients. Contamination of leafy vegetables can occur during any step in the production chain and, since there is no step that kills pathogens, a completely safe final product can never be guaranteed. Meat ingredients, for example poultry meat and ham, are generally heat-treated before preparation, but may be contaminated after this treatment, e.g . when diced or sliced. When several ingredients are mixed together, cross-contamination may occur. Preparation of mixed-ingredient salads requires human handling, which presents an additional risk of bacterial contamination. With high-protein ingredients, e.g . cooked meat, the mixed-ingredient salad represents an excellent substrate for bacterial growth. This article reviews current knowledge regarding human bacterial pathogen prevalence in mixed-ingredient salads and the potential for pathogen growth in this product during storage.

Is your lunch salad safe to eat? Occurrence of bacterial pathogens and potential for pathogen growth in pre-packed ready-to-eat mixed-ingredient salads

PubMed Central

Söderqvist, Karin

2017-01-01

ABSTRACT As part of a trend toward healthy convenience foods, ready-to-eat (RTE) mixed-ingredient salads have become popular products among consumers. A mixed-ingredient salad contains combinations of raw (e.g. leafy vegetables and tomatoes) and processed (e.g. chicken, salmon, ham, pasta and couscous) ingredients. Contamination of leafy vegetables can occur during any step in the production chain and, since there is no step that kills pathogens, a completely safe final product can never be guaranteed. Meat ingredients, for example poultry meat and ham, are generally heat-treated before preparation, but may be contaminated after this treatment, e.g. when diced or sliced. When several ingredients are mixed together, cross-contamination may occur. Preparation of mixed-ingredient salads requires human handling, which presents an additional risk of bacterial contamination. With high-protein ingredients, e.g. cooked meat, the mixed-ingredient salad represents an excellent substrate for bacterial growth. This article reviews current knowledge regarding human bacterial pathogen prevalence in mixed-ingredient salads and the potential for pathogen growth in this product during storage. PMID:29230273

Migrating microbes: what pathogens can tell us about population movements and human evolution.

PubMed

Houldcroft, Charlotte J; Ramond, Jean-Baptiste; Rifkin, Riaan F; Underdown, Simon J

2017-08-01

The biology of human migration can be observed from the co-evolutionary relationship with infectious diseases. While many pathogens are brief, unpleasant visitors to human bodies, others have the ability to become life-long human passengers. The story of a pathogen's genetic code may, therefore, provide insight into the history of its human host. The evolution and distribution of disease in Africa is of particular interest, because of the deep history of human evolution in Africa, the presence of a variety of non-human primates, and tropical reservoirs of emerging infectious diseases. This study explores which pathogens leave traces in the archaeological record, and whether there are realistic prospects that these pathogens can be recovered from sub-Saharan African archaeological contexts. Three stories are then presented of germs on a journey. The first is the story of HIV's spread on the back of colonialism and the railway networks over the last 150 years. The second involves the spread of Schistosoma mansoni, a parasite which shares its history with the trans-Atlantic slave trade and the origins of fresh-water fishing. Finally, we discuss the tantalising hints of hominin migration and interaction found in the genome of human herpes simplex virus 2. Evidence from modern African pathogen genomes can provide data on human behaviour and migration in deep time and contribute to the improvement of human quality-of-life and longevity.

Microfluidic devices for sample preparation and rapid detection of foodborne pathogens.

PubMed

Kant, Krishna; Shahbazi, Mohammad-Ali; Dave, Vivek Priy; Ngo, Tien Anh; Chidambara, Vinayaka Aaydha; Than, Linh Quyen; Bang, Dang Duong; Wolff, Anders

2018-03-10

Rapid detection of foodborne pathogens at an early stage is imperative for preventing the outbreak of foodborne diseases, known as serious threats to human health. Conventional bacterial culturing methods for foodborne pathogen detection are time consuming, laborious, and with poor pathogen diagnosis competences. This has prompted researchers to call the current status of detection approaches into question and leverage new technologies for superior pathogen sensing outcomes. Novel strategies mainly rely on incorporating all the steps from sample preparation to detection in miniaturized devices for online monitoring of pathogens with high accuracy and sensitivity in a time-saving and cost effective manner. Lab on chip is a blooming area in diagnosis, which exploits different mechanical and biological techniques to detect very low concentrations of pathogens in food samples. This is achieved through streamlining the sample handling and concentrating procedures, which will subsequently reduce human errors and enhance the accuracy of the sensing methods. Integration of sample preparation techniques into these devices can effectively minimize the impact of complex food matrix on pathogen diagnosis and improve the limit of detections. Integration of pathogen capturing bio-receptors on microfluidic devices is a crucial step, which can facilitate recognition abilities in harsh chemical and physical conditions, offering a great commercial benefit to the food-manufacturing sector. This article reviews recent advances in current state-of-the-art of sample preparation and concentration from food matrices with focus on bacterial capturing methods and sensing technologies, along with their advantages and limitations when integrated into microfluidic devices for online rapid detection of pathogens in foods and food production line. Copyright © 2018. Published by Elsevier Inc.

What is the Risk for Exposure to Vector-Borne Pathogens in United States National Parks?

PubMed Central

EISEN, LARS; WONG, DAVID; SHELUS, VICTORIA; EISEN, REBECCA J.

2015-01-01

United States national parks attract >275 million visitors annually and collectively present risk of exposure for staff and visitors to a wide range of arthropod vector species (most notably fleas, mosquitoes, and ticks) and their associated bacterial, protozoan, or viral pathogens. We assessed the current state of knowledge for risk of exposure to vector-borne pathogens in national parks through a review of relevant literature, including internal National Park Service documents and organismal databases. We conclude that, because of lack of systematic surveillance for vector-borne pathogens in national parks, the risk of pathogen exposure for staff and visitors is unclear. Existing data for vectors within national parks were not based on systematic collections and rarely include evaluation for pathogen infection. Extrapolation of human-based surveillance data from neighboring communities likely provides inaccurate estimates for national parks because landscape differences impact transmission of vector-borne pathogens and human-vector contact rates likely differ inside versus outside the parks because of differences in activities or behaviors. Vector-based pathogen surveillance holds promise to define when and where within national parks the risk of exposure to infected vectors is elevated. A pilot effort, including 5–10 strategic national parks, would greatly improve our understanding of the scope and magnitude of vector-borne pathogen transmission in these high-use public settings. Such efforts also will support messaging to promote personal protection measures and inform park visitors and staff of their responsibility for personal protection, which the National Park Service preservation mission dictates as the core strategy to reduce exposure to vector-borne pathogens in national parks. PMID:23540107

Mammalian Models for the Study of H7 Virus Pathogenesis and Transmission

PubMed Central

Belser, Jessica A.; Tumpey, Terrence M.

2018-01-01

Mammalian models, most notably the mouse and ferret, have been instrumental in the assessment of avian influenza virus pathogenicity and transmissibility, and have been used widely to characterize the molecular determinants that confer H5N1 virulence in mammals. However, while H7 influenza viruses have typically been associated with conjunctivitis and/or mild respiratory disease in humans, severe disease and death is also possible, as underscored by the recent emergence of H7N9 viruses in China. Despite the public health need to understand the pandemic potential of this virus subtype, H7 virus pathogenesis and transmission has not been as extensively studied. In this review, we discuss the heterogeneity of H7 subtype viruses isolated from humans, and the characterization of mammalian models to study the virulence of H7 subtype viruses associated with human infection, including viruses of both high and low pathogenicity and following multiple inoculation routes. The use of the ferret transmission model to assess the influence of receptor binding preference among contemporary H7 influenza viruses is described. These models have enabled the study of preventative and therapeutic agents, including vaccines and antivirals, to reduce disease burden, and have permitted a greater appreciation that not all highly pathogenic influenza viruses are created equal. PMID:24996862

Influenza virus isolation.

PubMed

Krauss, Scott; Walker, David; Webster, Robert G

2012-01-01

The isolation of influenza viruses is important for the diagnosis of respiratory diseases in lower animals and humans, for the detection of the infecting agent in surveillance programs, and is an essential element in the development and production of vaccine. Since influenza is caused by a zoonotic virus it is necessary to do surveillance in the reservoir species (aquatic waterfowls), intermediate hosts (quails, pigs), and in affected mammals including humans. Two of the hemagglutinin (HA) subtypes of influenza A viruses (H5 and H7) can evolve into highly pathogenic (HP) strains for gallinaceous poultry; some HP H5 and H7 strains cause lethal infection of humans. In waterfowls, low pathogenic avian influenza (LPAI) isolates are obtained primarily from the cloaca (or feces); in domestic poultry, the virus is more often recovered from the respiratory tract than from cloacal samples; in mammals, the virus is most often isolated from the respiratory tract, and in cases of high pathogenic avian influenza (HPAI) from the blood and internal organs of infected birds. Virus isolation procedures are performed by inoculation of clinical specimens into embryonated eggs (primarily chicken eggs) or onto a variety of primary or continuous tissue culture systems. Successful isolation of influenza virus depends on the quality of the sample and matching the appropriate culture method to the sample type.

Identification, molecular and functional characterization of calmodulin gene of Phytomonas serpens 15T that shares high similarity with its pathogenic counterparts Trypanosoma cruzi.

PubMed

de Souza, Tatiana de Arruda Campos Brasil; Graça-de Souza, Viviane Krominski; Lancheros, César Armando Contreras; Monteiro-Góes, Viviane; Krieger, Marco Aurélio; Goldenberg, Samuel; Yamauchi, Lucy Megumi; Yamada-Ogatta, Sueli Fumie

2011-03-01

In trypanosomatids, Ca²+-binding proteins can affect parasite growth, differentiation and invasion. Due to their importance for parasite maintenance, they become an attractive target for drug discovery and design. Phytomonas serpens 15T is a non-human pathogenic trypanosomatid that expresses important protein homologs of human pathogenic trypanosomatids. In this study, the coding sequence of calmodulin, a Ca²+-binding protein, of P. serpens 15T was cloned and characterized. The encoded polypeptide (CaMP) displayed high amino acid identity to homolog protein of Trypanosoma cruzi and four helix-loop-helix motifs were found. CaMP sequence analysis showed 20 amino acid substitutions compared to its mammalian counterparts. This gene is located on a chromosomal band with estimated size of 1,300 kb and two transcripts were detected by Northern blot analysis. A polyclonal antiserum raised against the recombinant protein recognized a polypeptide with an estimated size of 17 kDa in log-phase promastigote extracts. The recombinant CaMP retains its Ca²+-binding capacity.

Population Abundance of Potentially Pathogenic Organisms in Intestinal Microbiome of Jungle Crow (Corvus macrorhynchos) Shown with 16S rRNA Gene-Based Microbial Community Analysis

PubMed Central

Maeda, Isamu; Siddiki, Mohammad Shohel Rana; Nozawa-Takeda, Tsutomu; Tsukahara, Naoki; Tani, Yuri; Naito, Taki; Sugita, Shoei

2013-01-01

Jungle Crows (Corvus macrorhynchos) prefer human habitats because of their versatility in feeding accompanied with human food consumption. Therefore, it is important from a public health viewpoint to characterize their intestinal microbiota. However, no studies have been involved in molecular characterization of the microbiota based on huge and reliable number of data acquisition. In this study, 16S rRNA gene-based microbial community analysis coupled with the next-generation DNA sequencing techniques was applied to the taxonomic classification of intestinal microbiome for three jungle crows. Clustering of the reads into 130 operational taxonomic units showed that at least 70% of analyzed sequences for each crow were highly homologous to Eimeria sp., which belongs to the protozoan phylum Apicomplexa. The microbiotas of three crows also contained potentially pathogenic bacteria with significant percentages, such as the genera Campylobacter and Brachyspira. Thus, the profiling of a large number of 16S rRNA gene sequences in crow intestinal microbiomes revealed the high-frequency existence or vestige of potentially pathogenic microorganisms. PMID:24058905

Population abundance of potentially pathogenic organisms in intestinal microbiome of jungle crow (Corvus macrorhynchos) shown with 16S rRNA gene-based microbial community analysis.

PubMed

Maeda, Isamu; Siddiki, Mohammad Shohel Rana; Nozawa-Takeda, Tsutomu; Tsukahara, Naoki; Tani, Yuri; Naito, Taki; Sugita, Shoei

2013-01-01

Jungle Crows (Corvus macrorhynchos) prefer human habitats because of their versatility in feeding accompanied with human food consumption. Therefore, it is important from a public health viewpoint to characterize their intestinal microbiota. However, no studies have been involved in molecular characterization of the microbiota based on huge and reliable number of data acquisition. In this study, 16S rRNA gene-based microbial community analysis coupled with the next-generation DNA sequencing techniques was applied to the taxonomic classification of intestinal microbiome for three jungle crows. Clustering of the reads into 130 operational taxonomic units showed that at least 70% of analyzed sequences for each crow were highly homologous to Eimeria sp., which belongs to the protozoan phylum Apicomplexa. The microbiotas of three crows also contained potentially pathogenic bacteria with significant percentages, such as the genera Campylobacter and Brachyspira. Thus, the profiling of a large number of 16S rRNA gene sequences in crow intestinal microbiomes revealed the high-frequency existence or vestige of potentially pathogenic microorganisms.

Genetic Recombination between Human and Animal Parasites Creates Novel Strains of Human Pathogen

PubMed Central

Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

2015-01-01

Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT. PMID:25816228

Genetic recombination between human and animal parasites creates novel strains of human pathogen.

PubMed

Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

2015-03-01

Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.

sourceR: Classification and source attribution of infectious agents among heterogeneous populations

PubMed Central

French, Nigel

2017-01-01

Zoonotic diseases are a major cause of morbidity, and productivity losses in both human and animal populations. Identifying the source of food-borne zoonoses (e.g. an animal reservoir or food product) is crucial for the identification and prioritisation of food safety interventions. For many zoonotic diseases it is difficult to attribute human cases to sources of infection because there is little epidemiological information on the cases. However, microbial strain typing allows zoonotic pathogens to be categorised, and the relative frequencies of the strain types among the sources and in human cases allows inference on the likely source of each infection. We introduce sourceR, an R package for quantitative source attribution, aimed at food-borne diseases. It implements a Bayesian model using strain-typed surveillance data from both human cases and source samples, capable of identifying important sources of infection. The model measures the force of infection from each source, allowing for varying survivability, pathogenicity and virulence of pathogen strains, and varying abilities of the sources to act as vehicles of infection. A Bayesian non-parametric (Dirichlet process) approach is used to cluster pathogen strain types by epidemiological behaviour, avoiding model overfitting and allowing detection of strain types associated with potentially high “virulence”. sourceR is demonstrated using Campylobacter jejuni isolate data collected in New Zealand between 2005 and 2008. Chicken from a particular poultry supplier was identified as the major source of campylobacteriosis, which is qualitatively similar to results of previous studies using the same dataset. Additionally, the software identifies a cluster of 9 multilocus sequence types with abnormally high ‘virulence’ in humans. sourceR enables straightforward attribution of cases of zoonotic infection to putative sources of infection. As sourceR develops, we intend it to become an important and flexible resource for food-borne disease attribution studies. PMID:28558033

New Kind of War: Are We Prepared for Agroterrorism?

DTIC Science & Technology

2007-05-24

Department of Health and Human Services, Tommy Thompson 7 December 2004 In recent years, the world has seen a surge in highly toxic, animal-borne zoonotic ...and non- zoonotic diseases. Zoonotic diseases are those that can be passed from animals to humans either through direct or indirect contact, such as...highly pathogenic avian influenza (HPAI) and severe acute respiratory syndrome (SARS); while non- zoonotic diseases are those diseases which will

Inactivation of Staphylococcus aureus and native microflora in human milk by high pressure processing

NASA Astrophysics Data System (ADS)

Windyga, Bożena; Rutkowska, Małgorzata; Sokołowska, Barbara; Skąpska, Sylwia; Wesołowska, Aleksandra; Wilińska, Maria; Fonberg-Broczek, Monika; Rzoska, Sylwester J.

2015-04-01

The storage of unpreserved food, including breast milk, is associated with the growth of microorganisms, including pathogenic bacteria. It is therefore necessary to use suitable processes to eliminate pathogenic microorganisms and reduce the total microbial count in order to ensure product safety for consumers. In the present study, samples of milk obtained from volunteers donating to the human milk bank were artificially contaminated with Staphylococcus aureus ATCC 6538. This bacteria was the model microorganism of choice, being relatively resistant to high pressure as well as posing the most serious risk to infant health. The results obtained show that high pressure processing can reduce the count of S. aureus by about 5 log units at 4°C and about 8 log units at 50°C, and totally eliminate Enterobacteriaceae after 5 min of treatment, and result in a total microbial count reduction after 10 min treatment at 500 MPa at 20°C and 50°C. This suggests the possibility of this technology being applied to ensure the adequate safety and quality of human breast milk in human milk banks. This paper was presented at the LIIth European High Pressure Research Group (EHPRG 52) Meeting in Lyon (France), 7-12 September 2014.

Establishment of feeder-free culture system for human induced pluripotent stem cell on DAS nanocrystalline graphene

NASA Astrophysics Data System (ADS)

Lee, Hyunah; Nam, Donggyu; Choi, Jae-Kyung; Araúzo-Bravo, Marcos J.; Kwon, Soon-Yong; Zaehres, Holm; Lee, Taehee; Park, Chan Young; Kang, Hyun-Wook; Schöler, Hans R.; Kim, Jeong Beom

2016-02-01

The maintenance of undifferentiated human pluripotent stem cells (hPSC) under xeno-free condition requires the use of human feeder cells or extracellular matrix (ECM) coating. However, human-derived sources may cause human pathogen contamination by viral or non-viral agents to the patients. Here we demonstrate feeder-free and xeno-free culture system for hPSC expansion using diffusion assisted synthesis-grown nanocrystalline graphene (DAS-NG), a synthetic non-biological nanomaterial which completely rule out the concern of human pathogen contamination. DAS-NG exhibited advanced biocompatibilities including surface nanoroughness, oxygen containing functional groups and hydrophilicity. hPSC cultured on DAS-NG could maintain pluripotency in vitro and in vivo, and especially cell adhesion-related gene expression profile was comparable to those of cultured on feeders, while hPSC cultured without DAS-NG differentiated spontaneously with high expression of somatic cell-enriched adhesion genes. This feeder-free and xeno-free culture method using DAS-NG will facilitate the generation of clinical-grade hPSC.

Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes.

PubMed

Voyich, Jovanka M; Sturdevant, Daniel E; Braughton, Kevin R; Kobayashi, Scott D; Lei, Benfang; Virtaneva, Kimmo; Dorward, David W; Musser, James M; DeLeo, Frank R

2003-02-18

Group A Streptococcus (GAS) evades polymorphonuclear leukocyte (PMN) phagocytosis and killing to cause human disease, including pharyngitis and necrotizing fasciitis (flesh-eating syndrome). We show that GAS genes differentially regulated during phagocytic interaction with human PMNs comprise a global pathogen-protective response to innate immunity. GAS prophage genes and genes involved in virulence, oxidative stress, cell wall biosynthesis, and gene regulation were up-regulated during PMN phagocytosis. Genes encoding novel secreted proteins were up-regulated, and the proteins were produced during human GAS infections. We discovered an essential role for the Ihk-Irr two-component regulatory system in evading PMN-mediated killing and promoting host-cell lysis, processes that would facilitate GAS pathogenesis. Importantly, the irr gene was highly expressed during human GAS pharyngitis. We conclude that a complex pathogen genetic program circumvents human innate immunity to promote disease. The gene regulatory program revealed by our studies identifies previously undescribed potential vaccine antigens and targets for therapeutic interventions designed to control GAS infections.

Human platelet gel supernatant inactivates opportunistic wound pathogens on skin.

PubMed

Edelblute, Chelsea M; Donate, Amy L; Hargrave, Barbara Y; Heller, Loree C

2015-01-01

Activation of human platelets produces a gel-like substance referred to as platelet rich plasma or platelet gel. Platelet gel is used clinically to promote wound healing; it also exhibits antimicrobial properties that may aid in the healing of infected wounds. The purpose of this study was to quantify the efficacy of human platelet gel against the opportunistic bacterial wound pathogens Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus on skin. These opportunistic pathogens may exhibit extensive antibiotic resistance, necessitating the development of alternative treatment options. The antimicrobial efficacy of platelet gel supernatants was quantified using an in vitro broth dilution assay, an ex vivo inoculated skin assay, and in an in vivo skin decontamination assay. Human platelet gel supernatants were highly bactericidal against A. baumannii and moderately but significantly bactericidal against S. aureus in vitro and in the ex vivo skin model. P. aeruginosa was not inactivated in vitro; a low but significant inactivation level was observed ex vivo. These supernatants were quite effective at inactivating a model organism on skin in vivo. These results suggest application of platelet gel has potential clinical applicability, not only in the acceleration of wound healing, but also against relevant bacteria causing wound infections.

Optimise the microbial flora with milk and yoghurt to prevent disease.

PubMed

Morris, James A

2018-05-01

Pathogenic bacteria, which are temporary or permanent members of our microbial flora, cause or contribute to a wide range of human disease at all ages. Conditions include Alzheimer's disease, atherosclerosis, diabetes mellitus, obesity, cancer, autoimmunity and psychosis, amongst others. The mechanism of damage is inflammation which can be chronic or acute. An optimal microbial flora includes a wide range of pathogenic bacteria in low dose. This allows specific immunity to be developed and maintained with minimal inflammatory damage. Human milk has evolved to deliver an optimal microbial flora to the infant. Cow's milk has the potential, following appropriate fortification, to maintain an optimal human microbial flora throughout life. Yoghurt is a fermented milk product in which bacteria normally present in milk convert sugars to lactic acid. The acid suppresses the growth of pathogens in the oral cavity, oropharynx and oesophagus. Thus yoghurt can restore an optimal flora in these regions in the short term. Since bacteria are transported between epithelial surfaces, yoghurt will also optimise the flora elsewhere. The judicious use of milk and yogurt could prevent a high proportion of human disease. Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.

Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity

PubMed Central

Wang, Zhongfang; Loh, Liyen; Kedzierski, Lukasz; Kedzierska, Katherine

2016-01-01

Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and 35%, respectively. Ongoing circulation of H5N1 and H7N9 viruses in wild birds and poultry, and their ability to infect humans emphasizes their epidemic and pandemic potential and poses a public health threat. It is, thus, imperative to understand the host immune responses to the AIVs so we can control severe influenza disease caused by H5N1 or H7N9 and rationally design new immunotherapies and vaccines. This review summarizes our current knowledge on AIV epidemiology, disease symptoms, inflammatory processes underlying the AIV infection in humans, and recent studies on universal pre-existing CD8+ T cell immunity to AIVs. Immune responses driving the host recovery from AIV infection in patients hospitalized with severe influenza disease are also discussed. PMID:26973644

Field Testing of a Prototype Filter System for the Removal of the Human Pathogen Giardia intestinales from Ground Water

NASA Astrophysics Data System (ADS)

Rust, C.; Schulze-Makuch, D.; Bowman, R.; Meier, D.

2005-12-01

Pathogenic bacteria, viruses, and protozoans tend to be negatively charged in the pH range of most ground waters. Thus, naturally occurring and modified materials such as surfactant-modified zeolites (SMZ), which have net positive surface charges and hydrophobic properties, are suitable as barriers to impede pathogen migration in aquifer systems. In our experiments SMZ has been used to remove E. coli and the bacteriophage MS-2 from sewage water with a high success rate ( E. coli 100%, MS-2 > 90%). Testing was conducted both in the laboratory and the field. Laboratory experiments were conducted to test the removal efficiency of SMZ for Giardia intestinales using the Giardia cysts and microsphere analogs. The SMZ was effective at removing Giardia intestinales cysts from the groundwater, but removal rates were not as high as for bacteria and viruses in the earlier experiments. The removal efficiency varied with the particular formulation of the SMZ used. The most effective SMZ formulation is being further tested at our field site using water amended with microspheres to simulate Giardia behavior. The field site is an existing multiple well site at the University of Idaho in Moscow. The wells are completed in the Lolo Basalt Formation; a highly heterogeneous and anisotropic fractured basalt aquifer system typical of the subsurface of most of eastern Washington and northeastern Oregon. The SMZ pathogen filter is installed directly in the well bore and the concentrations of microsphere-amended ground water are measured before and after filtration. Pumping over an extended period is continuing in order to test the lifetime of our prototype filter system. Our tests and results are targeted at developing a prototype filter system for removing a multitude of human pathogens in drinking water.

Cell invasion of poultry-associated Salmonella enterica serovar Enteritidis isolates is associated with pathogenicity, motility and proteins secreted by the type III secretion system

PubMed Central

Zhou, Xiaohui; Addwebi, Tarek; Davis, Margaret A.; Orfe, Lisa; Call, Douglas R.; Guard, Jean; Besser, Thomas E.

2011-01-01

Salmonella enterica serovar Enteritidis (S. Enteritidis) is a major cause of food-borne gastroenteritis in humans worldwide. Poultry and poultry products are considered the major vehicles of transmission to humans. Using cell invasiveness as a surrogate marker for pathogenicity, we tested the invasiveness of 53 poultry-associated isolates of S. Enteritidis in a well-differentiated intestinal epithelial cell model (Caco-2). The method allowed classification of the isolates into low (n = 7), medium (n = 18) and high (n = 30) invasiveness categories. Cell invasiveness of the isolates did not correlate with the presence of the virulence-associated gene spvB or the ability of the isolates to form biofilms. Testing of representative isolates with high and low invasiveness in a mouse model revealed that the former were more invasive in vivo and caused more and earlier mortalities, whereas the latter were significantly less invasive in vivo, causing few or no mortalities. Further characterization of representative isolates with low and high invasiveness showed that most of the isolates with low invasiveness had impaired motility and impaired secretion of either flagella-associated proteins (FlgK, FljB and FlgL) or type III secretion system (TTSS)-secreted proteins (SipA and SipD) encoded on Salmonella pathogenicity island-1. In addition, isolates with low invasiveness had impaired ability to invade and/or survive within chicken macrophages. These data suggest that not all isolates of S. Enteritidis recovered from poultry may be equally pathogenic, and that the pathogenicity of S. Enteritidis isolates is associated, in part, with both motility and secretion of TTSS effector proteins. PMID:21292746

Sensitive genotyping of foodborne-associated human noroviruses and hepatitis A virus using an array-based platform

USDA-ARS?s Scientific Manuscript database

The viral pathogens, human norovirus (NoV) and hepatitis A virus (HAV), are significant contributors of foodborne associated outbreaks. To develop a typing tool for foodborne viruses, a focused, low-density DNA microarray was developed in conjunction with a rapid and high-throughput fluorescent meth...

Prevalence of Rickettsia species in Dermacentor variabilis ticks from Ontario, Canada.

PubMed

Wood, Heidi; Dillon, Liz; Patel, Samir N; Ralevski, Filip

2016-07-01

Relatively little is known about the prevalence of rickettsial species in Dermacentor ticks in eastern Canada. In this study, Dermacentor ticks from the province of Ontario, Canada, were tested for the presence of spotted fever group rickettsial (SFGR) species, Coxiella burnetii and Francisella tularensis. Rickettsia rickettsii was not detected in any ticks tested, but R. montanensis was detected at a prevalence of 2.2% in D. variabilis (17/778). Two other SFGR species, R. parkeri and Candidatus R. andeanae, were detected individually in 2 Amblyomma maculatum ticks. Rickettsia peacockii, a non-pathogenic endosymbiont, was detected in two D. andersonii ticks. Given the highly abundant nature of D. variabilis, surveillance for human pathogens in this species of tick has important public health implications, but the lack of detection of known human pathogens indicates a low risk of infection via this tick species in Ontario. However, the detection of R. parkeri in an adventive A. maculatum tick indicates that health care providers should be aware of the possibility of spotted fever rickettsioses in individuals with a history of travel outside of Ontario and symptoms compatible with a spotted fever rickettsiosis. Coxiella burnetii and Francisella tularensis, human pathogens also potentially transmitted by D. variabilis, were not detected in a subset of the ticks. Copyright © 2016 Elsevier GmbH. All rights reserved.

Interaction of the Human Contact System with Pathogens-An Update.

PubMed

Oehmcke-Hecht, Sonja; Köhler, Juliane

2018-01-01

The name human contact system is related to its mode of action, as "contact" with artificial negatively charged surfaces triggers its activation. Today, it is generally believed that the contact system is an inflammatory response mechanism not only against artificial material but also against misfolded proteins and foreign organisms. Upon activation, the contact system is involved in at least two distinct (patho)physiologic processes: i . the trigger of the intrinsic coagulation via factor XI and ii . the cleavage of high molecular weight kininogen with release of bradykinin and antimicrobial peptides (AMPs). Bradykinin is involved in the regulation of inflammatory processes, vascular permeability, and blood pressure. Due to the release of AMPs, the contact system is regarded as a branch of the innate immune defense against microorganisms. There is an increasing list of pathogens that interact with contact factors, in addition to bacteria also fungi and viruses bind and activate the system. In spite of that, pathogens have developed their own mechanisms to activate the contact system, resulting in manipulation of this host immune response. In this up-to-date review, we summarize present research on the interaction of pathogens with the human contact system, focusing particularly on bacterial and viral mechanisms that trigger inflammation via contact system activation.

Escherichia coli O157:H7 induces stronger plant immunity than Salmonella enterica Typhimurium SL1344.

PubMed

Roy, Debanjana; Panchal, Shweta; Rosa, Bruce A; Melotto, Maeli

2013-04-01

Consumption of fresh produce contaminated with bacterial human pathogens has resulted in various, sometimes deadly, disease outbreaks. In this study, we assessed plant defense responses induced by the fully pathogenic bacteria Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium SL1344 in both Arabidopsis thaliana and lettuce (Lactuca sativa). Unlike SL1344, O157:H7 induced strong plant immunity at both pre-invasion and post-invasion steps of infection. For instance, O157:H7 triggered stomatal closure even under high relative humidity, an environmental condition that generally weakens plant defenses against bacteria in the field and laboratory conditions. SL1344 instead induced a transient stomatal immunity. We also observed that PR1 gene expression was significantly higher in Arabidopsis leaves infected with O157:H7 compared with SL1344. These results suggest that plants may recognize and respond to some human pathogens more effectively than others. Furthermore, stomatal immunity can diminish the penetration of human pathogens through the leaf epidermis, resulting in low bacterial titers in the plant apoplast and suggesting that additional control measures can be employed to prevent food contamination. The understanding of how plant responses can diminish bacterial contamination is paramount in preventing outbreaks and improving the safety of food supplies.

So close and yet so far – Molecular Microbiology of Campylobacter fetus subspecies

PubMed Central

Sprenger, H.; Zechner, E. L.; Gorkiewicz, G.

2012-01-01

Campylobacter fetus comprises two subspecies, C. fetus subsp. fetus and C. fetus subsp. venerealis, which are considered emerging pathogens in humans and animals. Comparisons at the genome level have revealed modest subspecies-specific variation; nevertheless, these two subspecies show distinct host and niche preferences. C. fetus subsp. fetus is a commensal and pathogen of domesticated animals that can be transmitted to humans via contaminated food. The clinical features of human infection can be severe, especially in impaired hosts. In contrast, C. fetus subsp. venerealis is a sexually transmitted pathogen essentially restricted to cattle. Infections leading to bovine venereal campylobacteriosis cause substantial economic losses due to abortion and infertility. Recent genome sequencing of the two subspecies has advanced our understanding of C. fetus adaptations through comparative genomics and the identification of subspecies-specific gene regions predicted to be involved in pathogenesis. The most striking difference between the subspecies is the highly subspecies-specific association of a pathogenicity island in the C. fetus subsp. venerealis chromosome. The inserted region encodes a Type 4 secretion system, which contributes to virulence properties of this organism in vitro. This review describes the main differences in epidemiological, phenotypic, and molecular characteristics of the two subspecies and summarizes recent advances towards understanding the molecular mechanisms of C. fetus pathogenesis. PMID:24611123

Genome Dynamics in Legionella: The Basis of Versatility and Adaptation to Intracellular Replication

PubMed Central

Gomez-Valero, Laura; Buchrieser, Carmen

2013-01-01

Legionella pneumophila is a bacterial pathogen present in aquatic environments that can cause a severe pneumonia called Legionnaires’ disease. Soon after its recognition, it was shown that Legionella replicates inside amoeba, suggesting that bacteria replicating in environmental protozoa are able to exploit conserved signaling pathways in human phagocytic cells. Comparative, evolutionary, and functional genomics suggests that the Legionella–amoeba interaction has shaped this pathogen more than previously thought. A complex evolutionary scenario involving mobile genetic elements, type IV secretion systems, and horizontal gene transfer among Legionella, amoeba, and other organisms seems to take place. This long-lasting coevolution led to the development of very sophisticated virulence strategies and a high level of temporal and spatial fine-tuning of bacteria host–cell interactions. We will discuss current knowledge of the evolution of virulence of Legionella from a genomics perspective and propose our vision of the emergence of this human pathogen from the environment. PMID:23732852

The molecular biology of nairoviruses, an emerging group of tick-borne arboviruses.

PubMed

Lasecka, Lidia; Baron, Michael D

2014-06-01

The nairoviruses are a rapidly emerging group of tick-borne bunyaviruses that includes pathogens of humans (Crimean-Congo hemorrhagic fever virus [CCHFV]) and livestock (Nairobi sheep disease virus [NSDV], also known as Ganjam virus), as well as a large number of viruses for which the normal vertebrate host has not been established. Studies on this group of viruses have been fairly limited, not least because CCHFV is a BSL4 human pathogen, restricting the number of labs able to study the live virus, while NSDV, although highly pathogenic in naive animals, is not seen as a threat in developed countries, making it a low priority. Nevertheless, recent years have seen significant progress in our understanding of the biology of these viruses, particularly that of CCHFV, and this article seeks to draw together our existing knowledge to generate an overall picture of their molecular biology, underlining areas of particular ignorance for future studies.

Antibacterial screening of traditional herbal plants and standard antibiotics against some human bacterial pathogens.

PubMed

Awan, Uzma Azeem; Andleeb, Saiqa; Kiyani, Ayesha; Zafar, Atiya; Shafique, Irsa; Riaz, Nazia; Azhar, Muhammad Tehseen; Uddin, Hafeez

2013-11-01

Chloroformic and isoamyl alcohol extracts of Cinnnamomum zylanicum, Cuminum cyminum, Curcuma long Linn, Trachyspermum ammi and selected standard antibiotics were investigated for their in vitro antibacterial activity against six human bacterial pathogens. The antibacterial activity was evaluated and based on the zone of inhibition using agar disc diffusion method. The tested bacterial strains were Streptococcus pyogenes, Staphylococcus epidermidis, Klebsiella pneumonia, Staphylococcus aurues, Serratia marcesnces, and Pseudomonas aeruginosa. Ciprofloxacin showed highly significant action against K. pneumonia and S. epidermidis while Ampicillin and Amoxicillin indicated lowest antibacterial activity against tested pathogens. Among the plants chloroform and isoamyl alcohol extracts of C. cyminum, S. aromaticum and C. long Linn had significant effect against P. aeruginosa, S. marcesnces and S. pyogenes. Comparison of antibacterial activity of medicinal herbs and standard antibiotics was also recorded via activity index. Used medicinal plants have various phytochemicals which reasonably justify their use as antibacterial agent.

Genome dynamics in Legionella: the basis of versatility and adaptation to intracellular replication.

PubMed

Gomez-Valero, Laura; Buchrieser, Carmen

2013-06-01

Legionella pneumophila is a bacterial pathogen present in aquatic environments that can cause a severe pneumonia called Legionnaires' disease. Soon after its recognition, it was shown that Legionella replicates inside amoeba, suggesting that bacteria replicating in environmental protozoa are able to exploit conserved signaling pathways in human phagocytic cells. Comparative, evolutionary, and functional genomics suggests that the Legionella-amoeba interaction has shaped this pathogen more than previously thought. A complex evolutionary scenario involving mobile genetic elements, type IV secretion systems, and horizontal gene transfer among Legionella, amoeba, and other organisms seems to take place. This long-lasting coevolution led to the development of very sophisticated virulence strategies and a high level of temporal and spatial fine-tuning of bacteria host-cell interactions. We will discuss current knowledge of the evolution of virulence of Legionella from a genomics perspective and propose our vision of the emergence of this human pathogen from the environment.

Ensemble variant interpretation methods to predict enzyme activity and assign pathogenicity in the CAGI4 NAGLU (Human N-acetyl-glucosaminidase) and UBE2I (Human SUMO-ligase) challenges.

PubMed

Yin, Yizhou; Kundu, Kunal; Pal, Lipika R; Moult, John

2017-09-01

CAGI (Critical Assessment of Genome Interpretation) conducts community experiments to determine the state of the art in relating genotype to phenotype. Here, we report results obtained using newly developed ensemble methods to address two CAGI4 challenges: enzyme activity for population missense variants found in NAGLU (Human N-acetyl-glucosaminidase) and random missense mutations in Human UBE2I (Human SUMO E2 ligase), assayed in a high-throughput competitive yeast complementation procedure. The ensemble methods are effective, ranked second for SUMO-ligase and third for NAGLU, according to the CAGI independent assessors. However, in common with other methods used in CAGI, there are large discrepancies between predicted and experimental activities for a subset of variants. Analysis of the structural context provides some insight into these. Post-challenge analysis shows that the ensemble methods are also effective at assigning pathogenicity for the NAGLU variants. In the clinic, providing an estimate of the reliability of pathogenic assignments is the key. We have also used the NAGLU dataset to show that ensemble methods have considerable potential for this task, and are already reliable enough for use with a subset of mutations. © 2017 Wiley Periodicals, Inc.

Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health.

PubMed

Cabello, Felipe C; Godfrey, Henry P; Tomova, Alexandra; Ivanova, Larisa; Dölz, Humberto; Millanao, Ana; Buschmann, Alejandro H

2013-07-01

The worldwide growth of aquaculture has been accompanied by a rapid increase in therapeutic and prophylactic usage of antimicrobials including those important in human therapeutics. Approximately 80% of antimicrobials used in aquaculture enter the environment with their activity intact where they select for bacteria whose resistance arises from mutations or more importantly, from mobile genetic elements containing multiple resistance determinants transmissible to other bacteria. Such selection alters biodiversity in aquatic environments and the normal flora of fish and shellfish. The commonality of the mobilome (the total of all mobile genetic elements in a genome) between aquatic and terrestrial bacteria together with the presence of residual antimicrobials, biofilms, and high concentrations of bacteriophages where the aquatic environment may also be contaminated with pathogens of human and animal origin can stimulate exchange of genetic information between aquatic and terrestrial bacteria. Several recently found genetic elements and resistance determinants for quinolones, tetracyclines, and β-lactamases are shared between aquatic bacteria, fish pathogens, and human pathogens, and appear to have originated in aquatic bacteria. Excessive use of antimicrobials in aquaculture can thus potentially negatively impact animal and human health as well as the aquatic environment and should be better assessed and regulated. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Pathogen Reduction in Human Plasma Using an Ultrashort Pulsed Laser

PubMed Central

Tsen, Shaw-Wei D.; Kingsley, David H.; Kibler, Karen; Jacobs, Bert; Sizemore, Sara; Vaiana, Sara M.; Anderson, Jeanne; Tsen, Kong-Thon; Achilefu, Samuel

2014-01-01

Pathogen reduction is a viable approach to ensure the continued safety of the blood supply against emerging pathogens. However, the currently licensed pathogen reduction techniques are ineffective against non-enveloped viruses such as hepatitis A virus, and they introduce chemicals with concerns of side effects which prevent their widespread use. In this report, we demonstrate the inactivation of both enveloped and non-enveloped viruses in human plasma using a novel chemical-free method, a visible ultrashort pulsed laser. We found that laser treatment resulted in 2-log, 1-log, and 3-log reductions in human immunodeficiency virus, hepatitis A virus, and murine cytomegalovirus in human plasma, respectively. Laser-treated plasma showed ≥70% retention for most coagulation factors tested. Furthermore, laser treatment did not alter the structure of a model coagulation factor, fibrinogen. Ultrashort pulsed lasers are a promising new method for chemical-free, broad-spectrum pathogen reduction in human plasma. PMID:25372037

Antigenic Fingerprinting of Antibody Response in Humans following Exposure to Highly Pathogenic H7N7 Avian Influenza Virus: Evidence for Anti-PA-X Antibodies.

PubMed

Khurana, Surender; Chung, Ka Yan; Coyle, Elizabeth M; Meijer, Adam; Golding, Hana

2016-10-15

Infections with H7 highly pathogenic avian influenza (HPAI) viruses remain a major public health concern. Adaptation of low-pathogenic H7N7 to highly pathogenic H7N7 in Europe in 2015 raised further alarm for a potential pandemic. An in-depth understanding of antibody responses to HPAI H7 virus following infection in humans could provide important insight into virus gene expression as well as define key protective and serodiagnostic targets. Here we used whole-genome gene fragment phage display libraries (GFPDLs) expressing peptides of 15 to 350 amino acids across the complete genome of the HPAI H7N7 A/Netherlands/33/03 virus. The hemagglutinin (HA) antibody epitope repertoires of 15 H7N7-exposed humans identified clear differences between individuals with no hemagglutination inhibition (HI) titers (<1:10) and those with HI titers of >1:40. Several potentially protective H7N7 epitopes close to the HA receptor binding domain (RBD) and neuraminidase (NA) catalytic site were identified. Surface plasmon resonance (SPR) analysis identified a strong correlation between HA1 (but not HA2) binding antibodies and H7N7 HI titers. A proportion of HA1 binding in plasma was contributed by IgA antibodies. Antibodies against the N7 neuraminidase were less frequent but targeted sites close to the sialic acid binding site. Importantly, we identified strong antibody reactivity against PA-X, a putative virulence factor, in most H7N7-exposed individuals, providing the first evidence for in vivo expression of PA-X and its recognition by the immune system during human influenza A virus infection. This knowledge can help inform the development and selection of the most effective countermeasures for prophylactic as well as therapeutic treatments of HPAI H7N7 avian influenza virus. An outbreak of pathogenic H7N7 virus occurred in poultry farms in The Netherlands in 2003. Severe outcome included conjunctivitis, influenza-like illness, and one lethal infection. In this study, we investigated convalescent-phase sera from H7N7-exposed individuals by using a whole-genome phage display library (H7N7-GFPDL) to explore the complete repertoire of post-H7N7-exposure antibodies. PA-X is a recently identified influenza virus virulence protein generated by ribosomal frameshifting in segment 3 of influenza virus coding for PA. However, PA-X expression during influenza virus infection in humans is unknown. We identified strong antibody reactivity against PA-X in most H7N7-exposed individuals (but not in unexposed adults), providing the first evidence for in vivo expression of PA-X and its recognition by the immune system during human infection with pathogenic H7N7 avian influenza virus. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Relationships among bather density, levels of human waterborne pathogens, and fecal coliform counts in marine recreational beach water.

PubMed

Graczyk, Thaddeus K; Sunderland, Deirdre; Awantang, Grace N; Mashinski, Yessika; Lucy, Frances E; Graczyk, Zofi; Chomicz, Lidia; Breysse, Patrick N

2010-04-01

During summer months, samples of marine beach water were tested weekly for human waterborne pathogens in association with high and low bather numbers during weekends and weekdays, respectively. The numbers of bathers on weekends were significantly higher than on weekdays (P < 0.001), and this was associated with a significant (P < 0.04) increase in water turbidity. The proportion of water samples containing Cryptosporidium parvum, Giardia duodenalis, and Enterocytozoon bieneusi was significantly higher (P < 0.03) on weekends than on weekdays, and significantly (P < 0.01) correlated with enterococci counts. The concentration of all three waterborne pathogens was significantly correlated with bather density (P < 0.01). The study demonstrated that: (a) human pathogens were present in beach water on days deemed acceptable for bathing according to fecal bacterial standards; (b) enterococci count was a good indicator for the presence of Cryptosporidium, Giardia, and microsporidian spores in recreational marine beach water; (c) water should be tested for enterococci during times when bather numbers are high; (d) re-suspension of bottom sediments by bathers caused elevated levels of enterococci and waterborne parasites, thus bathers themselves can create a non-point source for water contamination; and (e) exposure to recreational bathing waters can play a role in epidemiology of microsporidiosis. In order to protect public health, it is recommended to: (a) prevent diapered children from entering beach water; (b) introduce bather number limits to recreational areas; (c) advise people with gastroenteritis to avoid bathing; and (d) use showers prior to and after bathing.

High diversity of human-pathogenic Enterocytozoon bieneusi genotypes in swine in northeast China.

PubMed

Li, Wei; Diao, Ruinan; Yang, Jinping; Xiao, Lihua; Lu, Yixin; Li, Yijing; Song, Mingxin

2014-03-01

Despite the advances in defining Enterocytozoon bieneusi genotypes worldwide, rare genotypic surveys have been documented on this ubiquitous pathogenic protozoan in mammals in China, especially the role of pigs in zoonotic transmission of microsporidiosis remains unclear. In this study, the distribution of E. bieneusi genotypes in 113 duodenal mucosal specimens of pigs with acute diarrhea from 15 cities in northeast China was determined by PCR and DNA sequence analysis of the ribosomal internal transcribed spacer. The organism was detected in 51 (45.1%) pigs from 12 cities, with infection rates of the nursery pigs (21/33, 63.6%) significantly higher than the preweaned (25/61, 41.0%; P < 0.05) and the growing (5/19, 26.3%; P < 0.01) ones. E. bieneusi belongs to nine known human-pathogenic genotypes (D, EbpA, EbpC, EbpD, H, Henan-I, Henan-III, Henan-IV, and O) and eight new genotypes (CS-1 to CS-8). Genotypes D, EbpA, EbpC, EbpD, Henan-I, Henan-III, and Henan-IV have been found in human infections and D, EbpA, EbpC, and EbpD in wastewater in central China. The new genotypes were genetically clustered into a group of existing E. bieneusi genotypes with zoonotic potential. Considering the discovery of a high prevalence and wide genetic diversity of E. bieneusi zoonotic strains in pigs in northeast China and the co-occurrence of seven known genotypes in pigs and humans and four in pigs and wastewater, pigs probably served as a reservoir for human microsporidiosis and an important source of water contamination in China.

A meta-analysis suggesting that the relationship between biodiversity and risk of zoonotic pathogen transmission is idiosyncratic.

PubMed

Salkeld, Daniel J; Padgett, Kerry A; Jones, James Holland

2013-05-01

Zoonotic pathogens are significant burdens on global public health. Because they are transmitted to humans from non-human animals, the transmission dynamics of zoonoses are necessarily influenced by the ecology of their animal hosts and vectors. The 'dilution effect' proposes that increased species diversity reduces disease risk, suggesting that conservation and public health initiatives can work synergistically to improve human health and wildlife biodiversity. However, the meta-analysis that we present here indicates a weak and highly heterogeneous relationship between host biodiversity and disease. Our results suggest that disease risk is more likely a local phenomenon that relies on the specific composition of reservoir hosts and vectors, and their ecology, rather than patterns of species biodiversity. © 2013 Blackwell Publishing Ltd/CNRS.

Pathogenic Mechanisms and Host Interactions in Staphylococcus epidermidis Device-Related Infection.

PubMed

Sabaté Brescó, Marina; Harris, Llinos G; Thompson, Keith; Stanic, Barbara; Morgenstern, Mario; O'Mahony, Liam; Richards, R Geoff; Moriarty, T Fintan

2017-01-01

Staphylococcus epidermidis is a permanent member of the normal human microbiota, commonly found on skin and mucous membranes. By adhering to tissue surface moieties of the host via specific adhesins, S. epidermidis is capable of establishing a lifelong commensal relationship with humans that begins early in life. In its role as a commensal organism, S. epidermidis is thought to provide benefits to human host, including out-competing more virulent pathogens. However, largely due to its capacity to form biofilm on implanted foreign bodies, S. epidermidis has emerged as an important opportunistic pathogen in patients receiving medical devices. S. epidermidis causes approximately 20% of all orthopedic device-related infections (ODRIs), increasing up to 50% in late-developing infections. Despite this prevalence, it remains underrepresented in the scientific literature, in particular lagging behind the study of the S. aureus . This review aims to provide an overview of the interactions of S. epidermidis with the human host, both as a commensal and as a pathogen. The mechanisms retained by S. epidermidis that enable colonization of human skin as well as invasive infection, will be described, with a particular focus upon biofilm formation. The host immune responses to these infections are also described, including how S. epidermidis seems to trigger low levels of pro-inflammatory cytokines and high levels of interleukin-10, which may contribute to the sub-acute and persistent nature often associated with these infections. The adaptive immune response to S. epidermidis remains poorly described, and represents an area which may provide significant new discoveries in the coming years.

Phylogenetic Analysis and Pathogenicity Assessment of Two Strains of Avian Influenza Virus Subtype H9N2 Isolated from Migratory Birds: High Homology of Internal Genes with Human H10N8 Virus.

PubMed

Ye, Ge; Liang, Chai Hong; Hua, Deng Guo; Song, Lei Yong; Xiang, Yang Guo; Guang, Chen; Lan, Chen Hua; Ping, Hua Yu

2016-01-01

Two human-infecting avian influenza viruses (AIVs), H7N9 and H10N8, have emerged in China, which further indicate that the H9N2 subtype of AIVs, as an internal gene donor, may have an important role in the generation of new viruses with cross-species transmissibility and pathogenicity. H9N2 viruses that contain such internal genes widely exist in poultry but are rarely reported in migratory birds. In this study, two strains of the H9N2 virus were isolated from fecal samples of migratory birds in 2014: one strain from Caizi Lake in Anhui Province and one from Chen Lake in Hubei Province of China. Nucleotide sequence analysis revealed high homology of all six internal genes of these two strains with the internal genes of the human H10N8 virus in Jiangxi Province, as well as with the human H7N9 virus. Phylogenetic analysis indicated a possible origin of these two strains from poultry in South China. Both of the two viruses tested could replicated in respiratory organs of infective mice without adaption, by both strains of the H9N2 AIVs from wild birds, suggesting their potential capacity for directly infecting mammals. Our findings indicate the existence of H9N2 viruses that contain internal genes highly homologous with human H10N8 or H7N9 viruses. Wild birds can contribute to the spread of the H9N2 virus that contains the "harmful" internal gene complex, leading to gene rearrangement with other influenza viruses and to the generation of new pathogenic viruses. Therefore, strengthening AIV surveillance in wild birds can promote an understanding of the presence and prevalence of viruses and provide scientific evidence for the prevention and control of AIVs and human-infecting AIVs.

Prevalence of tick-borne pathogens in Ixodes ricinus and Dermacentor reticulatus ticks from different geographical locations in Belarus.

PubMed

Reye, Anna L; Stegniy, Valentina; Mishaeva, Nina P; Velhin, Sviataslau; Hübschen, Judith M; Ignatyev, George; Muller, Claude P

2013-01-01

Worldwide, ticks are important vectors of human and animal pathogens. Besides Lyme Borreliosis, a variety of other bacterial and protozoal tick-borne infections are of medical interest in Europe. In this study, 553 questing and feeding Ixodes ricinus (n = 327) and Dermacentor reticulatus ticks (n = 226) were analysed by PCR for Borrelia, Rickettsia, Anaplasma, Coxiella, Francisella and Babesia species. Overall, the pathogen prevalence in ticks was 30.6% for I. ricinus and 45.6% for D. reticulatus. The majority of infections were caused by members of the spotted-fever group rickettsiae (24.4%), 9.4% of ticks were positive for Borrelia burgdorferi sensu lato, with Borrelia afzelii being the most frequently detected species (40.4%). Pathogens with low prevalence rates in ticks were Anaplasma phagocytophilum (2.2%), Coxiella burnetii (0.9%), Francisella tularensis subspecies (0.7%), Bartonella henselae (0.7%), Babesia microti (0.5%) and Babesia venatorum (0.4%). On a regional level, hotspots of pathogens were identified for A. phagocytophilum (12.5-17.2%), F. tularensis ssp. (5.5%) and C. burnetii (9.1%), suggesting established zoonotic cycles of these pathogens at least at these sites. Our survey revealed a high burden of tick-borne pathogens in questing and feeding I. ricinus and D. reticulatus ticks collected in different regions in Belarus, indicating a potential risk for humans and animals. Identified hotspots of infected ticks should be included in future surveillance studies, especially when F. tularensis ssp. and C. burnetii are involved.

Enteric bacterial pathogen detection in southern sea otters (Enhydra lutris nereis) is associated with coastal urbanization and freshwater runoff

PubMed Central

Miller, Melissa A.; Byrne, Barbara A.; Jang, Spencer S.; Dodd, Erin M.; Dorfmeier, Elene; Harris, Michael D.; Ames, Jack; Paradies, David; Worcester, Karen; Jessup, David A.; Miller, Woutrina A.

2009-01-01

Although protected for nearly a century, California’s sea otters have been slow to recover, in part due to exposure to fecally-associated protozoal pathogens like Toxoplasma gondii and Sarcocystis neurona. However, potential impacts from exposure to fecal bacteria have not been systematically explored. Using selective media, we examined feces from live and dead sea otters from California for specific enteric bacterial pathogens (Campylobacter, Salmonella, Clostridium perfringens, C. difficile and Escherichia coli O157:H7), and pathogens endemic to the marine environment (Vibrio cholerae, V. parahaemolyticus and Plesiomonas shigelloides). We evaluated statistical associations between detection of these pathogens in otter feces and demographic or environmental risk factors for otter exposure, and found that dead otters were more likely to test positive for C. perfringens, Campylobacter and V. parahaemolyticus than were live otters. Otters from more urbanized coastlines and areas with high freshwater runoff (near outflows of rivers or streams) were more likely to test positive for one or more of these bacterial pathogens. Other risk factors for bacterial detection in otters included male gender and fecal samples collected during the rainy season when surface runoff is maximal. Similar risk factors were reported in prior studies of pathogen exposure for California otters and their invertebrate prey, suggesting that land-sea transfer and/or facilitation of pathogen survival in degraded coastal marine habitat may be impacting sea otter recovery. Because otters and humans share many of the same foods, our findings may also have implications for human health. PMID:19720009

Prevention and control strategies for ticks and pathogen transmission.

PubMed

de La Fuente, J; Kocan, K M; Contreras, M

2015-04-01

Ticks and tick-borne pathogens have evolved together, resulting in a complex relationship in which the pathogen's life cycle is perfectly coordinated with the tick's feeding cycle, and the tick can harbour high pathogen levels without affecting its biology. Tick-borne diseases (TBDs) continue to emerge and/or spread, and pose an increasing threatto human and animal health. The disruptive impacts of global change have resulted in ecosystem instability and the future outcomes of management and control programmes for ticks and TBDs are difficult to predict. In particular, the selection of acaricide-resistant ticks has reduced the value of acaricides as a sole means of tick control. Vaccines provide an alternative control method, but the use of tick vaccines has not advanced since the first vaccines were registered in the early 1990s. An understanding of the complex molecular relationship between hosts, ticks and pathogens and the use of systems biology and vaccinomics approaches are needed to discover proteins with the relevant biological function in tick feeding, reproduction, development, immune response, the subversion of host immunity and pathogen transmission, all of which mediate tick and pathogen success. The same approaches will also be required to characterise candidate protective antigens and to validate vaccine formulations. Tick vaccines with a dual effect on tick infestations and pathogen transmission could reduce both tick infestations and their vector capacity for humans, animals and reservoir hosts. The development of integrated tick control strategies, including vaccines and synthetic and botanical acaricides, in combination with managing drug resistance and educating producers, should lead to the sustainable control of ticks and TBDs.

Vibrio vulnificus: new insights into a deadly opportunistic pathogen.

PubMed

Baker-Austin, Craig; Oliver, James D

2018-02-01

Vibrio vulnificus is a Gram-negative aquatic bacterium first isolated by the United States (US) Centers for Disease Control and Prevention (CDC) in 1964. This bacterium is part of the normal microbiota of estuarine waters and occurs in high numbers in molluscan shellfish around the world, particularly in warmer months. Infections in humans are derived from consumption of seafood produce and from water exposure. Vibrio vulnificus is a striking and enigmatic human pathogen, yet many aspects related to its biology, genomics, virulence capabilities and epidemiology remain elusive and poorly understood. This pathogen is responsible for over 95% of seafood-related deaths in the United States, and carries the highest fatality rate of any food-borne pathogen. Indeed, infections associated with this pathogen that progress to primary septicaemia have a similar case fatality rate to category BSL 3 and 4 pathogens, such as anthrax, bubonic plague, Ebola and Marburg fever. Interestingly, V. vulnificus infections disproportionately affect males (∼85% of cases) and older patients (> 40 years), especially those with underlying conditions such as liver diseases, diabetes and immune disorders. New insights from molecular studies and comparative genomic approaches have offered tantalising insights into this pathogen. A recent increase and geographical spread in reported infections, in particular wound cases, underlines the growing international importance of V. vulnificus, particularly in the context of coastal warming. We outline and explore here a range of current data gaps regarding this important pathogen, and provide some current thoughts on approaches to elucidate key aspects associated with this bacterium. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Burkholderia mallei and Burkholderia pseudomallei stimulate differential inflammatory responses from human alveolar type II cells (ATII) and macrophages.

PubMed

Lu, Richard; Popov, Vsevolod; Patel, Jignesh; Eaves-Pyles, Tonyia

2012-01-01

Alveolar type II pneumocytes (ATII) and alveolar macrophages (AM) play a crucial role in the lung's innate immune response. Burkholderia pseudomallei (BP) and Burkholderia mallei (BM) are facultative Gram-negative bacilli that cause melioidosis and glanders, respectively. The inhalation of these pathogens can cause lethal disease and death in humans. We sought to compare the pathogenesis of and host responses to BP and BM through contact with human primary ATII cells and monocytes-derived macrophages (MDM). We hypothesized that because BP and BM induce different disease outcomes, each pathogen would induce distinct, unique host immune responses from resident pulmonary cells. Our findings showed that BP adhered readily to ATII cells compared to BM. BP, but not BM, was rapidly internalized by macrophages where it replicated to high numbers. Further, BP-induced significantly higher levels of pro-inflammatory cytokine secretion from ATII cells (IL-6, IL-8) and macrophages (IL-6, TNFα) at 6 h post-infection compared to BM (p < 0.05). Interestingly, BM-induced the anti-inflammatory cytokine, IL-10, in ATII cells and macrophages at 6 h post-infection, with delayed induction of inflammatory cytokines at 24 h post-infection. Because BP is flagellated and produces LPS, we confirmed that it stimulated both Toll-like receptor (TLR) 4 and TLR5 via NF-κb activation while the non-flagellated BM stimulated only TLR4. These data show the differences in BP and BM pathogenicity in the lung when infecting human ATII cells and macrophages and demonstrate the ability of these pathogens to elicit distinct immune responses from resident lung cells which may open new targets for therapeutic intervention to fight against these pathogens.

Distinct Campylobacter fetus lineages adapted as livestock pathogens and human pathobionts in the intestinal microbiota.

PubMed

Iraola, Gregorio; Forster, Samuel C; Kumar, Nitin; Lehours, Philippe; Bekal, Sadjia; García-Peña, Francisco J; Paolicchi, Fernando; Morsella, Claudia; Hotzel, Helmut; Hsueh, Po-Ren; Vidal, Ana; Lévesque, Simon; Yamazaki, Wataru; Balzan, Claudia; Vargas, Agueda; Piccirillo, Alessandra; Chaban, Bonnie; Hill, Janet E; Betancor, Laura; Collado, Luis; Truyers, Isabelle; Midwinter, Anne C; Dagi, Hatice T; Mégraud, Francis; Calleros, Lucía; Pérez, Ruben; Naya, Hugo; Lawley, Trevor D

2017-11-08

Campylobacter fetus is a venereal pathogen of cattle and sheep, and an opportunistic human pathogen. It is often assumed that C. fetus infection occurs in humans as a zoonosis through food chain transmission. Here we show that mammalian C. fetus consists of distinct evolutionary lineages, primarily associated with either human or bovine hosts. We use whole-genome phylogenetics on 182 strains from 17 countries to provide evidence that C. fetus may have originated in humans around 10,500 years ago and may have "jumped" into cattle during the livestock domestication period. We detect C. fetus genomes in 8% of healthy human fecal metagenomes, where the human-associated lineages are the dominant type (78%). Thus, our work suggests that C. fetus is an unappreciated human intestinal pathobiont likely spread by human to human transmission. This genome-based evolutionary framework will facilitate C. fetus epidemiology research and the development of improved molecular diagnostics and prevention schemes for this neglected pathogen.

Health implications associated with exposure to farmed and wild sea turtles.

PubMed

Warwick, Clifford; Arena, Phillip C; Steedman, Catrina

2013-01-01

Exposure to sea turtles may be increasing with expanding tourism, although reports of problems arising from interaction with free-living animals appear of negligible human health and safety concern. Exposure both to wild-caught and captive-housed sea turtles, including consumption of turtle products, raises several health concerns for the public, including: microbiological (bacteria, viruses, parasites and fungi), macrobiological (macroparasites), and organic and inorganic toxic contaminants (biotoxins, organochlorines and heavy metals). We conducted a review of sea turtle associated human disease and its causative agents as well as a case study of the commercial sea turtle facility known as the Cayman Turtle Farm (which receives approximately 240,000 visitors annually) including the use of water sampling and laboratory microbial analysis which identified Pseudomonas aeruginosa, Aeromonas spp., Vibrio spp. and Salmonella spp. Our assessment is that pathogens and toxic contaminants may be loosely categorized to represent the following levels of potential risk: viruses and fungi = very low; protozoan parasites = very low to low; metazoan parasites, bacteria and environmental toxic contaminants = low or moderate to high; and biotoxin contaminant = moderate to very high. Farmed turtles and their consumable products may constitute a significant reservoir of potential human pathogen and toxin contamination. Greater awareness among health-care professionals regarding both potential pathogens and toxic contaminants from sea turtles, as well as key signs and symptoms of sea turtle-related human disease, is important for the prevention and control of salient disease.

A SIMPLE AND EFFECTIVE MULTIPLEX PCR TECHNIQUE FOR DETECTING HUMAN PATHOGENIC TAENIA EGGS IN HOUSEFLIES.

PubMed

Pornruseetriratn, Siritavee; Maipanich, Wanna; Sa-nguankiat, Surapol; Pubampen, Somchit; Poodeepiyasawat, Akkarin; Thaenkham, Urusa

2017-01-01

Taenia solium, T. saginata, and T. asiatica are cestode pathogens causing taeniasis in humans. Houseflies can transfer Taenia eggs to food. However, houseflies are thought to carry only small numbers of Taenia eggs, sometimes fewer than 10. Although several PCR-based methods have been developed to detect Taenia DNA, these require more than 10 eggs for adequate detection. We developed a multiplex PCR method with high specificity for the discrimination among the eggs of the three Taenia species, T. solium, T. saginata, and T. asiatica, using 18S ribosomal DNA (rDNA) as a genetic marker. This technique was found to be highly sensitive, capable of identifying the Taenia species from only one egg. This multiplex PCR technique using 18S rDNA specific primers should be suitable to diagnose Taenia eggs.

Clean water, clean hands or new vaccines?

PubMed

Luby, Stephen P

2017-06-01

Throughout human history, pathogens transmitted through feces from person to person have caused substantial mortality. Over a century ago civil engineers in high income countries developed approaches to collect and remove feces from the environment that in communities with high incomes and strong governments markedly reduced the burden of enteric disease. These approaches, however, have not been successfully extended to impoverished communities in low income countries. Water/sanitation/hygiene professionals have attempted, with only limited success, to reduce fecal exposure and human disease in the absence of definitive civil engineering approaches. Medical professionals have worked to develop vaccines against some of the most important fecal oral pathogens. Each of these approaches needs further development and adaptation to optimally address the burden of fecally transmitted diseases in impoverished communities. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Surveillance for Asian H5N1 avian influenza in the United States

USGS Publications Warehouse

Ip, Hon S.; Slota, Paul G.

2006-01-01

Increasing concern over the potential for migratory birds to introduce the Asian H5N1 strain of avian influenza to North America prompted the White House Policy Coordinating Committee for Pandemic Influenza Preparedness to request that the U.S. Departments of Agriculture (USDA) and Interior (DOI) develop a plan for the early detection of highly pathogenic avian influenza (HPAI) in the United States. To promote coordination among wildlife, agriculture, and human health agencies on HPAI surveillance efforts, the two Departments worked with representatives from the U.S. Department of Health and Human Services, the International Association of Fish and Wildlife Agencies, and the Alaska Department of Fish and Game to develop the U.S. Interagency Strategic Plan for Early Detection of Asian H5N1 Highly Pathogenic Avian Influenza in Wild Migratory Birds.

Tropical environments, human activities, and the transmission of infectious diseases.

PubMed

Sattenspiel, L

2000-01-01

Throughout recent history, the tropical regions of the world have been affected more severely by infectious diseases than the temperate world. Much of the success of infectious diseases in that region is due to both biological and environmental factors that encourage high levels of biodiversity in hosts, vectors, and pathogens, and social factors that compromise efforts to control diseases. Several of these factors are described. Discussion then shifts to specific types of host-pathogen relationships. The most important of these in the tropics is the relationship between humans, a pathogen, and a vector that carries the pathogen from one human to another. Mosquitoes are the vector responsible for the transmission of many vector-borne human diseases. Characteristics of mosquito-human interactions are described, including cultural behaviors humans have developed that both increase the chances of transmission and help to limit that transmission. The transmission of water-borne diseases, fecal-oral transmission, zoonotic diseases, respiratory illnesses, and sexually transmitted diseases are also discussed. Attention is paid to how diseases with these modes of transmission differ in characteristics and importance in tropical human populations compared to those in temperate regions. Following this general discussion, three case studies are presented in some detail. The diseases chosen for the case studies include cholera, lymphatic filariasis, and dracunculiasis (guinea worm). These three case studies taken together provide examples of the diversity of human host-pathogen interactions as well as ways that human activities have both promoted their spread and helped to control them. The transmission of all three diseases is related to the nature and quality of water sources. The transmission of cholera, a water-borne disease, is related to sanitation practices, physical characteristics of the environment such as temperature and humidity, and modern shipping practices. Lymphatic filariasis, a mosquito-borne disease, has increased in frequency in parts of Africa in recent decades as a consequence of large-scale agricultural development projects that have shifted the nature and quantity of water sources and potential mosquito breeding sites. Dracunculiasis is transmitted by a small crustacean that contaminates sources of drinking water. Because its transmission can be prevented by a simple change in human behavior, filtering all water with a small piece of cloth before using it, dracunculiasis has been the focus of a major eradication effort that is near success.

Potential in vitro antimicrobial efficacy of Holigarna arnottiana (Hook F).

PubMed

Manilal, Aseer; Idhayadhulla, Akbar

2014-01-01

To explore the in vitro antimicrobial potential of Holigarna arnottiana (H. arnottiana) against human and shrimp pathogenic bacteria and use GC-MS analysis to elucidate its antimicrobial principles. In the present study, organic extract of H. arnottiana was examined for in vitro antimicrobial potency against five clinical human pathogens, seven species of human type culture pathogens, six pathogenic Vibrio strains isolated from moribund tiger shrimp (Penaeus monodon) and seven type cultures (Microbial Type Culture Collection, MTCC) of prominent shrimp pathogens. The extraction of H. arnottiana with ethyl acetate yielded bioactive crude extract that efficiently repressed the growth of all tested pathogens. Among the pathogens tested, shrimp pathogens were the most susceptible organisms while clinical pathogens were found to be a little resistant. The chemical constituents of the H. arnottiana were analysed by GC-MS which revealed the presence of major compounds such as 3,7,11,15-tetramethyl-2-hexadecen-1-o1 (42.1%), 1-lodo-2-methylundecane (34.5%) and squalene (11.1%) which might have a functional role in the chemical defence against microbial invasion. Based on the finding it could be inferred that H. arnottiana would be a reliable source for developing shrimp and human bio-therapeutics in future. Copyright © 2014 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

Potential in vitro antimicrobial efficacy of Holigarna arnottiana (Hook F)

PubMed Central

Manilal, Aseer; Idhayadhulla, Akbar

2014-01-01

Objective To explore the in vitro antimicrobial potential of Holigarna arnottiana (H. arnottiana) against human and shrimp pathogenic bacteria and use GC-MS analysis to elucidate its antimicrobial principles. Methods In the present study, organic extract of H. arnottiana was examined for in vitro antimicrobial potency against five clinical human pathogens, seven species of human type culture pathogens, six pathogenic Vibrio strains isolated from moribund tiger shrimp (Penaeus monodon) and seven type cultures (Microbial Type Culture Collection, MTCC) of prominent shrimp pathogens. Results The extraction of H. arnottiana with ethyl acetate yielded bioactive crude extract that efficiently repressed the growth of all tested pathogens. Among the pathogens tested, shrimp pathogens were the most susceptible organisms while clinical pathogens were found to be a little resistant. The chemical constituents of the H. arnottiana were analysed by GC-MS which revealed the presence of major compounds such as 3,7,11,15-tetramethyl-2-hexadecen-1-o1 (42.1%), 1-lodo-2-methylundecane (34.5%) and squalene (11.1%) which might have a functional role in the chemical defence against microbial invasion. Conclusions Based on the finding it could be inferred that H. arnottiana would be a reliable source for developing shrimp and human bio-therapeutics in future. PMID:24144126

Biochemistry and Molecular Biology of Flaviviruses.

PubMed

Barrows, Nicholas J; Campos, Rafael K; Liao, Kuo-Chieh; Prasanth, K Reddisiva; Soto-Acosta, Ruben; Yeh, Shih-Chia; Schott-Lerner, Geraldine; Pompon, Julien; Sessions, October M; Bradrick, Shelton S; Garcia-Blanco, Mariano A

2018-04-25

Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA-protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

Vaccines for the future: learning from human immunology

PubMed Central

De Gregorio, Ennio; Rappuoli, Rino

2012-01-01

Summary Conventional vaccines have been extremely successful in preventing infections by pathogens expressing relatively conserved antigens through antibody‐mediated effector mechanisms. Thanks to vaccination some diseases have been eradicated and mortality due to infectious diseases has been significantly reduced. However, there are still many infections that are not preventable with vaccination, which represent a major cause of mortality worldwide. Some of these infections are caused by pathogens with a high degree of antigen variability that cannot be controlled only by antibodies, but require a mix of humoral and cellular immune responses. Novel technologies for antigen discovery, expression and formulation allow now for the development of vaccines that can better cope with pathogen diversity and trigger multifunctional immune responses. In addition, the application of new genomic assays and systems biology approaches in human immunology can help to better identify vaccine correlates of protection. The availability of novel vaccine technologies, together with the knowledge of the distinct human immune responses that are required to prevent different types of infection, should help to rationally design effective vaccines where conventional approaches have failed. PMID:21880117

Detection of Rickettsia and Ehrlichia spp. in Ticks Associated with Exotic Reptiles and Amphibians Imported into Japan.

PubMed

Andoh, Masako; Sakata, Akiko; Takano, Ai; Kawabata, Hiroki; Fujita, Hiromi; Une, Yumi; Goka, Koichi; Kishimoto, Toshio; Ando, Shuji

2015-01-01

One of the major routes of transmission of rickettsial and ehrlichial diseases is via ticks that infest numerous host species, including humans. Besides mammals, reptiles and amphibians also carry ticks that may harbor Rickettsia and Ehrlichia strains that are pathogenic to humans. Furthermore, reptiles and amphibians are exempt from quarantine in Japan, thus facilitating the entry of parasites and pathogens to the country through import. Accordingly, in the current study, we examined the presence of Rickettsia and Ehrlichia spp. genes in ticks associated with reptiles and amphibians originating from outside Japan. Ninety-three ticks representing nine tick species (genera Amblyomma and Hyalomma) were isolated from at least 28 animals spanning 10 species and originating from 12 countries (Ghana, Jordan, Madagascar, Panama, Russia, Sri Lanka, Sudan, Suriname, Tanzania, Togo, Uzbekistan, and Zambia). None of the nine tick species are indigenous in Japan. The genes encoding the common rickettsial 17-kDa antigen, citrate synthase (gltA), and outer membrane protein A (ompA) were positively detected in 45.2% (42/93), 40.9% (38/93), and 23.7% (22/93) of the ticks, respectively, by polymerase chain reaction (PCR). The genes encoding ehrlichial heat shock protein (groEL) and major outer membrane protein (omp-1) were PCR-positive in 7.5% (7/93) and 2.2% (2/93) of the ticks, respectively. The p44 gene, which encodes the Anaplasma outer membrane protein, was not detected. Phylogenetic analysis showed that several of the rickettsial and ehrlichial sequences isolated in this study were highly similar to human pathogen genes, including agents not previously detected in Japan. These data demonstrate the global transportation of pathogenic Rickettsia and Ehrlichia through reptile- and amphibian-associated ticks. These imported animals have potential to transfer pathogens into human life. These results highlight the need to control the international transportation of known and potential pathogens carried by ticks in reptiles, amphibians, and other animals, in order to improve national and international public health.

Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans

PubMed Central

Caza, Mélissa; Kronstad, James W.

2013-01-01

Iron is the most abundant transition metal in the human body and its bioavailability is stringently controlled. In particular, iron is tightly bound to host proteins such as transferrin to maintain homeostasis, to limit potential damage caused by iron toxicity under physiological conditions and to restrict access by pathogens. Therefore, iron acquisition during infection of a human host is a challenge that must be surmounted by every successful pathogenic microorganism. Iron is essential for bacterial and fungal physiological processes such as DNA replication, transcription, metabolism, and energy generation via respiration. Hence, pathogenic bacteria and fungi have developed sophisticated strategies to gain access to iron from host sources. Indeed, siderophore production and transport, iron acquisition from heme and host iron-containing proteins such as hemoglobin and transferrin, and reduction of ferric to ferrous iron with subsequent transport are all strategies found in bacterial and fungal pathogens of humans. This review focuses on a comparison of these strategies between bacterial and fungal pathogens in the context of virulence and the iron limitation that occurs in the human body as a mechanism of innate nutritional defense. PMID:24312900

Human and bovine viruses and bacteria at three Great Lakes beaches: Environmental variable associations and health risk

USGS Publications Warehouse

Corsi, Steven R.; Borchardt, Mark A.; Carvin, Rebecca B.; Burch, Tucker R; Spencer, Susan K.; Lutz, Michelle A.; McDermott, Colleen M.; Busse, Kimberly M.; Kleinheinz, Gregory; Feng, Xiaoping; Zhu, Jun

2016-01-01

Waterborne pathogens were measured at three beaches in Lake Michigan, environmental factors for predicting pathogen concentrations were identified, and the risk of swimmer infection and illness was estimated. Waterborne pathogens were detected in 96% of samples collected at three Lake Michigan beaches in summer, 2010. Samples were quantified for 22 pathogens in four microbial categories (human viruses, bovine viruses, protozoa, and pathogenic bacteria). All beaches had detections of human and bovine viruses and pathogenic bacteria indicating influence of multiple contamination sources at these beaches. Occurrence ranged from 40 to 87% for human viruses, 65–87% for pathogenic bacteria, and 13–35% for bovine viruses. Enterovirus, adenovirus A, Salmonella spp., Campylobacter jejuni, bovine polyomavirus, and bovine rotavirus A were present most frequently. Variables selected in multiple regression models used to explore environmental factors that influence pathogens included wave direction, cloud cover, currents, and water temperature. Quantitative Microbial Risk Assessment was done for C. jejuni, Salmonella spp., and enteroviruses to estimate risk of infection and illness. Median infection risks for one-time swimming events were approximately 3 × 10–5, 7 × 10–9, and 3 × 10–7 for C. jejuni, Salmonella spp., and enteroviruses, respectively. Results highlight the importance of investigating multiple pathogens within multiple categories to avoid underestimating the prevalence and risk of waterborne pathogens.

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

PubMed

Shin, So Youn; Kwon, Kye Chul; Park, Jong Woo; Kim, Ji Myung; Shin, So Young; Koo, Sun Hoe

2012-01-01

Bacterial meningitis is an infectious disease with high rates of mortality and high frequency of severe sequelae. Early identification of causative bacterial and viral pathogens is important for prompt and proper treatment of meningitis and for prevention of life-threatening clinical outcomes. In the present study, we evaluated the value of the Seeplex Meningitis ACE Detection kit (Seegene Inc., Korea), a newly developed multiplex PCR kit employing dual priming oligonucleotide methods, for diagnosing acute meningitis. Analytical sensitivity of the kit was studied using reference strains for each pathogen targeted by the kit, while it's analytical specificity was studied using the human genome DNA and 58 clinically well-identified reference strains. For clinical validation experiment, we used 27 control cerebrospinal fluid (CSF) samples and 78 clinical CSF samples collected from patients at the time of diagnosis of acute meningitis. The lower detection limits ranged from 10(1) copies/µL to 5×10(1) copies/µL for the 12 viral and bacterial pathogens targeted. No cross-reaction was observed. In the validation study, high detection rate of 56.4% was obtained. None of the control samples tested positive, i.e., false-positive results were absent. The Seeplex Meningitis ACE Detection kit showed high sensitivity, specificity, and detection rate for the identification of pathogens in clinical CSF samples. This kit may be useful for rapid identification of important acute meningitis-causing pathogens.

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

PubMed Central

Shin, So Youn; Kwon, Kye Chul; Park, Jong Woo; Kim, Ji Myung; Shin, So Young

2012-01-01

Background Bacterial meningitis is an infectious disease with high rates of mortality and high frequency of severe sequelae. Early identification of causative bacterial and viral pathogens is important for prompt and proper treatment of meningitis and for prevention of life-threatening clinical outcomes. In the present study, we evaluated the value of the Seeplex Meningitis ACE Detection kit (Seegene Inc., Korea), a newly developed multiplex PCR kit employing dual priming oligonucleotide methods, for diagnosing acute meningitis. Methods Analytical sensitivity of the kit was studied using reference strains for each pathogen targeted by the kit, while it's analytical specificity was studied using the human genome DNA and 58 clinically well-identified reference strains. For clinical validation experiment, we used 27 control cerebrospinal fluid (CSF) samples and 78 clinical CSF samples collected from patients at the time of diagnosis of acute meningitis. Results The lower detection limits ranged from 101 copies/µL to 5×101 copies/µL for the 12 viral and bacterial pathogens targeted. No cross-reaction was observed. In the validation study, high detection rate of 56.4% was obtained. None of the control samples tested positive, i.e., false-positive results were absent. Conclusions The Seeplex Meningitis ACE Detection kit showed high sensitivity, specificity, and detection rate for the identification of pathogens in clinical CSF samples. This kit may be useful for rapid identification of important acute meningitis-causing pathogens. PMID:22259778

Comparison of the h-Index Scores Among Pathogens Identified as Emerging Hazards in North America.

PubMed

Cox, R; McIntyre, K M; Sanchez, J; Setzkorn, C; Baylis, M; Revie, C W

2016-02-01

Disease surveillance must assess the relative importance of pathogen hazards. Here, we use the Hirsch index (h-index) as a novel method to identify and rank infectious pathogens that are likely to be a hazard to human health in the North American region. This bibliometric index was developed to quantify an individual's scientific research output and was recently used as a proxy measure for pathogen impact. Analysis of more than 3000 infectious organisms indicated that 651 were human pathogen species that had been recorded in the North American region. The h-index of these pathogens ranged from 0 to 584. The h-index of emerging pathogens was greater than non-emerging pathogens as was the h-index of frequently pathogenic pathogens when compared to non-pathogenic pathogens. As expected, the h-index of pathogens varied over time between 1960 and 2011. We discuss how the h-index can contribute to pathogen prioritization and as an indicator of pathogen emergence. © 2014 Blackwell Verlag GmbH.

Characterization of Clade 2.3.2.1 H5N1 Highly Pathogenic Avian Influenza Viruses Isolated from Wild Birds (Mandarin Duck and Eurasian Eagle Owl) in 2010 in Korea

PubMed Central

Choi, Jun-Gu; Kang, Hyun-Mi; Jeon, Woo-Jin; Choi, Kang-Seuk; Kim, Kwang-Il; Song, Byung Min; Lee, Hee-Soo; Kim, Jae-Hong; Lee, Youn-Jeong

2013-01-01

Starting in late November 2010, the H5N1 highly pathogenic avian influenza (HPAI) virus was isolated from many types of wild ducks and raptors and was subsequently isolated from poultry in Korea. We assessed the genetic and pathogenic properties of the HPAI viruses isolated from a fecal sample from a mandarin duck and a dead Eurasian eagle owl, the most affected wild bird species during the 2010/2011 HPAI outbreak in Korea. These viruses have similar genetic backgrounds and exhibited the highest genetic similarity with recent Eurasian clade 2.3.2.1 HPAI viruses. In animal inoculation experiments, regardless of their originating hosts, the two Korean isolates produced highly pathogenic characteristics in chickens, ducks and mice without pre-adaptation. These results raise concerns about veterinary and public health. Surveillance of wild birds could provide a good early warning signal for possible HPAI infection in poultry as well as in humans. PMID:23611846

Invasion of two tick-borne diseases across New England: harnessing human surveillance data to capture underlying ecological invasion processes

PubMed Central

Walter, Katharine S.; Pepin, Kim M.; Webb, Colleen T.; Gaff, Holly D.; Krause, Peter J.; Pitzer, Virginia E.; Diuk-Wasser, Maria A.

2016-01-01

Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach—occupancy modelling—to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease. PMID:27252022

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.

Human soil-borne pathogens and risks associated with land use change

NASA Astrophysics Data System (ADS)

Pereg, Lily

2017-04-01

Soil is a source of pathogenic, neutral and beneficial microorganisms. Natural events and anthropogenic activity can affect soil biodiversity and influence the balance and distribution of soil-borne human pathogens. Important bacterial and fungal pathogens, such as Bacillus anthracis, Coxiella bernetii, Clostridium tetani, Escherichia coli 0157:H7, Listeria monocytogenes, Aspergillus fumigatus and Sporothrix schenckii will be discussed. This presentation will concentrate on soil pathogenic microorganisms and the effects of land use change on their prevalence and distribution. In particular, the potential of agricultural soil cultivation to enhance pathogen transmission to human through the release of soil microbes into the air attached to dust particles, contamination of waterways and infection of food plants and animal. Emerging solutions, such as biocontrol and probiotics, will be discussed.

Prevalences of pathogenic and non-pathogenic Vibrio parahaemolyticus in mollusks from the Spanish Mediterranean Coast

PubMed Central

Lopez-Joven, Carmen; de Blas, Ignacio; Furones, M. Dolores; Roque, Ana

2015-01-01

Vibrio parahaemolyticus is a well-recognized pathogen of humans. To better understand the ecology of the human-pathogenic variants of this bacterium in the environment, a study on the prevalence in bivalves of pathogenic variants (tlh+ and tdh+ and/or trh+) versus a non-pathogenic one (only tlh+ as species marker for V. parahaemolyticus), was performed in two bays in Catalonia, Spain. Environmental factors that might affect dynamics of both variants of V. parahaemolyticus were taken into account. The results showed that the global prevalence of total V. parahaemolyticus found in both bays was 14.2% (207/1459). It was, however, significantly dependent on sampling point, campaign (year) and bivalve species. Pathogenic variants of V. parahaemolyticus (tdh+ and/or trh+) were detected in 3.8% of the samples (56/1459), meaning that the proportion of bivalves who contained tlh gene were contaminated by pathogenic V. parahaemolyticus strains is 27.1% (56/207). Moreover, the presence of pathogenic V. parahaemolyticus (trh+) was significantly correlated with water salinity, thus the probability of finding pathogenic V. parahaemolyticus decreased 1.45 times with every salinity unit (ppt) increased. Additionally, data showed that V. parahaemolyticus could establish close associations with Ruditapes spp. (P-value < 0.001), which could enhance the transmission of illness to human by pathogenic variants, when clams were eaten raw or slightly cooked. This study provides information on the abundance, ecology and characteristics of total and human-pathogenic V. parahaemolyticus variants associated with bivalves cultured in the Spanish Mediterranean Coast. PMID:26284033

Using open-access taxonomic and spatial information to create a comprehensive database for the study of mammalian and avian livestock and pet infections.

PubMed

McIntyre, K M; Setzkorn, C; Wardeh, M; Hepworth, P J; Radford, A D; Baylis, M

2014-10-01

What are all the species of pathogen that affect our livestock? As 6 out of every 10 human pathogens came from animals, with a good number from livestock and pets, it seems likely that the majority that emerge in the future, and which could threaten or devastate human health, will come from animals. Only 10 years ago, the first comprehensive pathogen list was compiled for humans; we still have no equivalent for animals. Here we describe the creation of a novel pathogen database, and present outputs from the database that demonstrate its value. The ENHanCEd Infectious Diseases database (EID2) is open-access and evidence-based, and it describes the pathogens of humans and animals, their host and vector species, and also their global occurrence. The EID2 systematically collates information on pathogens into a single resource using evidence from the NCBI Taxonomy database, the NCBI Nucleotide database, the NCBI MeSH (Medical Subject Headings) library and PubMed. Information about pathogens is assigned using data-mining of meta-data and semi-automated literature searches. Here we focus on 47 mammalian and avian hosts, including humans and animals commonly used in Europe as food or kept as pets. Currently, the EID2 evidence suggests that: • Within these host species, 793 (30.5%) pathogens were bacteria species, 395 (15.2%) fungi, 705 (27.1%) helminths, 372 (14.3%) protozoa and 332 (12.8%) viruses. • The odds of pathogens being emerging compared to not emerging differed by taxonomic division, and increased when pathogens had greater numbers of host species associated with them, and were zoonotic rather than non-zoonotic. • The odds of pathogens being zoonotic compared to non-zoonotic differed by taxonomic division and also increased when associated with greater host numbers. • The pathogens affecting the greatest number of hosts included: Escherichia coli, Giardia intestinalis, Toxoplasma gondii, Anaplasma phagocytophilum, Cryptosporidium parvum, Rabies virus, Staphylococcus aureus, Neospora caninum and Echinococcus granulosus. • The pathogens of humans and domestic animal hosts are characterised by 4223 interactions between pathogen and host species, with the greatest number found in: humans, sheep/goats, cattle, small mammals, pigs, dogs and equids. • The number of pathogen species varied by European country. The odds of a pathogen being found in Europe compared to the rest of the world differed by taxonomic division, and increased if they were emerging compared to not emerging, or had a larger number of host species associated with them. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

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.

Sexually transmissible infections among female sex workers: an international review with an emphasis on hard-to-access populations.

PubMed

Cwikel, Julie G; Lazer, Tal; Press, Fernanda; Lazer, Simcha

2008-03-01

Women who work commercially in sex work (female sex workers [FSW]) are considered a high-risk group for sexually transmissible infections (STI), yet the level of reported pathogens varies in studies around the world. This study reviewed STI rates reported in 42 studies of FSW around the world published between 1995 and 2006 and analysed the trends and types of populations surveyed, emphasising difficult to access FSW populations. Studies were retrieved by PUBMED and other search engines and were included if two or more pathogens were studied and valid laboratory methods were reported. The five most commonly assessed pathogens were Neisseria gonorrhea (prevalence 0.5-41.3), Chlamydia trachomatis (0.61-46.2), Treponema pallidum (syphilis; 1.5-60.5), HIV (0-76.6), and Trichomonas vaginalis (trichomoniasis; 0.11-51.0). Neisseria gonorrhea and C. trachomatis were the most commonly tested pathogens and high prevalence levels were found in diverse areas of the world. HIV was highly prevalent mostly in African countries. Although human papillomavirus infection was surveyed in few studies, prevalence rates were very high and its aetiological role in cervical cancer warrant its inclusion in future FSW monitoring. Hard-to-access FSW groups tended to have higher rates of STI. The five most commonly detected pathogens correspond to those that are highly prevalent in the general population, however there is an urgent need to develop rapid testing diagnostics for all five pathogens to increase prevention and treatment, especially in outreach programs to the most vulnerable groups among FSW.

Nano/Micro and Spectroscopic Approaches to Food Pathogen Detection

NASA Astrophysics Data System (ADS)

Cho, Il-Hoon; Radadia, Adarsh D.; Farrokhzad, Khashayar; Ximenes, Eduardo; Bae, Euiwon; Singh, Atul K.; Oliver, Haley; Ladisch, Michael; Bhunia, Arun; Applegate, Bruce; Mauer, Lisa; Bashir, Rashid; Irudayaraj, Joseph

2014-06-01

Despite continuing research efforts, timely and simple pathogen detection with a high degree of sensitivity and specificity remains an elusive goal. Given the recent explosion of sensor technologies, significant strides have been made in addressing the various nuances of this important global challenge that affects not only the food industry but also human health. In this review, we provide a summary of the various ongoing efforts in pathogen detection and sample preparation in areas related to Fourier transform infrared and Raman spectroscopy, light scattering, phage display, micro/nanodevices, and nanoparticle biosensors. We also discuss the advantages and potential limitations of the detection methods and suggest next steps for further consideration.

Leptospiral uveitis - there is more to it than meets the eye!

PubMed

Verma, A; Stevenson, B

2012-09-01

Leptospirosis, caused by pathogenic species of genus Leptospira, is a highly prevalent zoonotic disease throughout many parts of the world, and an important emerging disease within the United States. Uveitis is a common complication of systemic infection in humans. A similar condition in horses is characterized by recurrent bouts of inflammation. In this article, we review advances in our understanding of leptospiral uveitis and its pathogenic mechanisms. © 2012 Blackwell Verlag GmbH.

Comparative Genome Analysis of Campylobacter fetus Subspecies Revealed Horizontally Acquired Genetic Elements Important for Virulence and Niche Specificity

PubMed Central

Kienesberger, Sabine; Sprenger, Hanna; Wolfgruber, Stella; Halwachs, Bettina; Thallinger, Gerhard G.; Perez-Perez, Guillermo I.; Blaser, Martin J.; Zechner, Ellen L.; Gorkiewicz, Gregor

2014-01-01

Campylobacter fetus are important animal and human pathogens and the two major subspecies differ strikingly in pathogenicity. C. fetus subsp. venerealis is highly niche-adapted, mainly infecting the genital tract of cattle. C. fetus subsp. fetus has a wider host-range, colonizing the genital- and intestinal-tract of animals and humans. We report the complete genomic sequence of C. fetus subsp. venerealis 84-112 and comparisons to the genome of C. fetus subsp. fetus 82-40. Functional analysis of genes predicted to be involved in C. fetus virulence was performed. The two subspecies are highly syntenic with 92% sequence identity but C. fetus subsp. venerealis has a larger genome and an extra-chromosomal element. Aside from apparent gene transfer agents and hypothetical proteins, the unique genes in both subspecies comprise two known functional groups: lipopolysaccharide production, and type IV secretion machineries. Analyses of lipopolysaccharide-biosynthesis genes in C. fetus isolates showed linkage to particular pathotypes, and mutational inactivation demonstrated their roles in regulating virulence and host range. The comparative analysis presented here broadens knowledge of the genomic basis of C. fetus pathogenesis and host specificity. It further highlights the importance of surface-exposed structures to C. fetus pathogenicity and demonstrates how evolutionary forces optimize the fitness and host-adaptation of these pathogens. PMID:24416416

Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death.

PubMed

Schuenemann, Verena J; Bos, Kirsten; DeWitte, Sharon; Schmedes, Sarah; Jamieson, Joslyn; Mittnik, Alissa; Forrest, Stephen; Coombes, Brian K; Wood, James W; Earn, David J D; White, William; Krause, Johannes; Poinar, Hendrik N

2011-09-20

Although investigations of medieval plague victims have identified Yersinia pestis as the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348-1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human and Y. pestis DNA confirmed its authenticity as an ancient pathogen, thus representing the longest contiguous genomic sequence for an ancient pathogen to date. Comparison of our reconstructed plasmid against modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist, and genetic data carried on its pPCP1 plasmid were not responsible for the purported epidemiological differences between ancient and modern forms of Y. pestis infections.

Survey of Innate Immune Responses to Burkholderia pseudomallei in Human Blood Identifies a Central Role for Lipopolysaccharide

PubMed Central

Chantratita, Narisara; Tandhavanant, Sarunporn; Myers, Nicolle D.; Seal, Sudeshna; Arayawichanont, Arkhom; Kliangsa-ad, Aroonsri; Hittle, Lauren E.; Ernst, Robert K.; Emond, Mary J.; Wurfel, Mark M.; Day, Nicholas P. J.; Peacock, Sharon J.; West, T. Eoin

2013-01-01

B. pseudomallei is a gram-negative bacterium that causes the tropical infection melioidosis. In northeast Thailand, mortality from melioidosis approaches 40%. As exemplified by the lipopolysaccharide-Toll-like receptor 4 interaction, innate immune responses to invading bacteria are precipitated by activation of host pathogen recognition receptors by pathogen associated molecular patterns. Human melioidosis is characterized by up-regulation of pathogen recognition receptors and pro-inflammatory cytokine release. In contrast to many gram-negative pathogens, however, the lipopolysaccharide of B. pseudomallei is considered only weakly inflammatory. We conducted a study in 300 healthy Thai subjects to investigate the ex vivo human blood response to various bacterial pathogen associated molecular patterns, including lipopolysaccharide from several bacteria, and to two heat-killed B. pseudomallei isolates. We measured cytokine levels after stimulation of fresh whole blood with a panel of stimuli. We found that age, sex, and white blood cell count modulate the innate immune response to B. pseudomallei. We further observed that, in comparison to other stimuli, the innate immune response to B. pseudomallei is most highly correlated with the response to lipopolysaccharide. The magnitude of cytokine responses induced by B. pseudomallei lipopolysaccharide was significantly greater than those induced by lipopolysaccharide from Escherichia coli and comparable to many responses induced by lipopolysaccharide from Salmonella minnesota despite lower amounts of lipid A in the B. pseudomallei lipopolysaccharide preparation. In human monocytes stimulated with B. pseudomallei, addition of polymyxin B or a TLR4/MD-2 neutralizing antibody inhibited the majority of TNF-α production. Challenging existing views, our data indicate that the innate immune response to B. pseudomallei in human blood is largely driven by lipopolysaccharide, and that the response to B. pseudomallei lipopolysaccharide in blood is greater than the response to other lipopolysaccharide expressing isolates. Our findings suggest that B. pseudomallei lipopolysaccharide may play a central role in stimulating the host response in melioidosis. PMID:24303060

Challenges of influenza A viruses in humans and animals and current animal vaccines as an effective control measure

PubMed Central

2018-01-01

Influenza A viruses (IAVs) are genetically diverse and variable pathogens that share various hosts including human, swine, and domestic poultry. Interspecies and intercontinental viral spreads make the ecology of IAV more complex. Beside endemic IAV infections, human has been exposed to pandemic and zoonotic threats from avian and swine influenza viruses. Animal health also has been threatened by high pathogenic avian influenza viruses (in domestic poultry) and reverse zoonosis (in swine). Considering its dynamic interplay between species, prevention and control against IAV should be conducted effectively in both humans and animal sectors. Vaccination is one of the most efficient tools against IAV. Numerous vaccines against animal IAVs have been developed by a variety of vaccine technologies and some of them are currently commercially available. We summarize several challenges in control of IAVs faced by human and animals and discuss IAV vaccines for animal use with those application in susceptible populations. PMID:29399575

Species-specific and individual differences in Nipah virus replication in porcine and human airway epithelial cells.

PubMed

Sauerhering, Lucie; Zickler, Martin; Elvert, Mareike; Behner, Laura; Matrosovich, Tatyana; Erbar, Stephanie; Matrosovich, Mikhail; Maisner, Andrea

2016-07-01

Highly pathogenic Nipah virus (NiV) causes symptomatic infections in pigs and humans. The severity of respiratory symptoms is much more pronounced in pigs than in humans, suggesting species-specific differences of NiV replication in porcine and human airways. Here, we present a comparative study on productive NiV replication in primary airway epithelial cell cultures of the two species. We reveal that NiV growth substantially differs in primary cells between pigs and humans, with a more rapid spread of infection in human airway epithelia. Increased replication, correlated with higher endogenous expression levels of the main NiV entry receptor ephrin-B2, not only significantly differed between airway cells of the two species but also varied between cells from different human donors. To our knowledge, our study provides the first experimental evidence of species-specific and individual differences in NiV receptor expression and replication kinetics in primary airway epithelial cells. It remains to be determined whether and how these differences contribute to the viral host range and pathogenicity.

Potential effects of mixed infections in ticks on transmission dynamics of pathogens: comparative analysis of published records

USGS Publications Warehouse

Ginsberg, Howard S.

2008-01-01

Ticks are often infected with more than one pathogen, and several field surveys have documented nonrandom levels of coinfection. Levels of coinfection by pathogens in four tick species were analyzed using published infection data. Coinfection patterns of pathogens in field-collected ticks include numerous cases of higher or lower levels of coinfection than would be expected due to chance alone, but the vast majority of these cases can be explained on the basis of vertebrate host associations of the pathogens, without invoking interactions between pathogens within ticks. Nevertheless, some studies have demonstrated antagonistic interactions, and some have suggested potential mutualisms, between pathogens in ticks. Negative or positive interactions between pathogens within ticks can affect pathogen prevalence, and thus transmission patterns. Probabilistic projections suggest that the effect on transmission depends on initial conditions. When the number of tick bites is relatively low (e.g., for ticks biting humans) changes in prevalence in ticks are predicted to have a commensurate effects on pathogen transmission. In contrast, when the number of tick bites is high (e.g., for wild animal hosts) changes in pathogen prevalence in ticks have relatively little effect on levels of transmission to reservoir hosts, and thus on natural transmission cycles.

Use of cationic polymers to reduce pathogen levels during dairy manure separation.

PubMed

Liu, Zong; Carroll, Zachary S; Long, Sharon C; Gunasekaran, Sundaram; Runge, Troy

2016-01-15

Various separation technologies are used to deal with the enormous amounts of animal waste that large livestock operations generate. When the recycled waste stream is land applied, it is essential to lower the pathogen load to safeguard the health of livestock and humans. We investigated whether cationic polymers, used as a flocculent in the solid/liquid separation process, could reduce the pathogen indicator load in the animal waste stream. The effects of low charge density cationic polyacrylamide (CPAM) and high charge density cationic polydicyandiamide (PDCD) were investigated. Results demonstrated that CPAM was more effective than PDCD for manure coagulation and flocculation, while PDCD was more effective than CPAM in reducing the pathogen indicator loads. However, their combined use, CPAM followed by PDCD, resulted in both improved solids separation and pathogen indicator reduction. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Insect Immunity to Entomopathogenic Fungi.

PubMed

Lu, H-L; St Leger, R J

2016-01-01

The study of infection and immunity in insects has achieved considerable prominence with the appreciation that their host defense mechanisms share many fundamental characteristics with the innate immune system of vertebrates. Studies on the highly tractable model organism Drosophila in particular have led to a detailed understanding of conserved innate immunity networks, such as Toll. However, most of these studies have used opportunistic human pathogens and may not have revealed specialized immune strategies that have arisen through evolutionary arms races with natural insect pathogens. Fungi are the commonest natural insect pathogens, and in this review, we focus on studies using Metarhizium and Beauveria spp. that have addressed immune system function and pathogen virulence via behavioral avoidance, the use of physical barriers, and the activation of local and systemic immune responses. In particular, we highlight studies on the evolutionary genetics of insect immunity and discuss insect-pathogen coevolution. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicida

PubMed Central

Schmerk, Crystal L.; Duplantis, Barry N.; Wang, Diana; Burke, Robert D.; Chou, Alicia Y.; Elkins, Karen L.; Ludu, Jagjit S.; Nano, Francis E.

2009-01-01

Francisella tularensis is a highly virulent, intracellular pathogen that causes the disease tularaemia. A research surrogate for F. tularensis is Francisella novicida, which causes a tularaemia-like disease in mice, grows similarly in macrophages, and yet is unable to cause disease in humans. Both Francisella species contain a cluster of genes referred to as the Francisella pathogenicity island (FPI). Pathogenicity determinant protein A (PdpA), encoded by the pdpA gene, is located within the FPI and has been associated with the virulence of Francisella species. In this work we examined the properties of PdpA protein expression and localization as well as the phenotype of a F. novicida pdpA deletion mutant. Monoclonal antibody detection of PdpA showed that it is a soluble protein that is upregulated in iron-limiting conditions and undetectable in an mglA or mglB mutant background. Deletion of pdpA resulted in a strain that was highly attenuated for virulence in chicken embryos and mice. PMID:19372153

Anti-infective therapeutics from the Lepidopteran model host Galleria mellonella.

PubMed

Vilcinskas, Andreas

2011-01-01

The larvae of the greater wax moth Galleria mellonella prosper in use both as surrogate alternative model hosts for human pathogens and as a whole-animal-high-throughput-system for in vivo testing of antibiotics or mutant-libraries of pathogens. In addition, a broad spectrum of antimicrobial peptides and proteins has been identified in this insect during past decade among which some appear to be specific for Lepidoptera. Its arsenal of immunity-related effector molecules encompasses peptides and proteins exhibiting potent activity against bacteria, fungi or both, whose potential as new anti-infective therapeutics are presently being explored. Of particular interest is the insect metalloproteinase inhibitor (IMPI) which has been discovered in G. mellonella. The IMPI exhibits a specific and potent activity against thermolysin-like microbial metalloproteinases including a number of prominent virulence and/or pathogenic factors of human pathogens which are responsible for severe symptoms such as septicemia, hemorrhagic tissue bleeding, necrosis and enhancement of vascular permeability. The IMPI and antimicrobial peptides from G. mellonella may provide promising templates for the rational design of new drugs since evidence is available that the combination of antibiotics with inhibitors of pathogen-associated proteolytic enzymes yields synergistic therapeutic effects. The potential and limitations of insect-derived gene-encoded antimicrobial compounds as anti-infective therapeutics are discussed.

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

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.

New York City House Mice (Mus musculus) as Potential Reservoirs for Pathogenic Bacteria and Antimicrobial Resistance Determinants

PubMed Central

Williams, Simon H.; Che, Xiaoyu; Paulick, Ashley; Guo, Cheng; Lee, Bohyun; Muller, Dorothy; Uhlemann, Anne-Catrin; Lowy, Franklin D.; Corrigan, Robert M.

2018-01-01

ABSTRACT House mice (Mus musculus) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria. A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella, Salmonella, Clostridium difficile, and diarrheagenic Escherichia coli. Furthermore, genes mediating antimicrobial resistance to fluoroquinolones (qnrB) and β-lactam drugs (blaSHV and blaACT/MIR) were widely distributed. Culture and molecular strain typing of C. difficile revealed that mice harbor ribotypes associated with human disease, and screening of kidney samples demonstrated genetic evidence of pathogenic Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment. PMID:29666289

Comprehensive identification of Vibrio vulnificus genes required for growth in human serum.

PubMed

Carda-Diéguez, M; Silva-Hernández, F X; Hubbard, T P; Chao, M C; Waldor, M K; Amaro, C

2018-12-31

Vibrio vulnificus can be a highly invasive pathogen capable of spreading from an infection site to the bloodstream, causing sepsis and death. To survive and proliferate in blood, the pathogen requires mechanisms to overcome the innate immune defenses and metabolic limitations of this host niche. We created a high-density transposon mutant library in YJ016, a strain representative of the most virulent V. vulnificus lineage (or phylogroup) and used transposon insertion sequencing (TIS) screens to identify loci that enable the pathogen to survive and proliferate in human serum. Initially, genes underrepresented for insertions were used to estimate the V. vulnificus essential gene set; comparisons of these genes with similar TIS-based classification of underrepresented genes in other vibrios enabled the compilation of a common Vibrio essential gene set. Analysis of the relative abundance of insertion mutants in the library after exposure to serum suggested that genes involved in capsule biogenesis are critical for YJ016 complement resistance. Notably, homologues of two genes required for YJ016 serum-resistance and capsule biogenesis were not previously linked to capsule biogenesis and are largely absent from other V. vulnificus strains. The relative abundance of mutants after exposure to heat inactivated serum was compared with the findings from the serum screen. These comparisons suggest that in both conditions the pathogen relies on its Na + transporting NADH-ubiquinone reductase (NQR) complex and type II secretion system to survive/proliferate within the metabolic constraints of serum. Collectively, our findings reveal the potency of comparative TIS screens to provide knowledge of how a pathogen overcomes the diverse limitations to growth imposed by serum.

Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants

PubMed Central

Metzgar, David; Myers, Christopher A.; Russell, Kevin L.; Faix, Dennis; Blair, Patrick J.; Brown, Jason; Vo, Scott; Swayne, David E.; Thomas, Colleen; Stenger, David A.; Lin, Baochuan; Malanoski, Anthony P.; Wang, Zheng; Blaney, Kate M.; Long, Nina C.; Schnur, Joel M.; Saad, Magdi D.; Borsuk, Lisa A.; Lichanska, Agnieszka M.; Lorence, Matthew C.; Weslowski, Brian; Schafer, Klaus O.; Tibbetts, Clark

2010-01-01

For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents. PMID:20140251

Single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants.

PubMed

Metzgar, David; Myers, Christopher A; Russell, Kevin L; Faix, Dennis; Blair, Patrick J; Brown, Jason; Vo, Scott; Swayne, David E; Thomas, Colleen; Stenger, David A; Lin, Baochuan; Malanoski, Anthony P; Wang, Zheng; Blaney, Kate M; Long, Nina C; Schnur, Joel M; Saad, Magdi D; Borsuk, Lisa A; Lichanska, Agnieszka M; Lorence, Matthew C; Weslowski, Brian; Schafer, Klaus O; Tibbetts, Clark

2010-02-03

For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.

Pathogen Loading From Canada Geese Faeces in Freshwater: Potential Risks to Human Health Through Recreational Water Exposure.

PubMed

Gorham, T J; Lee, J

2016-05-01

Canada geese (Branta canadensis) faeces have been shown to contain pathogenic protozoa and bacteria in numerous studies over the past 15 years. Further, increases in both the Canada geese populations and their ideal habitat requirements in the United States (US) translate to a greater presence of these human pathogens in public areas, such as recreational freshwater beaches. Combining these factors, the potential health risk posed by Canada geese faeces at freshwater beaches presents an emerging public health issue that warrants further study. Here, literature concerning human pathogens in Canada geese faeces is reviewed and the potential impacts these pathogens may have on human health are discussed. Pathogens of potential concern include Campylobacter jejuni, Salmonella Typhimurium, Listeria monocytogenes, Helicobacter canadensis, Arcobacter spp., Enterohemorragic Escherichia coli pathogenic strains, Chlamydia psitacci, Cryptosporidium parvum and Giardia lamblia. Scenarios presenting potential exposure to pathogens eluted from faeces include bathers swimming in lakes, children playing with wet and dry sand impacted by geese droppings and other common recreational activities associated with public beaches. Recent recreational water-associated disease outbreaks in the US support the plausibility for some of these pathogens, including Cryptosporidium spp. and C. jejuni, to cause human illness in this setting. In view of these findings and the uncertainties associated with the real health risk posed by Canada geese faecal pathogens to users of freshwater lakes, it is recommended that beach managers use microbial source tracking and conduct a quantitative microbial risk assessment to analyse the local impact of Canada geese on microbial water quality during their decision-making process in beach and watershed management. © 2015 Blackwell Verlag GmbH.

Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen protein interactions.

PubMed

Wallqvist, Anders; Wang, Hao; Zavaljevski, Nela; Memišević, Vesna; Kwon, Keehwan; Pieper, Rembert; Rajagopala, Seesandra V; Reifman, Jaques

2017-01-01

Coxiella burnetii is an obligate Gram-negative intracellular pathogen and the etiological agent of Q fever. Successful infection requires a functional Type IV secretion system, which translocates more than 100 effector proteins into the host cytosol to establish the infection, restructure the intracellular host environment, and create a parasitophorous vacuole where the replicating bacteria reside. We used yeast two-hybrid (Y2H) screening of 33 selected C. burnetii effectors against whole genome human and murine proteome libraries to generate a map of potential host-pathogen protein-protein interactions (PPIs). We detected 273 unique interactions between 20 pathogen and 247 human proteins, and 157 between 17 pathogen and 137 murine proteins. We used orthology to combine the data and create a single host-pathogen interaction network containing 415 unique interactions between 25 C. burnetii and 363 human proteins. We further performed complementary pairwise Y2H testing of 43 out of 91 C. burnetii-human interactions involving five pathogen proteins. We used the combined data to 1) perform enrichment analyses of target host cellular processes and pathways, 2) examine effectors with known infection phenotypes, and 3) infer potential mechanisms of action for four effectors with uncharacterized functions. The host-pathogen interaction profiles supported known Coxiella phenotypes, such as adapting cell morphology through cytoskeletal re-arrangements, protein processing and trafficking, organelle generation, cholesterol processing, innate immune modulation, and interactions with the ubiquitin and proteasome pathways. The generated dataset of PPIs-the largest collection of unbiased Coxiella host-pathogen interactions to date-represents a rich source of information with respect to secreted pathogen effector proteins and their interactions with human host proteins.

Identification of hotspots and trends of fecal surface water pollution in developing countries

NASA Astrophysics Data System (ADS)

Reder, Klara; Flörke, Martina; Alcamo, Joseph

2015-04-01

Water is the essential resource ensuring human life on earth, which can only prosper when water is available and accessible. But of importance is not only the quantity of accessible water but also its quality, which in case of pollution may pose a risk to human health. The pollutants which pose a risk to human health are manifold, covering several groups such as pathogens, nutrients, human pharmaceuticals, heavy metals, and others. With regards to human health, pathogen contamination is of major interest as 4% of all death and 5.7% of disability or ill health in the world can be attributed to poor water supply, sanitation and personal and domestic hygiene. In developing countries, 2.6 billion people lacked access to improved sanitation in 2011. The lack of sanitation poses a risk to surface water pollution which is a threat to human health. A typical indicator for pathogen pollution is fecal coliform bacteria. The objective our study is to assess fecal pollution in the developing regions Africa, Asia and Latin America using the large-scale water quality model WorldQual. Model runs were carried-out to calculate in-stream concentrations and the respective loadings reaching rivers for the time period 1990 to 2010. We identified hotspots of fecal coliform loadings and in-stream concentrations which were further analyzed and ranked in terms of fecal surface water pollution. Main findings are that loadings mainly originate from the domestic sector, thus loadings are high in highly populated areas. In general, domestic loadings can be attributed to the two subsectors domestic sewered and domestic non sewered. The spatial distribution of both sectors varies across catchments. Hotspot pattern of in-stream concentrations are similar to the loadings pattern although they are different in seasonality. As the dilution varies with climate its dilution capacity is high during seasons with high precipitation, which in turn decreases the in-stream concentrations. The fecal pollution is increasing from 1990 to 2010 with increased loadings and larger number of river kilometers with high fecal pollution. Fecal pollution is mainly caused by the domestic sector, and hence, the sanitation type, collection and treatment (level) of collected wastewater are highly important to ensure good quality of water bodies.

Identifying Francisella tularensis genes required for growth in host cells

USDA-ARS?s Scientific Manuscript database

Technical Abstract: Francisella tularensis is a highly virulent Gram negative intracellular pathogen capable of infecting a vast diversity of hosts, ranging from amoebae to humans. A hallmark of F. tularensis virulence is its ability to quickly grow to high densities within a diverse set of host cel...

Investigation of pathogen infiltration into produce using Xradia Bio MicroCT

USDA-ARS?s Scientific Manuscript database

The internalization of human pathogens into plant tissues has received significant attention. Human pathogens can infiltrate plant tissue through stomata, cut edges, wounds on produce, or the plant vascular system. The nondestructive X-ray computed microtomography (MicroCT) technique is an X-ra...

Future challenges in the elimination of bacterial meningitis.

PubMed

Bottomley, Matthew J; Serruto, Davide; Sáfadi, Marco Aurélio Palazzi; Klugman, Keith P

2012-05-30

Despite the widespread implementation of several effective vaccines over the past few decades, bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Group B Streptococcus (GBS) still results in unacceptably high levels of human mortality and morbidity. A residual disease burden due to bacterial meningitis is also apparent due to a number of persistent or emerging pathogens, including Mycobacterium tuberculosis, Escherichia coli, Staphylococcus aureus, Salmonella spp. and Streptococcus suis. Here, we review the current status of bacterial meningitis caused by these pathogens, highlighting how past and present vaccination programs have attempted to counter these pathogens. We discuss how improved pathogen surveillance, implementation of current vaccines, and development of novel vaccines may be expected to further reduce bacterial meningitis and related diseases in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens.

PubMed

March, Sandra; Ramanan, Vyas; Trehan, Kartik; Ng, Shengyong; Galstian, Ani; Gural, Nil; Scull, Margaret A; Shlomai, Amir; Mota, Maria M; Fleming, Heather E; Khetani, Salman R; Rice, Charles M; Bhatia, Sangeeta N

2015-12-01

The development of therapies and vaccines for human hepatropic pathogens requires robust model systems that enable the study of host-pathogen interactions. However, in vitro liver models of infection typically use either hepatoma cell lines that exhibit aberrant physiology or primary human hepatocytes in culture conditions in which they rapidly lose their hepatic phenotype. To achieve stable and robust in vitro primary human hepatocyte models, we developed micropatterned cocultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive fibroblast cells. By using this system, which can be established over a period of days, and maintained over multiple weeks, we demonstrate how to recapitulate in vitro hepatic life cycles for the hepatitis B and C viruses and the Plasmodium pathogens P. falciparum and P. vivax. The MPCC platform can be used to uncover aspects of host-pathogen interactions, and it has the potential to be used for drug and vaccine development.

Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens

PubMed Central

March, Sandra; Ramanan, Vyas; Trehan, Kartik; Ng, Shengyong; Galstian, Ani; Gural, Nil; Scull, Margaret A.; Shlomai, Amir; Mota, Maria; Fleming, Heather E.; Khetani, Salman R.; Rice, Charles M.; Bhatia, Sangeeta N.

2018-01-01

Studying human hepatotropic pathogens such as hepatitis B and C viruses and malaria will be necessary for understanding host-pathogen interactions, and developing therapy and prophylaxis. Unfortunately, existing in vitro liver models typically employ either cell lines that exhibit aberrant physiology, or primary human hepatocytes in culture configurations wherein they rapidly lose their hepatic functional phenotype. Stable, robust, and reliable in vitro primary human hepatocyte models are needed as platforms for infectious disease applications. For this purpose, we describe the application of micropatterned co-cultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive cells. Using this system, we demonstrate how to recapitulate in vitro liver infection by the hepatitis B and C viruses and Plasmodium pathogens. In turn, the MPCC platform can be used to uncover aspects of host-pathogen interactions, and has the potential to be used for medium-throughput drug screening and vaccine development. PMID:26584444

Looking at protists as a source of pathogenic viruses.

PubMed

La Scola, Bernard

2014-12-01

In the environment, protozoa are predators of bacteria and feed on them. The possibility that some protozoa could be a source of human pathogens is consistent with the discovery that free-living amoebae were the reservoir of Legionella pneumophila, the agent of Legionnaires' disease. Later, while searching for Legionella in the environment using amoeba co-culture, the first giant virus, Acanthamoeba polyphaga mimivirus, was discovered. Since then, many other giant viruses have been isolated, including Marseilleviridae, Pithovirus sibericum, Cafeteria roenbergensis virus and Pandoravirus spp. The methods used to isolate all of these viruses are herein reviewed. By analogy to Legionella, it was originally suspected that these viruses could be human pathogens. After showing by indirect evidence, such as sero-epidemiologic studies, that it was possible for these viruses to be human pathogens, the recent isolation of some of these viruses (belonging to the Mimiviridae and Marseilleviridae families) in humans in the context of pathologic conditions shows that they are opportunistic human pathogens in some instances. Copyright © 2014 Elsevier Ltd. All rights reserved.

The use of pseudotypes to study viruses, virus sero-epidemiology and vaccination.

PubMed

Bentley, Emma M; Mather, Stuart T; Temperton, Nigel J

2015-06-12

The globalization of the world's economies, accompanied by increasing international travel, changing climates, altered human behaviour and demographics is leading to the emergence of different viral diseases, many of which are highly pathogenic and hence are considered of great public and animal health importance. To undertake basic research and therapeutic development, many of these viruses require handling by highly trained staff in BSL-3/4 facilities not readily available to the majority of the global R&D community. In order to circumvent the enhanced biosafety requirement, the development of non-pathogenic, replication-defective pseudotyped viruses is an effective and established solution to permit the study of many aspects of virus biology in a low containment biosafety level (BSL)-1/2 laboratory. Under the spectre of the unfolding Ebola crisis, this timely conference (the second to be organised by the Viral Pseudotype Unit, www.viralpseudotypeunit.info*) discusses the recent advances in pseudotype technology and how it is revolutionizing the study of important human and animal pathogens (human and avian influenza viruses, rabies/lyssaviruses, HIV, Marburg and Ebola viruses). Key topics addressed in this conference include the exploitation of pseudotypes for serology and serosurveillance, immunogenicity testing of current and next-generation vaccines and new pseudotype assay formats (multiplexing, kit development). The first pseudotype-focused Euroscicon conference organised by the Viral Pseudotype Unit was recently reviewed [1]. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.

The Battle for Iron between Humans and Microbes.

PubMed

Carver, Peggy L

2018-01-01

Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment. To describe complex 'tug of war' for iron that has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. A review of current literature was performed, to assess current approaches and controversies in iron therapy and chelation in humans. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection. The administration of iron chelating agents and siderophore- conjugate drugs to infected hosts seems a biologically plausible approach as adjunctive therapy in the treatment of infections caused by pathogens dependent on host iron supply (e.g. tuberculosis, malaria, and many bacterial and fungal pathogens); however, thus far, studies in humans have proved unsuccessful. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Immunological Control of Viral Infections in Bats and the Emergence of Viruses Highly Pathogenic to Humans

PubMed Central

Schountz, Tony; Baker, Michelle L.; Butler, John; Munster, Vincent

2017-01-01

Bats are reservoir hosts of many important viruses that cause substantial disease in humans, including coronaviruses, filoviruses, lyssaviruses, and henipaviruses. Other than the lyssaviruses, they do not appear to cause disease in the reservoir bats, thus an explanation for the dichotomous outcomes of infections of humans and bat reservoirs remains to be determined. Bats appear to have a few unusual features that may account for these differences, including evidence of constitutive interferon (IFN) activation and greater combinatorial diversity in immunoglobulin genes that do not undergo substantial affinity maturation. We propose these features may, in part, account for why bats can host these viruses without disease and how they may contribute to the highly pathogenic nature of bat-borne viruses after spillover into humans. Because of the constitutive IFN activity, bat-borne viruses may be shed at low levels from bat cells. With large naive antibody repertoires, bats may control the limited virus replication without the need for rapid affinity maturation, and this may explain why bats typically have low antibody titers to viruses. However, because bat viruses have evolved in high IFN environments, they have enhanced countermeasures against the IFN response. Thus, upon infection of human cells, where the IFN response is not constitutive, the viruses overwhelm the IFN response, leading to abundant virus replication and pathology. PMID:28959255

Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus.

PubMed

Collado, M C; Meriluoto, J; Salminen, S

2007-10-01

The aims of this study present were to assess and to evaluate in vitro the abilities of commercial probiotic strains derived from fermented milk products and related sources currently marketed in European countries, to inhibit, compete and displace the adhesion of selected potential pathogens to immobilized human mucus. The adhesion was assessed by measuring the radioactivity of bacteria adhered to the human mucus. We tested 12 probiotic strains against eight selected pathogens. All strains tested were able to adhere to mucus. All probiotic strains tested were able to inhibit and displace (P<0.05) the adhesion of Bacteroides, Clostridium, Staphylococcus and Enterobacter. In addition, the abilities to inhibit and to displace adhered pathogens depended on both the probiotic and the pathogen strains tested suggesting that several complementary mechanisms are implied in the processes. Our results indicate the need for a case-by-case assessment in order to select strains with the ability to inhibit or displace a specific pathogen. Probiotics could be useful to correct deviations observed in intestinal microbiota associated with specific diseases and also, to prevent pathogen infections. The competitive exclusion properties of probiotics as well as their ability to displace and inhibit pathogens are the most importance for therapeutic manipulation of the enteric microbiota. The application of such strategies could contribute to expand the beneficial properties on human health against pathogen infection.

Cross-species transmission potential between wild pigs, livestock, poultry, wildlife, and humans: Implications for disease risk management in North America

USGS Publications Warehouse

Miller, Ryan S.; Sweeney, Steven J.; Slootmaker, Chris; Grear, Daniel A.; DiSalvo, Paul A.; Kiser, Deborah; Shwiff, Stephanie A.

2017-01-01

Cross-species disease transmission between wildlife, domestic animals and humans is an increasing threat to public and veterinary health. Wild pigs are increasingly a potential veterinary and public health threat. Here we investigate 84 pathogens and the host species most at risk for transmission with wild pigs using a network approach. We assess the risk to agricultural and human health by evaluating the status of these pathogens and the co-occurrence of wild pigs, agriculture and humans. We identified 34 (87%) OIE listed swine pathogens that cause clinical disease in livestock, poultry, wildlife, and humans. On average 73% of bacterial, 39% of viral, and 63% of parasitic pathogens caused clinical disease in other species. Non-porcine livestock in the family Bovidae shared the most pathogens with swine (82%). Only 49% of currently listed OIE domestic swine diseases had published wild pig surveillance studies. The co-occurrence of wild pigs and farms increased annually at a rate of 1.2% with as much as 57% of all farms and 77% of all agricultural animals co-occurring with wild pigs. The increasing co-occurrence of wild pigs with livestock and humans along with the large number of pathogens shared is a growing risk for cross-species transmission.

Cross-species transmission potential between wild pigs, livestock, poultry, wildlife, and humans: implications for disease risk management in North America.

PubMed

Miller, Ryan S; Sweeney, Steven J; Slootmaker, Chris; Grear, Daniel A; Di Salvo, Paul A; Kiser, Deborah; Shwiff, Stephanie A

2017-08-10

Cross-species disease transmission between wildlife, domestic animals and humans is an increasing threat to public and veterinary health. Wild pigs are increasingly a potential veterinary and public health threat. Here we investigate 84 pathogens and the host species most at risk for transmission with wild pigs using a network approach. We assess the risk to agricultural and human health by evaluating the status of these pathogens and the co-occurrence of wild pigs, agriculture and humans. We identified 34 (87%) OIE listed swine pathogens that cause clinical disease in livestock, poultry, wildlife, and humans. On average 73% of bacterial, 39% of viral, and 63% of parasitic pathogens caused clinical disease in other species. Non-porcine livestock in the family Bovidae shared the most pathogens with swine (82%). Only 49% of currently listed OIE domestic swine diseases had published wild pig surveillance studies. The co-occurrence of wild pigs and farms increased annually at a rate of 1.2% with as much as 57% of all farms and 77% of all agricultural animals co-occurring with wild pigs. The increasing co-occurrence of wild pigs with livestock and humans along with the large number of pathogens shared is a growing risk for cross-species transmission.

Communicable Diseases Prioritized for Surveillance and Epidemiological Research: Results of a Standardized Prioritization Procedure in Germany, 2011

PubMed Central

Balabanova, Yanina; Gilsdorf, Andreas; Buda, Silke; Burger, Reinhard; Eckmanns, Tim; Gärtner, Barbara; Groß, Uwe; Haas, Walter; Hamouda, Osamah; Hübner, Johannes; Jänisch, Thomas; Kist, Manfred; Kramer, Michael H.; Ledig, Thomas; Mielke, Martin; Pulz, Matthias; Stark, Klaus; Suttorp, Norbert; Ulbrich, Uta; Wichmann, Ole; Krause, Gérard

2011-01-01

Introduction To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research. Methods We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups. Results 127 pathogens were scored. Eighty-six experts participated in the weighting; “Case fatality rate” was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus. Discussion While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings. PMID:21991334

[Survival Strategies of Aspergillus in the Human Body].

PubMed

Tashiro, Masato; Izumikawa, Koichi

2017-01-01

 The human body is a hostile environment for Aspergillus species, which originally live outside the human body. There are lots of elimination mechanisms against Aspergillus inhaled into the human body, such as high body temperature, soluble lung components, mucociliary clearance mechanism, or responses of phagocytes. Aspergillus fumigatus, which is the primary causative agent of human infections among the human pathogenic species of Aspergillus, defend itself from the hostile human body environment by various mechanisms, such as thermotolerance, mycotoxin production, and characteristic morphological features. Here we review mechanisms of defense in Aspergillus against elimination from the human body.

Chicken and Duck Myotubes Are Highly Susceptible and Permissive to Influenza Virus Infection

PubMed Central

Baquero-Perez, Belinda; Kuchipudi, Suresh V.; Ho, Jemima; Sebastian, Sujith; Puranik, Anita; Howard, Wendy; Brookes, Sharon M.; Brown, Ian H.

2014-01-01

ABSTRACT Skeletal muscle, at 30 to 40% of body mass, is the most abundant soft tissue in the body. Besides its primary function in movement and posture, skeletal muscle is a significant innate immune organ with the capacity to produce cytokines and chemokines and respond to proinflammatory cytokines. Little is known about the role of skeletal muscle during systemic influenza A virus infection in any host and particularly avian species. Here we used primary chicken and duck multinucleated myotubes to examine their susceptibility and innate immune response to influenza virus infections. Both chicken and duck myotubes expressed avian and human sialic acid receptors and were readily susceptible to low-pathogenicity (H2N3 A/mallard duck/England/7277/06) and high-pathogenicity (H5N1 A/turkey/England/50-92/91 and H5N1 A/turkey/Turkey/1/05) avian and human H1N1 (A/USSR/77) influenza viruses. Both avian host species produced comparable levels of progeny H5N1 A/turkey/Turkey/1/05 virus. Notably, the rapid accumulation of viral nucleoprotein and matrix (M) gene RNA in chicken and duck myotubes was accompanied by extensive cytopathic damage with marked myotube apoptosis (widespread microscopic blebs, caspase 3/7 activation, and annexin V binding at the plasma membrane). Infected chicken myotubes produced significantly higher levels of proinflammatory cytokines than did the corresponding duck cells. Additionally, in chicken myotubes infected with H5N1 viruses, the induction of interferon beta (IFN-β) and IFN-inducible genes, including the melanoma differentiation-associated protein 5 (MDA-5) gene, was relatively weak compared to infection with the corresponding H2N3 virus. Our findings highlight that avian skeletal muscle fibers are capable of productive influenza virus replication and are a potential tissue source of infection. IMPORTANCE Infection with high-pathogenicity H5N1 viruses in ducks is often asymptomatic, and skeletal muscle from such birds could be a source of infection of humans and animals. Little is known about the ability of influenza A viruses to replicate in avian skeletal muscle fibers. We show here that cultured chicken and duck myotubes were highly susceptible to infection with both low- and high-pathogenicity avian influenza viruses. Infected myotubes of both avian species displayed rapid virus accumulation, apoptosis, and extensive cellular damage. Our results indicate that avian skeletal muscle fibers of chicken and duck could be significant contributors to progeny production of highly pathogenic H5N1 viruses. PMID:25540384

Chicken and duck myotubes are highly susceptible and permissive to influenza virus infection.

PubMed

Baquero-Perez, Belinda; Kuchipudi, Suresh V; Ho, Jemima; Sebastian, Sujith; Puranik, Anita; Howard, Wendy; Brookes, Sharon M; Brown, Ian H; Chang, Kin-Chow

2015-03-01

Skeletal muscle, at 30 to 40% of body mass, is the most abundant soft tissue in the body. Besides its primary function in movement and posture, skeletal muscle is a significant innate immune organ with the capacity to produce cytokines and chemokines and respond to proinflammatory cytokines. Little is known about the role of skeletal muscle during systemic influenza A virus infection in any host and particularly avian species. Here we used primary chicken and duck multinucleated myotubes to examine their susceptibility and innate immune response to influenza virus infections. Both chicken and duck myotubes expressed avian and human sialic acid receptors and were readily susceptible to low-pathogenicity (H2N3 A/mallard duck/England/7277/06) and high-pathogenicity (H5N1 A/turkey/England/50-92/91 and H5N1 A/turkey/Turkey/1/05) avian and human H1N1 (A/USSR/77) influenza viruses. Both avian host species produced comparable levels of progeny H5N1 A/turkey/Turkey/1/05 virus. Notably, the rapid accumulation of viral nucleoprotein and matrix (M) gene RNA in chicken and duck myotubes was accompanied by extensive cytopathic damage with marked myotube apoptosis (widespread microscopic blebs, caspase 3/7 activation, and annexin V binding at the plasma membrane). Infected chicken myotubes produced significantly higher levels of proinflammatory cytokines than did the corresponding duck cells. Additionally, in chicken myotubes infected with H5N1 viruses, the induction of interferon beta (IFN-β) and IFN-inducible genes, including the melanoma differentiation-associated protein 5 (MDA-5) gene, was relatively weak compared to infection with the corresponding H2N3 virus. Our findings highlight that avian skeletal muscle fibers are capable of productive influenza virus replication and are a potential tissue source of infection. Infection with high-pathogenicity H5N1 viruses in ducks is often asymptomatic, and skeletal muscle from such birds could be a source of infection of humans and animals. Little is known about the ability of influenza A viruses to replicate in avian skeletal muscle fibers. We show here that cultured chicken and duck myotubes were highly susceptible to infection with both low- and high-pathogenicity avian influenza viruses. Infected myotubes of both avian species displayed rapid virus accumulation, apoptosis, and extensive cellular damage. Our results indicate that avian skeletal muscle fibers of chicken and duck could be significant contributors to progeny production of highly pathogenic H5N1 viruses. Copyright © 2015, Baquero-Perez et al.

Lactobacillus crispatus L1: high cell density cultivation and exopolysaccharide structure characterization to highlight potentially beneficial effects against vaginal pathogens

PubMed Central

2014-01-01

Background Vaginal lactic acid bacteria defend the host against pathogens through a combination of competitive exclusion, competition for nutrients, production of antimicrobial substances and through the activation of the immune system. A new human isolate named Lactobacillus crispatus L1 was characterized in this work, and a preliminary evaluation of its probiotic potential is described together with a process to obtain a high productivity of viable biomass. Results In a simulated digestion process 1.8⋅1010 cells∙ml−1 survived the gastric environment with 80% viability, without being affected by small intestine juices. Experiments on six different C sources were performed to analyze growth and organic acids production and, glucose, provided the best performances. A microfiltration strategy was exploited to improve the cellular yield in 2 L-fermentation processes, reaching 27 g · l−1 of dry biomass. Moreover, L. crispatus L1 demonstrated a greater stability to high concentrations of lactic acid, compared to other lactobacilli. The specific L. crispatus L1 exopolysaccharide was purified from the fermentation broth and characterized by NMR showing structural features and similarity to exopolysaccharides produced by pathogenic strains. Live L. crispatus L1 cells strongly reduced adhesion of a yeast pathogenic strain, Candida albicans in particular, in adherence assays. Interestingly a higher expression of the human defensin HBD-2 was also observed in vaginal cells treated with the purified exopolysaccharide, indicating a possible correlation with C. albicans growth inhibition. Conclusions The paper describes the evaluation of L. crispatus L1 as potential vaginal probiotic and the fermentation processes to obtain high concentrations of viable cells. PMID:24884965

Avian influenza A (H5N1).

PubMed

de Jong, Menno D; Hien, Tran Tinh

2006-01-01

Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have reached endemic levels among poultry in several southeast Asian countries and have caused a still increasing number of more than 100 reported human infections with high mortality. These developments have ignited global fears of an imminent influenza pandemic. The current knowledge of the virology, clinical spectrum, diagnosis and treatment of human influenza H5N1 virus infections is reviewed herein.

Cold plasma inactivation of human pathogens on foods and regulatory status update

USDA-ARS?s Scientific Manuscript database

Contamination of foods with human pathogens such as Salmonella, Listeria monocytogenes, Escherichia coli O157:H7, norovirus, and other pathogens is an ongoing challenge for growers and processors. In recent years, cold plasma has emerged as a promising antimicrobial treatment for fresh and fresh-cut...

Highly Pathogenic Avian Influenza H5N1, Thailand, 2004

PubMed Central

Chaitaweesub, Prasit; Songserm, Thaweesak; Chaisingh, Arunee; Hoonsuwan, Wirongrong; Buranathai, Chantanee; Parakamawongsa, Tippawon; Premashthira, Sith; Amonsin, Alongkorn; Gilbert, Marius; Nielen, Mirjam; Stegeman, Arjan

2005-01-01

In January 2004, highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was first confirmed in poultry and humans in Thailand. Control measures, e.g., culling poultry flocks, restricting poultry movement, and improving hygiene, were implemented. Poultry populations in 1,417 villages in 60 of 76 provinces were affected in 2004. A total of 83% of infected flocks confirmed by laboratories were backyard chickens (56%) or ducks (27%). Outbreaks were concentrated in the Central, the southern part of the Northern, and Eastern Regions of Thailand, which are wetlands, water reservoirs, and dense poultry areas. More than 62 million birds were either killed by HPAI viruses or culled. H5N1 virus from poultry caused 17 human cases and 12 deaths in Thailand; a number of domestic cats, captive tigers, and leopards also died of the H5N1 virus. In 2005, the epidemic is ongoing in Thailand. PMID:16318716

Analysis of peripheral B cells and autoantibodies against the anti-nicotinic acetylcholine receptor derived from patients with myasthenia gravis using single-cell manipulation tools

PubMed Central

Terakawa, Maki; Muneoka, Satoshi; Nagahira, Kazuhiro; Nagane, Yuriko; Yamate, Jyoji; Motomura, Masakatsu; Utsugisawa, Kimiaki

2017-01-01

The majority of patients with myasthenia gravis (MG), an organ-specific autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting in muscle weakness. Single cell manipulation technologies coupled with genetic engineering are very powerful tools to examine T cell and B cell repertoires and the dynamics of adaptive immunity. These tools have been utilized to develop mAbs in parallel with hybridomas, phage display technologies and B-cell immortalization. By applying a single cell technology and novel high-throughput cell-based binding assays, we identified peripheral B cells that produce pathogenic nAChR-Abs in patients with MG. Although anti-nAChR antibodies produced by individual peripheral B cells generally exhibited low binding affinity for the α-subunit of the nAChR and great sequence diversity, a small fraction of these antibodies bound with high affinity to native-structured nAChRs on cell surfaces. B12L, one such Ab isolated here, competed with a rat Ab (mAb35) for binding to the human nAChR and thus considered to recognize the main immunogenic region (MIR). By evaluating the Ab in in vitro cell-based assays and an in vivo rat passive transfer model, B12L was found to act as a pathogenic Ab in rodents and presumably in humans.These findings suggest that B cells in peripheral blood may impact MG pathogenicity. Our methodology can be applied not only to validate pathogenic Abs as molecular target of MG treatment, but also to discover and analyze Ab production systems in other human diseases. PMID:29040265

Analysis of peripheral B cells and autoantibodies against the anti-nicotinic acetylcholine receptor derived from patients with myasthenia gravis using single-cell manipulation tools.

PubMed

Makino, Tomohiro; Nakamura, Ryuichi; Terakawa, Maki; Muneoka, Satoshi; Nagahira, Kazuhiro; Nagane, Yuriko; Yamate, Jyoji; Motomura, Masakatsu; Utsugisawa, Kimiaki

2017-01-01

The majority of patients with myasthenia gravis (MG), an organ-specific autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting in muscle weakness. Single cell manipulation technologies coupled with genetic engineering are very powerful tools to examine T cell and B cell repertoires and the dynamics of adaptive immunity. These tools have been utilized to develop mAbs in parallel with hybridomas, phage display technologies and B-cell immortalization. By applying a single cell technology and novel high-throughput cell-based binding assays, we identified peripheral B cells that produce pathogenic nAChR-Abs in patients with MG. Although anti-nAChR antibodies produced by individual peripheral B cells generally exhibited low binding affinity for the α-subunit of the nAChR and great sequence diversity, a small fraction of these antibodies bound with high affinity to native-structured nAChRs on cell surfaces. B12L, one such Ab isolated here, competed with a rat Ab (mAb35) for binding to the human nAChR and thus considered to recognize the main immunogenic region (MIR). By evaluating the Ab in in vitro cell-based assays and an in vivo rat passive transfer model, B12L was found to act as a pathogenic Ab in rodents and presumably in humans.These findings suggest that B cells in peripheral blood may impact MG pathogenicity. Our methodology can be applied not only to validate pathogenic Abs as molecular target of MG treatment, but also to discover and analyze Ab production systems in other human diseases.

Molecular evidence for zoonotic transmission of an emergent, highly pathogenic Campylobacter jejuni clone in the United States.

PubMed

Sahin, Orhan; Fitzgerald, Collette; Stroika, Steven; Zhao, Shaohua; Sippy, Rachel J; Kwan, Patrick; Plummer, Paul J; Han, Jing; Yaeger, Michael J; Zhang, Qijing

2012-03-01

Campylobacter jejuni is a major zoonotic pathogen. A highly virulent, tetracycline-resistant C. jejuni clone (clone SA) has recently emerged in ruminant reservoirs and has become the predominant cause of sheep abortion in the United States. To determine whether clone SA is associated with human disease, we compared the clinical isolates of clone SA from sheep abortions with the human isolates of the PulseNet National Campylobacter databases at the CDC and the FDA using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and serotyping. The combined SmaI and KpnI PFGE pattern designations of clone SA from sheep were indistinguishable from those of 123 (9.03%) human C. jejuni isolates (total, 1,361) in the CDC database, among which 56 were associated with sporadic infections and 67 were associated with outbreaks that occurred in multiple states from 2003 to 2010. Most of the outbreaks were attributed to raw milk, while the sources for most of the sporadic cases were unknown. All clone SA isolates examined, including PFGE-matched human isolates, belong to sequence type 8 (ST-8) by MLST and serotype HS:1,8, further indicating the clonality of the related isolates from different host species. Additionally, C. jejuni clone SA was identified in raw milk, cattle feces, the feces and bile of healthy sheep, and abortion cases of cattle and goats, indicating the broad distribution of this pathogenic clone in ruminants. These results provide strong molecular and epidemiological evidence for zoonotic transmission of this emergent clone from ruminants to humans and indicate that C. jejuni clone SA is an important threat to public health.

Molecular Evidence for Zoonotic Transmission of an Emergent, Highly Pathogenic Campylobacter jejuni Clone in the United States

PubMed Central

Sahin, Orhan; Fitzgerald, Collette; Stroika, Steven; Zhao, Shaohua; Sippy, Rachel J.; Kwan, Patrick; Plummer, Paul J.; Han, Jing; Yaeger, Michael J.

2012-01-01

Campylobacter jejuni is a major zoonotic pathogen. A highly virulent, tetracycline-resistant C. jejuni clone (clone SA) has recently emerged in ruminant reservoirs and has become the predominant cause of sheep abortion in the United States. To determine whether clone SA is associated with human disease, we compared the clinical isolates of clone SA from sheep abortions with the human isolates of the PulseNet National Campylobacter databases at the CDC and the FDA using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and serotyping. The combined SmaI and KpnI PFGE pattern designations of clone SA from sheep were indistinguishable from those of 123 (9.03%) human C. jejuni isolates (total, 1,361) in the CDC database, among which 56 were associated with sporadic infections and 67 were associated with outbreaks that occurred in multiple states from 2003 to 2010. Most of the outbreaks were attributed to raw milk, while the sources for most of the sporadic cases were unknown. All clone SA isolates examined, including PFGE-matched human isolates, belong to sequence type 8 (ST-8) by MLST and serotype HS:1,8, further indicating the clonality of the related isolates from different host species. Additionally, C. jejuni clone SA was identified in raw milk, cattle feces, the feces and bile of healthy sheep, and abortion cases of cattle and goats, indicating the broad distribution of this pathogenic clone in ruminants. These results provide strong molecular and epidemiological evidence for zoonotic transmission of this emergent clone from ruminants to humans and indicate that C. jejuni clone SA is an important threat to public health. PMID:22189122

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.

Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities.

PubMed

Balakireva, Anastasia V; Zamyatnin, Andrey A

2016-10-18

Theterm gluten intolerance may refer to three types of human disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of prolamin proteins present mostly in wheat, but also in barley, rye and oat. Gluten can be subdivided into three major groups: S-rich, S-poor and high molecular weight proteins. Prolamins within the groups possess similar structures and properties. All gluten proteins are evolutionarily connected and share the same ancestral origin. Gluten proteins are highly resistant to hydrolysis mediated by proteases of the human gastrointestinal tract. It results in emergence of pathogenic peptides, which cause CD and allergy in genetically predisposed people. There is a hierarchy of peptide toxicity and peptide recognition by T cells. Nowadays, there are several ways to detoxify gluten peptides: the most common is gluten-free diet (GFD), which has proved its effectiveness; prevention programs, enzymatic therapy, correction of gluten pathogenicity pathways and genetically modified grains with reduced immunotoxicity. A deep understanding of gluten intolerance underlying mechanisms and detailed knowledge of gluten properties may lead to the emergence of novel effective approaches for treatment of gluten-related disorders.

Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha.

PubMed

Dharmani, Poonam; Strauss, Jaclyn; Ambrose, Christian; Allen-Vercoe, Emma; Chadee, Kris

2011-07-01

The etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial species Fusobacterium nucleatum is a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only live F. nucleatum induced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasive F. nucleatum isolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal that F. nucleatum may represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities

PubMed Central

Balakireva, Anastasia V.; Zamyatnin, Andrey A.

2016-01-01

Theterm gluten intolerance may refer to three types of human disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of prolamin proteins present mostly in wheat, but also in barley, rye and oat. Gluten can be subdivided into three major groups: S-rich, S-poor and high molecular weight proteins. Prolamins within the groups possess similar structures and properties. All gluten proteins are evolutionarily connected and share the same ancestral origin. Gluten proteins are highly resistant to hydrolysis mediated by proteases of the human gastrointestinal tract. It results in emergence of pathogenic peptides, which cause CD and allergy in genetically predisposed people. There is a hierarchy of peptide toxicity and peptide recognition by T cells. Nowadays, there are several ways to detoxify gluten peptides: the most common is gluten-free diet (GFD), which has proved its effectiveness; prevention programs, enzymatic therapy, correction of gluten pathogenicity pathways and genetically modified grains with reduced immunotoxicity. A deep understanding of gluten intolerance underlying mechanisms and detailed knowledge of gluten properties may lead to the emergence of novel effective approaches for treatment of gluten-related disorders. PMID:27763541

Tracking pathogen transmission at the human-wildlife interface: banded mongoose and Escherichia coli.

PubMed

Pesapane, R; Ponder, M; Alexander, K A

2013-06-01

A primary challenge to managing emerging infectious disease is identifying pathways that allow pathogen transmission at the human-wildlife interface. Using Escherichia coli as a model organism, we evaluated fecal bacterial transmission between banded mongoose (Mungos mungo) and humans in northern Botswana. Fecal samples were collected from banded mongoose living in protected areas (n = 87, 3 troops) and surrounding villages (n = 92, 3 troops). Human fecal waste was collected from the same environment (n = 46). Isolates were evaluated for susceptibility to 10 antibiotics. Resistant E. coli isolates from mongoose were compared to human isolates using rep-PCR fingerprinting and MLST-PCR. Antimicrobial resistant isolates were identified in 57 % of the mongoose fecal samples tested (range 31-78% among troops). At least one individual mongoose fecal sample demonstrated resistance to each tested antibiotic, and multidrug resistance was highest in the protected areas (40.9%). E. coli isolated from mongoose and human sources in this study demonstrated an extremely high degree of genetic similarity on rep-PCR (AMOVA, F ST = 0.0027, p = 0.18) with a similar pattern identified on MLST-PCR. Human waste may be an important source of microbial exposure to wildlife. Evidence of high levels of antimicrobial resistance even within protected areas identifies an emerging health threat and highlights the need for improved waste management in these systems.

From deep-sea volcanoes to human pathogens: a conserved quorum-sensing signal in Epsilonproteobacteria

PubMed Central

Pérez-Rodríguez, Ileana; Bolognini, Marie; Ricci, Jessica; Bini, Elisabetta; Vetriani, Costantino

2015-01-01

Chemosynthetic Epsilonproteobacteria from deep-sea hydrothermal vents colonize substrates exposed to steep thermal and redox gradients. In many bacteria, substrate attachment, biofilm formation, expression of virulence genes and host colonization are partly controlled via a cell density-dependent mechanism involving signal molecules, known as quorum sensing. Within the Epsilonproteobacteria, quorum sensing has been investigated only in human pathogens that use the luxS/autoinducer-2 (AI-2) mechanism to control the expression of some of these functions. In this study we showed that luxS is conserved in Epsilonproteobacteria and that pathogenic and mesophilic members of this class inherited this gene from a thermophilic ancestor. Furthermore, we provide evidence that the luxS gene is expressed—and a quorum-sensing signal is produced—during growth of Sulfurovum lithotrophicum and Caminibacter mediatlanticus, two Epsilonproteobacteria from deep-sea hydrothermal vents. Finally, we detected luxS transcripts in Epsilonproteobacteria-dominated biofilm communities collected from deep-sea hydrothermal vents. Taken together, our findings indicate that the epsiloproteobacterial lineage of the LuxS enzyme originated in high-temperature geothermal environments and that, in vent Epsilonproteobacteria, luxS expression is linked to the production of AI-2 signals, which are likely produced in situ at deep-sea vents. We conclude that the luxS gene is part of the ancestral epsilonproteobacterial genome and represents an evolutionary link that connects thermophiles to human pathogens. PMID:25397946

From deep-sea volcanoes to human pathogens: a conserved quorum-sensing signal in Epsilonproteobacteria.

PubMed

Pérez-Rodríguez, Ileana; Bolognini, Marie; Ricci, Jessica; Bini, Elisabetta; Vetriani, Costantino

2015-05-01

Chemosynthetic Epsilonproteobacteria from deep-sea hydrothermal vents colonize substrates exposed to steep thermal and redox gradients. In many bacteria, substrate attachment, biofilm formation, expression of virulence genes and host colonization are partly controlled via a cell density-dependent mechanism involving signal molecules, known as quorum sensing. Within the Epsilonproteobacteria, quorum sensing has been investigated only in human pathogens that use the luxS/autoinducer-2 (AI-2) mechanism to control the expression of some of these functions. In this study we showed that luxS is conserved in Epsilonproteobacteria and that pathogenic and mesophilic members of this class inherited this gene from a thermophilic ancestor. Furthermore, we provide evidence that the luxS gene is expressed--and a quorum-sensing signal is produced--during growth of Sulfurovum lithotrophicum and Caminibacter mediatlanticus, two Epsilonproteobacteria from deep-sea hydrothermal vents. Finally, we detected luxS transcripts in Epsilonproteobacteria-dominated biofilm communities collected from deep-sea hydrothermal vents. Taken together, our findings indicate that the epsiloproteobacterial lineage of the LuxS enzyme originated in high-temperature geothermal environments and that, in vent Epsilonproteobacteria, luxS expression is linked to the production of AI-2 signals, which are likely produced in situ at deep-sea vents. We conclude that the luxS gene is part of the ancestral epsilonproteobacterial genome and represents an evolutionary link that connects thermophiles to human pathogens.

Occurrence and Persistence of Bacterial Pathogens and Indicator Organisms in Beach Sand along the California Coast

PubMed Central

Yamahara, Kevan M.; Sassoubre, Lauren M.; Goodwin, Kelly D.

2012-01-01

This report documents the presence of fecal indicators and bacterial pathogens in sand at 53 California marine beaches using both culture-dependent and -independent (PCR and quantitative PCR [QPCR]) methods. Fecal indicator bacteria were widespread in California beach sand, with Escherichia coli and enterococci detected at 68% and 94% of the beaches surveyed, respectively. Somatic coliphages and a Bacteroidales human-specific fecal marker were detected at 43% and 13% of the beaches, respectively. Dry sand samples from almost 30% of the beaches contained at least one of the following pathogens: Salmonella spp., Campylobacter spp., Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA), which were detected at 15%, 13%, 14%, and 3% of tested beaches, respectively. Fecal indicators and pathogens were poorly correlated to one another and to land cover. Sands were dry at the time of collection, and those with relatively high moisture tended to have higher concentrations or a more frequent occurrence of both indicators and pathogens. Using culture-dependent assays, fecal indicators decayed faster than pathogens in microcosm experiments using unaltered beach sand seeded with sewage and assessed by culture-dependent assays. The following order of persistence was observed (listed from most to least persistent): Campylobacter > Salmonella > somatic coliphages > enterococci > E. coli > F+ phages. In contrast, pathogens decayed faster than fecal indicators in culture-independent assays: enterococci > Bacteroidales human-specific marker > Salmonella > Campylobacter. Microcosm experiments demonstrated that both indicators and pathogens were mobilized by wetting with seawater. Decay rates measured by QPCR were lower than those measured with culture-dependent methods. Enterococcal persistence and possible growth were observed for wetted microcosms relative to unwetted controls. PMID:22247142

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

PubMed Central

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

2015-01-01

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

PB2-Q591K Mutation Determines the Pathogenicity of Avian H9N2 Influenza Viruses for Mammalian Species

PubMed Central

Wang, Congrong; Lee, Horace Hok Yeung; Yang, Zi Feng; Mok, Chris Ka Pun; Zhang, Zhi

2016-01-01

Background Influenza A subtype H9N2 is widespread and prevalent in poultry. It has repeatedly transmitted zoonotically to cause mild influenza-like illness in humans and is regarded as a potential pandemic candidate. In additon, the six internal genes of H7N9 and H10N8 viruses which caused infection in human in China as well as some of the highly pathogenic H5N1 strains are origined from H9N2. Previous studies have shown that the mammalian adaptation PB2-Q591K contributes to the pathogenicity of H5N1 and H7N9 viruses. However, the role of the PB2-Q591K mutation in H9N2 subtype is still not well understood. Methods To define and compare the individual role of PB2-Q591K substitution in the PB2 gene segment of H9N2 in relation to polymerase activity, replication competence and the pathogenicity using in vitro and in vivo models. Results The PB2-Q591K mutation in H9N2 virus enhanced the polymerase activity and virus replication in human NHBE cells when compared to the wild type strain. Mice infected with the PB2 mutant showed significant weight loss, higher virus replication and immune responses in the lungs. Conclusions Our evidences suggest that the PB2-Q591K, in addition to the -E627K mutation in H9N2 enhanced the pathogenicity in mammalian host. PMID:27684944

Integrated inference and evaluation of host–fungi interaction networks

PubMed Central

Remmele, Christian W.; Luther, Christian H.; Balkenhol, Johannes; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus T.

2015-01-01

Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host–pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse. To establish large-scale host–fungi interaction networks on a systems biology scale, we develop an extended inference approach based on protein orthology and data on gene functions. Using human and yeast intraspecies networks as template, we derive a large network of pathogen–host interactions (PHI). Rigorous filtering and refinement steps based on cellular localization and pathogenicity information of predicted interactors yield a primary scaffold of fungi–human and fungi–mouse interaction networks. Specific enrichment of known pathogenicity-relevant genes indicates the biological relevance of the predicted PHI. A detailed inspection of functionally relevant subnetworks reveals novel host–fungal interaction candidates such as the Candida virulence factor PLB1 and the anti-fungal host protein APP. Our results demonstrate the applicability of interolog-based prediction methods for host–fungi interactions and underline the importance of filtering and refinement steps to attain biologically more relevant interactions. This integrated network framework can serve as a basis for future analyses of high-throughput host–fungi transcriptome and proteome data. PMID:26300851

Structural alterations by five disease-causing mutations in the low-pH conformation of human dihydrolipoamide dehydrogenase (hLADH) analyzed by molecular dynamics - Implications in functional loss and modulation of reactive oxygen species generation by pathogenic hLADH forms.

PubMed

Ambrus, Attila; Mizsei, Reka; Adam-Vizi, Vera

2015-07-01

Human dihydrolipoamide dehydrogenase (hLADH) is a flavoenzyme component (E3) of the human alpha-ketoglutarate dehydrogenase complex (α-KGDHc) and few other dehydrogenase complexes. Pathogenic mutations of hLADH cause severe metabolic diseases (atypical forms of E3 deficiency) that often escalate to cardiological or neurological presentations and even premature death; the pathologies are generally accompanied by lactic acidosis. hLADH presents a distinct conformation under acidosis (pH 5.5-6.8) with lower physiological activity and the capacity of generating reactive oxygen species (ROS). It has been shown by our laboratory that selected pathogenic mutations, besides lowering the physiological activity of hLADH, significantly stimulate ROS generation by hLADH, especially at lower pH, which might play a role in the pathogenesis of E3-deficiency in respective cases. Previously, we generated by molecular dynamics (MD) simulation the low-pH hLADH structure and analyzed the structural changes induced in this structure by eight of the pathogenic mutations of hLADH. In the absence of high resolution mutant structures these pieces of information are crucial for the mechanistic investigation of the molecular pathogeneses of the hLADH protein. In the present work we analyzed by molecular dynamics simulation the structural changes induced in the low-pH conformation of hLADH by five pathogenic mutations of hLADH; the structures of these disease-causing mutants of hLADH have never been examined before.

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

Alternative Fecal Indicators and Their Empirical Relationships with Enteric Viruses, Salmonella enterica, and Pseudomonas aeruginosa in Surface Waters of a Tropical Urban Catchment

PubMed Central

Liang, L.; Goh, S. G.; Vergara, G. G. R. V.; Fang, H. M.; Rezaeinejad, S.; Chang, S. Y.; Bayen, S.; Lee, W. A.; Sobsey, M. D.; Rose, J. B.

2014-01-01

The suitability of traditional microbial indicators (i.e., Escherichia coli and enterococci) has been challenged due to the lack of correlation with pathogens and evidence of possible regrowth in the natural environment. In this study, the relationships between alternative microbial indicators of potential human fecal contamination (Bacteroides thetaiotaomicron, Methanobrevibacter smithii, human polyomaviruses [HPyVs], and F+ and somatic coliphages) and pathogens (Salmonella spp., Pseudomonas aeruginosa, rotavirus, astrovirus, norovirus GI, norovirus GII, and adenovirus) were compared with those of traditional microbial indicators, as well as environmental parameters (temperature, conductivity, salinity, pH, dissolved oxygen, total organic carbon, total suspended solids, turbidity, total nitrogen, and total phosphorus). Water samples were collected from surface waters of urban catchments in Singapore. Salmonella and P. aeruginosa had significant positive correlations with most of the microbial indicators, especially E. coli and enterococci. Norovirus GII showed moderately strong positive correlations with most of the microbial indicators, except for HPyVs and coliphages. In general, high geometric means and significant correlations between human-specific markers and pathogens suggest the possibility of sewage contamination in some areas. The simultaneous detection of human-specific markers (i.e., B. thetaiotaomicron, M. smithii, and HPyVs) with E. coli and enterococcus supports the likelihood of recent fecal contamination, since the human-specific markers are unable to regrow in natural surface waters. Multiple-linear-regression results further confirm that the inclusion of M. smithii and HPyVs, together with traditional indicators, would better predict the occurrence of pathogens. Further study is needed to determine the applicability of such models to different geographical locations and environmental conditions. PMID:25416765

Alternative fecal indicators and their empirical relationships with enteric viruses, Salmonella enterica, and Pseudomonas aeruginosa in surface waters of a tropical urban catchment.

PubMed

Liang, L; Goh, S G; Vergara, G G R V; Fang, H M; Rezaeinejad, S; Chang, S Y; Bayen, S; Lee, W A; Sobsey, M D; Rose, J B; Gin, K Y H

2015-02-01

The suitability of traditional microbial indicators (i.e., Escherichia coli and enterococci) has been challenged due to the lack of correlation with pathogens and evidence of possible regrowth in the natural environment. In this study, the relationships between alternative microbial indicators of potential human fecal contamination (Bacteroides thetaiotaomicron, Methanobrevibacter smithii, human polyomaviruses [HPyVs], and F+ and somatic coliphages) and pathogens (Salmonella spp., Pseudomonas aeruginosa, rotavirus, astrovirus, norovirus GI, norovirus GII, and adenovirus) were compared with those of traditional microbial indicators, as well as environmental parameters (temperature, conductivity, salinity, pH, dissolved oxygen, total organic carbon, total suspended solids, turbidity, total nitrogen, and total phosphorus). Water samples were collected from surface waters of urban catchments in Singapore. Salmonella and P. aeruginosa had significant positive correlations with most of the microbial indicators, especially E. coli and enterococci. Norovirus GII showed moderately strong positive correlations with most of the microbial indicators, except for HPyVs and coliphages. In general, high geometric means and significant correlations between human-specific markers and pathogens suggest the possibility of sewage contamination in some areas. The simultaneous detection of human-specific markers (i.e., B. thetaiotaomicron, M. smithii, and HPyVs) with E. coli and enterococcus supports the likelihood of recent fecal contamination, since the human-specific markers are unable to regrow in natural surface waters. Multiple-linear-regression results further confirm that the inclusion of M. smithii and HPyVs, together with traditional indicators, would better predict the occurrence of pathogens. Further study is needed to determine the applicability of such models to different geographical locations and environmental conditions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures

PubMed Central

Fernandes, Maria Cecilia; Dillon, Laura A. L.; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M.

2016-01-01

ABSTRACT Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. PMID:27165796

Copper-catalyzed azide-alkyne cycloaddition (click chemistry)-based Detection of Global Pathogen-host AMPylation on Self-assembled Human Protein Microarrays*

PubMed Central

Yu, Xiaobo; Woolery, Andrew R.; Luong, Phi; Hao, Yi Heng; Grammel, Markus; Westcott, Nathan; Park, Jin; Wang, Jie; Bian, Xiaofang; Demirkan, Gokhan; Hang, Howard C.; Orth, Kim; LaBaer, Joshua

2014-01-01

AMPylation (adenylylation) is a recently discovered mechanism employed by infectious bacteria to regulate host cell signaling. However, despite significant effort, only a few host targets have been identified, limiting our understanding of how these pathogens exploit this mechanism to control host cells. Accordingly, we developed a novel nonradioactive AMPylation screening platform using high-density cell-free protein microarrays displaying human proteins produced by human translational machinery. We screened 10,000 unique human proteins with Vibrio parahaemolyticus VopS and Histophilus somni IbpAFic2, and identified many new AMPylation substrates. Two of these, Rac2, and Rac3, were confirmed in vivo as bona fide substrates during infection with Vibrio parahaemolyticus. We also mapped the site of AMPylation of a non-GTPase substrate, LyGDI, to threonine 51, in a region regulated by Src kinase, and demonstrated that AMPylation prevented its phosphorylation by Src. Our results greatly expanded the repertoire of potential host substrates for bacterial AMPylators, determined their recognition motif, and revealed the first pathogen-host interaction AMPylation network. This approach can be extended to identify novel substrates of AMPylators with different domains or in different species and readily adapted for other post-translational modifications. PMID:25073739

Developing a Salivary Antibody Multiplex Immunoassay to ...

EPA Pesticide Factsheets

The etiology and impacts of human exposure to environmental pathogens are of major concern worldwide and, thus, the ability to assess exposure and infections using cost effective, high-throughput approaches would be indispensable. The principal objective of this work is to develop an immunoassay capable of measuring the presence of antibodies in human saliva to multiple pathogens simultaneously. Saliva is particularly attractive in this application because it is noninvasive, cheaper and easier to collect than serum. Antigens from environmental pathogens were coupled to carboxylated microspheres (beads) and used to measure antibodies in very small volumes of human saliva samples using the Luminex xMAP solution-phase assay. Beads were coupled to antigens from Campylobacter jejuni, Helicobacter pylori, Toxoplasma gondii, noroviruses (G I.1 and G II.4) and hepatitis A virus. To ensure that the antigens were sufficiently coupled to the beads, coupling was confirmed using species-specific, animal-derived primary detection antibodies, followed by incubation with biotinylated anti-species secondary detection antibodies and streptavidin-R-phycoerythrin reporter (SAPE). As a control to measure non-specific binding, one bead set was treated identically to the others except it was not coupled to any antigen. The antigen coupled and control beads were then incubated with prospectively-collected human saliva samples, analyzed on a Luminex 100 platform, and the presence

Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei.

PubMed

Abdelbaqi, Suha; Deslouches, Berthony; Steckbeck, Jonathan; Montelaro, Ronald; Reed, Douglas S

2016-02-01

Broad-spectrum antimicrobials are needed to effectively treat patients infected in the event of a pandemic or intentional release of a pathogen prior to confirmation of the pathogen's identity. Engineered cationic antimicrobial peptides (eCAPs) display activity against a number of bacterial pathogens including multi-drug-resistant strains. Two lead eCAPs, WLBU2 and WR12, were compared with human cathelicidin (LL-37) against three highly pathogenic bacteria: Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. Both WLBU2 and WR12 demonstrated bactericidal activity greater than that of LL-37, particularly against F. tularensis and Y. pestis. Only WLBU2 had bactericidal activity against B. pseudomallei. WLBU2, WR12 and LL-37 were all able to inhibit the growth of the three bacteria in vitro. Because these bacteria can be facultative intracellular pathogens, preferentially infecting macrophages and dendritic cells, we evaluated the activity of WLBU2 against F. tularensis in an ex vivo infection model with J774 cells, a mouse macrophage cell line. In that model WLBU2 was able to achieve greater than 50% killing of F. tularensis at a concentration of 12.5 μM. These data show the therapeutic potential of eCAPs, particularly WLBU2, as a broad-spectrum antimicrobial for treating highly pathogenic bacterial infections.

The Z Proteins of Pathogenic but Not Nonpathogenic Arenaviruses Inhibit RIG-i-Like Receptor-Dependent Interferon Production

PubMed Central

Xing, Junji; Ly, Hinh

2014-01-01

ABSTRACT Arenavirus pathogens cause a wide spectrum of diseases in humans ranging from central nervous system disease to lethal hemorrhagic fevers with few treatment options. The reason why some arenaviruses can cause severe human diseases while others cannot is unknown. We find that the Z proteins of all known pathogenic arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Lassa, Junin, Machupo, Sabia, Guanarito, Chapare, Dandenong, and Lujo viruses, can inhibit retinoic acid-inducible gene 1 (RIG-i) and Melanoma Differentiation-Associated protein 5 (MDA5), in sharp contrast to those of 14 other nonpathogenic arenaviruses. Inhibition of the RIG-i-like receptors (RLRs) by pathogenic Z proteins is mediated by the protein-protein interactions of Z and RLRs, which lead to the disruption of the interactions between RLRs and mitochondrial antiviral signaling (MAVS). The Z-RLR interactive interfaces are located within the N-terminal domain (NTD) of the Z protein and the N-terminal CARD domains of RLRs. Swapping of the LCMV Z NTD into the nonpathogenic Pichinde virus (PICV) genome does not affect virus growth in Vero cells but significantly inhibits the type I interferon (IFN) responses and increases viral replication in human primary macrophages. In summary, our results show for the first time an innate immune-system-suppressive mechanism shared by the diverse pathogenic arenaviruses and thus shed important light on the pathogenic mechanism of human arenavirus pathogens. IMPORTANCE We show that all known human-pathogenic arenaviruses share an innate immune suppression mechanism that is based on viral Z protein-mediated RLR inhibition. Our report offers important insights into the potential mechanism of arenavirus pathogenesis, provides a convenient way to evaluate the pathogenic potential of known and/or emerging arenaviruses, and reveals a novel target for the development of broad-spectrum therapies to treat this group of diverse pathogens. More broadly, our report provides a better understanding of the mechanisms of viral immune suppression and host-pathogen interactions. PMID:25552708

Human Health Risk Implications of Multiple Sources of Faecal Indicator Bacteria in a Recreational Waterbody

EPA Science Inventory

We evaluate the influence of multiple sources of faecal indicator bacteria in recreational water bodies on potential human health risk by considering waters impacted by human and animal sources, human and non-pathogenic sources, and animal and non-pathogenic sources. We illustrat...

High Frequency and Diversity of Antimicrobial Activities Produced by Nasal Staphylococcus Strains against Bacterial Competitors

PubMed Central

Janek, Daniela; Zipperer, Alexander; Kulik, Andreas; Krismer, Bernhard; Peschel, Andreas

2016-01-01

The human nasal microbiota is highly variable and dynamic often enclosing major pathogens such as Staphylococcus aureus. The potential roles of bacteriocins or other mechanisms allowing certain bacterial clones to prevail in this nutrient-poor habitat have hardly been studied. Of 89 nasal Staphylococcus isolates, unexpectedly, the vast majority (84%) was found to produce antimicrobial substances in particular under habitat-specific stress conditions, such as iron limitation or exposure to hydrogen peroxide. Activity spectra were generally narrow but highly variable with activities against certain nasal members of the Actinobacteria, Proteobacteria, Firmicutes, or several groups of bacteria. Staphylococcus species and many other Firmicutes were insusceptible to most of the compounds. A representative bacteriocin was identified as a nukacin-related peptide whose inactivation reduced the capacity of the producer Staphylococcus epidermidis IVK45 to limit growth of other nasal bacteria. Of note, the bacteriocin genes were found on mobile genetic elements exhibiting signs of extensive horizontal gene transfer and rearrangements. Thus, continuously evolving bacteriocins appear to govern bacterial competition in the human nose and specific bacteriocins may become important agents for eradication of notorious opportunistic pathogens from human microbiota. PMID:27490492

Transcriptome analysis of Cronobacter sakazakii ATCC BAA-894 after interaction with human intestinal epithelial cell line HCT-8.

PubMed

Jing, Chun-e; Du, Xin-jun; Li, Ping; Wang, Shuo

2016-01-01

Cronobacter spp. are opportunistic pathogens that are responsible for infections including severe meningitis, septicemia, and necrotizing enterocolitis in neonates and infants. To date, questions still remain regarding the mechanisms of pathogenicity and virulence determinants for each bacterial strain. In this study, we established an in vitro model for Cronobacter sakazakii ATCC BAA-894 infection of HCT-8 human colorectal epithelial cells. The transcriptome profile of C. sakazakii ATCC BAA-894 after interaction with HCT-8 cells was determined using high-throughput whole-transcriptome sequencing (RNA sequencing (RNA-seq)). Gene expression profiles indicated that 139 genes were upregulated and 72 genes were downregulated in the adherent C. sakazakii ATCC BAA-894 strain on HCT-8 cells compared to the cultured bacteria in the cell-free medium. Expressions of some flagella genes and virulence factors involved in adherence were upregulated. High osmolarity and osmotic stress-associated genes were highly upregulated, as well as genes responsible for the synthesis of lipopolysaccharides and outer membrane proteins, iron acquisition systems, and glycerol and glycerophospholipid metabolism. In sum, our study provides further insight into the mechanisms underlying C. sakazakii pathogenesis in the human gastrointestinal tract.

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

PubMed Central

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

2011-01-01

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

Dynamics of fecal indicator bacteria, bacterial pathogen genes, and organic wastewater contaminants in the Little Calumet River: Portage Burns Waterway, Indiana

USGS Publications Warehouse

Haack, Sheridan K.; Duris, Joseph W.

2013-01-01

Little information exists on the co-occurrence of fecal indicator bacteria (FIB), bacterial pathogens, and organic wastewater-associated chemicals (OWCs) within Great Lakes tributaries. Fifteen watershed sites and one beach site adjacent to the Little Calumet River–Portage Burns Waterway (LCRPBW) on Lake Michigan were tested on four dates for pH, dissolved oxygen, specific conductance, chloride, color, ammonia- and nitrate-nitrogen, soluble phosphorus, sulfate, turbidity, and atrazine; for concentrations of FIB; and for genes indicating the presence of human-pathogenic enterococci (ENT) and of Shiga-toxin producing Escherichia coli (EC) from various animal sources. Nineteen samples were also tested for 60 OWCs. Half of the watershed samples met EC recreational water quality standards; none met ENT standards. Human-wastewater-associated OWC detections were correlated with human-influence indicators such as population/km2, chloride concentrations, and the presence of WWTP effluents, but EC and ENT concentrations were not. Bacterial pathogen genes indicated rural human and several potential animal sources. OWCs of human or ecosystem health concern (musk fragrances AHTN and HHCB, alkylphenols, carbamazepine) and 3 bacterial pathogen genes were detected at the mouth of the LCRPBW, but no such OWCs and only 1 pathogen gene were detected at the beach. The LCRPBW has significant potential to deliver FIB, potential bacterial pathogens, and OWCs of human or ecosystem health concern to the nearshore of Lake Michigan, under conditions enhancing nearshore transport of the river plume. Nearshore mixing of lake and river water, and the lack of relationship between OWCs and FIB or pathogen genes, pose numerous challenges for watershed and nearshore assessment and remediation.

Discovery and Testing of Ricin Therapeutics

DTIC Science & Technology

2012-06-01

variants lung disease ER degradation Fabri disease α -D-galactosidase neurological disease ER degradation Oculocutaneous albinism tyrosinase...against other pathogens and human diseases . 15. SUBJECT TERMS Ricin toxin, dislocation, small weight compounds, chemical inhibitors, high-content screen...the U.S. Departments of Health and Human Services (HHS) and Centers for Disease Control and Prevention (CDC). The toxin’s ability to kill cells and

Tackling the growing threat of dengue: Phyllanthus niruri-mediated synthesis of silver nanoparticles and their mosquitocidal properties against the dengue vector Aedes aegypti (Diptera: Culicidae)

USDA-ARS?s Scientific Manuscript database

Mosquitoes transmit pathogens that cause millions of human deaths each year. Dengue virus is transmitted to humans in tropical and subtropical areas by Aedes aegypti (Diptera: Culicidae). The use of synthetic insecticides to control this mosquito is accompanied by high operational costs and adverse...

Experimental Infection of Rattus norvegicus by the Group II Intermediate Pathogen, Leptospira licerasiae.

PubMed

Fernandez, Carla; Lubar, Aristea A; Vinetz, Joseph M; Matthias, Michael A

2018-06-25

Leptospira licerasiae serovar Varillal, a group II intermediate pathogen species/serovar discovered in the Peruvian Amazon city of Iquitos, is commonly recognized in this region by sera from humans (at least 40% seroprevalence) without a known clinical history of leptospirosis. This high frequency of human seroreactivity remains unexplained. To test the hypothesis that the oral route of infection might explain the high rate of human seroreactivity against L. licerasiae , an experimental infection model using Rattus norvegicus was developed, given that rats were one of the original reservoir hosts identified as being colonized by this leptospire. Sprague-Dawley rats were experimentally exposed via mucosa, direct gastric gavage, or parenteral inoculation with nine different isolates of L. licerasiae originally isolated from Peruvian humans, peridomiciliary rodents, and wildlife. As shown by quantitative polymerase chain reaction of kidney tissue, Leptospira infection via these routes of infection was equally successful. Importantly, the data show that L. licerasiae infects R. norvegicus via the oral route demonstration, leading to renal colonization. Not only do these findings confirm the infectiousness of group II Leptospira , but also they underscore the potential importance of oral as well as mucosal and transcutaneous routes of Leptospira infection.

Inorganic nanoparticles for transfection of mammalian cells and removal of viruses from aqueous solutions.

PubMed

Link, Nils; Brunner, Tobias J; Dreesen, Imke A J; Stark, Wendelin J; Fussenegger, Martin

2007-12-01

Owing to their small size, synthetic nanoparticles show unprecedented biophysical and biochemical properties which may foster novel advances in life-science research. Using flame-spray synthesis technology we have produced non-coated aluminum-, calcium-, cerium-, and zirconium-derived inorganic metal oxide nanoparticles which not only exhibit high affinity for nucleic acids, but can sequester such compounds from aqueous solution. This non-covalent DNA-binding capacity was successfully used to transiently transfect a variety of mammalian cells including human, reaching transfection efficiencies which compared favorably with classic calcium phosphate precipitation (CaP) procedures and lipofection. In this straightforward protocol, transfection was enabled by simply mixing nanoparticles with DNA in solution prior to addition to the target cell population. Transiently transfected cells showed higher production levels of the human secreted glycoprotein SEAP compared to isogenic populations transfected with established technologies. Inorganic metal oxide nanoparticles also showed a high binding capacity to human-pathogenic viruses including adenovirus, adeno-associated virus and human immunodeficiency virus type 1 and were able to clear these pathogens from aqueous solutions. The DNA transfection and viral clearance capacities of inorganic metal oxide nanoparticles may provide cost-effective biopharmaceutical manufacturing and water treatment in developing countries.

Relationship of periodontal clinical parameters with bacterial composition in human dental plaque.

PubMed

Fujinaka, Hidetake; Takeshita, Toru; Sato, Hirayuki; Yamamoto, Tetsuji; Nakamura, Junji; Hase, Tadashi; Yamashita, Yoshihisa

2013-06-01

More than 600 bacterial species have been identified in the oral cavity, but only a limited number of species show a strong association with periodontitis. The purpose of the present study was to provide a comprehensive outline of the microbiota in dental plaque related to periodontal status. Dental plaque from 90 subjects was sampled, and the subjects were clustered based on bacterial composition using the terminal restriction fragment length polymorphism of 16S rRNA genes. Here, we evaluated (1) periodontal clinical parameters between clusters; (2) the correlation of subgingival bacterial composition with supragingival bacterial composition; and (3) the association between bacterial interspecies in dental plaque using a graphical Gaussian model. Cluster 1 (C1) having high prevalence of pathogenic bacteria in subgingival plaque showed increasing values of the parameters. The values of the parameters in Cluster 2a (C2a) having high prevalence of non-pathogenic bacteria were markedly lower than those in C1. A cluster having low prevalence of non-pathogenic bacteria in supragingival plaque showed increasing values of the parameters. The bacterial patterns between subgingival plaque and supragingival plaque were significantly correlated. Chief pathogens, such as Porphyromonas gingivalis, formed a network with other pathogenic species in C1, whereas a network of non-pathogenic species, such as Rothia sp. and Lautropia sp., tended to compete with a network of pathogenic species in C2a. Periodontal status relates to non-pathogenic species as well as to pathogenic species, suggesting that the bacterial interspecies connection affects dental plaque virulence.

Enterobacteria associated with houseflies (Musca domestica) as an infection risk indicator in swine production farms.

PubMed

Cervelin, V; Fongaro, G; Pastore, J B; Engel, F; Reimers, M A; Viancelli, A

2018-04-23

Houseflies (Musca domestica) spend part of their life development on animal or human manure. Manure is high in pathogenic microbes; thus, houseflies have been known as a mechanical vector for various important zoonotic diseases. Therefore, the present study showcases captured houseflies from intensive swine production regions (which are areas of high manure concentration) in Southern Brazil, and analyses their bodies' to the presence of Escherichia coli and Salmonella sp. and the sensitivity of these bacteria to various antibiotics. Additionally, Quantitative Microbiology Risk Assessment was performed simulating the contamination of lettuce by flies' bacteria and subsequent lettuce consumption by an adult human being. Houseflies were captured in swine buildings and farm houses from five farms. E. coli quantification values ranged from 10 4 to 10 6 CFU/20 flies, and all sampling sites had positive results from bacteria presence in the collected houseflies. On the other hand, Salmonella sp. presence was observed in only three farms, where the quantification ranged from 10 2 to 10 5 CFU/20 flies. The bacteria showed to be resistant to at least two from the four tested antibiotics (ampicillin, Cefalotin, Ciprofloxacin and Norfloxacin) antibiotics used in human or veterinary medicine. Infection probability analyses showed risk of human infection by E.coli, indicating possible transmission of zoonotic pathogens through flies. In this context, it was possible to conclude that there is a need for flies control, especially in swine farms where zoonotic pathogens can be abundant, to minimize the health impact of the vectorization of enteric bacteria. Copyright © 2018 Elsevier B.V. All rights reserved.

Microbial pollution in wildlife: Linking agricultural manuring and bacterial antibiotic resistance in red-billed choughs.

PubMed

Blanco, Guillermo; Lemus, Jesús A; Grande, Javier

2009-05-01

The spread of pathogens in the environment due to human activities (pathogen pollution) may be involved in the emergence of many diseases in humans, livestock and wildlife. When manure from medicated livestock and urban effluents is spread onto agricultural land, both residues of antibiotics and bacteria carrying antibiotic resistance may be introduced into the environment. The transmission of bacterial resistance from livestock and humans to wildlife remains poorly understood even while wild animals may act as reservoirs of resistance that may be amplified and spread in the environment. We determined bacterial resistance to antibiotics in wildlife using the red-billed chough Pyrrhocorax pyrrhocorax as a potential bioindicator of soil health, and evaluated the role of agricultural manuring with waste of different origins in the acquisition and characteristics of such resistance. Agricultural manure was found to harbor high levels of bacterial resistance to multiple antibiotics. Choughs from areas where manure landspreading is a common agricultural practice harbor a high bacterial resistance to multiple antibiotics, resembling the resistance profile found in the waste (pig slurry and sewage sludge) used in each area. The transfer of bacterial resistance to wildlife should be considered as an important risk for environmental health when agricultural manuring involves fecal material containing multiresistant enteric bacteria including pathogens from livestock operations and urban areas. The assessment of bacterial resistance in wild animals may be valuable for the monitoring of environmental health and for the management of emergent infectious diseases influenced by the impact of different human activities in the environment.

Control of highly pathogenic avian influenza in Quang Tri province, Vietnam: voices from the human-animal interface.

PubMed

Farrell, Penny C; Hunter, Cynthia; Truong, Bui; Bunning, Michel

2015-01-01

Highly pathogenic avian influenza (HPAI) is caused by the haemagglutinin 5, neuraminidase 1 (H5N1) influenza A virus. Around 80% of households in rural Vietnam raise poultry, which provides food security and nutrition to their households and beyond. Of these, around 15-20% are semi-commercial producers, producing at least 28% of the country's chicken. Through learning the experiences of these semi-commercial farmers, this study aimed to explore the local understandings and sociocultural aspects of HPAI's impact, particularly the aetiology, diagnosis, and the prevention and control methods in one Vietnamese rural province. This study was conducted in Quang Tri province, Vietnam. Quang Tri province has eight districts. Five of these districts were at high risk of HPAI during the study period, of which three were selected for the present study. Within these three districts, six communes were randomly selected for the study from the list of intervention communes in Quang Tri province. Six out of the 26 intervention communes in Quang Tri were therefore selected. Participants were randomly selected and recruited from lists of semi-commercial farmers, village animal health workers, village human health workers and local authorities so that the study population (representative population) included an amount of variability similar to that of the wider population. A key benefit of this village-level control program was the residential proximity of animal and human health professionals. Participants were well aware of the typical clinical signs for avian influenza and of the reporting process for suspect cases. However there was extensive room for improvement in Quang Tri province regarding access to the HPAI vaccine, essential medical equipment for animal use, and available financial support. This qualitative research study provided an important insight for in-country policy makers and international stakeholders. It is vital that there are continued efforts to prevent and control highly pathogenic avian influenza through support programs that provide locally appropriate information and resources to those at the human-animal interface.

An Integrated Lab-on-Chip for Rapid Identification and Simultaneous Differentiation of Tropical Pathogens

PubMed Central

Sato, Mitsuharu; Watthanaworawit, Wanitda; Ling, Clare L.; Mauduit, Marjorie; Malleret, Benoît; Grüner, Anne-Charlotte; Tan, Rosemary; Nosten, François H.; Snounou, Georges; Rénia, Laurent; Ng, Lisa F. P.

2014-01-01

Tropical pathogens often cause febrile illnesses in humans and are responsible for considerable morbidity and mortality. The similarities in clinical symptoms provoked by these pathogens make diagnosis difficult. Thus, early, rapid and accurate diagnosis will be crucial in patient management and in the control of these diseases. In this study, a microfluidic lab-on-chip integrating multiplex molecular amplification and DNA microarray hybridization was developed for simultaneous detection and species differentiation of 26 globally important tropical pathogens. The analytical performance of the lab-on-chip for each pathogen ranged from 102 to 103 DNA or RNA copies. Assay performance was further verified with human whole blood spiked with Plasmodium falciparum and Chikungunya virus that yielded a range of detection from 200 to 4×105 parasites, and from 250 to 4×107 PFU respectively. This lab-on-chip was subsequently assessed and evaluated using 170 retrospective patient specimens in Singapore and Thailand. The lab-on-chip had a detection sensitivity of 83.1% and a specificity of 100% for P. falciparum; a sensitivity of 91.3% and a specificity of 99.3% for P. vivax; a positive 90.0% agreement and a specificity of 100% for Chikungunya virus; and a positive 85.0% agreement and a specificity of 100% for Dengue virus serotype 3 with reference methods conducted on the samples. Results suggested the practicality of an amplification microarray-based approach in a field setting for high-throughput detection and identification of tropical pathogens. PMID:25078474

Pathogenic diversity amongst serotype C VGIII and VGIV Cryptococcus gattii isolates

PubMed Central

Rodrigues, Jéssica; Fonseca, Fernanda L.; Schneider, Rafael O.; Godinho, Rodrigo M. da C.; Firacative, Carolina; Maszewska, Krystyna; Meyer, Wieland; Schrank, Augusto; Staats, Charley; Kmetzsch, Livia; Vainstein, Marilene H.; Rodrigues, Marcio L.

2015-01-01

Cryptococcus gattii is one of the causative agents of human cryptococcosis. Highly virulent strains of serotype B C. gattii have been studied in detail, but little information is available on the pathogenic properties of serotype C isolates. In this study, we analyzed pathogenic determinants in three serotype C C. gattii isolates (106.97, ATCC 24066 and WM 779). Isolate ATCC 24066 (molecular type VGIII) differed from isolates WM 779 and 106.97 (both VGIV) in capsule dimensions, expression of CAP genes, chitooligomer distribution, and induction of host chitinase activity. Isolate WM 779 was more efficient than the others in producing pigments and all three isolates had distinct patterns of reactivity with antibodies to glucuronoxylomannan. This great phenotypic diversity reflected in differential pathogenicity. VGIV isolates WM 779 and 106.97 were similar in their ability to cause lethality and produced higher pulmonary fungal burden in a murine model of cryptococcosis, while isolate ATCC 24066 (VGIII) was unable to reach the brain and caused reduced lethality in intranasally infected mice. These results demonstrate a high diversity in the pathogenic potential of isolates of C. gattii belonging to the molecular types VGIII and VGIV. PMID:26153364

Circulation of Alphacoronavirus, Betacoronavirus and Paramyxovirus in Hipposideros bat species in Zimbabwe.

PubMed

Bourgarel, Mathieu; Pfukenyi, Davies M; Boué, Vanina; Talignani, Loïc; Chiweshe, Ngoni; Diop, Fodé; Caron, Alexandre; Matope, Gift; Missé, Dorothée; Liégeois, Florian

2018-03-01

Bats carry a great diversity of zoonotic viruses with a high-impact on human health and livestock. Since the emergence of new coronaviruses and paramyxoviruses in humans (e.g. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Nipah virus), numerous studies clearly established that bats can maintain some of these viruses. Improving our understanding on the role of bats in the epidemiology of the pathogens they harbour is necessary to prevent cross-species spill over along the wild/domestic/human gradient. In this study, we screened bat faecal samples for the presence of Coronavirus and Paramyxovirus in two caves frequently visited by local people to collect manure and/or to hunt bats in Zimbabwe. We amplified partial RNA-dependent RNA polymerase genes of Alpha and Betacoronavirus together with the partial polymerase gene of Paramyxovirus. Identified coronaviruses were related to pathogenic human strains and the paramyxovirus belonged to the recently described Jeilongvirus genus. Our results highlighted the importance of monitoring virus circulation in wildlife, especially bats, in the context of intense human-wildlife interfaces in order to strengthen prevention measures among local populations and to implement sentinel surveillance in sites with high zoonotic diseases transmission potential. Copyright © 2018 Elsevier B.V. All rights reserved.

Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis

PubMed Central

Nakatsuji, Teruaki; Chen, Tiffany H.; Narala, Saisindhu; Chun, Kimberly A.; Two, Aimee M.; Yun, Tong; Shafiq, Faiza; Kotol, Paul F.; Bouslimani, Amina; Melnik, Alexey V.; Latif, Haythem; Kim, Ji-Nu; Lockhart, Alexandre; Artis, Keli; David, Gloria; Taylor, Patricia; Streib, Joanne; Dorrestein, Pieter C.; Grier, Alex; Gill, Steven R.; Zengler, Karsten; Hata, Tissa R.; Leung, Donald Y. M.; Gallo, Richard L.

2017-01-01

The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S.aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S.aureus. The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis. These AMPs were strain-specific, highly potent, selectively killed S.aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S.aureus. These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease. PMID:28228596

Evaluating the importance of faecal sources in human-impacted waters.

PubMed

Schoen, Mary E; Soller, Jeffrey A; Ashbolt, Nicholas J

2011-04-01

Quantitative microbial risk assessment (QMRA) was used to evaluate the relative contribution of faecal indicators and pathogens when a mixture of human sources impacts a recreational waterbody. The waterbody was assumed to be impacted with a mixture of secondary-treated disinfected municipal wastewater and untreated (or poorly treated) sewage, using Norovirus as the reference pathogen and enterococci as the reference faecal indicator. The contribution made by each source to the total waterbody volume, indicator density, pathogen density, and illness risk was estimated for a number of scenarios that accounted for pathogen and indicator inactivation based on the age of the effluent (source-to-receptor), possible sedimentation of microorganisms, and the addition of a non-pathogenic source of faecal indicators (such as old sediments or an animal population with low occurrence of human-infectious pathogens). The waterbody indicator density was held constant at 35 CFU 100 mL(-1) enterococci to compare results across scenarios. For the combinations evaluated, either the untreated sewage or the non-pathogenic source of faecal indicators dominated the recreational waterbody enterococci density assuming a culture method. In contrast, indicator density assayed by qPCR, pathogen density, and bather gastrointestinal illness risks were largely dominated by secondary disinfected municipal wastewater, with untreated sewage being increasingly less important as the faecal indicator load increased from a non-pathogenic source. The results support the use of a calibrated qPCR total enterococci indicator, compared to a culture-based assay, to index infectious human enteric viruses released in treated human wastewater, and illustrate that the source contributing the majority of risk in a mixture may be overlooked when only assessing faecal indicators by a culture-based method. Published by Elsevier Ltd.

A treatment plant receiving waste water from multiple bulk drug manufacturers is a reservoir for highly multi-drug resistant integron-bearing bacteria.

PubMed

Marathe, Nachiket P; Regina, Viduthalai R; Walujkar, Sandeep A; Charan, Shakti Singh; Moore, Edward R B; Larsson, D G Joakim; Shouche, Yogesh S

2013-01-01

The arenas and detailed mechanisms for transfer of antibiotic resistance genes between environmental bacteria and pathogens are largely unclear. Selection pressures from antibiotics in situations where environmental bacteria and human pathogens meet are expected to increase the risks for such gene transfer events. We hypothesize that waste-water treatment plants (WWTPs) serving antibiotic manufacturing industries may provide such spawning grounds, given the high bacterial densities present there together with exceptionally strong and persistent selection pressures from the antibiotic-contaminated waste. Previous analyses of effluent from an Indian industrial WWTP that processes waste from bulk drug production revealed the presence of a range of drugs, including broad spectrum antibiotics at extremely high concentrations (mg/L range). In this study, we have characterized the antibiotic resistance profiles of 93 bacterial strains sampled at different stages of the treatment process from the WWTP against 39 antibiotics belonging to 12 different classes. A large majority (86%) of the strains were resistant to 20 or more antibiotics. Although there were no classically-recognized human pathogens among the 93 isolated strains, opportunistic pathogens such as Ochrobactrum intermedium, Providencia rettgeri, vancomycin resistant Enterococci (VRE), Aerococcus sp. and Citrobacter freundii were found to be highly resistant. One of the O. intermedium strains (ER1) was resistant to 36 antibiotics, while P. rettgeri (OSR3) was resistant to 35 antibiotics. Class 1 and 2 integrons were detected in 74/93 (80%) strains each, and 88/93 (95%) strains harbored at least one type of integron. The qPCR analysis of community DNA also showed an unprecedented high prevalence of integrons, suggesting that the bacteria living under such high selective pressure have an appreciable potential for genetic exchange of resistance genes via mobile gene cassettes. The present study provides insight into the mechanisms behind and the extent of multi-drug resistance among bacteria living under an extreme antibiotic selection pressure.

A Treatment Plant Receiving Waste Water from Multiple Bulk Drug Manufacturers Is a Reservoir for Highly Multi-Drug Resistant Integron-Bearing Bacteria

PubMed Central

Walujkar, Sandeep A.; Charan, Shakti Singh; Moore, Edward R. B.; Larsson, D. G. Joakim; Shouche, Yogesh S.

2013-01-01

The arenas and detailed mechanisms for transfer of antibiotic resistance genes between environmental bacteria and pathogens are largely unclear. Selection pressures from antibiotics in situations where environmental bacteria and human pathogens meet are expected to increase the risks for such gene transfer events. We hypothesize that waste-water treatment plants (WWTPs) serving antibiotic manufacturing industries may provide such spawning grounds, given the high bacterial densities present there together with exceptionally strong and persistent selection pressures from the antibiotic-contaminated waste. Previous analyses of effluent from an Indian industrial WWTP that processes waste from bulk drug production revealed the presence of a range of drugs, including broad spectrum antibiotics at extremely high concentrations (mg/L range). In this study, we have characterized the antibiotic resistance profiles of 93 bacterial strains sampled at different stages of the treatment process from the WWTP against 39 antibiotics belonging to 12 different classes. A large majority (86%) of the strains were resistant to 20 or more antibiotics. Although there were no classically-recognized human pathogens among the 93 isolated strains, opportunistic pathogens such as Ochrobactrum intermedium, Providencia rettgeri, vancomycin resistant Enterococci (VRE), Aerococcus sp. and Citrobacter freundii were found to be highly resistant. One of the O. intermedium strains (ER1) was resistant to 36 antibiotics, while P. rettgeri (OSR3) was resistant to 35 antibiotics. Class 1 and 2 integrons were detected in 74/93 (80%) strains each, and 88/93 (95%) strains harbored at least one type of integron. The qPCR analysis of community DNA also showed an unprecedented high prevalence of integrons, suggesting that the bacteria living under such high selective pressure have an appreciable potential for genetic exchange of resistance genes via mobile gene cassettes. The present study provides insight into the mechanisms behind and the extent of multi-drug resistance among bacteria living under an extreme antibiotic selection pressure. PMID:24204801

Disease Risk in a Dynamic Environment: The Spread of Tick-Borne Pathogens in Minnesota, USA

PubMed Central

Robinson, Stacie J.; Neitzel, David F.; Moen, Ronald A.; Craft, Meggan E.; Hamilton, Karin E.; Johnson, Lucinda B.; Mulla, David J.; Munderloh, Ulrike G.; Redig, Patrick T.; Smith, Kirk E.; Turner, Clarence L.; Umber, Jamie K.; Pelican, Katharine M.

2015-01-01

As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease. PMID:25281302

[Important vector-borne infectious diseases among humans in Germany. Epidemiological aspects].

PubMed

Frank, C; Faber, M; Hellenbrand, W; Wilking, H; Stark, K

2014-05-01

Vector-borne infections pathogenic to humans play an important role in Germany. The relevant zoonotic pathogens are either endemic throughout Germany (e.g. Borrelia burgdorferi sensu latu) or only in specific regions, e.g. tick-borne encephalitis (TBE) virus and hantavirus. They cause a substantial burden of disease. Prevention and control largely rely on public advice and the application of personal protective measures (e.g. TBE virus vaccination and protection against vectors). High quality surveillance and targeted epidemiological studies are fundamental for the evaluation of temporal and spatial risks of infection and the effectiveness of preventive measures. Aside from endemic pathogens, vector-borne infections acquired abroad, mostly transmitted by mosquitoes, have to be systematically and intensively monitored as well, to assess the risk of infection for German residents traveling abroad and to adequately evaluate the risk of autochthonous transmission. Related issues, such as invasive species of mosquitoes in Germany and climate change, have to be taken into consideration. Such pathogens include West Nile, dengue and chikungunya viruses, as well as malaria parasites (Plasmodium species). The article presents an overview of the epidemiological situation of selected relevant vector-borne infections in Germany.

Opportunistic pathogens and faecal indicators in drinking water associated biofilms in Cluj, Romania.

PubMed

Farkas, A; Drăgan-Bularda, M; Ciatarâş, D; Bocoş, B; Tigan, S

2012-09-01

Biofouling occurs without exception in all water systems, with undesirable effects such as biocorrosion and deterioration of water quality. Drinking water associated biofilms represent a potential risk to human health by harbouring pathogenic or toxin-releasing microorganisms. This is the first study investigating the attached microbiota, with potential threat to human health, in a public water system in Romania. The presence and the seasonal variation of viable faecal indicators and opportunistic pathogens were investigated within naturally developed biofilms in a drinking water treatment plant. Bacterial frequencies were correlated with microbial loads in biofilms as well as with physical and chemical characteristics of biofilms and raw water. The biofilms assessed in the current study proved to be extremely active microbial consortia. High bacterial numbers were recovered by cultivation, including Pseudomonas aeruginosa, Escherichia coli, Aeromonas hydrophila, intestinal enterococci and Clostridium perfringens. There were no Legionella spp. detected in any biofilm sample. Emergence of opportunistic pathogens in biofilms was not significantly affected by the surface material, but by the treatment process. Implementation of a water safety plan encompassing measures to prevent microbial contamination and to control biofouling would be appropriate.

Disease risk in a dynamic environment: the spread of tick-borne pathogens in Minnesota, USA.

PubMed

Robinson, Stacie J; Neitzel, David F; Moen, Ronald A; Craft, Meggan E; Hamilton, Karin E; Johnson, Lucinda B; Mulla, David J; Munderloh, Ulrike G; Redig, Patrick T; Smith, Kirk E; Turner, Clarence L; Umber, Jamie K; Pelican, Katharine M

2015-03-01

As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease.

Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005.

PubMed

Adlhoch, C; Gossner, C; Koch, G; Brown, I; Bouwstra, R; Verdonck, F; Penttinen, P; Harder, T

2014-12-18

Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences from outbreaks of A(H5N1) in Europe demonstrated that early detection to control HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission and prevention of human cases.

Pathogens transmitted in animal feces in low- and middle-income countries.

PubMed

Delahoy, Miranda J; Wodnik, Breanna; McAliley, Lydia; Penakalapati, Gauthami; Swarthout, Jenna; Freeman, Matthew C; Levy, Karen

2018-05-01

Animals found in close proximity to humans in low-and middle-income countries (LMICs) harbor many pathogens capable of infecting humans, transmissible via their feces. Contact with animal feces poses a currently unquantified-though likely substantial-risk to human health. In LMIC settings, human exposure to animal feces may explain some of the limited success of recent water, sanitation, and hygiene interventions that have focused on limiting exposure to human excreta, with less attention to containing animal feces. We conducted a review to identify pathogens that may substantially contribute to the global burden of disease in humans through their spread in animal feces in the domestic environment in LMICs. Of the 65 potentially pathogenic organisms considered, 15 were deemed relevant, based on burden of disease and potential for zoonotic transmission. Of these, five were considered of highest concern based on a substantial burden of disease for which transmission in animal feces is potentially important: Campylobacter, non-typhoidal Salmonella (NTS), Lassa virus, Cryptosporidium, and Toxoplasma gondii. Most of these have a wide range of animal hosts, except Lassa virus, which is spread through the feces of rats indigenous to sub-Saharan Africa. Combined, these five pathogens cause close to one million deaths annually. More than half of these deaths are attributed to invasive NTS. We do not estimate an overall burden of disease from improperly managed animal feces in LMICs, because it is unknown what proportion of illnesses caused by these pathogens can be attributed to contact with animal feces. Typical water quantity, water quality, and handwashing interventions promoted in public health and development address transmission routes for both human and animal feces; however, sanitation interventions typically focus on containing human waste, often neglecting the residual burden of disease from pathogens transmitted via animal feces. This review compiles evidence on which pathogens may contribute to the burden of disease through transmission in animal feces; these data will help prioritize intervention types and regions that could most benefit from interventions aimed at reducing human contact with animal feces. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

An Alternative Chemical Redox Method for the Production of Bispecific Antibodies: Implication in Rapid Detection of Food Borne Pathogens

PubMed Central

Owais, Mohammad; Kazmi, Shadab; Tufail, Saba; Zubair, Swaleha

2014-01-01

Bi-functional antibodies with the ability to bind two unrelated epitopes have remarkable potential in diagnostic and bio-sensing applications. In the present study, bispecific antibodies that recognize human red blood cell (RBC) and the food borne pathogen Listeria monocytogenes (L. monocytogenes) were engineered. The procedure involves initial reduction of a mixture of anti-RBC and anti-Listeria antibodies followed by gradual re-oxidation of the reduced disulphides. This facilitates association of the separated antibody chains and formation of hybrid immunoglobulins with affinity for the L. monocytogenes and human RBC. The bispecific antibodies caused the agglutination of the RBCs only in the presence of L. monocytogenes cells. The agglutination process necessitated the specific presence of L. monocytogenes and the red colored clumps formed were readily visible with naked eyes. The RBC agglutination assay described here provides a remarkably simple approach for the rapid and highly specific screening of various pathogens in their biological niches. PMID:24637674

Microbial Survey of Pennsylvania Surface Water Used for Irrigating Produce Crops.

PubMed

Draper, Audrey D; Doores, Stephanie; Gourama, Hassan; LaBorde, Luke F

2016-06-01

Recent produce-associated foodborne illness outbreaks have been attributed to contaminated irrigation water. This study examined microbial levels in Pennsylvania surface waters used for irrigation, relationships between microbial indicator organisms and water physicochemical characteristics, and the potential use of indicators for predicting the presence of human pathogens. A total of 153 samples taken from surface water sources used for irrigation in southeastern Pennsylvania were collected from 39 farms over a 2-year period. Samples were analyzed for six microbial indicator organisms (aerobic plate count, Enterobacteriaceae, coliform, fecal coliforms, Escherichia coli, and enterococci), two human pathogens (Salmonella and E. coli O157), and seven physical and environmental characteristics (pH, conductivity, turbidity, air and water temperature, and sampling day and 3-day-accumulated precipitation levels). Indicator populations were highly variable and not predicted by water and environmental characteristics. Only five samples were confirmed positive for Salmonella, and no E. coli O157 was detected in any samples. Predictive relationships between microbial indicators and the occurrence of pathogens could therefore not be determined.

In vitro antifungal potentials of bioactive compound oleic acid, 3-(octadecyloxy) propyl ester isolated from Lepidagathis cristata Willd. (Acanthaceae) inflorescence.

PubMed

Abubacker, Maghdu Nainamohamed; Devi, Palaniyappan Kamala

2014-09-01

To identify bioactive compound oleic acid, 3-(octadecyloxy) propyl ester from Lepidagathis cristata Willd. (L. cristata) and to assess antifungal potentials of the isolated compound. Aqueous extracts of L. cristata inflorescence were used for this study. The major bioactive compound isolated was tested for antifungal activities. The major bioactive compound oleic acid, 3-(octadecyloxy) propyl ester was isolated from the inflorescence of L. cristata. The bioactive compound was tested for antifungal potentials and found to be highly effective to plant pathogenic fungi Colletotrichum fulcatum NCBT 146, Fusarium oxysporum NCBT 156 and Rhizoctonia solani NCBT 196 as well as for the human pathogenic fungi Curvularia lunata MTCC 2030 and Microsporum canis MTCC 2820. The results justify the antifungal potentials of both plant and human pathogenic fungi. The plant bioactive compound will be helpful in herbal antifungal formulations. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Antimicrobial Mechanisms of Macrophages and the Immune Evasion Strategies of Staphylococcus aureus

PubMed Central

Flannagan, Ronald S.; Heit, Bryan; Heinrichs, David E.

2015-01-01

Habitually professional phagocytes, including macrophages, eradicate microbial invaders from the human body without overt signs of infection. Despite this, there exist select bacteria that are professional pathogens, causing significant morbidity and mortality across the globe and Staphylococcus aureus is no exception. S. aureus is a highly successful pathogen that can infect virtually every tissue that comprises the human body causing a broad spectrum of diseases. The profound pathogenic capacity of S. aureus can be attributed, in part, to its ability to elaborate a profusion of bacterial effectors that circumvent host immunity. Macrophages are important professional phagocytes that contribute to both the innate and adaptive immune response, however from in vitro and in vivo studies, it is evident that they fail to eradicate S. aureus. This review provides an overview of the antimicrobial mechanisms employed by macrophages to combat bacteria and describes the immune evasion strategies and some representative effectors that enable S. aureus to evade macrophage-mediated killing. PMID:26633519

Overview and challenges of molecular technologies in the veterinary microbiology laboratory.

PubMed

Cunha, Mónica V; Inácio, João

2015-01-01

Terrestrial, aquatic, and aerial animals, either domestic or wild, humans, and plants all face similar health threats caused by infectious agents. Multifaceted anthropic pressure caused by an increasingly growing and resource-demanding human population has affected biodiversity at all scales, from the DNA molecule to the pathogen, to the ecosystem level, leading to species declines and extinctions and, also, to host-pathogen coevolution processes. Technological developments over the last century have also led to quantic jumps in laboratorial testing that have highly impacted animal health and welfare, ameliorated animal management and animal trade, safeguarded public health, and ultimately helped to "secure" biodiversity. In particular, the field of molecular diagnostics experienced tremendous technical progresses over the last two decades that significantly have contributed to our ability to study microbial pathogens in the clinical and research laboratories. This chapter highlights the strengths, weaknesses, opportunities, and threats (or challenges) of molecular technologies in the framework of a veterinary microbiology laboratory, in view of the latest advances.

Livestock abundance predicts vampire bat demography, immune profiles and bacterial infection risk

PubMed Central

Czirják, Gábor Á.; Volokhov, Dmitriy V.; Carrera, Jorge E.; Camus, Melinda S.; Navara, Kristen J.; Chizhikov, Vladimir E.; Fenton, M. Brock; Simmons, Nancy B.; Recuenco, Sergio E.; Gilbert, Amy T.

2018-01-01

Human activities create novel food resources that can alter wildlife–pathogen interactions. If resources amplify or dampen, pathogen transmission probably depends on both host ecology and pathogen biology, but studies that measure responses to provisioning across both scales are rare. We tested these relationships with a 4-year study of 369 common vampire bats across 10 sites in Peru and Belize that differ in the abundance of livestock, an important anthropogenic food source. We quantified innate and adaptive immunity from bats and assessed infection with two common bacteria. We predicted that abundant livestock could reduce starvation and foraging effort, allowing for greater investments in immunity. Bats from high-livestock sites had higher microbicidal activity and proportions of neutrophils but lower immunoglobulin G and proportions of lymphocytes, suggesting more investment in innate relative to adaptive immunity and either greater chronic stress or pathogen exposure. This relationship was most pronounced in reproductive bats, which were also more common in high-livestock sites, suggesting feedbacks between demographic correlates of provisioning and immunity. Infection with both Bartonella and haemoplasmas were correlated with similar immune profiles, and both pathogens tended to be less prevalent in high-livestock sites, although effects were weaker for haemoplasmas. These differing responses to provisioning might therefore reflect distinct transmission processes. Predicting how provisioning alters host–pathogen interactions requires considering how both within-host processes and transmission modes respond to resource shifts. This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’. PMID:29531144

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

Treesearch

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

2009-01-01

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

Antimicrobial and antiviral effect of high-temperature short-time (HTST) pasteurization applied to human milk.

PubMed

Terpstra, Fokke G; Rechtman, David J; Lee, Martin L; Hoeij, Klaske Van; Berg, Hijlkeline; Van Engelenberg, Frank A C; Van't Wout, Angelica B

2007-03-01

In the United States, concerns over the transmission of infectious diseases have led to donor human milk generally being subjected to pasteurization prior to distribution and use. The standard method used by North American milk banks is Holder pasteurization (63 degrees C for 30 minutes). The authors undertook an experiment to validate the effects of a high-temperature short-time (HTST) pasteurization process (72 degrees C for 16 seconds) on the bioburden of human milk. It was concluded that HTST is effective in the elimination of bacteria as well as of certain important pathogenic viruses.

Hostile takeover: Manipulation of HIF-1 signaling in pathogen-associated cancers (Review).

PubMed

Zhu, Caixia; Zhu, Qing; Wang, Chong; Zhang, Liming; Wei, Fang; Cai, Qiliang

2016-10-01

Hypoxia-inducible factor (HIF)-1 is a central regulator in the adaptation process of cell response to hypoxia (low oxygen). Emerging evidence has demonstrated that HIF-1 plays an important role in the development and progression of many types of human diseases, including pathogen-associated cancers. In the present review, we summarize the recent understandings of how human pathogenic agents including viruses, bacteria and parasites deregulate cellular HIF-1 signaling pathway in their associated cancer cells, and highlight the common molecular mechanisms of HIF-1 signaling activated by these pathogenic infection, which could act as potential diagnostic markers and new therapeutic strategies against human infectious cancers.

Microevolution of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Humans, Egypt, 2007–2011

PubMed Central

Younan, Mary; Poh, Mee Kian; Elassal, Emad; Davis, Todd; Rivailler, Pierre; Balish, Amanda L.; Simpson, Natosha; Jones, Joyce; Deyde, Varough; Loughlin, Rosette; Perry, Ije; Gubareva, Larisa; ElBadry, Maha A.; Truelove, Shaun; Gaynor, Anne M.; Mohareb, Emad; Amin, Magdy; Cornelius, Claire; Pimentel, Guillermo; Earhart, Kenneth; Naguib, Amel; Abdelghani, Ahmed S.; Refaey, Samir; Klimov, Alexander I.; Kandeel, Amr

2013-01-01

We analyzed highly pathogenic avian influenza A(H5N1) viruses isolated from humans infected in Egypt during 2007–2011. All analyzed viruses evolved from the lineage of subtype H5N1 viruses introduced into Egypt in 2006; we found minimal evidence of reassortment and no exotic introductions. The hemagglutinin genes of the viruses from 2011 formed a monophyletic group within clade 2.2.1 that also included human viruses from 2009 and 2010 and contemporary viruses from poultry; this finding is consistent with zoonotic transmission. Although molecular markers suggestive of decreased susceptibility to antiviral drugs were detected sporadically in the neuraminidase and matrix 2 proteins, functional neuraminidase inhibition assays did not identify resistant viruses. No other mutations suggesting a change in the threat to public health were detected in the viral proteomes. However, a comparison of representative subtype H5N1 viruses from 2011 with older subtype H5N1 viruses from Egypt revealed substantial antigenic drift. PMID:23260983

Infection Risk for Persons Exposed to Highly Pathogenic Avian Influenza A H5 Virus-Infected Birds, United States, December 2014-March 2015.

PubMed

Arriola, Carmen S; Nelson, Deborah I; Deliberto, Thomas J; Blanton, Lenee; Kniss, Krista; Levine, Min Z; Trock, Susan C; Finelli, Lyn; Jhung, Michael A

2015-12-01

Newly emerged highly pathogenic avian influenza (HPAI) A H5 viruses have caused outbreaks among birds in the United States. These viruses differ genetically from HPAI H5 viruses that previously caused human illness, most notably in Asia and Africa. To assess the risk for animal-to-human HPAI H5 virus transmission in the United States, we determined the number of persons with self-reported exposure to infected birds, the number with an acute respiratory infection (ARI) during a 10-day postexposure period, and the number with ARI who tested positive for influenza by real-time reverse transcription PCR or serologic testing for each outbreak during December 15, 2014-March 31, 2015. During 60 outbreaks in 13 states, a total of 164 persons were exposed to infected birds. ARI developed in 5 of these persons within 10 days of exposure. H5 influenza virus infection was not identified in any persons with ARI, suggesting a low risk for animal-to-human HPAI H5 virus transmission.

Highly divergent hepaciviruses from African cattle.

PubMed

Corman, Victor Max; Grundhoff, Adam; Baechlein, Christine; Fischer, Nicole; Gmyl, Anatoly; Wollny, Robert; Dei, Dickson; Ritz, Daniel; Binger, Tabea; Adankwah, Ernest; Marfo, Kwadwo Sarfo; Annison, Lawrence; Annan, Augustina; Adu-Sarkodie, Yaw; Oppong, Samuel; Becher, Paul; Drosten, Christian; Drexler, Jan Felix

2015-06-01

The hepatitis C virus (HCV; genus Hepacivirus) is a highly relevant human pathogen. Unique hepaciviruses (HV) were discovered recently in animal hosts. The direct ancestor of HCV has not been found, but the genetically most closely related animal HVs exist in horses. To investigate whether other peridomestic animals also carry HVs, we analyzed sera from Ghanaian cattle for HVs by reverse transcription-PCR (RT-PCR). Nine of 106 specimens from different sampling sites contained HV RNA (8.5%) at median viral loads of 1.6 × 10(5) copies/ml. Infection seemed unrelated to cattle age and gender. Near-full-genome sequencing of five representative viruses confirmed taxonomic classifications. Cattle HVs formed two distinct phylogenetic lineages that differed by up to 17.7% on the nucleotide level in the polyprotein-encoding region, suggesting cocirculation of different virus subtypes. A conserved microRNA122-binding site in the 5' internal ribosomal entry site suggested liver tropism of cattle HVs. Phylogenetic analyses suggested the circulation of HVs in cattle for several centuries. Cattle HVs were genetically highly divergent from all other HVs, including HCV. HVs from genetically related equine and bovine hosts were not monophyletic, corroborating host shifts during the evolution of the genus Hepacivirus. Similar to equine HVs, the genetic diversity of cattle HVs was low compared to that of HCV genotypes. This suggests an influence of the human-modified ecology of peridomestic animals on virus diversity. Further studies should investigate the occurrence of cattle HVs in other geographic areas and breeds, virus pathogenicity in cattle, and the potential exposure of human risk groups, such as farmers, butchers, and abattoir workers. HCV (genus Hepacivirus) is a major human pathogen, causing liver failure and cancer. Unique hepaciviruses (HVs) were discovered over the last few years in animals, but the direct ancestor of HCV has not been found. The animal HV most closely related to HCV so far originated from horses, suggesting that other livestock animals also harbor HVs. Therefore, we investigated African cattle and discovered previously unknown HVs at high prevalence and viral loads. Because of the agricultural importance of cattle, it may be relevant to investigate HV pathogenicity. The frequent exposure of humans to cattle also may warrant investigations of the zoonotic potential of these viruses. Evolutionary analyses suggested that cattle HVs have existed for centuries. Despite the genetic relatedness of their animal hosts, HVs from cattle and horses were not phylogenetically related, corroborating frequent host shifts during the evolution of the genus Hepacivirus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Structure of Protein Geranylgeranyltransferase-I from the Human Pathogen Candida albicans Complexed with a Lipid Substrate

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

Hast, Michael A.; Beese, Lorena S.

2008-11-21

Protein geranylgeranyltransferase-I (GGTase-I) catalyzes the transfer of a 20-carbon isoprenoid lipid to the sulfur of a cysteine residue located near the C terminus of numerous cellular proteins, including members of the Rho superfamily of small GTPases and other essential signal transduction proteins. In humans, GGTase-I and the homologous protein farnesyltransferase (FTase) are targets of anticancer therapeutics because of the role small GTPases play in oncogenesis. Protein prenyltransferases are also essential for many fungal and protozoan pathogens that infect humans, and have therefore become important targets for treating infectious diseases. Candida albicans, a causative agent of systemic fungal infections in immunocompromisedmore » individuals, is one pathogen for which protein prenylation is essential for survival. Here we present the crystal structure of GGTase-I from C. albicans (CaGGTase-I) in complex with its cognate lipid substrate, geranylgeranylpyrophosphate. This structure provides a high-resolution picture of a non-mammalian protein prenyltransferase. There are significant variations between species in critical areas of the active site, including the isoprenoid-binding pocket, as well as the putative product exit groove. These differences indicate the regions where specific protein prenyltransferase inhibitors with antifungal activity can be designed.« less

Hydrologic, land cover, and seasonal patterns of waterborne pathogens in Great Lakes tributaries

USGS Publications Warehouse

Lenaker, Peter L.; Corsi, Steven; Borchardt, Mark A.; Spencer, Susan K.; Baldwin, Austin K.; Lutz, Michelle A.

2017-01-01

Great Lakes tributaries are known to deliver waterborne pathogens from a host of sources. To examine the hydrologic, land cover, and seasonal patterns of waterborne pathogens (i.e. protozoa (2), pathogenic bacteria (4) human viruses, (8) and bovine viruses (8)) eight rivers were monitored in the Great Lakes Basin over 29 months from February 2011 to June 2013. Sampling locations represented a wide variety of land cover classes from urban to agriculture to forest. A custom automated pathogen sampler was deployed at eight sampling locations which provided unattended, flow-weighted, large-volume (120–1630 L) sampling. Human and bovine viruses and pathogenic bacteria were detected by real-time qPCR in 16%, 14%, and 1.4% of 290 samples collected while protozoa were never detected. The most frequently detected pathogens were: bovine polyomavirus (11%), and human adenovirus C, D, F (9%). Human and bovine viruses were present in 16.9% and 14.8% of runoff-event samples (n = 189) resulting from precipitation and snowmelt, and 13.9% and 12.9% of low-flow samples (n = 101), respectively, indicating multiple delivery mechanisms could be influential. Data indicated human and bovine virus prevalence was different depending on land cover within the watershed. Occurrence, concentration, and flux of human viruses were greatest in samples from the three sampling locations with greater than 25% urban influence than those with less than 25% urban influence. Similarly, occurrence, concentration, and flux of bovine viruses were greatest in samples from the two sampling locations with greater than 50 cattle/km2 than those with less than 50 cattle/km2. In seasonal analysis, human and bovine viruses occurred more frequently in spring and winter seasons than during the fall and summer. Concentration, occurrence, and flux in the context of hydrologic condition, seasonality, and land use must be considered for each watershed individually to develop effective watershed management strategies for pathogen reduction.

Cis-encoded non-coding antisense RNAs in streptococci and other low GC Gram (+) bacterial pathogens

PubMed Central

Cho, Kyu Hong; Kim, Jeong-Ho

2015-01-01

Due to recent advances of bioinformatics and high throughput sequencing technology, discovery of regulatory non-coding RNAs in bacteria has been increased to a great extent. Based on this bandwagon, many studies searching for trans-acting small non-coding RNAs in streptococci have been performed intensively, especially in the important human pathogen, group A and B streptococci. However, studies for cis-encoded non-coding antisense RNAs in streptococci have been scarce. A recent study shows antisense RNAs are involved in virulence gene regulation in group B streptococcus, S. agalactiae. This suggests antisense RNAs could have important roles in the pathogenesis of streptococcal pathogens. In this review, we describe recent discoveries of chromosomal cis-encoded antisense RNAs in streptococcal pathogens and other low GC Gram (+) bacteria to provide a guide for future studies. PMID:25859258

Peromyscus as a model system for human hepatitis C: An opportunity to advance our understanding of a complex host parasite system.

PubMed

Vandegrift, Kurt J; Critchlow, Justin T; Kapoor, Amit; Friedman, David A; Hudson, Peter J

2017-01-01

Worldwide, there are 185 million people infected with hepatitis C virus and approximately 350,000 people die each year from hepatitis C associated liver diseases. Human hepatitis C research has been hampered by the lack of an appropriate in vivo model system. Most of the in vivo research has been conducted on chimpanzees, which is complicated by ethical concerns, small sample sizes, high costs, and genetic heterogeneity. The house mouse system has led to greater understanding of a wide variety of human pathogens, but it is unreasonable to expect Mus musculus to be a good model system for every human pathogen. Alternative animal models can be developed in these cases. Ferrets (influenza), cotton rats (human respiratory virus), and woodchucks (hepatitis B) are all alternative models that have led to a greater understanding of human pathogens. Rodent models are tractable, genetically amenable and inbred and outbred strains can provide homogeneity in results. Recently, a rodent homolog of hepatitis C was discovered and isolated from the liver of a Peromyscus maniculatus. This represents the first small mammal (mouse) model system for human hepatitis C and it offers great potential to contribute to our understanding and ultimately aid in our efforts to combat this serious public health concern. Peromyscus are available commercially and can be used to inform questions about the origin, transmission, persistence, pathology, and rational treatment of hepatitis C. Here, we provide a disease ecologist's overview of this new virus and some suggestions for useful future experiments. Copyright © 2016. Published by Elsevier Ltd.

Contamination of soils with microbial pathogens originating from effluent water used for agricultural irrigation

NASA Astrophysics Data System (ADS)

Bernstein, N.

2009-04-01

The use of wastewater for agricultural irrigation is steadily increasing world-wide and due to shortages of fresh water is common today in most arid regions of the world. The use of treated wastewater for agricultural irrigation may result in soil exposure to pathogens, creating potential public health problems. A variety of human pathogens are present in raw sewage water. Although their concentrations decrease during the wastewater reclamation process, the secondary treated effluents most commonly used for irrigation today still contain bacterial human pathogens. A range of bacterial pathogens, introduced through contaminated irrigation water or manure, are capable of surviving for long periods in soil and water where they have the potential to contaminate crops in the field. Therefore, there is a risk of direct contamination of crops by human pathogens from the treated effluents used for irrigation, as well as a risk of indirect contamination of the crops from contaminated soil at the agricultural site. Contradictory to previous notion, recent studies have demonstrated that human pathogens can enter plants through their roots and translocate and survive in edible, aerial plant tissues. The practical implications of these new findings for food safety are still not clear, but no doubt reflect the pathogenic microorganisms' ability to survive and multiply in the irrigated soil, water, and the harvested edible crop.

Comparison of anti-pathogenic activities of the human and bovine milk N-glycome: Fucosylation is a key factor.

PubMed

Wang, Wen-Li; Wang, Wei; Du, Ya-Min; Wu, Hong; Yu, Xiao-Bo; Ye, Ke-Ping; Li, Chun-Bao; Jung, Yong-Sam; Qian, Ying-Juan; Voglmeir, Josef; Liu, Li

2017-11-15

Health differences between breast- and formula-fed infants have long been apparent despite great efforts in improving the function of baby formula by adjusting the levels of various milk nutritional components. However, the N-glycome, a type of oligosaccharide decorating a diverse range of proteins, has not been extensively studied in milk regarding its biological function. In this study, the anti-pathogenic function of the enzymatically released human and bovine milk N-glycome against 5 food-borne pathogens was investigated. The human milk N-glycome showed significantly higher activity than bovine milk. After enzymatic defucosylation of human and bovine N-glycan pool, UHPLC peak shifts were observed in both suggesting heavy fucosylation of samples. Furthermore, the anti-pathogenic activity of the defulosylated N-glycome decreased significantly, and the significance of functional difference between the two almost disappeared. This result indicates the essential role of fucosylation for the anti-pathogenic function of the milk N-glycome, especially in human milk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chlamydia trachomatis Is Resistant to Inclusion Ubiquitination and Associated Host Defense in Gamma Interferon-Primed Human Epithelial Cells.

PubMed

Haldar, Arun K; Piro, Anthony S; Finethy, Ryan; Espenschied, Scott T; Brown, Hannah E; Giebel, Amanda M; Frickel, Eva-Maria; Nelson, David E; Coers, Jörn

2016-12-13

The cytokine gamma interferon (IFN-γ) induces cell-autonomous immunity to combat infections with intracellular pathogens, such as the bacterium Chlamydia trachomatis The present study demonstrates that IFN-γ-primed human cells ubiquitinate and eliminate intracellular Chlamydia-containing vacuoles, so-called inclusions. We previously described how IFN-γ-inducible immunity-related GTPases (IRGs) employ ubiquitin systems to mark inclusions for destruction in mouse cells and, furthermore, showed that the rodent pathogen Chlamydia muridarum blocks ubiquitination of its inclusions by interfering with mouse IRG function. Here, we report that ubiquitination of inclusions in human cells is independent of IRG and thus distinct from the murine pathway. We show that C. muridarum is susceptible to inclusion ubiquitination in human cells, while the closely related human pathogen C. trachomatis is resistant. C. muridarum, but not C. trachomatis, inclusions attract several markers of cell-autonomous immunity, including the ubiquitin-binding protein p62, the ubiquitin-like protein LC3, and guanylate-binding protein 1. Consequently, we find that IFN-γ priming of human epithelial cells triggers the elimination of C. muridarum, but not C. trachomatis, inclusions. This newly described defense pathway is independent of indole-2,3-dioxygenase, a known IFN-γ-inducible anti-Chlamydia resistance factor. Collectively, our observations indicate that C. trachomatis evolved mechanisms to avoid a human-specific, ubiquitin-mediated response as part of its unique adaptation to its human host. Chlamydia trachomatis is the leading cause of sexually transmitted bacterial infections and responsible for significant morbidity, including pelvic inflammatory disease, infertility, and ectopic pregnancies in women. As an obligate intracellular pathogen, C. trachomatis is in perpetual conflict with cell-intrinsic defense programs executed by its human host. Our study defines a novel anti-Chlamydia host resistance pathway active in human epithelial cells. This defense program promotes the deposition of the small antimicrobial protein ubiquitin on vacuoles containing Chlamydia We show that this ubiquitin-based resistance pathway of human cells is highly effective against a Chlamydia species adapted to rodents but ineffective against human-adapted C. trachomatis This observation indicates that C. trachomatis evolved strategies to avoid entrapment within ubiquitin-labeled vacuoles as part of its adaptation to the human innate immune system. Copyright © 2016 Haldar et al.

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.

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

Probiotic Potential of Lactobacillus Strains with Antimicrobial Activity against Some Human Pathogenic Strains

PubMed Central

Shokryazdan, Parisa; Sieo, Chin Chin; Kalavathy, Ramasamy; Liang, Juan Boo; Alitheen, Noorjahan Banu; Faseleh Jahromi, Mohammad; Ho, Yin Wan

2014-01-01

The objective of this study was to isolate, identify, and characterize some lactic acid bacterial strains from human milk, infant feces, and fermented grapes and dates, as potential probiotics with antimicrobial activity against some human pathogenic strains. One hundred and forty bacterial strains were isolated and, after initial identification and a preliminary screening for acid and bile tolerance, nine of the best isolates were selected and further identified using 16 S rRNA gene sequences. The nine selected isolates were then characterized in vitro for their probiotic characteristics and their antimicrobial activities against some human pathogens. Results showed that all nine isolates belonged to the genus Lactobacillus. They were able to tolerate pH 3 for 3 h, 0.3% bile salts for 4 h, and 1.9 mg/mL pancreatic enzymes for 3 h. They exhibited good ability to attach to intestinal epithelial cells and were not resistant to the tested antibiotics. They also showed good antimicrobial activities against the tested pathogenic strains of humans, and most of them exhibited stronger antimicrobial activity than the reference strain L. casei Shirota. Thus, the nine Lactobacillus strains could be considered as potential antimicrobial probiotic strains against human pathogens and should be further studied for their human health benefits. PMID:25105147

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

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.

Interpreting short tandem repeat variations in humans using mutational constraint

PubMed Central

Gymrek, Melissa; Willems, Thomas; Reich, David; Erlich, Yaniv

2017-01-01

Identifying regions of the genome that are depleted of mutations can reveal potentially deleterious variants. Short tandem repeats (STRs), also known as microsatellites, are among the largest contributors of de novo mutations in humans. However, per-locus studies of STR mutations have been limited to highly ascertained panels of several dozen loci. Here, we harnessed bioinformatics tools and a novel analytical framework to estimate mutation parameters for each STR in the human genome by correlating STR genotypes with local sequence heterozygosity. We applied our method to obtain robust estimates of the impact of local sequence features on mutation parameters and used this to create a framework for measuring constraint at STRs by comparing observed vs. expected mutation rates. Constraint scores identified known pathogenic variants with early onset effects. Our metric will provide a valuable tool for prioritizing pathogenic STRs in medical genetics studies. PMID:28892063

Influenza: forecast for a pandemic.

PubMed

de la Barrera, Claudia Alvarado; Reyes-Terán, Gustavo

2005-01-01

Recently, great speculation about a possible influenza pandemic has been made. However, the facts supporting the possibility of this threat are less discussed. During the last decade highly pathogenic strains of avian influenza virus, including the H5N1 subtype, crossed the species barriers from birds to humans and caused fatal disease. The Z strain of H5N1 subtype is characterized by pathogenicity to a larger number of animal species and by resistance to the older class of antiviral drugs. At present, two out of three general conditions for the onset of a pandemic have been met; namely, the emergence of a new virus and its ability to replicate in humans causing serious illness. Should the virus achieve efficient human-to-human transmission, the next influenza pandemic might occur. This review addresses these biological and epidemiological aspects of influenza in the context of history and characteristics of previous epidemics, as well as concrete actions that can be undertaken considering current understanding of influenza pathogenesis, treatment, and control possibilities.

Molecular Epidemiology of Human Intestinal Amoebas in Iran

PubMed Central

Hooshyar, H; Rostamkhani, P; Rezaian, M

2012-01-01

Many microscopic-based epidemiological surveys on the prevalence of human intestinal pathogenic and non-pathogenic protozoa including intestinal amoeba performed in Iran show a high prevalence of human intestinal amoeba in different parts of Iran. Such epidemiological studies on amoebiasis are confusing, mainly due to recently appreciated distinction between the Entamoeba histolytica, E. dispar and E. moshkovskii. Differential diagnosis can be done by some methods such as PCR-based methods, monoclonal antibodies and the analysis of isoenzyme typing, however the molecular study of these protozoa in Iran is low. Based on molecular studies, it seems that E. dispar is predominant species especially in the central and northern areas of Iran and amoebiasis due to E. histolytica is a rare infection in the country. It is suggested that infection with E. moshkovskii may be common among Iranians. Considering the importance of molecular epidemiology of amoeba in Iran and also the current data, the present study reviews the data currently available on the molecular distribution of intestinal human amoeba in Iran. PMID:23193500

Molecular Identification and Epidemiological Features of Human Adenoviruses Associated with Acute Respiratory Infections in Hospitalized Children in Southern China, 2012-2013.

PubMed

Chen, Yi; Liu, Fanghua; Wang, Changbing; Zhao, Mingqi; Deng, Li; Zhong, Jiayu; Zhang, Yingying; Ye, Jun; Jing, Shuping; Cheng, Zetao; Guan, Yongxin; Ma, Yi; Sun, Yuanyuan; Zhu, Bing; Zhang, Qiwei

2016-01-01

Acute respiratory infections (ARI) are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV) is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. Total 4,130 children with ARI requiring hospitalization from 2012 to 2013 were retrospectively studied. Throat swab specimens were collected from each patient. Fluorescence Quantitative PCR was performed to detect adenovirus as well as other common ARI-related pathogens. The seven HAdV hypervariable regions (HVRs) of the hexon gene from fifty-seven HAdVs-positive samples collected in the seasonal peaks were sequenced. Phylogenetic analysis of HVRs was also conducted to confirm the molecular types and genetic variation. In addition, epidemiological features and co-infection with other human respiratory pathogens were investigated and analyzed. Of 4,130 hospitalized pediatric patients tested, the positive rates of respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and HAdV were 13.7%, 13.2%, and 12.0%, respectively. The HAdV positive patients accounted for 7.9%, 17.2%, 17.5% and 10.7% in age groups <1, 1-3, 3-6 and 6-14 years, respectively. Eighty-four HAdV positive children were co-infected with other respiratory pathogens (84/495, 17.0%). The most common co-infection pathogens with HAdV were MP (57.1%) and Human Bocavirus (HBoV) (16.7%). The majority of HAdV infected patients were totally recovered (96.9%, 480/495); However, four (0.8%) patients, who were previously healthy and at the age of 2 years or younger died of pneumonia. Seasonal peaks of HAdV infection occurred in the summer season of 2012 and 2013; the predominant HAdV type was HAdV-3 (70%), followed by HAdV-7 (28%). These epidemiological features were different from those in Northern China. The HAdV-55 was identified and reported for the first time in Guangzhou metropolitan area. Phylogenetic analysis indicated that all the HVR sequences of the hexon gene of HAdV-3 and -7 strains have high similarity within their individual types, and these strains were also similar to those circulating in China currently, indicating the conservation of hexon genes of both HAdV-3 and HAdV-7. Knowledge of the epidemiological features and molecular types of HAdV, a major pathogen of pediatric ARI, as well as other co-infected respiratory pathogens circulating in Guangzhou, southern China, is vital to predict and prevent future disease outbreaks in children. This study will certainly facilitate HAdV vaccine development and treatment of HAdV infections in children.

Microbial (Pathogen)/Recreational Water Quality Criteria

EPA Pesticide Factsheets

Documents pertaining to Recreational Human Health Ambient Water Quality Criteria for Microbial Organisms (Pathogens). These documents include safe levels for cyanotoxins microcystin and cylindrospermopsin, and Coliphage to protect human health.

Use of molecular markers to compare Fusarium verticillioides pathogenic strains isolated from plants and humans.

PubMed

Chang, S C; Macêdo, D P C; Souza-Motta, C M; Oliveira, N T

2013-08-12

Fusarium verticillioides is a pathogen of agriculturally important crops, especially maize. It is considered one of the most important pathogens responsible for fumonisin contamination of food products, which causes severe, chronic, and acute intoxication in humans and animals. Moreover, it is recognized as a cause of localized infections in immunocompetent patients and disseminated infections among severely immunosuppressed patients. Several molecular tools have been used to analyze the intraspecific variability of fungi. The objective of this study was to use molecular markers to compare pathogenic isolates of F. verticillioides and isolates of the same species obtained from clinical samples of patients with Fusarium mycoses. The molecular markers that we used were inter-simple sequence repeat markers (primers GTG5 and GACA4), intron splice site primer (primer EI1), random amplified polymorphic DNA marker (primer OPW-6), and restriction fragment length polymorphism-internal transcribed spacer (ITS) from rDNA. From the data obtained, clusters were generated based on the UPGMA clustering method. The amplification products obtained using primers ITS4 and ITS5 and loci ITS1-5.8-ITS2 of the rDNA yielded fragments of approximately 600 bp for all the isolates. Digestion of the ITS region fragment using restriction enzymes such as EcoRI, DraI, BshI, AluI, HaeIII, HinfI, MspI, and PstI did not permit differentiation among pathogenic and clinical isolates. The inter-simple sequence repeat, intron splice site primer, and random amplified polymorphic DNA markers presented high genetic homogeneity among clinical isolates in contrast to the high variability found among the phytopathogenic isolates of F. verticillioides.

Feasibility of sulfate-calcined eggshells for removing pathogenic bacteria and antibiotic resistance genes from landfill leachates.

PubMed

Ye, Mao; Sun, Mingming; Chen, Xu; Feng, Yanfang; Wan, Jinzhong; Liu, Kuan; Tian, Da; Liu, Manqiang; Wu, Jun; Schwab, Arthur P; Jiang, Xin

2017-05-01

High abundance of human pathogen and antibiotic resistance genes (ARGs) in landfill leachate has become an emerging threat against human health. Therefore, sulfate- and calcination-modified eggshells as green agricultural bioresource were applied to test the feasibility of removing pathogenic bacteria and ARGs from leachate. The highest removal of Escherichia coli (E. coil) and gentamycin resistant gene (gmrA) from artificial contaminated landfill leachate was achieved by the application of eggshell with combined treatment of sulfate and calcination. The 16S and gmrA gene copies of E. coil declined significantly from 1.78E8±8.7E6 and 4.12E8±5.9E6 copies mL -1 to 1.32E7±2.6E6 and 2.69E7±7.2E6 copies mL -1 , respectively, within 24h dynamic adsorption equilibrium process (p<0.05). Moreover, according to the Langmuir kinetic model, the greatest adsorption amount (1.56×10 9 CFU E. coil per gram of modified eggshells) could be obtained at neutral pH of 7.5. The optimal adsorption eggshells were then screened to the further application in three typical landfill leachates in Nanjing, eastern China. Significant decrease in species and abundance of pathogenic bacteria and ARGs (tet, sul, erm, qnr, and ampC) indicated its great efficiency to purify landfill leachates. This study demonstrated that sulfate-calcined eggshells can be an environmentally-friendly and highly efficient bioadsorbent to the management of reducing dissemination risk of pathogen and ARGs in landfill leachate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Bacteroides and total coliforms as indicators of recent combined sewer overflows and rain events in urban creeks

USGS Publications Warehouse

McGinnis, Shannon; Spencer, Susan K.; Firnstahl, Aaron; Stokdyk, Joel; Borchardt, Mark A.; McCarthy, David; Murphy, Heather

2018-01-01

Combined sewer overflows (CSOs) are a known source of human fecal pollution and human pathogens in urban water bodies, which may present a significant public health threat. To monitor human fecal contamination in water, bacterial fecal indicator organisms (FIOs) are traditionally used. However, because FIOs are not specific to human sources and do not correlate with human pathogens, alternative fecal indicators detected using qPCR are becoming of interest to policymakers. For this reason, this study measured correlations between the number and duration of CSOs and mm of rainfall, concentrations of traditional FIOs and alternative indicators, and the presence of human pathogens in two urban creeks. Samples were collected May–July 2016 and analyzed for concentrations of FIOs (total coliforms and E. coli) using membrane filtration as well as for three alternative fecal indicators (human Bacteroides HF183 marker, human polyomavirus (HPoV), pepper mild mottle virus (PMMoV)) and nine human pathogens using qPCR. Four of the nine pathogens analyzed were detected at these sites including adenovirus, Enterohemorrhagic E. coli, norovirus, and Salmonella. Among all indicators studied, human Bacteroides and total coliforms were significantly correlated with recent CSO and rainfall events, while E. coli, PMMoV, and HPoV did not show consistent significant correlations. Further, human Bacteroides were a more specific indicator, while total coliforms were a more sensitive indicator of CSO and rainfall events. Results may have implications for the use and interpretation of these indicators in future policy or monitoring programs.

Human Bacteroides and total coliforms as indicators of recent combined sewer overflows and rain events in urban creeks.

PubMed

McGinnis, Shannon; Spencer, Susan; Firnstahl, Aaron; Stokdyk, Joel; Borchardt, Mark; McCarthy, David T; Murphy, Heather M

2018-07-15

Combined sewer overflows (CSOs) are a known source of human fecal pollution and human pathogens in urban water bodies, which may present a significant public health threat. To monitor human fecal contamination in water, bacterial fecal indicator organisms (FIOs) are traditionally used. However, because FIOs are not specific to human sources and do not correlate with human pathogens, alternative fecal indicators detected using qPCR are becoming of interest to policymakers. For this reason, this study measured correlations between the number and duration of CSOs and mm of rainfall, concentrations of traditional FIOs and alternative indicators, and the presence of human pathogens in two urban creeks. Samples were collected May-July 2016 and analyzed for concentrations of FIOs (total coliforms and E. coli) using membrane filtration as well as for three alternative fecal indicators (human Bacteroides HF183 marker, human polyomavirus (HPoV), pepper mild mottle virus (PMMoV)) and nine human pathogens using qPCR. Four of the nine pathogens analyzed were detected at these sites including adenovirus, Enterohemorrhagic E. coli, norovirus, and Salmonella. Among all indicators studied, human Bacteroides and total coliforms were significantly correlated with recent CSO and rainfall events, while E. coli, PMMoV, and HPoV did not show consistent significant correlations. Further, human Bacteroides were a more specific indicator, while total coliforms were a more sensitive indicator of CSO and rainfall events. Results may have implications for the use and interpretation of these indicators in future policy or monitoring programs. Copyright © 2018 Elsevier B.V. All rights reserved.

Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses

PubMed Central

Wang, Zheng; Malanoski, Anthony P; Lin, Baochuan; Kidd, Carolyn; Long, Nina C; Blaney, Kate M; Thach, Dzung C; Tibbetts, Clark; Stenger, David A

2008-01-01

Background Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. Results Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. Conclusion This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses. PMID:19046445

Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

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

Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.

2008-05-10

Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-{gamma} enzyme-linked immunospot responses of low magnitude were observed after immunizationmore » with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus.« less

Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics

PubMed Central

Kane, Trevor L.; Carothers, Katelyn E.; Lee, Shaun W.

2018-01-01

Background Staphylococcus aureus is a major bacterial pathogen capable of causing a range of infections in humans from gastrointestinal disease, skin and soft tissue infections, to severe outcomes such as sepsis. Staphylococcal infections in humans can be frequent and recurring, with treatments becoming less effective due to the growing persistence of antibiotic resistant S. aureus strains. Due to the prevalence of antibiotic resistance, and the current limitations on antibiotic development, an active and highly promising avenue of research has been to develop strategies to specifically inhibit the activity of virulence factors produced S. aureus as an alternative means to treat disease. Objective In this review we specifically highlight several major virulence factors produced by S. aureus for which recent advances in antivirulence approaches may hold promise as an alternative means to treating diseases caused by this pathogen. Strategies to inhibit virulence factors can range from small molecule inhibitors, to antibodies, to mutant and toxoid forms of the virulence proteins. Conclusion The major prevalence of antibiotic resistant strains of S. aureus combined with the lack of new antibiotic discoveries highlight the need for vigorous research into alternative strategies to combat diseases caused by this highly successful pathogen. Current efforts to develop specific antivirulence strategies, vaccine approaches, and alternative therapies for treating severe disease caused by S. aureus have the potential to stem the tide against the limitations that we face in the post-antibiotic era. PMID:27894236

Treatment of Lyme borreliosis

PubMed Central

2009-01-01

Borrelia burgdorferi sensu lato is the causative agent of Lyme borreliosis in humans. This inflammatory disease can affect the skin, the peripheral and central nervous system, the musculoskeletal and cardiovascular system and rarely the eyes. Early stages are directly associated with viable bacteria at the site of inflammation. The pathogen-host interaction is complex and has been elucidated only in part. B. burgdorferi is highly susceptible to antibiotic treatment and the majority of patients profit from this treatment. Some patients develop chronic persistent disease despite repeated antibiotics. Whether this is a sequel of pathogen persistence or a status of chronic auto-inflammation, auto-immunity or a form of fibromyalgia is highly debated. Since vaccination is not available, prevention of a tick bite or chemoprophylaxis is important. If the infection is manifest, then treatment strategies should target not only the pathogen by using antibiotics but also the chronic inflammation by using anti-inflammatory drugs. PMID:20067594

Gorilla gorilla gorilla gut: a potential reservoir of pathogenic bacteria as revealed using culturomics and molecular tools.

PubMed

Bittar, Fadi; Keita, Mamadou B; Lagier, Jean-Christophe; Peeters, Martine; Delaporte, Eric; Raoult, Didier

2014-11-24

Wild apes are considered to be the most serious reservoir and source of zoonoses. However, little data are available about the gut microbiota and pathogenic bacteria in gorillas. For this propose, a total of 48 fecal samples obtained from 21 Gorilla gorilla gorilla individuals (as revealed via microsatellite analysis) were screened for human bacterial pathogens using culturomics and molecular techniques. By applying culturomics to one index gorilla and using specific media supplemented by plants, we tested 12,800 colonies and identified 147 different bacterial species, including 5 new species. Many opportunistic pathogens were isolated, including 8 frequently associated with human diseases; Mycobacterium bolletii, Proteus mirabilis, Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens, Escherichia coli, Staphylococcus aureus and Clostridium botulinum. The genus Treponema accounted for 27.4% of the total reads identified at the genus level via 454 pyrosequencing. Using specific real-time PCR on 48 gorilla fecal samples, in addition to classical human pathogens, we also observed the fastidious bacteria Bartonella spp. Borrelia spp., Coxiella burnetii and Tropheryma whipplei in the gorilla population. We estimated that the prevalence of these pathogens vary between 4.76% and 85.7%. Therefore, gorillas share many bacterial pathogens with humans suggesting that they could be a reservoir for their emergence.

Gorilla gorilla gorilla gut: a potential reservoir of pathogenic bacteria as revealed using culturomics and molecular tools

PubMed Central

Bittar, Fadi; Keita, Mamadou B.; Lagier, Jean-Christophe; Peeters, Martine; Delaporte, Eric; Raoult, Didier

2014-01-01

Wild apes are considered to be the most serious reservoir and source of zoonoses. However, little data are available about the gut microbiota and pathogenic bacteria in gorillas. For this propose, a total of 48 fecal samples obtained from 21 Gorilla gorilla gorilla individuals (as revealed via microsatellite analysis) were screened for human bacterial pathogens using culturomics and molecular techniques. By applying culturomics to one index gorilla and using specific media supplemented by plants, we tested 12,800 colonies and identified 147 different bacterial species, including 5 new species. Many opportunistic pathogens were isolated, including 8 frequently associated with human diseases; Mycobacterium bolletii, Proteus mirabilis, Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens, Escherichia coli, Staphylococcus aureus and Clostridium botulinum. The genus Treponema accounted for 27.4% of the total reads identified at the genus level via 454 pyrosequencing. Using specific real-time PCR on 48 gorilla fecal samples, in addition to classical human pathogens, we also observed the fastidious bacteria Bartonella spp. Borrelia spp., Coxiella burnetii and Tropheryma whipplei in the gorilla population. We estimated that the prevalence of these pathogens vary between 4.76% and 85.7%. Therefore, gorillas share many bacterial pathogens with humans suggesting that they could be a reservoir for their emergence. PMID:25417711

Long-Term Live Cell Imaging of Cell Migration: Effects of Pathogenic Fungi on Human Epithelial Cell Migration.

PubMed

Wöllert, Torsten; Langford, George M

2016-01-01

Long-term live cell imaging was used in this study to determine the responses of human epithelial cells to pathogenic biofilms formed by Candida albicans. Epithelial cells of the skin represent the front line of defense against invasive pathogens such as C. albicans but under certain circumstances, especially when the host's immune system is compromised, the skin barrier is breached. The mechanisms by which the fungal pathogen penetrates the skin and invade the deeper layers are not fully understood. In this study we used keratinocytes grown in culture as an in vitro model system to determine changes in host cell migration and the actin cytoskeleton in response to virulence factors produced by biofilms of pathogenic C. albicans. It is clear that changes in epithelial cell migration are part of the response to virulence factors secreted by biofilms of C. albicans and the actin cytoskeleton is the downstream effector that mediates cell migration. Our goal is to understand the mechanism by which virulence factors hijack the signaling pathways of the actin cytoskeleton to alter cell migration and thereby invade host tissues. To understand the dynamic changes of the actin cytoskeleton during infection, we used long-term live cell imaging to obtain spatial and temporal information of actin filament dynamics and to identify signal transduction pathways that regulate the actin cytoskeleton and its associated proteins. Long-term live cell imaging was achieved using a high resolution, multi-mode epifluorescence microscope equipped with specialized light sources, high-speed cameras with high sensitivity detectors, and specific biocompatible fluorescent markers. In addition to the multi-mode epifluorescence microscope, a spinning disk confocal long-term live cell imaging system (Olympus CV1000) equipped with a stage incubator to create a stable in vitro environment for long-term real-time and time-lapse microscopy was used. Detailed descriptions of these two long-term live cell imaging systems are provided.

Application of Lactobacillus johnsonii expressing phage endolysin for control of Clostridium perfringens.

PubMed

Gervasi, T; Lo Curto, R; Minniti, E; Narbad, A; Mayer, M J

2014-10-01

Clostridium perfringens is frequently found in food and the environment and produces potent toxins that have a negative impact on both human and animal health and particularly on the poultry industry. Lactobacillus johnsonii FI9785, isolated from the chicken gastrointestinal tract, has been demonstrated to exclude Cl. perfringens in poultry. We have investigated the interaction of wild-type Lact. johnsonii FI9785 or an engineered strain expressing a cell wall-hydrolysing endolysin with Cl. perfringens in vitro, using a batch culture designed to simulate human gastrointestinal tract conditions. Co-culture experiments indicated that acid production by Lact. johnsonii is important in pathogen control. The co-culture of the endolysin-secreting Lact. johnsonii with Cl. perfringens showed that the engineered strain had the potential to control the pathogen, but the ability to reduce Cl. perfringens numbers was not consistent. Results obtained indicate that survival of high numbers of Lact. johnsonii will be essential for effective pathogen control. Significance and impact of the study: The bacterium Lactobacillus johnsonii FI9785 reduces numbers of the pathogen Clostridium perfringens in vitro. Biocontrol was improved by engineering the strain to produce and export a cell wall-hydrolysing endolysin, but good survival of the producer strain is essential. The production of bacteriophage endolysins by commensal bacteria has the potential to improve competitive exclusion of pathogens in the gastrointestinal tract. © 2014 The Society for Applied Microbiology.

Comparison of the pathogenic potential of highly pathogenic avian influenza (HPAI) H5N6, and H5N8 viruses isolated in South Korea during the 2016-2017 winter season.

PubMed

Kwon, Hyeok-Il; Kim, Eun-Ha; Kim, Young-Il; Park, Su-Jin; Si, Young-Jae; Lee, In-Won; Nguyen, Hiep Dinh; Yu, Kwang Min; Yu, Min-Ah; Jung, Ju Hwan; Choi, Won-Suk; Kwon, Jin Jung; Ahn, Su Jeong; Baek, Yun Hee; Van Lai, Dam; Lee, Ok-Jun; Kim, Si-Wook; Song, Min-Suk; Yoon, Sun-Woo; Kim, Chul-Joong; Webby, Richard J; Mo, In-Pil; Choi, Young Ki

2018-03-14

Highly pathogenic avian influenza (HPAI) A(H5N6) and A(H5N8) virus infections resulted in the culling of more than 37 million poultry in the Republic of Korea during the 2016/17 winter season. Here we characterize two representative viruses, A/Environment/Korea/W541/2016 [Em/W541(H5N6)] and A/Common Teal/Korea/W555/2017 [CT/W555(H5N8)], and evaluate their zoonotic potential in various animal models. Both Em/W541(H5N6) and CT /W555(H5N8) are novel reassortants derived from various gene pools of wild bird viruses present in migratory waterfowl arising from eastern China. Despite strong preferential binding to avian virus-type receptors, the viruses were able to grow in human respiratory tract tissues. Em/W541(H5N6) was found to be highly pathogenic in both chickens and ducks, while CT/W555(H5N8) caused lethal infections in chickens but did not induce remarkable clinical illness in ducks. In mice, both viruses appeared to be moderately pathogenic and displayed limited tissue tropism relative to HPAI H5N1 viruses. Em/W541(H5N6) replicated to moderate levels in the upper respiratory tract of ferrets and was detected in the lungs, brain, spleen, liver, and colon. Unexpectedly, two of three ferrets in direct contact with Em/W541(H5N6)-infected animals shed virus and seroconverted at 14 dpi. CT/W555(H5N8) was less pathogenic than the H5N6 virus in ferrets and no transmission was detected. Given the co-circulation of different, phenotypically distinct, subtypes of HPAI H5Nx viruses for the first time in South Korea, detailed virologic investigations are imperative given the capacity of these viruses to evolve and cause human infections.

Assessing the Biohazard Potential of Putative Martian Organisms for Exploration Class Human Space Missions

NASA Technical Reports Server (NTRS)

Warmflash, David; Larios-Sanz, Maia; Jones, Jeffrey; Fox, George E.; McKay, David S.

2007-01-01

Exploration Class missions to Mars will require precautions against potential contamination by any native microorganisms that may be incidentally pathogenic to humans. While the results of NASA's Viking biology experiments of 1976 have been generally interpreted as inconclusive for surface organisms, the possibility of native surface life has never been ruled out and more recent studies suggest that the case for biological interpretation of the Viking Labeled Release data may now be stronger than it was when the experiments were originally conducted. It is possible that, prior to the first human landing on Mars, robotic craft and sample return missions will provide enough data to know with certainty whether or not future human landing sites harbor extant life forms. However, if native life is confirmed, it will be problematic to determine whether any of its species may present a medical risk to astronauts. Therefore, it will become necessary to assess empirically the risk that the planet contains pathogens based on terrestrial examples of pathogenicity and to take a reasonably cautious approach to bio-hazard protection. A survey of terrestrial pathogens was conducted with special emphasis on those pathogens whose evolution has not depended on the presence of animal hosts. The history of the development and implementation of Apollo anticontamination protocol and recent recommendations of the NRC Space Studies Board regarding Mars were reviewed. Organisms can emerge in nature in the absence of indigenous animal hosts and both infectious and non-infectious human pathogens are theoretically possible on Mars. The prospect of Martian surface life, together with the existence of a diversity of routes by which pathogenicity has emerged on Earth, suggests that the possibility of human pathogens on Mars, while low, is not zero. Since the discovery and study of Martian life can have long-term benefits for humanity, the risk that Martian life might include pathogens should not be an obstacle to human exploration. As a precaution, however, it is recommended that EVA suits be decontaminated when astronauts enter surface habitats when returning from field activity and that biosafety protocol approximating laboratory BSL 2 be developed for astronauts working in laboratories on the Martian surface. Quarantine of astronauts and Martian materials arriving on Earth should also be part of a human Mars mission and this and the surface biosafety program should be integral to human expeditions from the earliest stages of the mission planning.

Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses.

PubMed

Chan, Renee W Y; Chan, Michael C W; Nicholls, John M; Malik Peiris, J S

2013-12-05

The tropism of influenza viruses for the human respiratory tract is a key determinant of host-range, and consequently, of pathogenesis and transmission. Insights can be obtained from clinical and autopsy studies of human disease and relevant animal models. Ex vivo cultures of the human respiratory tract and in vitro cultures of primary human cells can provide complementary information provided they are physiologically comparable in relevant characteristics to human tissues in vivo, e.g. virus receptor distribution, state of differentiation. We review different experimental models for their physiological relevance and summarize available data using these cultures in relation to highly pathogenic avian influenza H5N1, in comparison where relevant, with other influenza viruses. Transformed continuous cell-lines often differ in important ways to the corresponding tissues in vivo. The state of differentiation of primary human cells (respiratory epithelium, macrophages) can markedly affect virus tropism and host responses. Ex vivo cultures of human respiratory tissues provide a close resemblance to tissues in vivo and may be used to risk assess animal viruses for pandemic threat. Physiological factors (age, inflammation) can markedly affect virus receptor expression and virus tropism. Taken together with data from clinical studies on infected humans and relevant animal models, data from ex vivo and in vitro cultures of human tissues and cells can provide insights into virus transmission and pathogenesis and may provide understanding that leads to novel therapeutic interventions. Copyright © 2013 Elsevier B.V. All rights reserved.

Fecal indicator sources in small creeks

USDA-ARS?s Scientific Manuscript database

Fecal indicator organisms (FIO) in surface water have been widely adopted as surrogates for human gastro-intestinal pathogens, despite available data indicating that the correlations are quite low. Nonetheless, high levels of FIO are a source of concern for agricultural, recreational and industrial ...

USING VISUAL PLUMES PREDICTIONS TO MODULATE COMBINED SEWER OVERFLOW (CSO) RATES

EPA Science Inventory

High concentrations of pathogens and toxic residues in creeks and rivers can pose risks to human health and ecological systems. Combined Sewer Overflows (CSOs) discharging into these watercourses often contribute significantly to elevating pollutant concentrations during wet weat...

Sewage disinfection towards protection of drinking water resources.

PubMed

Kolch, A

2000-01-01

Wastewater applied in agriculture for irrigation could replace the use of natural drinking-water resources. With respect to high concentrations of human pathogens wastewater has to be disinfected prior to use. This paper introduces disinfection methods with emphasis on UV irradiation.

Pathogenesis and Transmission of Novel Highly Pathogenic Avian Influenza H5N2 and H5N8 Viruses in Ferrets and Mice

PubMed Central

Pulit-Penaloza, Joanna A.; Sun, Xiangjie; Creager, Hannah M.; Zeng, Hui; Belser, Jessica A.; Maines, Taronna R.

2015-01-01

ABSTRACT A novel highly pathogenic avian influenza (HPAI) H5N8 virus, first detected in January 2014 in poultry and wild birds in South Korea, has spread throughout Asia and Europe and caused outbreaks in Canada and the United States by the end of the year. The spread of H5N8 and the novel reassortant viruses, H5N2 and H5N1 (H5Nx), in domestic poultry across multiple states in the United States pose a potential public health risk. To evaluate the potential of cross-species infection, we determined the pathogenicity and transmissibility of two Asian-origin H5Nx viruses in mammalian animal models. The newly isolated H5N2 and H5N8 viruses were able to cause severe disease in mice only at high doses. Both viruses replicated efficiently in the upper and lower respiratory tracts of ferrets; however, the clinical symptoms were generally mild, and there was no evidence of systemic dissemination of virus to multiple organs. Moreover, these influenza H5Nx viruses lacked the ability to transmit between ferrets in a direct contact setting. We further assessed viral replication kinetics of the novel H5Nx viruses in a human bronchial epithelium cell line, Calu-3. Both H5Nx viruses replicated to a level comparable to a human seasonal H1N1 virus, but significantly lower than a virulent Asian-lineage H5N1 HPAI virus. Although the recently isolated H5N2 and H5N8 viruses displayed moderate pathogenicity in mammalian models, their ability to rapidly spread among avian species, reassort, and generate novel strains underscores the need for continued risk assessment in mammals. IMPORTANCE In 2015, highly pathogenic avian influenza (HPAI) H5 viruses have caused outbreaks in domestic poultry in multiple U.S. states. The economic losses incurred with H5N8 and H5N2 subtype virus infection have raised serious concerns for the poultry industry and the general public due to the potential risk of human infection. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals, which is an essential component of pandemic risk assessment. This study demonstrates that the newly isolated H5N2 and H5N8 viruses lacked the ability to transmit between ferrets and exhibited low to moderate virulence in mammals. In human bronchial epithelial (Calu-3) cells, both H5N8 and H5N2 viruses replicated to a level comparable to a human seasonal virus, but significantly lower than a virulent Asian-lineage H5N1 (A/Thailand/16/2004) virus. The results of this study are important for the evaluation of public health risk. PMID:26223637

Pathogenesis and Transmission of Novel Highly Pathogenic Avian Influenza H5N2 and H5N8 Viruses in Ferrets and Mice.

PubMed

Pulit-Penaloza, Joanna A; Sun, Xiangjie; Creager, Hannah M; Zeng, Hui; Belser, Jessica A; Maines, Taronna R; Tumpey, Terrence M

2015-10-01

A novel highly pathogenic avian influenza (HPAI) H5N8 virus, first detected in January 2014 in poultry and wild birds in South Korea, has spread throughout Asia and Europe and caused outbreaks in Canada and the United States by the end of the year. The spread of H5N8 and the novel reassortant viruses, H5N2 and H5N1 (H5Nx), in domestic poultry across multiple states in the United States pose a potential public health risk. To evaluate the potential of cross-species infection, we determined the pathogenicity and transmissibility of two Asian-origin H5Nx viruses in mammalian animal models. The newly isolated H5N2 and H5N8 viruses were able to cause severe disease in mice only at high doses. Both viruses replicated efficiently in the upper and lower respiratory tracts of ferrets; however, the clinical symptoms were generally mild, and there was no evidence of systemic dissemination of virus to multiple organs. Moreover, these influenza H5Nx viruses lacked the ability to transmit between ferrets in a direct contact setting. We further assessed viral replication kinetics of the novel H5Nx viruses in a human bronchial epithelium cell line, Calu-3. Both H5Nx viruses replicated to a level comparable to a human seasonal H1N1 virus, but significantly lower than a virulent Asian-lineage H5N1 HPAI virus. Although the recently isolated H5N2 and H5N8 viruses displayed moderate pathogenicity in mammalian models, their ability to rapidly spread among avian species, reassort, and generate novel strains underscores the need for continued risk assessment in mammals. In 2015, highly pathogenic avian influenza (HPAI) H5 viruses have caused outbreaks in domestic poultry in multiple U.S. states. The economic losses incurred with H5N8 and H5N2 subtype virus infection have raised serious concerns for the poultry industry and the general public due to the potential risk of human infection. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals, which is an essential component of pandemic risk assessment. This study demonstrates that the newly isolated H5N2 and H5N8 viruses lacked the ability to transmit between ferrets and exhibited low to moderate virulence in mammals. In human bronchial epithelial (Calu-3) cells, both H5N8 and H5N2 viruses replicated to a level comparable to a human seasonal virus, but significantly lower than a virulent Asian-lineage H5N1 (A/Thailand/16/2004) virus. The results of this study are important for the evaluation of public health risk. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

PubMed

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

2018-01-01

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

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

PubMed Central

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

2018-01-01

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

Crossover fungal pathogens: the biology and pathogenesis of fungi capable of crossing kingdoms to infect plants and humans.

PubMed

Gauthier, Gregory M; Keller, Nancy P

2013-12-01

The outbreak of fungal meningitis associated with contaminated methylprednisolone acetate has thrust the importance of fungal infections into the public consciousness. The predominant pathogen isolated from clinical specimens, Exserohilum rostratum (teleomorph: Setosphaeria rostrata), is a dematiaceous fungus that infects grasses and rarely humans. This outbreak highlights the potential for fungal pathogens to infect both plants and humans. Most crossover or trans-kingdom pathogens are soil saprophytes and include fungi in Ascomycota and Mucormycotina phyla. To establish infection, crossover fungi must overcome disparate, host-specific barriers, including protective surfaces (e.g. cuticle, skin), elevated temperature, and immune defenses. This review illuminates the underlying mechanisms used by crossover fungi to cause infection in plants and mammals, and highlights critical events that lead to human infection by these pathogens. Several genes including veA, laeA, and hapX are important in regulating biological processes in fungi important for both invasive plant and animal infections. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of saliva-based exposure assays for detecting exposure to waterborne pathogens

EPA Pesticide Factsheets

Identifying which pathogens we are exposed to can be challenging because many types of pathogens can be found in water and many pathogens have similar symptoms. EPA scientists have developed a simple way to measure human exposure to waterborne pathogens.

Detection of Rickettsia and Ehrlichia spp. in Ticks Associated with Exotic Reptiles and Amphibians Imported into Japan

PubMed Central

Andoh, Masako; Sakata, Akiko; Takano, Ai; Kawabata, Hiroki; Fujita, Hiromi; Une, Yumi; Goka, Koichi; Kishimoto, Toshio; Ando, Shuji

2015-01-01

One of the major routes of transmission of rickettsial and ehrlichial diseases is via ticks that infest numerous host species, including humans. Besides mammals, reptiles and amphibians also carry ticks that may harbor Rickettsia and Ehrlichia strains that are pathogenic to humans. Furthermore, reptiles and amphibians are exempt from quarantine in Japan, thus facilitating the entry of parasites and pathogens to the country through import. Accordingly, in the current study, we examined the presence of Rickettsia and Ehrlichia spp. genes in ticks associated with reptiles and amphibians originating from outside Japan. Ninety-three ticks representing nine tick species (genera Amblyomma and Hyalomma) were isolated from at least 28 animals spanning 10 species and originating from 12 countries (Ghana, Jordan, Madagascar, Panama, Russia, Sri Lanka, Sudan, Suriname, Tanzania, Togo, Uzbekistan, and Zambia). None of the nine tick species are indigenous in Japan. The genes encoding the common rickettsial 17-kDa antigen, citrate synthase (gltA), and outer membrane protein A (ompA) were positively detected in 45.2% (42/93), 40.9% (38/93), and 23.7% (22/93) of the ticks, respectively, by polymerase chain reaction (PCR). The genes encoding ehrlichial heat shock protein (groEL) and major outer membrane protein (omp-1) were PCR-positive in 7.5% (7/93) and 2.2% (2/93) of the ticks, respectively. The p44 gene, which encodes the Anaplasma outer membrane protein, was not detected. Phylogenetic analysis showed that several of the rickettsial and ehrlichial sequences isolated in this study were highly similar to human pathogen genes, including agents not previously detected in Japan. These data demonstrate the global transportation of pathogenic Rickettsia and Ehrlichia through reptile- and amphibian-associated ticks. These imported animals have potential to transfer pathogens into human life. These results highlight the need to control the international transportation of known and potential pathogens carried by ticks in reptiles, amphibians, and other animals, in order to improve national and international public health. PMID:26207382

Molecular Detection of Tick-Borne Pathogens in Humans with Tick Bites and Erythema Migrans, in the Netherlands

PubMed Central

Jahfari, Setareh; Hofhuis, Agnetha; Fonville, Manoj; van der Giessen, Joke; van Pelt, Wilfrid; Sprong, Hein

2016-01-01

Background Tick-borne diseases are the most prevalent vector-borne diseases in Europe. Knowledge on the incidence and clinical presentation of other tick-borne diseases than Lyme borreliosis and tick-borne encephalitis is minimal, despite the high human exposure to these pathogens through tick bites. Using molecular detection techniques, the frequency of tick-borne infections after exposure through tick bites was estimated. Methods Ticks, blood samples and questionnaires on health status were collected from patients that visited their general practitioner with a tick bite or erythema migrans in 2007 and 2008. The presence of several tick-borne pathogens in 314 ticks and 626 blood samples of this cohort were analyzed using PCR-based methods. Using multivariate logistic regression, associations were explored between pathogens detected in blood and self-reported symptoms at enrolment and during a three-month follow-up period. Results Half of the ticks removed from humans tested positive for Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis, Rickettsia helvetica, Rickettsia monacensis, Borrelia miyamotoi and several Babesia species. Among 92 Borrelia burgdorferi s. l. positive ticks, 33% carried another pathogen from a different genus. In blood of sixteen out of 626 persons with tick bites or erythema migrans, DNA was detected from Candidatus Neoehrlichia mikurensis (n = 7), Anaplasma phagocytophilum (n = 5), Babesia divergens (n = 3), Borrelia miyamotoi (n = 1) and Borrelia burgdorferi s. l. (n = 1). None of these sixteen individuals reported any overt symptoms that would indicate a corresponding illness during the three-month follow-up period. No associations were found between the presence of pathogen DNA in blood and; self-reported symptoms, with pathogen DNA in the corresponding ticks (n = 8), reported tick attachment duration, tick engorgement, or antibiotic treatment at enrolment. Conclusions Based on molecular detection techniques, the probability of infection with a tick-borne pathogen other than Lyme spirochetes after a tick bite is roughly 2.4%, in the Netherlands. Similarly, among patients with erythema migrans, the probability of a co-infection with another tick-borne pathogen is approximately 2.7%. How often these infections cause disease symptoms or to what extend co-infections affect the course of Lyme borreliosis needs further investigations. PMID:27706159

High Prevalence of Human Liver Infection by Amphimerus spp. Flukes, Ecuador

PubMed Central

Calvopiña, Manuel; Cevallos, William; Kumazawa, Hideo; Eisenberg, Joseph

2011-01-01

Amphimerus spp. flukes are known to infect mammals, but human infections have not been confirmed. Microscopy of fecal samples from 397 persons from Ecuador revealed Opisthorchiidae eggs in 71 (24%) persons. Light microscopy of adult worms and scanning electron microscopy of eggs were compatible with descriptions of Amphimerus spp. This pathogen was only observed in communities that consumed undercooked fish. PMID:22172165

Pathogenesis of the 1918 pandemic and H5N1 influenza virus infection in a guinea pig model: The antiviral potential of exogenous alpha-interferon to reduce virus shedding

USDA-ARS?s Scientific Manuscript database

Although highly pathogenic avian influenza H5N1 viruses have yet to acquire the ability to transmit efficiently among humans, the geographic expansion, and continued outbreaks in humans and avian species underscore the need for more effective influenza vaccines and antivirals. Additional small anim...

A Novel Multi-Locus Sequence Typing Scheme Reveals High Genetic Diversity of Human Pathogenic Members of the Fusarium incarnatum-F. equiseti and F. chlamydosporum Species Complexes within the U. S.

USDA-ARS?s Scientific Manuscript database

Results of the present study reveal that members of the Fusarium incarnatum-equiseti (FIESC) and F. chlamydosporum species complexes (FCSC) collectively account for approximately 15% of all fusarial infections of humans and other animals within the U. S. Moreover, the diverse toxins these fungi pro...

Epidemiology of viral pathogens of free-ranging dogs and Indian foxes in a human-dominated landscape in central India.

PubMed

Belsare, A V; Vanak, A T; Gompper, M E

2014-08-01

There is an increasing concern that free-ranging domestic dog (Canis familiaris) populations may serve as reservoirs of pathogens which may be transmitted to wildlife. We documented the prevalence of antibodies to three viral pathogens, canine parvovirus (CPV), canine distemper virus (CDV) and canine adenovirus (CAV), in free-ranging dog and sympatric Indian fox (Vulpes bengalensis) populations in and around the Great Indian Bustard Wildlife Sanctuary, in Maharashtra, central India. A total of 219 dogs and 33 foxes were sampled during the study period. Ninety-three percentage of dogs and 87% of foxes were exposed to one or more of the three pathogens. Exposure rates in dogs were high: >88% for CPV, >72% for CDV and 71% for CAV. A large proportion of adult dogs had antibodies against these pathogens due to seroconversion following earlier natural infection. The high prevalence of exposure to these pathogens across the sampling sessions, significantly higher exposure rates of adults compared with juveniles, and seroconversion in some unvaccinated dogs documented during the study period suggests that these pathogens are enzootic. The prevalence of exposure to CPV, CDV and CAV in foxes was 48%, 18% and 52%, respectively. Further, a high rate of mortality was documented in foxes with serologic evidence of ongoing CDV infection. Dogs could be playing a role in the maintenance and transmission of these pathogens in the fox population, but our findings show that most dogs in the population are immune to these pathogens by virtue of earlier natural infection, and therefore, these individuals make little current or future contribution to viral maintenance. Vaccination of this cohort will neither greatly improve their collective immune status nor contribute to herd immunity. Our findings have potentially important implications for dog disease control programmes that propose using canine vaccination as a tool for conservation management of wild carnivore populations. © 2014 Blackwell Verlag GmbH.

Abundances and profiles of antibiotic resistance genes as well as co-occurrences with human bacterial pathogens in ship ballast tank sediments from a shipyard in Jiangsu Province, China.

PubMed

Lv, Baoyi; Cui, Yuxue; Tian, Wen; Li, Jing; Xie, Bing; Yin, Fang

2018-08-15

Ship ballasting operations may transfer harmful aquatic organisms across global ocean. This study aims to reveal the occurrences and abundances of antibiotic resistance genes (ARGs) and human bacterial pathogens (HBPs) in ballast tank sediments. Nine samples were collected and respectively analyzed by real-time quantitative PCR and high-throughput sequencing technologies. Ten ARGs (aadA1, blaCTX-M, blaTEM, ermB, mefA, strB, sul1, sul2, tetM, and tetQ) and the Class-I integron gene (intI1) were highly prevalent (10 5 -10 9 gene copies/g) in ballast tank sediments. The sul1 was the most abundant ARG with the concentration of 10 8 -10 9 copies/g and intI1 was much more abundant than the ARGs in ballast tank sediments. The strong positive correlations between intI1 and ARGs (blaCTX-M, sul1, sul2 and tetM) indicated the potential spread of ARGs via horizontal gene transfer. In ballast tank sediments, 44 bacterial species were identified as HBPs and accounted for 0.13-21.46% of the total bacterial population although the three indicator pathogenic microbes (Vibrio cholerae, Escherichia coli, and Enterococci) proposed by the International Maritime Organization were not detected. Pseudomonas pseudoalcaligenes, Enterococcus hirae, Shigella sonnei and Bacillus anthracis were the dominant pathogens in ballast tank sediments. Zn and P in sediments had positive effects on the ARGs. Network analysis results indicated that sul1 and sul2 genes existed in several bacterial pathogens. Ballast tank sediments could be regarded as a carrier for the migration of ARGs. It is important to manage ballast tank sediments reasonably in order to prevent the dissemination of ARGs and bacterial pathogens. Copyright © 2018 Elsevier Inc. All rights reserved.

Abundance & distribution of trombiculid mites & Orientia tsutsugamushi, the vectors & pathogen of scrub typhus in rodents & shrews collected from Puducherry & Tamil Nadu, India.

PubMed

Candasamy, Sadanandane; Ayyanar, Elango; Paily, Kummankottil; Karthikeyan, Patricia Anitha; Sundararajan, Agatheswaran; Purushothaman, Jambulingam

2016-12-01

Human cases of scrub typhus are reported every year from Puducherry and adjoining areas in southern India. However, information on the presence of causative agent, Orientia tsutsugamushi, and its vectors is lacking. Hence, the objective of the study was to find out the vector as well as pathogen distribution in rodents and shrews present in the scrub typhus-reported areas in southern India. Trombiculid mites were collected by combing rats and shrews collected using Sherman traps and identified to species level following standard taxonomical keys. The serum samples of the animals were used for Weil-Felix test and the clots containing blood cells were used for DNA extraction and polymerase chain reaction (PCR). A total of 181 animals comprising four rodent species and one shrew species were collected from 12 villages. High proportion of chiggers was collected from the shrew, Suncus murinus (79.1%) and Rattus rattus (47.6%). A total of 10,491 trombiculid mites belonging to nine species were collected. Leptotrombidium deliense, the known vector of scrub typhus pathogen, was the predominant species (71.0%) and the chigger (L. deliense) index was 41.1 per animal. Of the 50 animals screened for the pathogen, 28 showed agglutination against OX-K in Weil-Felix test indicating the presence of antibodies against O. tsutsugamushi, the causative agent of scrub typhus. PCR carried out with the DNA extracted from blood samples of two of the animals were positive for GroEl gene of O. tsutsugamushi. L. deliense index was well above the critical limit of chigger load, indicating that all the villages were receptive for high risk of transmission of scrub typhus to human. Pathogen positivity was higher among animals collected from villages recorded for higher chigger indices due to active transmission between the chigger mites and reservoir host animals. The results are suggestive of routine vector/pathogen surveillance at hot spots to initiate timely preventive measures.