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

Streptococcus dysgalactiae subsp. dysgalactiae isolated from milk of the bovine udder as emerging pathogens: In vitro and in vivo infection of human cells and zebrafish as biological models.

PubMed

Alves-Barroco, Cinthia; Roma-Rodrigues, Catarina; Raposo, Luís R; Brás, Catarina; Diniz, Mário; Caço, João; Costa, Pedro M; Santos-Sanches, Ilda; Fernandes, Alexandra R

2018-03-25

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is a major cause of bovine mastitis and has been regarded as an animal-restricted pathogen, although rare infections have been described in humans. Previous studies revealed the presence of virulence genes encoded by phages of the human pathogen Group A Streptococcus pyogenes (GAS) in SDSD isolated from the milk of bovine udder with mastitis. The isolates SDSD VSD5 and VSD13 could adhere and internalize human primary keratinocyte cells, suggesting a possible human infection potential of bovine isolates. In this work, the in vitro and in vivo potential of SDSD to internalize/adhere human cells of the respiratory track and zebrafish as biological models was evaluated. Our results showed that, in vitro, bovine SDSD strains could interact and internalize human respiratory cell lines and that this internalization was dependent on an active transport mechanism and that, in vivo, SDSD are able to cause invasive infections producing zebrafish morbidity and mortality. The infectious potential of these isolates showed to be isolate-specific and appeared to be independent of the presence or absence of GAS phage-encoded virulence genes. Although the infection ability of the bovine SDSD strains was not as strong as the human pathogenic S. pyogenes in the zebrafish model, results suggested that these SDSD isolates are able to interact with human cells and infect zebrafish, a vertebrate infectious model, emerging as pathogens with zoonotic capability. © 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

A Bacterial Cause of Cancer: An Historical Essay

PubMed Central

2017-01-01

Abstract This article reviews the history of the discovery of microbes that increase the risk of cancer of some tissues with a special emphasis on the bacterium Helicobacter pylori and the role played by two Australian physicians, neither schooled in research, who had open minds about the shibboleth that mycobacteria (acid‐fast organisms) can survive the acid environment of the stomach, but that other pathogenic bacteria cannot. They discovered one of the most important human pathogens, Helicobacter pylori, and showed it capable of inducing severe gastric inflammatory disease. Subsequently, others built on their observations and showed it capable of inducing two gastric neoplasms: carcinoma and lymphoma. The Oncologist 2017;22:542–548 PMID:28432224

Bacteria from Animals as a Pool of Antimicrobial Resistance Genes

PubMed Central

Argudín, Maria Angeles; Deplano, Ariane; Meghraoui, Alaeddine; Dodémont, Magali; Heinrichs, Amelie; Denis, Olivier; Nonhoff, Claire; Roisin, Sandrine

2017-01-01

Antimicrobial agents are used in both veterinary and human medicine. The intensive use of antimicrobials in animals may promote the fixation of antimicrobial resistance genes in bacteria, which may be zoonotic or capable to transfer these genes to human-adapted pathogens or to human gut microbiota via direct contact, food or the environment. This review summarizes the current knowledge of the use of antimicrobial agents in animal health and explores the role of bacteria from animals as a pool of antimicrobial resistance genes for human bacteria. This review focused in relevant examples within the ESC(K)APE (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile (Klebsiella pneumoniae), Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae) group of bacterial pathogens that are the leading cause of nosocomial infections throughout the world. PMID:28587316

Prevalence, pathogenic capability, virulence genes, biofilm formation, and antibiotic resistance of Listeria in goat and sheep milk confirms need of hygienic milking conditions.

PubMed

Osman, Kamelia M; Zolnikov, Tara Rava; Samir, Ahmed; Orabi, Ahmed

2014-01-01

Goat and sheep milk is consumed by human populations throughout the world; as a result, it has been proposed as an alternative, nutrient-rich milk to feed infants allergic to cow's milk. Unfortunately, potentially harmful bacteria have not been thoroughly tested in goat or sheep milk. Listeria monocytogenes is a harmful bacterium that causes adverse health effects if ingested by humans. The purpose of this study was to estimate the prevalence and characterize the phenotype, genotype, virulence factors, biofilm formation, and antibiopotential of Listeria isolated from the milk of goat and sheep. Udder milk samples were collected from 107 goats and 102 sheep and screened for mastitis using the California mastitis test (CMT). Samples were then examined for the presence of pathogenic Listeria spp; if detected, the isolation of pathogenic Listeria (L. monocytogenes and Listeria ivanovii) was completed using isolation and identification techniques recommended by the International Organization for Standards (ISO 11290-1, 1996), in addition to serological, in vitro and in vivo pathogenicity tests. The isolates were subjected to PCR assay for virulence associated genes (hlyA, plcA, actA, and iap). Pathogenic Listeria spp. were isolated from 5·6% of goat and 3·9% sheep milk samples, with 33·3 and 25% of these selected samples respectively containing L. monocytogenes. The results of this study provide evidence of the low-likelihood of contamination leading to the presence of L. monocytogenes in raw goat and sheep milk; however, this study also confirmed a strong in vitro ability for biofilm formation and pathogenic capability of L. monocytogenes if discovered in the milk. L. monocytogenes may be present in goat and sheep milk and in order to reduce the exposure, hygienic milking conditions must be employed for the milk to be considered a safe alternative for human consumption.

Prevalence, pathogenic capability, virulence genes, biofilm formation, and antibiotic resistance of Listeria in goat and sheep milk confirms need of hygienic milking conditions

PubMed Central

Osman, Kamelia M; Zolnikov, Tara Rava; Samir, Ahmed; Orabi, Ahmed

2014-01-01

Goat and sheep milk is consumed by human populations throughout the world; as a result, it has been proposed as an alternative, nutrient-rich milk to feed infants allergic to cow’s milk. Unfortunately, potentially harmful bacteria have not been thoroughly tested in goat or sheep milk. Listeria monocytogenes is a harmful bacterium that causes adverse health effects if ingested by humans. The purpose of this study was to estimate the prevalence and characterize the phenotype, genotype, virulence factors, biofilm formation, and antibiopotential of Listeria isolated from the milk of goat and sheep. Udder milk samples were collected from 107 goats and 102 sheep and screened for mastitis using the California mastitis test (CMT). Samples were then examined for the presence of pathogenic Listeria spp; if detected, the isolation of pathogenic Listeria (L. monocytogenes and Listeria ivanovii) was completed using isolation and identification techniques recommended by the International Organization for Standards (ISO 11290-1, 1996), in addition to serological, in vitro and in vivo pathogenicity tests. The isolates were subjected to PCR assay for virulence associated genes (hlyA, plcA, actA, and iap). Pathogenic Listeria spp. were isolated from 5.6% of goat and 3.9% sheep milk samples, with 33.3 and 25% of these selected samples respectively containing L. monocytogenes. The results of this study provide evidence of the low-likelihood of contamination leading to the presence of L. monocytogenes in raw goat and sheep milk; however, this study also confirmed a strong in vitro ability for biofilm formation and pathogenic capability of L. monocytogenes if discovered in the milk. L. monocytogenes may be present in goat and sheep milk and in order to reduce the exposure, hygienic milking conditions must be employed for the milk to be considered a safe alternative for human consumption. PMID:24548157

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.

Culture Collections and Public Health Research

USDA-ARS?s Scientific Manuscript database

Listeria monocytogenes is a foodborne pathogen capable of causing serious invasive illness in humans and other animals, and a leading cause of food recalls. The establishment and growth of a research collection of Listeria isolates has been critical in developing an evolutionary genetic framework, n...

Evolutionarily distinct bacteriophage endolysins featuring conserved peptidoglycan cleavage sites protect mice from MRSA infection

USDA-ARS?s Scientific Manuscript database

Staphylococcus aureus is a Gram-positive pathogen relevant for both human and animal health. With multi-drug resistant S. aureus strains becoming increasingly prevalent, alternative therapeutics are urgently needed. Bacteriophage endolysins (peptidoglycan hydrolases, PGH) are capable of killing Gra...

Crossing borders -- the global dimension of rust monitoring

USDA-ARS?s Scientific Manuscript database

Rust pathogens are highly mobile trans-boundary organisms capable of rapid, long distance movements, either by wind-assisted or accidental human-mediated transmission. Emergence of new virulent races in one country can very rapidly have implications for other countries or regions. Detection of stem ...

Persistence of salmonella Typhimurium in Nopal

USDA-ARS?s Scientific Manuscript database

Having documented information available on the capability of Salmonella to remain in the cladode tissue it is important to understand the role of nopal on the lifecycle of enteropathogenic bacteria in humans, as well as for management and control programs of theses pathogens in plants. Because of th...

Iquitos Virus: A Novel Reassortant Orthobunyavirus Associated with Human Illness in Peru

PubMed Central

Aguilar, Patricia V.; Barrett, Alan D.; Saeed, Mohammad F.; Watts, Douglas M.; Russell, Kevin; Guevara, Carolina; Ampuero, Julia S.; Suarez, Luis; Cespedes, Manuel; Montgomery, Joel M.; Halsey, Eric S.; Kochel, Tadeusz J.

2011-01-01

Oropouche (ORO) virus, a member of the Simbu serogroup, is one of the few human pathogens in the Orthobunyavirus genus in the family Bunyaviridae. Genetic analyses of ORO-like strains from Iquitos, Peru, identified a novel reassortant containing the S and L segments of ORO virus and the M segment of a novel Simbu serogroup virus. This new pathogen, which we named Iquitos (IQT) virus, was first isolated during 1999 from a febrile patient in Iquitos, an Amazonian city in Peru. Subsequently, the virus was identified as the cause of outbreaks of “Oropouche fever” during 2005 and 2006 in Iquitos. In addition to the identification of 17 isolates of IQT virus between 1999 and 2006, surveys for neutralizing antibody among Iquitos residents revealed prevalence rates of 14.9% for ORO virus and 15.4% for IQT virus. Limited studies indicate that prior infection with ORO virus does not seem to protect against disease caused with the IQT virus infection. Identification of a new Orthobunyavirus human pathogen in the Amazon region of Peru highlights the need for strengthening surveillance activities and laboratory capabilities, and investigating the emergence of new pathogens in tropical regions of South America. PMID:21949892

Healthy plants: necessary for a balanced 'One Health' concept.

PubMed

Fletcher, Jacqueline; Franz, David; Leclerc, J Eugene

2009-01-01

All life forms depend ultimately upon sunlight to create the energy 'currency' required for the functions of living. Green plants can make that conversion directly but the rest of us would perish without access to foods derived, directly or indirectly, from plants. We also require their fibre which we use for clothing, building and other purposes. However, plants, just as humans and animals, are attacked by pathogens that cause a myriad of symptoms that can lead to reduced yields, lower quality products and diminished nutritional value. Plant pathogens share many features with their human and animal counterparts. Some pathogens - whether of humans, animals, or plants - have nimble genomes or the ability to pirate genes from other organisms via mobile elements. Some have developed the ability to cross kingdoms in their host ranges. Many others share virulence factors, such as the type III secretion system (T3SS) or mechanisms for sensing population density, that work equally well in all kingdoms. Certain pathogens of hosts in all kingdoms rely upon insect vectors and use similar mechanisms to ensure dispersal (and sometimes survival) in this way. Plant-pathogen interactions have more direct consequence for humans when the microbes are human pathogens such as Escherichia coli 0157:H7 and Salmonella spp., which can contaminate fresh produce or when they produce metabolites, such as mycotoxins, which are harmful when consumed. Finally, national biosecurity concerns and the need for prevention, preparedness and forensic capabilities cross all kingdom barriers. Thus, our communities that focus on one of these kingdoms have much to learn from one another and a complete and balanced 'One Health' initiative must be tripartite, embracing the essential components of healthy plants, healthy animals and healthy people.

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...

Inactivation of avirulent Yersinia pestis in beef bologna by gamma irradiation

USDA-ARS?s Scientific Manuscript database

Yersinia pestis, a psychrotrophic pathogen capable of growth at refrigeration temperatures, can cause pharyngeal and gastrointestinal plague in humans as a result of eating contaminated foods. Because Y. pestis is listed as a select agent for food safety and defense, evaluation of food safety interv...

Evaluation of reference genes in Vibrio parahaemolyticus for gene expression analysis using quantitative RT-PCR

USDA-ARS?s Scientific Manuscript database

Vibrio parahaemolyticus is a significant human pathogen capable of causing foodborne gastroenteritis associated with the consumption of contaminated raw or undercooked seafood. Quantitative RT-PCR (qRT-PCR) is a useful tool for studying gene expression in V. parahaemolyticus to characterize the viru...

Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium.

PubMed

Smith, I M; Baker, A; Arneborg, N; Jespersen, L

2015-11-01

The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast-mediated epithelial cell barrier protection from Salmonella invasion, thus encouraging future efforts aimed at confirming the observed effects in vivo and driving further strain development towards novel yeast probiotics. © 2015 The Society for Applied Microbiology.

[New insight into bacterial zoonotic pathogens posing health hazards to humans].

PubMed

Ciszewski, Marcin; Czekaj, Tomasz; Szewczyk, Eligia Maria

2014-01-01

This article presents the problem of evolutionary changes of zoonotic pathogens responsible for human diseases. Everyone is exposed to the risk of zoonotic infection, particularly employees having direct contact with animals, i.e. veterinarians, breeders, butchers and workers of animal products' processing industry. The article focuses on pathogens monitored by the European Centre for Disease Prevention and Control (ECDC), which has been collecting statistical data on zoonoses from all European Union countries for 19 years and publishing collected data in annual epidemiological reports. Currently, the most important 11 pathogens responsible for causing human zoonotic diseases are being monitored, of which seven are bacteria: Salmonella spp., Campylobacter spp., Listeria monocytogenes, Mycobacterium bovis, Brucella spp., Coxiella burnetti and Verotoxin-producing E. coli (VTEC)/Shiga-like toxin producing E. coli (STEC). As particularly important are considered foodborne pathogens. The article also includes new emerging zoonotic bacteria, which are not currently monitored by ECDC but might pose a serious epidemiological problem in a foreseeable future: Streptococcus iniae, S. suis, S. dysgalactiae and staphylococci: Staphylococcus intermedius, S. pseudintermedius. Those species have just crossed the animal-human interspecies barrier. The exact mechanism of this phenomenon remains unknown, it is connected, however, with genetic variability, capability to survive in changing environment. These abilities derive from DNA rearrangement and horizontal gene transfer between bacterial cells. Substantial increase in the number of scientific publications on this subject, observed over the last few years, illustrates the importance of the problem.

Mycoplasmas and their host: emerging and re-emerging minimal pathogens.

PubMed

Citti, Christine; Blanchard, Alain

2013-04-01

Commonly known as mycoplasmas, bacteria of the class Mollicutes include the smallest and simplest life forms capable of self replication outside of a host. Yet, this minimalism hides major human and animal pathogens whose prevalence and occurrence have long been underestimated. Owing to advances in sequencing methods, large data sets have become available for a number of mycoplasma species and strains, providing new diagnostic approaches, typing strategies, and means for comprehensive studies. A broader picture is thus emerging in which mycoplasmas are successful pathogens having evolved a number of mechanisms and strategies for surviving hostile environments and adapting to new niches or hosts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mobilome differences between Salmonella enterica serovars Anatum and Typhimurium isolated from cattle and humans and potential impact on virulence

USDA-ARS?s Scientific Manuscript database

Salmonella enterica subsp. enterica is an important group of pathogens capable of inhabiting a range of niches and hosts with varying degrees of impact, from commensal colonization to invasive infection. Recent outbreaks of multi-drug resistant S. enterica, attributed to consumption of contaminated ...

Pathogen-Sensing and Regulatory T Cells: Integrated Regulators of Immune Responses

PubMed Central

Grossman, Zvi; Paul, William E.

2014-01-01

We present the concept that pathogen-sensing and Tregs mutually regulate immune responses to conventional and tumor antigens through countervailing effects on dendritic cells. Normally, conventional CD4 T cells recognizing their cognate antigen-presented by a dendritic cell will respond only if the dendritic cell also receives a signal through its pathogen-sensing/ danger / adjuvant recognition systems (the pathogen-sensing triad). However, if Tregs capable of interacting with the same DC are absent, dendritic cells are competent to present antigens, both foreign and self, even without the stimulation provided by the pathogen-sensing triad. Tregs recognizing an antigen presented by the DC that is also presenting antigen to a conventional CD4 T cell will prevent such responses but a signal delivered by a member of the pathogen-sensing traid will overcome the Tregs’inhibitory action and will allow responses to go forward. These considerations take on special meaning for responses to “weak antigens” such as many of the antigens displayed by spontaneous human tumors. PMID:24894087

Zebrafish and Streptococcal Infections.

PubMed

Saralahti, A; Rämet, M

2015-09-01

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

A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus.

PubMed

Tigabu, Bersabeh; Rasmussen, Lynn; White, E Lucile; Tower, Nichole; Saeed, Mohammad; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W; Noah, James W

2014-04-01

Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.

A BSL-4 High-Throughput Screen Identifies Sulfonamide Inhibitors of Nipah Virus

PubMed Central

Tigabu, Bersabeh; Rasmussen, Lynn; White, E. Lucile; Tower, Nichole; Saeed, Mohammad; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W.

2014-01-01

Abstract Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses. PMID:24735442

Nutritional Requirements and Their Importance for Virulence of Pathogenic Cryptococcus Species

PubMed Central

Watkins, Rhys A.; Johnston, Simon A.

2017-01-01

Cryptococcus sp. are basidiomycete yeasts which can be found widely, free-living in the environment. Interactions with natural predators, such as amoebae in the soil, are thought to have promoted the development of adaptations enabling the organism to survive inside human macrophages. Infection with Cryptococcus in humans occurs following inhalation of desiccated yeast cells or spore particles and may result in fatal meningoencephalitis. Human disease is caused almost exclusively by the Cryptococcus neoformans species complex, which predominantly infects immunocompromised patients, and the Cryptococcus gattii species complex, which is capable of infecting immunocompetent individuals. The nutritional requirements of Cryptococcus are critical for its virulence in animals. Cryptococcus has evolved a broad range of nutrient acquisition strategies, many if not most of which also appear to contribute to its virulence, enabling infection of animal hosts. In this review, we summarise the current understanding of nutritional requirements and acquisition in Cryptococcus and offer perspectives to its evolution as a significant pathogen of humans. PMID:28974017

Treatment alternatives of slaughterhouse wastes, and their effect on the inactivation of different pathogens: a review.

PubMed

Franke-Whittle, Ingrid H; Insam, Heribert

2013-05-01

Slaughterhouse wastes are a potential reservoir of bacterial, viral, prion and parasitic pathogens, capable of infecting both animals and humans. A quick, cost effective and safe disposal method is thus essential in order to reduce the risk of disease following animal slaughter. Different methods for the disposal of such wastes exist, including composting, anaerobic digestion (AD), alkaline hydrolysis (AH), rendering, incineration and burning. Composting is a disposal method that allows a recycling of the slaughterhouse waste nutrients back into the earth. The high fat and protein content of slaughterhouse wastes mean however, that such wastes are an excellent substrate for AD processes, resulting in both the disposal of wastes, a recycling of nutrients (soil amendment with sludge), and in methane production. Concerns exist as to whether AD and composting processes can inactivate pathogens. In contrast, AH is capable of the inactivation of almost all known microorganisms. This review was conducted in order to compare three different methods of slaughterhouse waste disposal, as regards to their ability to inactivate various microbial pathogens. The intention was to investigate whether AD could be used for waste disposal (either alone, or in combination with another process) such that both energy can be obtained and potentially hazardous materials be disposed of.

Treatment alternatives of slaughterhouse wastes, and their effect on the inactivation of different pathogens: A review

PubMed Central

2013-01-01

Slaughterhouse wastes are a potential reservoir of bacterial, viral, prion and parasitic pathogens, capable of infecting both animals and humans. A quick, cost effective and safe disposal method is thus essential in order to reduce the risk of disease following animal slaughter. Different methods for the disposal of such wastes exist, including composting, anaerobic digestion (AD), alkaline hydrolysis (AH), rendering, incineration and burning. Composting is a disposal method that allows a recycling of the slaughterhouse waste nutrients back into the earth. The high fat and protein content of slaughterhouse wastes mean however, that such wastes are an excellent substrate for AD processes, resulting in both the disposal of wastes, a recycling of nutrients (soil amendment with sludge), and in methane production. Concerns exist as to whether AD and composting processes can inactivate pathogens. In contrast, AH is capable of the inactivation of almost all known microorganisms. This review was conducted in order to compare three different methods of slaughterhouse waste disposal, as regards to their ability to inactivate various microbial pathogens. The intention was to investigate whether AD could be used for waste disposal (either alone, or in combination with another process) such that both energy can be obtained and potentially hazardous materials be disposed of. PMID:22694189

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.

Zoonotic pathogens from feral swine that pose a significant threat to public health.

PubMed

Brown, V R; Bowen, R A; Bosco-Lauth, A M

2018-06-01

The natural fecundity of suids, great ability to adapt to new habitats and desire for local hunting opportunities leading to translocation of feral pigs to regions where they are not yet established have all been instrumental in the home range expansion of feral swine. Feral swine populations in the United States continue to expand, wreaking havoc on agricultural lands, further compromising threatened and endangered species, and posing a microbiological threat to humans, domestic livestock and companion animals. This manuscript thoroughly reviews zoonotic diseases of concern including brucellosis, bovine tuberculosis, leptospirosis, enteric pathogens, both Salmonella spp. and shiga toxin-producing Escherichia coli, and hepatitis E. These pathogens are not a comprehensive list of microbes that are capable of infecting both humans and feral swine, but rather have been selected as they are known to infect US feral swine, direct transmission between wild suids and humans has previously been documented, or they have been shown to be readily transmitted during processing or consumption of feral swine pork. Humans that interact directly or indirectly with feral swine are at much higher risk for the development of a number of zoonotic pathogens. Numerous case reports document transmission events from feral swine and wild boar to humans, and the resulting diseases may be mild and self-limiting, chronic or fatal. Individuals that interact with feral swine should take preventative measures to minimize the risk of disease transmission and all meat should be thoroughly cooked. Additionally, public health campaigns to increase knowledge of the risks associated with feral swine are imperative. © 2018 Blackwell Verlag GmbH.

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.

Calpains: Potential Targets for Alternative Chemotherapeutic Intervention Against Human Pathogenic Trypanosomatids

PubMed Central

M.H, Branquinha; F.A, Marinho; L.S, Sangenito; S.S.C, Oliveira; K.C, Gonçalves; V, Ennes-Vidal; C.M, d’Avila-Levy; A.L.S, Santos

2013-01-01

The treatment for both leishmaniasis and trypanosomiasis, which are severe human infections caused by trypanosomatids belonging to Leishmania and Trypanosoma genera, respectively, is extremely limited because of concerns of toxicity and efficacy with the available anti-protozoan drugs, as well as the emergence of drug resistance. Consequently, the urgency for the discovery of new trypanosomatid targets and novel bioactive compounds is particularly necessary. In this context, the investigation of changes in parasite gene expression between drug resistant/sensitive strains and in the up-regulation of virulence-related genes in infective forms has brought to the fore the involvement of calpain-like proteins in several crucial pathophysiological processes performed by trypanosomatids. These studies were encouraged by the publication of the complete genome sequences of three human pathogenic trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, which allowed in silico analyses that in turn directed the identification of numerous genes with interesting chemotherapeutic characteristics, including a large family of calpain-related proteins, in which to date 23 genes were assigned as calpains in T. brucei, 40 in T. cruzi and 33 in L. braziliensis. In the present review, we intend to add to these biochemical/biological reports the investigations performed upon the inhibitory capability of calpain inhibitors against human pathogenic trypanosomatids. PMID:23899207

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

Production of the plant hormone auxin by Salmonella and its role in the interactions with plants and animals

USDA-ARS?s Scientific Manuscript database

The ability of human enteric pathogens to colonize plants and use them as alternate hosts is now well established. Salmonella enterica, similarly to other phytobacteria, appears to be capable of producing the plant hormone auxin (IAA) via IpdC, an indole pyruvate (IPyA) decarboxylase. ipdC is a key ...

gyrB as a phylogenetic discriminator for members of the Bacillus anthracis-cereus-thuringiensis group

NASA Technical Reports Server (NTRS)

La Duc, Myron T.; Satomi, Masataka; Agata, Norio; Venkateswaran, Kasthuri

2004-01-01

Bacillus anthracis, the causative agent of the human disease anthrax, Bacillus cereus, a food-borne pathogen capable of causing human illness, and Bacillus thuringiensis, a well-characterized insecticidal toxin producer, all cluster together within a very tight clade (B. cereus group) phylogenetically and are indistinguishable from one another via 16S rDNA sequence analysis. As new pathogens are continually emerging, it is imperative to devise a system capable of rapidly and accurately differentiating closely related, yet phenotypically distinct species. Although the gyrB gene has proven useful in discriminating closely related species, its sequence analysis has not yet been validated by DNA:DNA hybridization, the taxonomically accepted "gold standard". We phylogenetically characterized the gyrB sequences of various species and serotypes encompassed in the "B. cereus group," including lab strains and environmental isolates. Results were compared to those obtained from analyses of phenotypic characteristics, 16S rDNA sequence, DNA:DNA hybridization, and virulence factors. The gyrB gene proved more highly differential than 16S, while, at the same time, as analytical as costly and laborious DNA:DNA hybridization techniques in differentiating species within the B. cereus group.

Neither non-toxigenic Staphylococcus aureus nor commensal S. epidermidi activates NLRP3 inflammasomes in human conjunctival goblet cells

PubMed Central

Li, Dayu; Hodges, Robin R; Bispo, Paulo; Gilmore, Michael S; Gregory-Ksander, Meredith; Dartt, Darlene A

2017-01-01

Purpose The conjunctiva is a wet mucosal surface surrounding the cornea that is continuously exposed to pathogens. Nevertheless, persistent inflammation is not observed. We examined if the NOD-like receptor pyrin domain 3 (NLRP3) inflammasome functions as a sensor that distinguishes commensal and non-pathogenic bacteria from pathogenic bacteria in human conjunctival goblet cells. Methods Goblet cells were grown from human conjunctiva and co-cultured with commensal Staphylococcus epidermidis, isogenic non-toxigenic S. aureus ACL135 and as a control toxigenic S. aureus RN6390. Activation of the NLRP3 inflammasome was determined by measuring changes in NF-κB activity, expression of pro-interleukin (IL)-1β and NLRP3, activation of caspase-1 and secretion of mature IL-1β. Goblet cell mucin secretion was measured in parallel. Results While all three strains of bacteria were able to bind to goblet cells, neither commensal S. epidermidis nor isogenic non-toxigenic S. aureus ACL135 was able to stimulate an increase in (1) NF-κB activity, (2) pro-IL-1β and NLRP3 expression, (3) caspase-1 activation, (4) mature IL-1β and (5) mucin secretion. Toxigenic S. aureus, the positive control, increased these values: knockdown of NLRP3 with small interfering RNA (siRNA) completely abolished the toxigenic S. aureus-induced expression of pro-IL-1β and secretion of mature IL-1β. Conclusions We conclude that NLRP3 serves as a sensor capable of discriminating commensal and non-pathogenic bacteria from pathogenic bacteria in conjunctival goblet cells, and that activation of the NLRP3 inflammasome induced by pathogenic bacteria mediates secretion of both mature IL-1β and large secretory mucins from these cells. PMID:29354725

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.

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

PubMed Central

Willinger, Tim; Rongvaux, Anthony; Takizawa, Hitoshi; Yancopoulos, George D.; Valenzuela, David M.; Murphy, Andrew J.; Auerbach, Wojtek; Eynon, Elizabeth E.; Stevens, Sean; Manz, Markus G.; Flavell, Richard A.

2011-01-01

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and function of human myeloid cells and the absence of human immune responses at mucosal surfaces, such as the lung. To overcome this, we generated human IL-3/GM-CSF knock-in (hIL-3/GM-CSF KI) mice. These mice faithfully expressed human GM-CSF and IL-3 and developed pulmonary alveolar proteinosis because of elimination of mouse GM-CSF. We demonstrate that hIL-3/GM-CSF KI mice engrafted with human CD34+ hematopoietic cells had improved human myeloid cell reconstitution in the lung. In particular, hIL-3/GM-CSF KI mice supported the development of human alveolar macrophages that partially rescued the pulmonary alveolar proteinosis syndrome. Moreover, human alveolar macrophages mounted correlates of a human innate immune response against influenza virus. The hIL-3/GM-CSF KI mice represent a unique mouse model that permits the study of human mucosal immune responses to lung pathogens. PMID:21262803

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

Microwaving human faecal sludge as a viable sanitation technology option for treatment and value recovery - A critical review.

PubMed

Afolabi, Oluwasola O D; Sohail, M

2017-02-01

The prolonged challenges and terrible consequences of poor sanitation, especially in developing economies, call for the exploration of new sustainable sanitation technologies. Such technologies must be: capable of effectively treating human faecal wastes without any health or environmental impacts; scalable to address rapid increases in population and urbanization; capable of meeting environmental regulations and standards for faecal management; and competitive with existing strategies. Further and importantly, despite its noxiousness and pathogenic load, the chemical composition of human faecal sludge indicates that it could be considered a potentially valuable, nutrient-rich renewable resource, rather than a problematic waste product. New approaches to faecal sludge management must consequently seek to incorporate a 'valuable resource recovery' approach, compatible with stringent treatment requirements. This review intends to advance the understanding of human faecal sludge as a sustainable organic-rich resource that is typically high in moisture (up to 97 per cent), making it a suitable candidate for dielectric heating, i.e. microwave irradiation, to promote faecal treatment, while also recovering value-added products such as ammonia liquor concentrate (suitable for fertilizers) and chars (suitable for fuel) - which can provide an economic base to sustain the technology. Additionally, microwaving human faecal sludge represents a thermally effective approach that can destroy pathogens, eradicate the foul odour associated human faecal sludge, while also preventing hazardous product formations and/or emissions, aside from other benefits such as improved dewaterability and heavy metals recovery. Key technological parameters crucial for scaling the technology as a complementary solution to the challenges of onsite sanitation are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of nitroethane, 2-nitro-1-propanol, lauric acid, Lauricidin and the Hawaiian marine algae, Chaetoceros, for potential broad-spectrum control of anaerobically grown lactic acid bacteria

USDA-ARS?s Scientific Manuscript database

The gastrointestinal tract of bovines often contains bacteria that contribute to disorders of the rumen and may also contain foodborne or opportunistic human pathogens as well as bacteria capable of causing mastitis in cows. Thus, there is a need to develop broad-spectrum therapies that are effecti...

Development of a dual vaccine for prevention of Brucella abortus infection and Escherichia coli O157:H7 intestinal colonization.

PubMed

Iannino, Florencia; Herrmann, Claudia K; Roset, Mara S; Briones, Gabriel

2015-05-05

Zoonoses that affect human and animal health have an important economic impact. In the study now presented, a bivalent vaccine has been developed that has the potential for preventing the transmission from cattle to humans of two bacterial pathogens: Brucella abortus and Shiga toxin-producing Escherichia coli (STEC). A 66kDa chimeric antigen, composed by EspA, Intimin, Tir, and H7 flagellin (EITH7) from STEC, was constructed and expressed in B. abortus Δpgm vaccine strain (BabΔpgm). Mice orally immunized with BabΔpgm(EITH7) elicited an immune response with the induction of anti-EITH7 antibodies (IgA) that clears an intestinal infection of E. coli O157:H7 three times faster (t=4 days) than mice immunized with BabΔpgm carrier strain (t=12 days). As expected, mice immunized with BabΔpgm(EITH7) strain also elicited a protective immune response against B. abortus infection. A Brucella-based vaccine platform is described capable of eliciting a combined protective immune response against two bacterial pathogens with diverse lifestyles-the intracellular pathogen B. abortus and the intestinal extracellular pathogen STEC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular methods for pathogen and microbial community detection and characterization: current and potential application in diagnostic microbiology.

PubMed

Sibley, Christopher D; Peirano, Gisele; Church, Deirdre L

2012-04-01

Clinical microbiology laboratories worldwide have historically relied on phenotypic methods (i.e., culture and biochemical tests) for detection, identification and characterization of virulence traits (e.g., antibiotic resistance genes, toxins) of human pathogens. However, limitations to implementation of molecular methods for human infectious diseases testing are being rapidly overcome allowing for the clinical evaluation and implementation of diverse technologies with expanding diagnostic capabilities. The advantages and limitation of molecular techniques including real-time polymerase chain reaction, partial or whole genome sequencing, molecular typing, microarrays, broad-range PCR and multiplexing will be discussed. Finally, terminal restriction fragment length polymorphism (T-RFLP) and deep sequencing are introduced as technologies at the clinical interface with the potential to dramatically enhance our ability to diagnose infectious diseases and better define the epidemiology and microbial ecology of a wide range of complex infections. Copyright © 2012 Elsevier B.V. All rights reserved.

Development of an Integrated Metabolomic Profiling Approach for Infectious Diseases Research

PubMed Central

Lv, Haitao; Hung, Chia S.; Chaturvedi, Kaveri S.; Hooton, Thomas M.; Henderson, Jeffrey P.

2013-01-01

Metabolomic profiling offers direct insights into the chemical environment and metabolic pathway activities at sites of human disease. During infection, this environment may receive important contributions from both host and pathogen. Here we apply untargeted metabolomics approach to identify compounds associated with an E. coli urinary tract infection population. Correlative and structural data from minimally processed samples were obtained using an optimized LC-MS platform capable of resolving ∼2300 molecular features. Principal components analysis readily distinguished patient groups and multiple supervised chemometric analyses resolved robust metabolomic shifts between groups. These analyses revealed nine compounds whose provisional structures suggest candidate infection-associated endocrine, catabolic, and lipid pathways. Several of these metabolite signatures may derive from microbial processing of host metabolites. Overall, this study highlights the ability of metabolomic approaches to directly identify compounds encountered by, and produced from, bacterial pathogens within human hosts. PMID:21922104

Microbial hitchhikers on marine plastic debris: Human exposure risks at bathing waters and beach environments.

PubMed

Keswani, Anisha; Oliver, David M; Gutierrez, Tony; Quilliam, Richard S

2016-07-01

Marine plastic debris is well characterized in terms of its ability to negatively impact terrestrial and marine environments, endanger coastal wildlife, and interfere with navigation, tourism and commercial fisheries. However, the impacts of potentially harmful microorganisms and pathogens colonising plastic litter are not well understood. The hard surface of plastics provides an ideal environment for opportunistic microbial colonisers to form biofilms and might offer a protective niche capable of supporting a diversity of different microorganisms, known as the "Plastisphere". This biotope could act as an important vector for the persistence and spread of pathogens, faecal indicator organisms (FIOs) and harmful algal bloom species (HABs) across beach and bathing environments. This review will focus on the existent knowledge and research gaps, and identify the possible consequences of plastic-associated microbes on human health, the spread of infectious diseases and bathing water quality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Langerhans Cells and Their Role in Oral Mucosal Diseases

PubMed Central

Upadhyay, Juhi; Upadhyay, Ram B; Agrawal, Pankaj; Jaitley, Shweta; Shekhar, Rhitu

2013-01-01

Dendritic cells are arguably the most potent antigen-presenting cells and may be the only cells capable of initiating the adaptive immune response. The epithelial residents of dendritic cells are Langerhans cells, which serve as the “sentinels” of the mucosa, altering the immune system not only to pathogen entry but also of tolerance to self antigen and commensal microbes. Oral mucosal Langerhans cells are capable of engaging and internalizing a wide variety of pathogens and have been found responsive to nickel in patients with nickel allergies, oral Candida species, oral lichen planus, lichenoid drug eruptions, graft versus host diseases, periodontal diseases median rhomboid glossitis, human immunodeficiency virus infection, hairy leukoplakia of the tongue, and oral squamous cell carcinoma. Review focuses on the role of antigen-presenting cells in particular Langerhans cells to better understand the mechanisms underlying immune responses. In this review, comprehensive detail about mucosal diseases has been compiled using the PubMed database and through textbooks. PMID:24251267

Proteomic analyses of host and pathogen responses during bovine mastitis.

PubMed

Boehmer, Jamie L

2011-12-01

The pursuit of biomarkers for use as clinical screening tools, measures for early detection, disease monitoring, and as a means for assessing therapeutic responses has steadily evolved in human and veterinary medicine over the past two decades. Concurrently, advances in mass spectrometry have markedly expanded proteomic capabilities for biomarker discovery. While initial mass spectrometric biomarker discovery endeavors focused primarily on the detection of modulated proteins in human tissues and fluids, recent efforts have shifted to include proteomic analyses of biological samples from food animal species. Mastitis continues to garner attention in veterinary research due mainly to affiliated financial losses and food safety concerns over antimicrobial use, but also because there are only a limited number of efficacious mastitis treatment options. Accordingly, comparative proteomic analyses of bovine milk have emerged in recent years. Efforts to prevent agricultural-related food-borne illness have likewise fueled an interest in the proteomic evaluation of several prominent strains of bacteria, including common mastitis pathogens. The interest in establishing biomarkers of the host and pathogen responses during bovine mastitis stems largely from the need to better characterize mechanisms of the disease, to identify reliable biomarkers for use as measures of early detection and drug efficacy, and to uncover potentially novel targets for the development of alternative therapeutics. The following review focuses primarily on comparative proteomic analyses conducted on healthy versus mastitic bovine milk. However, a comparison of the host defense proteome of human and bovine milk and the proteomic analysis of common veterinary pathogens are likewise introduced.

Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus.

PubMed

Faber, Milosz; Li, Jianwei; Kean, Rhonda B; Hooper, D Craig; Alugupalli, Kishore R; Dietzschold, Bernhard

2009-07-07

Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.

The presence of highly disruptive 16S rRNA mutations in clinical samples indicates a wider role for mutations of the mitochondrial ribosome in human disease

PubMed Central

Elson, Joanna L.; Smith, Paul M.; Greaves, Laura C.; Lightowlers, Robert N.; Chrzanowska-Lightowlers, Zofia M.A.; Taylor, Robert W.; Vila-Sanjurjo, Antón

2015-01-01

Mitochondrial DNA mutations are well recognized as an important cause of disease, with over two hundred variants in the protein encoding and mt-tRNA genes associated with human disorders. In contrast, the two genes encoding the mitochondrial rRNAs (mt-rRNAs) have been studied in far less detail. This is because establishing the pathogenicity of mt-rRNA mutations is a major diagnostic challenge. Only two disease causing mutations have been identified at these loci, both mapping to the small subunit (SSU). On the large subunit (LSU), however, the evidence for the presence of pathogenic LSU mt-rRNA changes is particularly sparse. We have previously expanded the list of deleterious SSU mt-rRNA mutations by identifying highly disruptive base changes capable of blocking the activity of the mitoribosomal SSU. To do this, we used a new methodology named heterologous inferential analysis (HIA). The recent arrival of near-atomic-resolution structures of the human mitoribosomal LSU, has enhanced the power of our approach by permitting the analysis of the corresponding sites of mutation within their natural structural context. Here, we have used these tools to determine whether LSU mt-rRNA mutations found in the context of human disease and/or ageing could disrupt the function of the mitoribosomal LSU. Our results clearly show that, much like the for SSU mt-rRNA, LSU mt-rRNAs mutations capable of compromising the function of the mitoribosomal LSU are indeed present in clinical samples. Thus, our work constitutes an important contribution to an emerging view of the mitoribosome as an important element in human health. PMID:26349026

Assessment of Climate Change and Vector-borne Diseases in the United States

NASA Astrophysics Data System (ADS)

Monaghan, A. J.; Beard, C. B.; Eisen, R. J.; Barker, C. M.; Garofalo, J.; Hahn, M.; Hayden, M.; Ogden, N.; Schramm, P.

2016-12-01

Vector-borne diseases are illnesses that are transmitted by vectors, which include mosquitoes, ticks, and fleas. The seasonality, distribution, and prevalence of vector-borne diseases are influenced significantly by climate factors, primarily high and low temperature extremes and precipitation patterns. In this presentation we summarize key findings from Chapter 5 ("Vector-borne Diseases") of the recently published USGCRP Scientific Assessment of the Impacts of Climate Change on Human Health in the United States. Climate change is expected to alter geographic and seasonal distributions of vectors and vector-borne diseases, leading to earlier activity and northward range expansion of ticks capable of carrying the bacteria that cause Lyme disease and other pathogens, and influencing the distribution, abundance and prevalence of infection in mosquitoes that transmit West Nile virus and other pathogens. The emergence or reemergence of vector-borne pathogens is also likely.

[Usefulness of the molecular techniques for detecting and/or identifing of parasites and fungi in humans and animals or pathogens transmitted by ticks (Part I)].

PubMed

Myjak, P; Majewska, A C; Bajer, A; Siński, E; Wedrychowicz, H; Gołab, E; Budak, A; Stańczak, J

2001-01-01

After a long period of using basic microscopic, immunological and biochemical methods for diagnosis, rapid development of nucleic acids investigation enabled introduction of specific and sensitive methods of detection of pathogenic agents on the molecular level. Among others, polymerase chain reaction (PCR), discovered in mid of 80'ies and then automatized, offered an attractive alternative to conventional testing systems. In this paper we describe reliable diagnostic tests widely used in the world, including Poland, and capable of detecting different disease agents as parasites and fungi in clinical specimens and pathogens of emerging zoonotic diseases in ticks. The possibilities of using molecular methods for determination of Plasmodium falciparum drug resistance is also discussed. Moreover, the report offers information concerning kinds of molecular tests and institutions in which there are executed.

Serotype O18 avian pathogenic and neonatal meningitis Escherichia coli strains employ similar pathogenic strategies for the onset of meningitis.

PubMed

Krishnan, Subramanian; Chang, Alexander C; Hodges, Jacqueline; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette; Nicholson, Bryon A; Nolan, Lisa K; Prasadarao, Nemani V

2015-01-01

Neonatal meningitis Escherichia coli K1 (NMEC) are thought to be transmitted from mothers to newborns during delivery or by nosocomial infections. However, the source of E. coli K1 causing these infections is not clear. Avian pathogenic E. coli (APEC) have the potential to cause infection in humans while human E. coli have potential to cause colibacillosis in poultry, suggesting that these strains may lack host specificity. APEC strains are capable of causing meningitis in newborn rats; however, it is unclear whether these bacteria use similar mechanisms to that of NMEC to establish disease. Using four representative APEC and NMEC strains that belong to serotype O18, we demonstrate that these strains survive in human serum similar to that of the prototypic NMEC strain E44, a derivative of RS218. These bacteria also bind and enter both macrophages and human cerebral microvascular endothelial cells (HCMEC/D3) with similar frequency as that of E44. The amino acid sequences of the outer membrane protein A (OmpA), an important virulence factor in the pathogenesis of meningitis, are identical within these representative APEC and NMEC strains. Further, these strains also require FcγRI-α chain (CD64) and Ecgp96 as receptors for OmpA in macrophages and HCMEC/D3, respectively, to bind and enter these cells. APEC and NMEC strains induce meningitis in newborn mice with varying degree of pathology in the brains as assessed by neutrophil recruitment and neuronal apoptosis. Together, these results suggest that serotype O18 APEC strains utilize similar pathogenic mechanisms as those of NMEC strains in causing meningitis.

Antimicrobial activity of an aspartic protease from Salpichroa origanifolia fruits.

PubMed

Díaz, M E; Rocha, G F; Kise, F; Rosso, A M; Guevara, M G; Parisi, M G

2018-05-08

Plant proteases play a fundamental role in several processes like growth, development and in response to biotic and abiotic stress. In particular, aspartic proteases (AP) are expressed in different plant organs and have antimicrobial activity. Previously, we purified an AP from Salpichroa origanifolia fruits called salpichroin. The aim of this work was to determine the cytotoxic activity of this enzyme on selected plant and human pathogens. For this purpose, the growth of the selected pathogens was analysed after exposure to different concentrations of salpichroin. The results showed that the enzyme was capable of inhibiting Fusarium solani and Staphylococcus aureus in a dose-dependent manner. It was determined that 1·2 μmol l -1 of salpichroin was necessary to inhibit 50% of conidial germination, and the minimal bactericidal concentration was between 1·9 and 2·5 μmol l -1 . Using SYTOX Green dye we were able to demonstrate that salpichroin cause membrane permeabilization. Moreover, the enzyme treated with its specific inhibitor pepstatin A did not lose its antibacterial activity. This finding demonstrates that the cytotoxic activity of salpichroin is due to the alteration of the cell plasma membrane barrier but not due to its proteolytic activity. Antimicrobial activity of the AP could represent a potential alternative for the control of pathogens that affect humans or crops of economic interest. This study provides insights into the antimicrobial activity of an aspartic protease isolated from Salpichroa origanifolia fruits on plant and human pathogens. The proteinase inhibited Fusarium solani and Staphylococcus aureus in a dose-dependent manner due to the alteration of the cell plasma membrane barrier but not due to its proteolytic activity. Antimicrobial activity of salpichroin suggests its potential applications as an important tool for the control of pathogenic micro-organisms affecting humans and crops of economic interest. Therefore, it would represent a new alternative to avoid the problems of environmental pollution and antimicrobial resistance. © 2018 The Society for Applied Microbiology.

Alterations in the host defense properties of human milk following prolonged storage or pasteurization.

PubMed

Akinbi, Henry; Meinzen-Derr, Jareen; Auer, Christine; Ma, Yan; Pullum, Derek; Kusano, Ryosuke; Reszka, Krzysztof J; Zimmerly, Kira

2010-09-01

Preterm infants are often fed pasteurized donor milk or mother's milk that has been stored frozen for up to 4 weeks. Our objectives were to assess the impact of pasteurization or prolonged storage at -20 degrees C on the immunologic components of human milk and the capability of the different forms of human milk to support bacterial proliferation. The concentrations and activities of major host defense proteins in the whey fractions of mother's milk stored for 4 weeks at -20 degrees C or pasteurized human donor milk were compared with freshly expressed human milk. Proliferation of bacteria incubated in the 3 forms of human milk was assessed. Relative to freshly expressed human milk, the concentrations of lysozyme, lactoferrin, lactoperoxidase, and secretory immunoglobulin A were reduced 50% to 82% in pasteurized donor milk and the activities of lysozyme and lactoperoxidase were 74% to 88% lower (P < 0.01). Proliferation of bacterial pathogens in pasteurized donor milk was enhanced 1.8- to 4.6-fold compared with fresh or frozen human milk (P < 0.01). The immunomodulatory proteins in human milk are reduced by pasteurization and, to a lesser extent, by frozen storage, resulting in decreased antibacterial capability. Stringent procedure to minimize bacterial contamination is essential during handling of pasteurized milk.

Draft Genome Sequences of Acinetobacter baumannii Isolates from Wounded Military Personnel.

PubMed

Arivett, Brock A; Ream, Dave C; Fiester, Steven E; Kidane, Destaalem; Actis, Luis A

2016-08-25

Acinetobacter baumannii is a Gram-negative bacterium capable of causing hospital-acquired infections that has been grouped with Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species as ESKAPE pathogens because of their extensive drug resistance phenotypes and increasing risk to human health. Twenty-four multidrug-resistant A. baumannii strains isolated from wounded military personnel were sequenced and annotated. Copyright © 2016 Arivett et al.

[New approaches to oral cavity opportunistic microbiota study].

PubMed

Tets, G V; Vikina, D S; Vecherkovskaia, M F; Domorad, A A; Kharlamova, V V; Tets, V V

2013-01-01

Identification of some bacteria of the oral microbiota in humans including opportunistic pathogens capable of causing infections of various locations is a challenging problem for dentistry. Lack of knowledge on oral microbiota is the result of the absence of appropriate culture technique for isolation of pure cultures of those bacteria. The paper presents the study on mixed oral microbial biofilms with isolation and identification of insufficiently explored or still unknown aerobic opportunistic bacteria.

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.

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

Activation of the TREM-1 pathway in human monocytes by periodontal pathogens and oral commensal bacteria.

PubMed

Varanat, M; Haase, E M; Kay, J G; Scannapieco, F A

2017-08-01

Periodontitis is a highly prevalent disease caused in part by an aberrant host response to the oral multi-species biofilm. A balance between the oral bacteria and host immunity is essential for oral health. Imbalances in the oral microbiome lead to an uncontrolled host inflammatory response and subsequent periodontal disease (i.e. gingivitis and periodontitis). TREM-1 is a signaling receptor present on myeloid cells capable of acting synergistically with other pattern recognition receptors leading to amplification of inflammatory responses. The aim of this study was to investigate the activation of the TREM-1 pathway in the human monocyte-like cell line THP-1 exposed to both oral pathogens and commensals. The relative expression of the genes encoding TREM-1 and its adapter protein DAP12 were determined by quantitative real-time polymerase chain reaction. The surface expression of TREM-1 was determined by flow cytometry. Soluble TREM-1 and cytokines were measured by enzyme-linked immunosorbent assay. The results demonstrate that both commensal and pathogenic oral bacteria activate the TREM-1 pathway, resulting in a proinflammatory TREM-1 activity-dependent increase in proinflammatory cytokine production. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Naval Health Research Center Respiratory Disease Laboratory.

PubMed

Ryan, M; Gray, G; Hawksworth, A; Malasig, M; Hudspeth, M; Poddar, S

2000-07-01

Concern about emerging and reemerging respiratory pathogens prompted the development of a respiratory disease reference laboratory at the Naval Health Research Center. Professionals working in this laboratory have instituted population-based surveillance for pathogens that affect military trainees and responded to threats of increased respiratory disease among high-risk military groups. Capabilities of this laboratory that are unique within the Department of Defense include adenovirus testing by viral shell culture and microneutralization serotyping, influenza culture and hemagglutination inhibition serotyping, and other special testing for Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma pneumonia, and Chlamydia pneumoniae. Projected capabilities of this laboratory include more advanced testing for these pathogens and testing for other emerging pathogens, including Bordetella pertussis, Legionella pneumoniae, and Haemophilus influenzae type B. Such capabilities make the laboratory a valuable resource for military public health.

Shiga toxin-converting phages and the emergence of new pathogenic Escherichia coli: a world in motion

PubMed Central

Tozzoli, Rosangela; Grande, Laura; Michelacci, Valeria; Ranieri, Paola; Maugliani, Antonella; Caprioli, Alfredo; Morabito, Stefano

2014-01-01

Shiga toxin (Stx)-producing Escherichia coli (STEC) are pathogenic E. coli causing diarrhea, hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). STEC are characterized by a constellation of virulence factors additional to Stx and have long been regarded as capable to cause HC and HUS when possessing the ability of inducing the attaching and effacing (A/E) lesion to the enterocyte, although strains isolated from such severe infections sometimes lack this virulence feature. Interestingly, the capability to cause the A/E lesion is shared with another E. coli pathogroup, the Enteropathogenic E. coli (EPEC). In the very recent times, a different type of STEC broke the scene causing a shift in the paradigm for HUS-associated STEC. In 2011, a STEC O104:H4 caused a large outbreak with more than 800 HUS and 50 deaths. Such a strain presented the adhesion determinants of Enteroaggregative E. coli (EAggEC). We investigated the possibility that, besides STEC and EAggEC, other pathogenic E. coli could be susceptible to infection with stx-phages. A panel of stx2-phages obtained from STEC isolated from human disease was used to infect experimentally E. coli strains representing all the known pathogenic types, including both diarrheagenic E. coli (DEC) and extra-intestinal pathogenic E. coli (ExPEC). We observed that all the E. coli pathogroups used in the infection experiments were susceptible to the infection. Our results suggest that the stx2-phages used may not have specificity for E. coli adapted to the intestinal environment, at least in the conditions used. Additionally, we could only observe transient lysogens suggesting that the event of stable stx2-phage acquisition occurs rarely. PMID:24999453

Evolution, epidemiology, and population genetics of black flies (Diptera: Simuliidae).

PubMed

Adler, Peter H; Cheke, Robert A; Post, Rory J

2010-10-01

More than 2000 species of black flies feed on vertebrate blood; 1.5% of all species are vectors of pathogens that cause human diseases. Of nine simuliid-borne animal diseases, only two, mansonellosis and onchocerciasis, afflict humans. Onchocerciasis is a debilitating disease infecting an estimated 40 million people in Africa, Latin America, and Yemen, whereas mansonellosis is a mild disease in the Neotropics. Cytogenetic studies of natural populations of more than 500 species of black flies have revealed that the classic morphospecies of taxonomists is typically a complex of two or more reproductively isolated entities, or sibling (cryptic) species. Most vectors of human pathogens are sibling species, each ecologically unique in traits such as breeding habitats, dispersal capabilities, and degree of vector competence. We review the evolution of black flies, the cytogenetics that have revealed about 260 cytologically distinct entities, the molecular studies that continue to expose additional hidden biodiversity, and a case study of the epidemiology of the Simulium damnosum complex, the largest species complex of blood-feeding arthropods on Earth and the premier group of black flies responsible for human onchocerciasis. Copyright 2010 Elsevier B.V. All rights reserved.

Modeling the combined influence of host dispersal and waterborne fate and transport on pathogen spread in complex landscapes

PubMed Central

Lu, Ding; McDowell, Julia Z.; Davis, George M.; Spear, Robert C.; Remais, Justin V.

2012-01-01

Environmental models, often applied to questions on the fate and transport of chemical hazards, have recently become important in tracing certain environmental pathogens to their upstream sources of contamination. These tools, such as first order decay models applied to contaminants in surface waters, offer promise for quantifying the fate and transport of pathogens with multiple environmental stages and/or multiple hosts, in addition to those pathogens whose environmental stages are entirely waterborne. Here we consider the fate and transport capabilities of the human schistosome Schistosoma japonicum, which exhibits two waterborne stages and is carried by an amphibious intermediate snail host. We present experimentally-derived dispersal estimates for the intermediate snail host and fate and transport estimates for the passive downstream diffusion of cercariae, the waterborne, human-infective parasite stage. Using a one dimensional advective transport model exhibiting first-order decay, we simulate the added spatial reach and relative increase in cercarial concentrations that dispersing snail hosts contribute to downstream sites. Simulation results suggest that snail dispersal can substantially increase the concentrations of cercariae reaching downstream locations, relative to no snail dispersal, effectively putting otherwise isolated downstream sites at increased risk of exposure to cercariae from upstream sources. The models developed here can be applied to other infectious diseases with multiple life-stages and hosts, and have important implications for targeted ecological control of disease spread. PMID:23162675

Long-Term Survival and Intracellular Replication of Mycoplasma hominis in Trichomonas vaginalis Cells: Potential Role of the Protozoon in Transmitting Bacterial Infection

PubMed Central

Dessì, Daniele; Delogu, Giuseppe; Emonte, Eleonora; Catania, Maria Rosaria; Fiori, Pier Luigi; Rappelli, Paola

2005-01-01

The existence of a symbiotic relationship between Trichomonas vaginalis and Mycoplasma hominis, which is the first reported example of symbiosis between two obligate human pathogens, has been recently reported by our research group. In this work, we examined the cellular location of M. hominis in respect to T. vaginalis. By using gentamicin protection assays, double immunofluorescence, and confocal microscopy, we obtained strong evidence that M. hominis is located within protozoan cells. 5-Bromodeoxyuridine incorporation assays showed that intracellularly located mycoplasmas actively synthesize DNA. Our results demonstrate that M. hominis has the capability of entering trichomonad cells and of replicating inside the protozoon. These findings suggest that symbiosis might provide the bacteria, during human infection, with the capability to resist to environmental stresses, such as host defense mechanisms and pharmacological therapies. PMID:15664961

Microbe Detector

NASA Technical Reports Server (NTRS)

1977-01-01

The AutoMicrobic System (AMS) represents years of intensive research and development by McDonnell Douglas Corp. that originated with a NASA study aimed at development of a fully automated microbial detection and identification system for spacecraft use. A urine specimen is placed into the system, where it is subjected to different freeze-dried microbe nutrients for the nine most common pathogens. An electro-optical scanner studies each specimen once an hour through a 4-to-13 hour cycle, operating automatically. Changes in cell growths on each culture are monitored by computer. The presence of pathogens is indicated when growth reaches a predetermined level. The system also enumerates the pathogens and specifies the type. Developed initially to handle urine testing, AMS soon is expected to allow analyses of blood, spinal fluid, and other body fluids. An additional capability under development is "susceptibility testing," or the determination of which microbe-killing agents-such as penicillin or other antibiotics-would be most effective in eliminating the pathogens. The whole process of detecting, identifying, and enumerating the pathogens and determining susceptibility is accomplished in less half the time required for the manual procedure. The AMS minimizes human error, reduces technician time , and increases laboratory output.

An emerging cyberinfrastructure for biodefense pathogen and pathogen-host data.

PubMed

Zhang, C; Crasta, O; Cammer, S; Will, R; Kenyon, R; Sullivan, D; Yu, Q; Sun, W; Jha, R; Liu, D; Xue, T; Zhang, Y; Moore, M; McGarvey, P; Huang, H; Chen, Y; Zhang, J; Mazumder, R; Wu, C; Sobral, B

2008-01-01

The NIAID-funded Biodefense Proteomics Resource Center (RC) provides storage, dissemination, visualization and analysis capabilities for the experimental data deposited by seven Proteomics Research Centers (PRCs). The data and its publication is to support researchers working to discover candidates for the next generation of vaccines, therapeutics and diagnostics against NIAID's Category A, B and C priority pathogens. The data includes transcriptional profiles, protein profiles, protein structural data and host-pathogen protein interactions, in the context of the pathogen life cycle in vivo and in vitro. The database has stored and supported host or pathogen data derived from Bacillus, Brucella, Cryptosporidium, Salmonella, SARS, Toxoplasma, Vibrio and Yersinia, human tissue libraries, and mouse macrophages. These publicly available data cover diverse data types such as mass spectrometry, yeast two-hybrid (Y2H), gene expression profiles, X-ray and NMR determined protein structures and protein expression clones. The growing database covers over 23 000 unique genes/proteins from different experiments and organisms. All of the genes/proteins are annotated and integrated across experiments using UniProt Knowledgebase (UniProtKB) accession numbers. The web-interface for the database enables searching, querying and downloading at the level of experiment, group and individual gene(s)/protein(s) via UniProtKB accession numbers or protein function keywords. The system is accessible at http://www.proteomicsresource.org/.

Computational Analysis of Host-Pathogen Protein Interactions between Humans and Different Strains of Enterohemorrhagic Escherichia coli.

PubMed

Bose, Tungadri; Venkatesh, K V; Mande, Sharmila S

2017-01-01

Serotype O157:H7, an enterohemorrhagic Escherichia coli (EHEC), is known to cause gastrointestinal and systemic illnesses ranging from diarrhea and hemorrhagic colitis to potentially fatal hemolytic uremic syndrome. Specific genetic factors like ompA, nsrR , and LEE genes are known to play roles in EHEC pathogenesis. However, these factors are not specific to EHEC and their presence in several non-pathogenic strains indicates that additional factors are involved in pathogenicity. We propose a comprehensive effort to screen for such potential genetic elements, through investigation of biomolecular interactions between E. coli and their host. In this work, an in silico investigation of the protein-protein interactions (PPIs) between human cells and four EHEC strains (viz., EDL933, Sakai, EC4115, and TW14359) was performed in order to understand the virulence and host-colonization strategies of these strains. Potential host-pathogen interactions (HPIs) between human cells and the "non-pathogenic" E. coli strain MG1655 were also probed to evaluate whether and how the variations in the genomes could translate into altered virulence and host-colonization capabilities of the studied bacterial strains. Results indicate that a small subset of HPIs are unique to the studied pathogens and can be implicated in virulence. This subset of interactions involved E. coli proteins like YhdW, ChuT, EivG, and HlyA. These proteins have previously been reported to be involved in bacterial virulence. In addition, clear differences in lineage and clade-specific HPI profiles could be identified. Furthermore, available gene expression profiles of the HPI-proteins were utilized to estimate the proportion of proteins which may be involved in interactions. We hypothesized that a cumulative score of the ratios of bound:unbound proteins (involved in HPIs) would indicate the extent of colonization. Thus, we designed the Host Colonization Index (HCI) measure to determine the host colonization potential of the E. coli strains. Pathogenic strains of E. coli were observed to have higher HCIs as compared to a non-pathogenic laboratory strain. However, no significant differences among the HCIs of the two pathogenic groups were observed. Overall, our findings are expected to provide additional insights into EHEC pathogenesis and are likely to aid in designing alternate preventive and therapeutic strategies.

Comparison of commercial systems for extraction of nucleic acids from DNA/RNA respiratory pathogens.

PubMed

Yang, Genyan; Erdman, Dean E; Kodani, Maja; Kools, John; Bowen, Michael D; Fields, Barry S

2011-01-01

This study compared six automated nucleic acid extraction systems and one manual kit for their ability to recover nucleic acids from human nasal wash specimens spiked with five respiratory pathogens, representing Gram-positive bacteria (Streptococcus pyogenes), Gram-negative bacteria (Legionella pneumophila), DNA viruses (adenovirus), segmented RNA viruses (human influenza virus A), and non-segmented RNA viruses (respiratory syncytial virus). The robots and kit evaluated represent major commercially available methods that are capable of simultaneous extraction of DNA and RNA from respiratory specimens, and included platforms based on magnetic-bead technology (KingFisher mL, Biorobot EZ1, easyMAG, KingFisher Flex, and MagNA Pure Compact) or glass fiber filter technology (Biorobot MDX and the manual kit Allprep). All methods yielded extracts free of cross-contamination and RT-PCR inhibition. All automated systems recovered L. pneumophila and adenovirus DNA equivalently. However, the MagNA Pure protocol demonstrated more than 4-fold higher DNA recovery from the S. pyogenes than other methods. The KingFisher mL and easyMAG protocols provided 1- to 3-log wider linearity and extracted 3- to 4-fold more RNA from the human influenza virus and respiratory syncytial virus. These findings suggest that systems differed in nucleic acid recovery, reproducibility, and linearity in a pathogen specific manner. Published by Elsevier B.V.

Molecular detection of emerging tick-borne pathogens in Vojvodina, Serbia.

PubMed

Potkonjak, Aleksandar; Gutiérrez, Ricardo; Savić, Sara; Vračar, Vuk; Nachum-Biala, Yaarit; Jurišić, Aleksandar; Kleinerman, Gabriela; Rojas, Alicia; Petrović, Aleksandra; Baneth, Gad; Harrus, Shimon

2016-02-01

Ticks play an important role in disease transmission globally due to their capability to serve as vectors for human and animal pathogens. The Republic of Serbia is an endemic area for a large number of tick-borne diseases. However, current knowledge on these diseases in Serbia is limited. The aim of this study was to investigate the presence of new emerging tick-borne pathogens in ticks collected from dogs and the vegetation from different parts of Vojvodina, Serbia. A total of 187 ticks, including 124 Rhipicephalus sanguineus, 45 Ixodes ricinus and 18 Dermacentor reticulatus were collected from dogs. In addition, 26 questing I. ricinus ticks were collected from the vegetation, using the flagging method, from 4 different localities in Vojvodina, Serbia. DNA was extracted from each tick individually and samples were tested by either conventional or real-time PCR assays for the presence of Rickettsia spp.-DNA (gltA and ompA gene fragments), Ehrlichia/Anaplasma spp.-DNA (16S rRNA gene fragment) and Hepatozoon spp./Babesia spp.-DNA (18S rRNA gene fragment). In addition, all I. ricinus DNA samples were tested for Bartonella spp.-DNA (ITS locus) by real-time PCR. In this study, the presence of novel emerging tick-borne pathogens including Rickettsia raoultii, Rickettsia massiliae, Babesia venatorum, Babesia microti, Hepatozoon canis and Candidatus Neoehrlichia mikurensis was identified for the first time in Serbia. Our findings also confirmed the presence of Rickettsia monacensis, Babesia canis and Anaplasma phagocytophilum in ticks from Serbia. The findings of the current study highlight the great diversity of tick-borne pathogens of human and animal importance in Serbia. Physicians, public health workers and veterinarians should increase alertness to the presence of these tick-borne pathogens in this country. Copyright © 2015 Elsevier GmbH. All rights reserved.

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

Lawrence Livermore National Laboratory Workshop Characterization of Pathogenicity, Virulence and Host-Pathogen Interactions

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

Krishnan, A

2006-08-30

The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improvingmore » our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the area of host-pathogen interactions as well as policy makers from federal agencies. The main objectives of the workshop are: (1) to assess the current national needs, capabilities, near-term technologies, and future challenges in applying various diagnostics tools to public health and bio-defense; (2) to evaluate the utility and feasibility of host-response and pathogen biomarker profiling in the diagnosis and management of infectious diseases; and (3) to create a comprehensive developmental strategy from proof-of-concept, through validation, to deployment of appropriate advanced technology for the clinical/public health and bio-defense environments.« less

Antibiotic resistance is widespread in urban aquatic environments of Rio de Janeiro, Brazil.

PubMed

Coutinho, Felipe H; Silveira, Cynthia B; Pinto, Leonardo H; Salloto, Gigliola R B; Cardoso, Alexander M; Martins, Orlando B; Vieira, Ricardo P; Clementino, Maysa M

2014-10-01

Bacterial resistance to antibiotics has become a public health issue. Over the years, pathogenic organisms with resistance traits have been studied due to the threat they pose to human well-being. However, several studies raised awareness to the often disregarded importance of environmental bacteria as sources of resistance mechanisms. In this work, we analyze the diversity of antibiotic-resistant bacteria occurring in aquatic environments of the state of Rio de Janeiro, Brazil, that are subjected to distinct degrees of anthropogenic impacts. We access the diversity of aquatic bacteria capable of growing in increasing ampicillin concentrations through 16S rRNA gene libraries. This analysis is complemented by the characterization of antibiotic resistance profiles of isolates obtained from urban aquatic environments. We detect communities capable of tolerating antibiotic concentrations up to 600 times higher than the clinical levels. Among the resistant organisms are included potentially pathogenic species, some of them classified as multiresistant. Our results extend the knowledge of the diversity of antibiotic resistance among environmental microorganisms and provide evidence that the diversity of drug-resistant bacteria in aquatic habitats can be influenced by pollution.

Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans

PubMed Central

Douglas, Lois M.; Konopka, James. B.

2017-01-01

Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans. PMID:26920878

Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans.

PubMed

Douglas, Lois M; Konopka, James B

2016-03-01

Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans.

UniDrug-target: a computational tool to identify unique drug targets in pathogenic bacteria.

PubMed

Chanumolu, Sree Krishna; Rout, Chittaranjan; Chauhan, Rajinder S

2012-01-01

Targeting conserved proteins of bacteria through antibacterial medications has resulted in both the development of resistant strains and changes to human health by destroying beneficial microbes which eventually become breeding grounds for the evolution of resistances. Despite the availability of more than 800 genomes sequences, 430 pathways, 4743 enzymes, 9257 metabolic reactions and protein (three-dimensional) 3D structures in bacteria, no pathogen-specific computational drug target identification tool has been developed. A web server, UniDrug-Target, which combines bacterial biological information and computational methods to stringently identify pathogen-specific proteins as drug targets, has been designed. Besides predicting pathogen-specific proteins essentiality, chokepoint property, etc., three new algorithms were developed and implemented by using protein sequences, domains, structures, and metabolic reactions for construction of partial metabolic networks (PMNs), determination of conservation in critical residues, and variation analysis of residues forming similar cavities in proteins sequences. First, PMNs are constructed to determine the extent of disturbances in metabolite production by targeting a protein as drug target. Conservation of pathogen-specific protein's critical residues involved in cavity formation and biological function determined at domain-level with low-matching sequences. Last, variation analysis of residues forming similar cavities in proteins sequences from pathogenic versus non-pathogenic bacteria and humans is performed. The server is capable of predicting drug targets for any sequenced pathogenic bacteria having fasta sequences and annotated information. The utility of UniDrug-Target server was demonstrated for Mycobacterium tuberculosis (H37Rv). The UniDrug-Target identified 265 mycobacteria pathogen-specific proteins, including 17 essential proteins which can be potential drug targets. UniDrug-Target is expected to accelerate pathogen-specific drug targets identification which will increase their success and durability as drugs developed against them have less chance to develop resistances and adverse impact on environment. The server is freely available at http://117.211.115.67/UDT/main.html. The standalone application (source codes) is available at http://www.bioinformatics.org/ftp/pub/bioinfojuit/UDT.rar.

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.

Global dynamic analysis of a H7N9 avian-human influenza model in an outbreak region.

PubMed

Chen, Yongxue; Wen, Yongxian

2015-02-21

In 2013 in China a new type of avian influenza virus, H7N9, began to infect humans and had aroused severe fatality in the infected humans. We know that the spread is from poultry to humans, and the H7N9 avian influenza is low pathogenic in the poultry world but highly pathogenic in the human world, but the transmission mechanism is unclear. Since it has no signs of human-to-human transmission and outbreaks are isolated in some cities in China, in order to investigate the transmission mechanism of human infection with H7N9 avian influenza, an eco-epidemiological model in an outbreak region is proposed and analyzed dynamically. Researches and reports show that gene mutation makes the new virus be capable of infecting humans, therefore the mutation factor is taken into account in the model. The global dynamic analysis is conducted, different thresholds are identified, persistence and global qualitative behaviors are obtained. The impact of H7N9 avian influenza on the people population is concerned. Finally, the numerical simulations are carried out to support the theoretical analysis and to investigate the disease control measures. It seems that we may take people׳s hygiene and prevention awareness factor as a significant policy to achieve the aim of both the disease control and the economic returns. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2011-01-01

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

A putative marker for human pathogenic strains of Anaplasma phagocytophilum correlates with geography and host, but not human tropism.

PubMed

Foley, Janet; Stephenson, Nicole; Cubilla, Michelle Pires; Qurollo, Barbara; Breitschwerdt, Edward B

2016-03-01

Anaplasma phagocytophilum is an Ixodes species tick-transmitted bacterium that is capable of infecting a variety of host species, although there is a diversity of bacterial strains with differing host tropism. Recent analysis of A. phagocytophilum strains suggested that "drhm", a gene locus designated "distantly related to human marker" (drhm), which was predicted to be an integral membrane protein with possible transporter functions was not present in available canine and human isolates. By assessing 117 strains from 14 host species from across the US, we extended this analysis. Phylogenetic clades were associated with geography, but not host species. Additionally, a virulent clade that lacks drhm and infects dogs, horses, and humans in northeastern US was identified. Copyright © 2015 Elsevier GmbH. All rights reserved.

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

Isolation of lactic acid bacteria from swine milk and characterization of potential probiotic strains with antagonistic effects against swine-associated gastrointestinal pathogens.

PubMed

Quilodrán-Vega, Sandra Rayén; Villena, Julio; Valdebenito, José; Salas, María José; Parra, Cristian; Ruiz, Alvaro; Kitazawa, Haruki; García, Apolinaria

2016-06-01

Probiotics are usually isolated from the gastrointestinal tract of humans and animals. The search of probiotics in human milk is a recent field of research, as the existence of the human milk microbiome was discovered only about a decade ago. To our knowledge, no reports regarding the potential probiotic effect of bacteria from swine milk have been published. In this work, we isolated several lactic acid bacteria from swine milk and evaluated them for them potential as probiotics. Among the isolated strains, Lactobacillus curvatus TUCO-5E showed antagonistic effects against swine-associated gastrointestinal pathogens. TUCO-5E was able to reduce the growth of enterotoxigenic and enterohemorrhagic Escherichia coli strains as well as pathogenic salmonella. In vitro exclusion and displacement assays in intestinal epithelial cells showed a remarkable antagonistic effect for L. curvatus TUCO-5E against Salmonella sp. strain TUCO-I7 and Salmonella enterica ATCC 13096. Moreover, by using a mouse model of Salmonella infection, we were able to demonstrate that preventative administration of L. curvatus TUCO-5E for 5 consecutive days was capable of decreasing the number of Salmonella enterica serovar Typhimurium in the liver and spleen of treated mice, compared with the controls, and prevented dissemination of the pathogen to the blood stream. Therefore, we have demonstrated here that swine milk is an interesting source of beneficial bacteria. In addition, the results of this work suggest that L. curvatus TUCO-5E is a good candidate to study in vivo the protective effect of probiotics against intestinal infection and damage induced by Salmonella infection in the porcine host.

Giardia co-infection promotes the secretion of antimicrobial peptides beta-defensin 2 and trefoil factor 3 and attenuates attaching and effacing bacteria-induced intestinal disease.

PubMed

Manko, Anna; Motta, Jean-Paul; Cotton, James A; Feener, Troy; Oyeyemi, Ayodele; Vallance, Bruce A; Wallace, John L; Buret, Andre G

2017-01-01

Our understanding of polymicrobial gastrointestinal infections and their effects on host biology remains incompletely understood. Giardia duodenalis is an ubiquitous intestinal protozoan parasite infecting animals and humans. Concomitant infections with Giardia and other gastrointestinal pathogens commonly occur. In countries with poor sanitation, Giardia infection has been associated with decreased incidence of diarrheal disease and fever, and reduced serum inflammatory markers release, via mechanisms that remain obscure. This study analyzed Giardia spp. co-infections with attaching and effacing (A/E) pathogens, and assessed whether and how the presence of Giardia modulates host responses to A/E enteropathogens, and alters intestinal disease outcome. In mice infected with the A/E pathogen Citrobacter rodentium, co-infection with Giardia muris significantly attenuated weight loss, macro- and microscopic signs of colitis, bacterial colonization and translocation, while concurrently enhancing the production and secretion of antimicrobial peptides (AMPs) mouse β-defensin 3 and trefoil factor 3 (TFF3). Co-infection of human intestinal epithelial cells (Caco-2) monolayers with G. duodenalis trophozoites and enteropathogenic Escherichia coli (EPEC) enhanced the production of the AMPs human β-defensin 2 (HBD-2) and TFF3; this effect was inhibited with treatment of G. duodenalis with cysteine protease inhibitors. Collectively, these results suggest that Giardia infections are capable of reducing enteropathogen-induced colitis while increasing production of host AMPs. Additional studies also demonstrated that Giardia was able to directly inhibit the growth of pathogenic bacteria. These results reveal novel mechanisms whereby Giardia may protect against gastrointestinal disease induced by a co-infecting A/E enteropathogen. Our findings shed new light on how microbial-microbial interactions in the gut may protect a host during concomitant infections.

Giardia co-infection promotes the secretion of antimicrobial peptides beta-defensin 2 and trefoil factor 3 and attenuates attaching and effacing bacteria-induced intestinal disease

PubMed Central

Manko, Anna; Motta, Jean-Paul; Cotton, James A.; Feener, Troy; Oyeyemi, Ayodele; Vallance, Bruce A.; Wallace, John L.

2017-01-01

Our understanding of polymicrobial gastrointestinal infections and their effects on host biology remains incompletely understood. Giardia duodenalis is an ubiquitous intestinal protozoan parasite infecting animals and humans. Concomitant infections with Giardia and other gastrointestinal pathogens commonly occur. In countries with poor sanitation, Giardia infection has been associated with decreased incidence of diarrheal disease and fever, and reduced serum inflammatory markers release, via mechanisms that remain obscure. This study analyzed Giardia spp. co-infections with attaching and effacing (A/E) pathogens, and assessed whether and how the presence of Giardia modulates host responses to A/E enteropathogens, and alters intestinal disease outcome. In mice infected with the A/E pathogen Citrobacter rodentium, co-infection with Giardia muris significantly attenuated weight loss, macro- and microscopic signs of colitis, bacterial colonization and translocation, while concurrently enhancing the production and secretion of antimicrobial peptides (AMPs) mouse β-defensin 3 and trefoil factor 3 (TFF3). Co-infection of human intestinal epithelial cells (Caco-2) monolayers with G. duodenalis trophozoites and enteropathogenic Escherichia coli (EPEC) enhanced the production of the AMPs human β-defensin 2 (HBD-2) and TFF3; this effect was inhibited with treatment of G. duodenalis with cysteine protease inhibitors. Collectively, these results suggest that Giardia infections are capable of reducing enteropathogen-induced colitis while increasing production of host AMPs. Additional studies also demonstrated that Giardia was able to directly inhibit the growth of pathogenic bacteria. These results reveal novel mechanisms whereby Giardia may protect against gastrointestinal disease induced by a co-infecting A/E enteropathogen. Our findings shed new light on how microbial-microbial interactions in the gut may protect a host during concomitant infections. PMID:28622393

The Airborne Metagenome in an Indoor Urban Environment

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

Tringe, Susannah; Zhang, Tao; Liu, Xuguo

2008-02-12

The indoor atmosphere is an ecological unit that impacts on public health. To investigate the composition of organisms in this space, we applied culture-independent approaches to microbes harvested from the air of two densely populated urban buildings, from which we analyzed 80 megabases genomic DNA sequence and 6000 16S rDNA clones. The air microbiota is primarily bacteria, including potential opportunistic pathogens commonly isolated from human-inhabited environments such as hospitals, but none of the data contain matches to virulent pathogens or bioterror agents. Comparison of air samples with each other and nearby environments suggested that the indoor air microbes are notmore » random transients from surrounding outdoor environments, but rather originate from indoor niches. Sequence annotation by gene function revealed specific adaptive capabilities enriched in the air environment, including genes potentially involved in resistance to desiccation and oxidative damage. This baseline index of air microbiota will be valuable for improving designs of surveillance for natural or man-made release of virulent pathogens.« less

A network-patch methodology for adapting agent-based models for directly transmitted disease to mosquito-borne disease.

PubMed

Manore, Carrie A; Hickmann, Kyle S; Hyman, James M; Foppa, Ivo M; Davis, Justin K; Wesson, Dawn M; Mores, Christopher N

2015-01-01

Mosquito-borne diseases cause significant public health burden and are widely re-emerging or emerging. Understanding, predicting, and mitigating the spread of mosquito-borne disease in diverse populations and geographies are ongoing modelling challenges. We propose a hybrid network-patch model for the spread of mosquito-borne pathogens that accounts for individual movement through mosquito habitats, extending the capabilities of existing agent-based models (ABMs) to include vector-borne diseases. The ABM are coupled with differential equations representing 'clouds' of mosquitoes in patches accounting for mosquito ecology. We adapted an ABM for humans using this method and investigated the importance of heterogeneity in pathogen spread, motivating the utility of models of individual behaviour. We observed that the final epidemic size is greater in patch models with a high risk patch frequently visited than in a homogeneous model. Our hybrid model quantifies the importance of the heterogeneity in the spread of mosquito-borne pathogens, guiding mitigation strategies.

The Airborne Metagenome in an Indoor Urban Environment

PubMed Central

Liu, Xuguo; Yu, Yiting; Lee, Wah Heng; Yap, Jennifer; Yao, Fei; Suan, Sim Tiow; Ing, Seah Keng; Haynes, Matthew; Rohwer, Forest; Wei, Chia Lin; Tan, Patrick; Bristow, James; Rubin, Edward M.; Ruan, Yijun

2008-01-01

The indoor atmosphere is an ecological unit that impacts on public health. To investigate the composition of organisms in this space, we applied culture-independent approaches to microbes harvested from the air of two densely populated urban buildings, from which we analyzed 80 megabases genomic DNA sequence and 6000 16S rDNA clones. The air microbiota is primarily bacteria, including potential opportunistic pathogens commonly isolated from human-inhabited environments such as hospitals, but none of the data contain matches to virulent pathogens or bioterror agents. Comparison of air samples with each other and nearby environments suggested that the indoor air microbes are not random transients from surrounding outdoor environments, but rather originate from indoor niches. Sequence annotation by gene function revealed specific adaptive capabilities enriched in the air environment, including genes potentially involved in resistance to desiccation and oxidative damage. This baseline index of air microbiota will be valuable for improving designs of surveillance for natural or man-made release of virulent pathogens. PMID:18382653

Yeasts: providing questions and answers for modern biology.

PubMed

Dickinson, J R

2000-01-01

Yeasts are to be found in virtually every conceivable niche on this planet and are amazingly varied in their shapes ('morphologies'), life cycles, metabolic capabilities, potentials for use in industrial processes, abilities to spoil food and drink or to act as dangerous human pathogens. This review describes four very different species of yeast to illustrate some of the diversity which exists and, in the case of one of them, Saccharomyces cerevisiae (the familiar baker's or brewer's yeast), the extent of both our knowledge and ignorance.

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.

Identification of Borrelia protein candidates in mouse skin for potential diagnosis of disseminated Lyme borreliosis.

PubMed

Grillon, Antoine; Westermann, Benoît; Cantero, Paola; Jaulhac, Benoît; Voordouw, Maarten J; Kapps, Delphine; Collin, Elody; Barthel, Cathy; Ehret-Sabatier, Laurence; Boulanger, Nathalie

2017-12-01

In vector-borne diseases, the skin plays an essential role in the transmission of vector-borne pathogens between the vertebrate host and blood-feeding arthropods and in pathogen persistence. Borrelia burgdorferi sensu lato is a tick-borne bacterium that causes Lyme borreliosis (LB) in humans. This pathogen may establish a long-lasting infection in its natural vertebrate host where it can persist in the skin and some other organs. Using a mouse model, we demonstrate that Borrelia targets the skin regardless of the route of inoculation, and can persist there at low densities that are difficult to detect via qPCR, but that were infective for blood-feeding ticks. Application of immunosuppressive dermocorticoids at 40 days post-infection (PI) significantly enhanced the Borrelia population size in the mouse skin. We used non-targeted (Ge-LC-MS/MS) and targeted (SRM-MS) proteomics to detect several Borrelia-specific proteins in the mouse skin at 40 days PI. Detected Borrelia proteins included flagellin, VlsE and GAPDH. An important problem in LB is the lack of diagnosis methods capable of detecting active infection in humans suffering from disseminated LB. The identification of Borrelia proteins in skin biopsies may provide new approaches for assessing active infection in disseminated manifestations.

Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target

PubMed Central

Krzyzosiak, Wlodzimierz J.; Sobczak, Krzysztof; Wojciechowska, Marzena; Fiszer, Agnieszka; Mykowska, Agnieszka; Kozlowski, Piotr

2012-01-01

This review presents detailed information about the structure of triplet repeat RNA and addresses the simple sequence repeats of normal and expanded lengths in the context of the physiological and pathogenic roles played in human cells. First, we discuss the occurrence and frequency of various trinucleotide repeats in transcripts and classify them according to the propensity to form RNA structures of different architectures and stabilities. We show that repeats capable of forming hairpin structures are overrepresented in exons, which implies that they may have important functions. We further describe long triplet repeat RNA as a pathogenic agent by presenting human neurological diseases caused by triplet repeat expansions in which mutant RNA gains a toxic function. Prominent examples of these diseases include myotonic dystrophy type 1 and fragile X-associated tremor ataxia syndrome, which are triggered by mutant CUG and CGG repeats, respectively. In addition, we discuss RNA-mediated pathogenesis in polyglutamine disorders such as Huntington's disease and spinocerebellar ataxia type 3, in which expanded CAG repeats may act as an auxiliary toxic agent. Finally, triplet repeat RNA is presented as a therapeutic target. We describe various concepts and approaches aimed at the selective inhibition of mutant transcript activity in experimental therapies developed for repeat-associated diseases. PMID:21908410

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

Yeast pro- and paraprobiotics have the capability to bind pathogenic bacteria associated with animal disease

USDA-ARS?s Scientific Manuscript database

Live yeast probiotics and yeast cell wall components (paraprobiotics) may serve as an alternative to the use of antibiotics in prevention and treatment of infections caused by pathogenic bacteria. Probiotics and paraprobiotics can bind directly to pathogens, which limits binding of the pathogens to ...

Differences in Virulence Between Legionella pneumophila Isolates From Human and Non-human Sources Determined in Galleria mellonella Infection Model

PubMed Central

Sousa, Patrícia S.; Silva, Inês N.; Moreira, Leonilde M.; Veríssimo, António; Costa, Joana

2018-01-01

Legionella pneumophila is a ubiquitous bacterium in freshwater environments and in many man-made water systems capable of inducing pneumonia in humans. Despite its ubiquitous character most studies on L. pneumophila virulence focused on clinical strains and isolates from man-made environments, so little is known about the nature and extent of virulence variation in strains isolated from natural environments. It has been established that clinical isolates are less diverse than man-made and natural environmental strains, suggesting that only a subset of environmental isolates is specially adapted to infect humans. In this work we intended to determine if unrelated L. pneumophila strains, isolated from different environments and with distinct virulence-related genetic backgrounds, displayed differences in virulence, using the Wax Moth Galleria mellonella infection model. We found that all tested strains were pathogenic in G. mellonella, regardless of their origin. Indeed, a panoply of virulence-related phenotypes was observed sustaining the existence of significant differences on the ability of L. pneumophila strains to induce disease. Taken together our results suggest that the occurrence of human infection is not related with the increased capability of some strains to induce disease since we also found a concentration threshold above which L. pneumophila strains are equally able to cause disease. In addition, no link could be established between the sequence-type (ST) and L. pneumophila pathogenicity. We envision that in man-made water distribution systems environmental filtering selection and biotic competition acts structuring L. pneumophila populations by selecting more resilient and adapted strains that can rise to high concentration if no control measures are implemented. Therefore, public health strategies based on the sequence based typing (STB) scheme analysis should take into account that the major disease-associated clones of L. pneumophila were not related with higher virulence in G. mellonella infection model, and that potential variability of virulence-related phenotypes was found within the same ST. PMID:29670859

Antimicrobial Peptides: Insights into Membrane Permeabilization, Lipopolysaccharide Fragmentation and Application in Plant Disease Control.

PubMed

Datta, Aritreyee; Ghosh, Anirban; Airoldi, Cristina; Sperandeo, Paola; Mroue, Kamal H; Jiménez-Barbero, Jesús; Kundu, Pallob; Ramamoorthy, Ayyalusamy; Bhunia, Anirban

2015-07-06

The recent increase in multidrug resistance against bacterial infections has become a major concern to human health and global food security. Synthetic antimicrobial peptides (AMPs) have recently received substantial attention as potential alternatives to conventional antibiotics because of their potent broad-spectrum antimicrobial activity. These peptides have also been implicated in plant disease control for replacing conventional treatment methods that are polluting and hazardous to the environment and to human health. Here, we report de novo design and antimicrobial studies of VG16, a 16-residue active fragment of Dengue virus fusion peptide. Our results reveal that VG16KRKP, a non-toxic and non-hemolytic analogue of VG16, shows significant antimicrobial activity against Gram-negative E. coli and plant pathogens X. oryzae and X. campestris, as well as against human fungal pathogens C. albicans and C. grubii. VG16KRKP is also capable of inhibiting bacterial disease progression in plants. The solution-NMR structure of VG16KRKP in lipopolysaccharide features a folded conformation with a centrally located turn-type structure stabilized by aromatic-aromatic packing interactions with extended N- and C-termini. The de novo design of VG16KRKP provides valuable insights into the development of more potent antibacterial and antiendotoxic peptides for the treatment of human and plant infections.

Human cytokine responses induced by Gram-positive cell walls of normal intestinal microbiota

PubMed Central

Chen, T; Isomäki, P; Rimpiläinen, M; Toivanen, P

1999-01-01

The normal microbiota plays an important role in the health of the host, but little is known of how the human immune system recognizes and responds to Gram-positive indigenous bacteria. We have investigated cytokine responses of peripheral blood mononuclear cells (PBMC) to Gram-positive cell walls (CW) derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (Eu.a.), Eubacterium limosum(Eu.l.), Lactobacillus casei(L.c.), and Lactobacillus fermentum (L.f.). Our results indicate that Gram-positive CW of the normal intestinal microbiota can induce cytokine responses of the human PBMC. The profile, level and kinetics of these responses are similar to those induced by lipopolysaccharide (LPS) or CW derived from a pathogen, Streptococcus pyogenes (S.p.). Bacterial CW are capable of inducing production of a proinflammatory cytokine, tumour necrosis factor-alpha (TNF-α), and an anti-inflammatory cytokine, IL-10, but not that of IL-4 or interferon-gamma (IFN-γ). Monocytes are the main cell population in PBMC to produce TNF-α and IL-10. Induction of cytokine secretion is serum-dependent; both CD14-dependent and -independent pathways are involved. These findings suggest that the human cytokine responses induced by Gram-positive CW of the normal intestinal microbiota are similar to those induced by LPS or Gram-positive CW of the pathogens. PMID:10540188

Louse- and flea-borne rickettsioses: biological and genomic analyses

PubMed Central

Gillespie, Joseph J.; Ammerman, Nicole C.; Beier-Sexton, Magda; Sobral, Bruno S.; Azad, Abdu F.

2009-01-01

In contrast to 15 or more validated and/or proposed tick-borne spotted fever group species, only three named medically important rickettsial species are associated with insects. These insect-borne rickettsiae are comprised of two highly pathogenic species, Rickettsia prowazekii (the agent of epidemic typhus) and R. typhi (the agent of murine typhus), as well as R. felis, a species with unconfirmed pathogenicity. Rickettsial association with obligate hematophagous insects such as the human body louse (R. prowazekii transmitted by Pediculus h. humanus) and several flea species (R. typhi and R. felis, as well as R. prowazekii in sylvatic form) provides rickettsiae the potential for further multiplications, longer transmission cycles and rapid spread among susceptible human populations. Both human body lice and fleas are intermittent feeders capable of multiple blood meals per generation, facilitating the efficient transmission of rickettsiae to several disparate hosts within urban/rural ecosystems. While taking into consideration the existing knowledge of rickettsial biology and genomic attributes, we have analyzed and summarized the interacting features that are unique to both the rickettsiae and their vector fleas and lice. Furthermore, factors that underlie rickettsial changing ecology, where native mammalian populations are involved in the maintenance of rickettsial cycle and transmission, are discussed. PMID:19036234

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

A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe

PubMed Central

McIntyre, K. Marie; Setzkorn, Christian; Hepworth, Philip J.; Morand, Serge; Morse, Andrew P.; Baylis, Matthew

2014-01-01

Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps. PMID:25136810

Leptospira Species in Feral Cats and Black Rats from Western Australia and Christmas Island.

PubMed

Dybing, Narelle A; Jacobson, Caroline; Irwin, Peter; Algar, David; Adams, Peter J

2017-05-01

Leptospirosis is a neglected, re-emerging bacterial disease with both zoonotic and conservation implications. Rats and livestock are considered the usual sources of human infection, but all mammalian species are capable of carrying Leptospira spp. and transmitting pathogenic leptospires in their urine, and uncertainty remains about the ecology and transmission dynamics of Leptospira in different regions. In light of a recent case of human leptospirosis on tropical Christmas Island, this study aimed to investigate the role of introduced animals (feral cats and black rats) as carriers of pathogenic Leptospira spp. on Christmas Island and to compare this with two different climatic regions of Western Australia (one island and one mainland). Kidney samples were collected from black rats (n = 68) and feral cats (n = 59) from Christmas Island, as well as feral cats from Dirk Hartog Island (n = 23) and southwest Western Australia (n = 59). Molecular (PCR) screening detected pathogenic leptospires in 42.4% (95% confidence interval 29.6-55.9) of cats and 2.9% (0.4-10.2) of rats from Christmas Island. Sequencing of cat- and rat-positive samples from Christmas Island showed 100% similarity for Leptospira interrogans. Pathogenic leptospires were not detected in cats from Dirk Hartog Island or southwest Western Australia. These findings were consistent with previous reports of higher Leptospira spp. prevalence in tropical regions compared with arid and temperate regions. Despite the abundance of black rats on Christmas Island, feral cats appear to be the more important reservoir species for the persistence of pathogenic L. interrogans on the island. This research highlights the importance of disease surveillance and feral animal management to effectively control potential disease transmission.

Experimental comparison of pathogenic potential of two sibling species Anisakis simplex s.s. and Anisakis pegreffii in Wistar rat.

PubMed

del Carmen Romero, María; Valero, Adela; Navarro-Moll, María Concepción; Martín-Sánchez, Joaquina

2013-08-01

There are little data available on the pathology caused by the sibling species Anisakis simplex s.s. and Anisakis pegreffii. The differences shown in their ability to penetrate the muscle of fish may also be manifested in humans. The purpose of this study is to confirm possible differences in pathogenicity between A. simplex s.s. and A. pegreffii using an experimental model which simulates infection in humans. Female Wistar rats were infected with 190 Anisakis type I L3 larvae from the Iberian coastline. After the animal was sacrificed, these L3 larvae were then recovered and identified via PCR-RFLP of the ITS1-5.8S-ITS2. A logistic regression analysis was performed searching for association between experimental pathogenic potential and species. The distribution of A. simplex s.s. and A. pegreffii between Atlantic and Mediterranean waters of the Iberian Peninsula showed statistically significant differences (P < 0.001) which were not observed in the hybrid genotypes (P > 0.3). 21.6% showed pathogenic potential, interpreted as the capacity of the larvae to cause lesions, stick to the gastrointestinal wall or penetrate it. The species variable showed association with the pathogenic role of the larva (P = 0.008). Taking A. simplex s.s. as our reference, the OR for A. pegreffii is 0.351 (P = 0.028). Despite this difference, A. pegreffii is also capable of causing anisakiasis, being responsible for 14.3% of the penetrations of the gastric mucosa found in rats, which justifies both species being considered aetiologic agents of this parasitic disorder. © 2013 John Wiley & Sons Ltd.

Fierce Competition between Toxoplasma and Chlamydia for Host Cell Structures in Dually Infected Cells

PubMed Central

Romano, Julia D.; de Beaumont, Catherine; Carrasco, Jose A.; Ehrenman, Karen; Bavoil, Patrik M.

2013-01-01

The prokaryote Chlamydia trachomatis and the protozoan Toxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similar modus operandi to colonize their host cell and salvage nutrients from organelles. In order to gain fundamental knowledge on the pathogenicity of these microorganisms, we have established a cell culture model whereby single fibroblasts are coinfected by C. trachomatis and T. gondii. We previously reported that the two pathogens compete for the same nutrient pools in coinfected cells and that Toxoplasma holds a significant competitive advantage over Chlamydia. Here we have expanded our coinfection studies by examining the respective abilities of Chlamydia and Toxoplasma to co-opt the host cytoskeleton and recruit organelles. We demonstrate that the two pathogen-containing vacuoles migrate independently to the host perinuclear region and rearrange the host microtubular network around each vacuole. However, Toxoplasma outcompetes Chlamydia to the host microtubule-organizing center to the detriment of the bacterium, which then shifts to a stress-induced persistent state. Solely in cells preinfected with Chlamydia, the centrosomes become associated with the chlamydial inclusion, while the Toxoplasma parasitophorous vacuole displays growth defects. Both pathogens fragment the host Golgi apparatus and recruit Golgi elements to retrieve sphingolipids. This study demonstrates that the productive infection by both Chlamydia and Toxoplasma depends on the capability of each pathogen to successfully adhere to a finely tuned developmental program that aims to remodel the host cell for the pathogen's benefit. In particular, this investigation emphasizes the essentiality of host organelle interception by intravacuolar pathogens to facilitate access to nutrients. PMID:23243063

Fierce competition between Toxoplasma and Chlamydia for host cell structures in dually infected cells.

PubMed

Romano, Julia D; de Beaumont, Catherine; Carrasco, Jose A; Ehrenman, Karen; Bavoil, Patrik M; Coppens, Isabelle

2013-02-01

The prokaryote Chlamydia trachomatis and the protozoan Toxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similar modus operandi to colonize their host cell and salvage nutrients from organelles. In order to gain fundamental knowledge on the pathogenicity of these microorganisms, we have established a cell culture model whereby single fibroblasts are coinfected by C. trachomatis and T. gondii. We previously reported that the two pathogens compete for the same nutrient pools in coinfected cells and that Toxoplasma holds a significant competitive advantage over Chlamydia. Here we have expanded our coinfection studies by examining the respective abilities of Chlamydia and Toxoplasma to co-opt the host cytoskeleton and recruit organelles. We demonstrate that the two pathogen-containing vacuoles migrate independently to the host perinuclear region and rearrange the host microtubular network around each vacuole. However, Toxoplasma outcompetes Chlamydia to the host microtubule-organizing center to the detriment of the bacterium, which then shifts to a stress-induced persistent state. Solely in cells preinfected with Chlamydia, the centrosomes become associated with the chlamydial inclusion, while the Toxoplasma parasitophorous vacuole displays growth defects. Both pathogens fragment the host Golgi apparatus and recruit Golgi elements to retrieve sphingolipids. This study demonstrates that the productive infection by both Chlamydia and Toxoplasma depends on the capability of each pathogen to successfully adhere to a finely tuned developmental program that aims to remodel the host cell for the pathogen's benefit. In particular, this investigation emphasizes the essentiality of host organelle interception by intravacuolar pathogens to facilitate access to nutrients.

AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora

PubMed Central

Dong, Yi-Hu; Xu, Jin-Ling; Li, Xian-Zhen; Zhang, Lian-Hui

2000-01-01

N-acylhomoserine lactones, known as autoinducers (AIs), are widely conserved signal molecules present in quorum-sensing systems of many Gram-negative bacteria. AIs are involved in the regulation of diverse biological functions, including expression of pathogenic genes in the plant pathogens Pseudomonas solanacearum, several Erwinia species, and the human pathogen Pseudomonas aeruginosa. A bacterial isolate, Bacillus sp. 240B1, is capable of enzymatic inactivation of AIs. The gene (aiiA) for AI inactivation from Bacillus sp. 240B1 has been cloned and shown to encode a protein of 250 amino acids. Sequence alignment indicates that AiiA contains a “HXHXDH” zinc-binding motif that is conserved in several groups of metallohydrolases. Site-directed mutagenesis showed that conserved aspartate and most histidine residues are required for AiiA activity. Expression of aiiA in transformed Erwinia carotovora strain SCG1 significantly reduces the release of AI, decreases extracellular pectolytic enzyme activities, and attenuates pathogenicity on potato, eggplant, Chinese cabbage, carrot, celery, cauliflower, and tobacco. Our results indicate that the AI-inactivation approach represents a promising strategy for prevention of diseases in which virulence is regulated by AIs. PMID:10716724

Degradable polyphosphoester-based silver-loaded nanoparticles as therapeutics for bacterial lung infections

NASA Astrophysics Data System (ADS)

Zhang, Fuwu; Smolen, Justin A.; Zhang, Shiyi; Li, Richen; Shah, Parth N.; Cho, Sangho; Wang, Hai; Raymond, Jeffery E.; Cannon, Carolyn L.; Wooley, Karen L.

2015-01-01

In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate.In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate. Electronic supplementary information (ESI) available: Materials, experimental details, and characterization. See DOI: 10.1039/c4nr07103d

Infection of Amblyomma ovale with Rickettsia species Atlantic rainforest in Serra do Mar, São Paulo State, Brazil.

PubMed

Luz, Hermes Ribeiro; McIntosh, Douglas; Furusawa, Guilherme P; Flausino, Walter; Rozental, Tatiana; Lemos, Elba R S; Landulfo, Gabriel A; Faccini, João Luiz H

2016-10-01

Rickettsia rickettsii and Rickettsia sp. strain Atlantic rainforest, that is considered to represent a genetic variant of Rickettsia parkeri, are confirmed as being capable of infecting humans in Brazil. This study reports the detection and characterization, by PCR and nucleotide sequencing, of Rickettsia sp. strain Atlantic rain forest in Amblyomma ovale parasitizing a human, in ticks infesting dogs and in free-living ticks collected from the environment where the human infestation was recorded. The data contribute to our knowledge of infection rates in A. ovale with Rickettsia sp. strain Atlantic rainforest and identified an additional location in the state of São Paulo populated with ticks infected with this emerging pathogen. Copyright © 2016 Elsevier GmbH. All rights reserved.

Function of the CRISPR-Cas System of the Human Pathogen Clostridium difficile

PubMed Central

Boudry, Pierre; Semenova, Ekaterina; Monot, Marc; Datsenko, Kirill A.; Lopatina, Anna; Sekulovic, Ognjen; Ospina-Bedoya, Maicol; Fortier, Louis-Charles; Severinov, Konstantin; Dupuy, Bruno

2015-01-01

ABSTRACT Clostridium difficile is the cause of most frequently occurring nosocomial diarrhea worldwide. As an enteropathogen, C. difficile must be exposed to multiple exogenous genetic elements in bacteriophage-rich gut communities. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems allow bacteria to adapt to foreign genetic invaders. Our recent data revealed active expression and processing of CRISPR RNAs from multiple type I-B CRISPR arrays in C. difficile reference strain 630. Here, we demonstrate active expression of CRISPR arrays in strain R20291, an epidemic C. difficile strain. Through genome sequencing and host range analysis of several new C. difficile phages and plasmid conjugation experiments, we provide evidence of defensive function of the CRISPR-Cas system in both C. difficile strains. We further demonstrate that C. difficile Cas proteins are capable of interference in a heterologous host, Escherichia coli. These data set the stage for mechanistic and physiological analyses of CRISPR-Cas-mediated interactions of important global human pathogen with its genetic parasites. PMID:26330515

Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire.

PubMed

Yeung, Yik Andy; Foletti, Davide; Deng, Xiaodi; Abdiche, Yasmina; Strop, Pavel; Glanville, Jacob; Pitts, Steven; Lindquist, Kevin; Sundar, Purnima D; Sirota, Marina; Hasa-Moreno, Adela; Pham, Amber; Melton Witt, Jody; Ni, Irene; Pons, Jaume; Shelton, David; Rajpal, Arvind; Chaparro-Riggers, Javier

2016-11-18

Staphylococcus aureus is both an important pathogen and a human commensal. To explore this ambivalent relationship between host and microbe, we analysed the memory humoral response against IsdB, a protein involved in iron acquisition, in four healthy donors. Here we show that in all donors a heavily biased use of two immunoglobulin heavy chain germlines generated high affinity (pM) antibodies that neutralize the two IsdB NEAT domains, IGHV4-39 for NEAT1 and IGHV1-69 for NEAT2. In contrast to the typical antibody/antigen interactions, the binding is primarily driven by the germline-encoded hydrophobic CDRH-2 motifs of IGHV1-69 and IGHV4-39, with a binding mechanism nearly identical for each antibody derived from different donors. Our results suggest that IGHV1-69 and IGHV4-39, while part of the adaptive immune system, may have evolved under selection pressure to encode a binding motif innately capable of recognizing and neutralizing a structurally conserved protein domain involved in pathogen iron acquisition.

Determination of virulence and antibiotic resistance pattern of biofilm producing Listeria species isolated from retail raw milk.

PubMed

Osman, Kamelia M; Samir, Ahmed; Abo-Shama, Usama H; Mohamed, Essam H; Orabi, Ahmed; Zolnikov, Tara

2016-11-08

One of the foodborne pathogens is Listeria monocytogenes, which causes serious invasive illness in elderly and immunocompromised patients, pregnant women, newborns and infants ranking second after salmonellosis because of its high case fatality rate. Listerial cow mastitis marked by abnormal milk, increased cell counts and reduced production has not been reported. Therefore, apparently healthy cows can be reservoirs of L. monocytogenes. A number of 203 udder milk samples from apparently healthy animals (buffalo, n = 100; cow, n = 103) were collected and tested for Listeria. Isolated colonies on the PALCAM agar were Listeria species confirmed according to their biochemical and the Christie-Atkins-Munch-Petersen (CAMP) reactions. The Listeria species pathogenicity of was tested by phosphatidylinositol-specific phospholipase C, DL-alanine-β-naphthylamide HCl, Dalanine-p-nitroanilide tests, chick embryo, mice inoculation tests, Vero cell cytotoxicity and biofilm formation. The virulence-associated genes, hlyA, plcB, actA and iap associated with Listeria were molecularly assayed. The 17 isolated Listeria spp. represented a prevalence rate of 8.4 %. Of these 3 (1.4 %), 2 (1 %), 5 (2.5 %), 4 (2 %) and 3 (1.5 %) were confirmed as L. monocytogenes, L. innocua, L. welshimeri, L. seelegeri, respectively. While the L. monocytogenes isolate displayed all the four virulence-associated genes, L. seelegeri carried the hlyA gene only. The L. monocytogenes had a strong in vitro affinity to form a biofilm, in particular serotype 4 which is associated with human infections. L. monocytogenes showed resistance for 9/27 antibiotics. The biofilm forming capability of the Listeria spps. makes them particularly successful in colonizing surfaces within the host thus being responsible for persistence infections and due to their antimicrobial resistant phenotype that this structure confers. In addition, strains belonging to serotypes associated with human infections and characterized by pathogenic potential (serotype 4) are capable to persist within the processing plants forming biofilm and thus being a medical hazard.

Biogeography of Human Infectious Diseases: A Global Historical Analysis

PubMed Central

Cashdan, Elizabeth

2014-01-01

Objectives Human pathogen richness and prevalence vary widely across the globe, yet we know little about whether global patterns found in other taxa also predict diversity in this important group of organisms. This study (a) assesses the relative importance of temperature, precipitation, habitat diversity, and population density on the global distributions of human pathogens and (b) evaluates the species-area predictions of island biogeography for human pathogen distributions on oceanic islands. Methods Historical data were used in order to minimize the influence of differential access to modern health care on pathogen prevalence. The database includes coded data (pathogen, environmental and cultural) for a worldwide sample of 186 non-industrial cultures, including 37 on islands. Prevalence levels for 10 pathogens were combined into a pathogen prevalence index, and OLS regression was used to model the environmental determinants of the prevalence index and number of pathogens. Results Pathogens (number and prevalence index) showed the expected latitudinal gradient, but predictors varied by latitude. Pathogens increased with temperature in high-latitude zones, while mean annual precipitation was a more important predictor in low-latitude zones. Other environmental factors associated with more pathogens included seasonal dry extremes, frost-free climates, and human population density outside the tropics. Islands showed the expected species-area relationship for all but the smallest islands, and the relationship was not mediated by habitat diversity. Although geographic distributions of free-living and parasitic taxa typically have different determinants, these data show that variables that influence the distribution of free-living organisms also shape the global distribution of human pathogens. Understanding the cause of these distributions is potentially important, since geographical variation in human pathogens has an important influence on global disparities in human welfare. PMID:25271730

Biogeography of human infectious diseases: a global historical analysis.

PubMed

Cashdan, Elizabeth

2014-01-01

Human pathogen richness and prevalence vary widely across the globe, yet we know little about whether global patterns found in other taxa also predict diversity in this important group of organisms. This study (a) assesses the relative importance of temperature, precipitation, habitat diversity, and population density on the global distributions of human pathogens and (b) evaluates the species-area predictions of island biogeography for human pathogen distributions on oceanic islands. Historical data were used in order to minimize the influence of differential access to modern health care on pathogen prevalence. The database includes coded data (pathogen, environmental and cultural) for a worldwide sample of 186 non-industrial cultures, including 37 on islands. Prevalence levels for 10 pathogens were combined into a pathogen prevalence index, and OLS regression was used to model the environmental determinants of the prevalence index and number of pathogens. Pathogens (number and prevalence index) showed the expected latitudinal gradient, but predictors varied by latitude. Pathogens increased with temperature in high-latitude zones, while mean annual precipitation was a more important predictor in low-latitude zones. Other environmental factors associated with more pathogens included seasonal dry extremes, frost-free climates, and human population density outside the tropics. Islands showed the expected species-area relationship for all but the smallest islands, and the relationship was not mediated by habitat diversity. Although geographic distributions of free-living and parasitic taxa typically have different determinants, these data show that variables that influence the distribution of free-living organisms also shape the global distribution of human pathogens. Understanding the cause of these distributions is potentially important, since geographical variation in human pathogens has an important influence on global disparities in human welfare.

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.

Resequencing Pathogen Microarray (RPM) for prospective detection and identification of emergent pathogen strains and variants

NASA Astrophysics Data System (ADS)

Tibbetts, Clark; Lichanska, Agnieszka M.; Borsuk, Lisa A.; Weslowski, Brian; Morris, Leah M.; Lorence, Matthew C.; Schafer, Klaus O.; Campos, Joseph; Sene, Mohamadou; Myers, Christopher A.; Faix, Dennis; Blair, Patrick J.; Brown, Jason; Metzgar, David

2010-04-01

High-density resequencing microarrays support simultaneous detection and identification of multiple viral and bacterial pathogens. Because detection and identification using RPM is based upon multiple specimen-specific target pathogen gene sequences generated in the individual test, the test results enable both a differential diagnostic analysis and epidemiological tracking of detected pathogen strains and variants from one specimen to the next. The RPM assay enables detection and identification of pathogen sequences that share as little as 80% sequence similarity to prototype target gene sequences represented as detector tiles on the array. This capability enables the RPM to detect and identify previously unknown strains and variants of a detected pathogen, as in sentinel cases associated with an infectious disease outbreak. We illustrate this capability using assay results from testing influenza A virus vaccines configured with strains that were first defined years after the design of the RPM microarray. Results are also presented from RPM-Flu testing of three specimens independently confirmed to the positive for the 2009 Novel H1N1 outbreak strain of influenza virus.

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.

Genetic and biological characterization of three poultry-origin H5N6 avian influenza viruses with all internal genes from genotype S H9N2 viruses.

PubMed

Liu, Kaituo; Gu, Min; Hu, Shunlin; Gao, Ruyi; Li, Juan; Shi, Liwei; Sun, Wenqi; Liu, Dong; Gao, Zhao; Xu, Xiulong; Hu, Jiao; Wang, Xiaoquan; Liu, Xiaowen; Chen, Sujuan; Peng, Daxin; Jiao, Xinan; Liu, Xiufan

2018-04-01

During surveillance for avian influenza viruses, three H5N6 viruses were isolated in chickens obtained from live bird markets in eastern China, between January 2015 and April 2016. Sequence analysis revealed a high genomic homology between these poultry isolates and recent human H5N6 variants whose internal genes were derived from genotype S H9N2 avian influenza viruses. Glycan binding assays revealed that all avian H5N6 viruses were capable of binding to both human-type SAα-2,6Gal receptors and avian-type SAα-2,3Gal receptors. Their biological characteristics were further studied in BALB/c mice, specific-pathogen-free chickens, and mallard ducks. All three isolates had low pathogenicity in mice but were highly pathogenic to chickens, as evidenced by 100% mortality 36-120 hours post infection at a low dose of 10 3.0 EID 50 and through effective contact transmission. Moreover, all three poultry H5N6 isolates caused asymptomatic infections in ducks, which may serve as a reservoir host for their maintenance and dissemination; these migrating waterfowl could cause a potential global pandemic. Our study suggests that continuous epidemiological surveillance in poultry should be implemented for the early prevention of future influenza outbreaks.

Cavity-Enhanced Absorption Spectroscopy and Photoacoustic Spectroscopy for Human Breath Analysis

NASA Astrophysics Data System (ADS)

Wojtas, J.; Tittel, F. K.; Stacewicz, T.; Bielecki, Z.; Lewicki, R.; Mikolajczyk, J.; Nowakowski, M.; Szabra, D.; Stefanski, P.; Tarka, J.

2014-12-01

This paper describes two different optoelectronic detection techniques: cavity-enhanced absorption spectroscopy and photoacoustic spectroscopy. These techniques are designed to perform a sensitive analysis of trace gas species in exhaled human breath for medical applications. With such systems, the detection of pathogenic changes at the molecular level can be achieved. The presence of certain gases (biomarkers), at increased concentration levels, indicates numerous human diseases. Diagnosis of a disease in its early stage would significantly increase chances for effective therapy. Non-invasive, real-time measurements, and high sensitivity and selectivity, capable of minimum discomfort for patients, are the main advantages of human breath analysis. At present, monitoring of volatile biomarkers in breath is commonly useful for diagnostic screening, treatment for specific conditions, therapy monitoring, control of exogenous gases (such as bacterial and poisonous emissions), as well as for analysis of metabolic gases.

Fate of pathogenic bacteria in microcosms mimicking human body sites.

PubMed

Castellani, Francesco; Ghidini, Valentina; Tafi, Maria Carla; Boaretti, Marzia; Lleo, Maria M

2013-07-01

During the infectious process, pathogens may reach anatomical sites where they are exposed to substances interfering with their growth. These substances can include molecules produced by the host, and his resident microbial population, as well as exogenous antibacterial drugs. Suboptimal concentrations of inhibitory molecules and stress conditions found in vivo (high or low temperatures, lack of oxygen, extreme pH) might induce in bacteria the activation of survival mechanisms blocking their division capability but allowing them to stay alive. These "dormant" bacteria can be reactivated in particular circumstances and would be able to express their virulence traits. In this study, it was evaluated the effect of some environmental conditions, such as optimal and suboptimal temperatures, direct light and antibiotic sub-inhibitory concentrations doses of antibiotic, on the human pathogens Escherichia coli and Enterococcus faecalis when incubated in fluids accumulated in the body of patients with different pathologies. It is shown that inoculation in a number of accumulated body fluids and the presence of gentamicin, reliable conditions encountered during pathological states, induce stress-responding strategies enabling bacteria to persist in microcosms mimicking the human body. Significant differences were detected in Gram-negative and Gram-positive species with E. faecalis surviving, as starved or viable but non-culturable forms, in any microcosm and condition tested and E. coli activating a viable but non-culturable state only in some clinical samples. The persistence of bacteria under these conditions, being non-culturable, might explain some recurrent infections without isolation of the causative agent after application of the standard microbiological methods.

An emerging cyberinfrastructure for biodefense pathogen and pathogen–host data

PubMed Central

Zhang, C.; Crasta, O.; Cammer, S.; Will, R.; Kenyon, R.; Sullivan, D.; Yu, Q.; Sun, W.; Jha, R.; Liu, D.; Xue, T.; Zhang, Y.; Moore, M.; McGarvey, P.; Huang, H.; Chen, Y.; Zhang, J.; Mazumder, R.; Wu, C.; Sobral, B.

2008-01-01

The NIAID-funded Biodefense Proteomics Resource Center (RC) provides storage, dissemination, visualization and analysis capabilities for the experimental data deposited by seven Proteomics Research Centers (PRCs). The data and its publication is to support researchers working to discover candidates for the next generation of vaccines, therapeutics and diagnostics against NIAID's Category A, B and C priority pathogens. The data includes transcriptional profiles, protein profiles, protein structural data and host–pathogen protein interactions, in the context of the pathogen life cycle in vivo and in vitro. The database has stored and supported host or pathogen data derived from Bacillus, Brucella, Cryptosporidium, Salmonella, SARS, Toxoplasma, Vibrio and Yersinia, human tissue libraries, and mouse macrophages. These publicly available data cover diverse data types such as mass spectrometry, yeast two-hybrid (Y2H), gene expression profiles, X-ray and NMR determined protein structures and protein expression clones. The growing database covers over 23 000 unique genes/proteins from different experiments and organisms. All of the genes/proteins are annotated and integrated across experiments using UniProt Knowledgebase (UniProtKB) accession numbers. The web-interface for the database enables searching, querying and downloading at the level of experiment, group and individual gene(s)/protein(s) via UniProtKB accession numbers or protein function keywords. The system is accessible at http://www.proteomicsresource.org/. PMID:17984082

Proteus mirabilis uroepithelial cell adhesin (UCA) fimbria plays a role in the colonization of the urinary tract.

PubMed

Pellegrino, Rafael; Scavone, Paola; Umpiérrez, Ana; Maskell, Duncan J; Zunino, Pablo

2013-03-01

Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Proteus mirabilis is an opportunistic pathogen, capable of causing severe UTIs, with serious kidney damage that may even lead to death. Several virulence factors are involved in the pathogenicity of this bacterium. Among these, adherence to the uroepithelium mediated by fimbriae appears to be a significant bacterial attribute related to urovirulence. Proteus mirabilis expresses several types of fimbriae that could be involved in the pathogenesis of UTI, including uroepithelial cell adhesin (UCA). In this report, we used an uropathogenic P. mirabilis wild-type strain and an isogenic ucaA mutant unable to express UCA to study the pathogenic role of this fimbria in UTI. Ability of the mutant to adhere to desquamated uroepithelial cells and to infect mice using different experimental UTI models was significantly impaired. These results allow us to conclude that P. mirabilis UCA plays an important role in the colonization of the urinary tract. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Novel approaches to improve the intrinsic microbiological safety of powdered infant milk formula.

PubMed

Kent, Robert M; Fitzgerald, Gerald F; Hill, Colin; Stanton, Catherine; Ross, R Paul

2015-02-12

Human milk is recognised as the best form of nutrition for infants. However; in instances where breast-feeding is not possible, unsuitable or inadequate, infant milk formulae are used as breast milk substitutes. These formulae are designed to provide infants with optimum nutrition for normal growth and development and are available in either powdered or liquid forms. Powdered infant formula is widely used for convenience and economic reasons. However; current manufacturing processes are not capable of producing a sterile powdered infant formula. Due to their immature immune systems and permeable gastro-intestinal tracts, infants can be more susceptible to infection via foodborne pathogenic bacteria than other age-groups. Consumption of powdered infant formula contaminated by pathogenic microbes can be a cause of serious illness. In this review paper, we discuss the current manufacturing practices present in the infant formula industry, the pathogens of greatest concern, Cronobacter and Salmonella and methods of improving the intrinsic safety of powdered infant formula via the addition of antimicrobials such as: bioactive peptides; organic acids; probiotics and prebiotics.

Novel Approaches to Improve the Intrinsic Microbiological Safety of Powdered Infant Milk Formula

PubMed Central

Kent, Robert M.; Fitzgerald, Gerald F.; Hill, Colin; Stanton, Catherine; Ross, R. Paul

2015-01-01

Human milk is recognised as the best form of nutrition for infants. However; in instances where breast-feeding is not possible, unsuitable or inadequate, infant milk formulae are used as breast milk substitutes. These formulae are designed to provide infants with optimum nutrition for normal growth and development and are available in either powdered or liquid forms. Powdered infant formula is widely used for convenience and economic reasons. However; current manufacturing processes are not capable of producing a sterile powdered infant formula. Due to their immature immune systems and permeable gastro-intestinal tracts, infants can be more susceptible to infection via foodborne pathogenic bacteria than other age-groups. Consumption of powdered infant formula contaminated by pathogenic microbes can be a cause of serious illness. In this review paper, we discuss the current manufacturing practices present in the infant formula industry, the pathogens of greatest concern, Cronobacter and Salmonella and methods of improving the intrinsic safety of powdered infant formula via the addition of antimicrobials such as: bioactive peptides; organic acids; probiotics and prebiotics. PMID:25685987

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

PubMed

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

2012-04-04

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

Risks Posed by Reston, the Forgotten Ebolavirus

PubMed Central

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

2016-01-01

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

Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein.

PubMed

Chaves, Edilânia Gomes Araújo; Weber, Simone Schneider; Báo, Sonia Nair; Pereira, Luiz Augusto; Bailão, Alexandre Melo; Borges, Clayton Luiz; Soares, Célia Maria de Almeida

2015-02-27

Despite being important thermal dimorphic fungi causing Paracoccidioidomycosis, the pathogenic mechanisms that underlie the genus Paracoccidioides remain largely unknown. Microbial pathogens express molecules that can interact with human plasminogen, a protein from blood plasma, which presents fibrinolytic activity when activated into plasmin. Additionally, plasmin exhibits the ability of degrading extracellular matrix components, favoring the pathogen spread to deeper tissues. Previous work from our group demonstrated that Paracoccidioides presents enolase, as a protein able to bind and activate plasminogen, increasing the fibrinolytic activity of the pathogen, and the potential for adhesion and invasion of the fungus to host cells. By using proteomic analysis, we aimed to identify other proteins of Paracoccidioides with the ability of binding to plasminogen. In the present study, we employed proteomic analysis of the secretome, in order to identify plasminogen-binding proteins of Paracoccidioides, Pb01. Fifteen proteins were present in the fungal secretome, presenting the ability to bind to plasminogen. Those proteins are probable targets of the fungus interaction with the host; thus, they could contribute to the invasiveness of the fungus. For validation tests, we selected the protein fructose 1,6-bisphosphate aldolase (FBA), described in other pathogens as a plasminogen-binding protein. The protein FBA at the fungus surface and the recombinant FBA (rFBA) bound human plasminogen and promoted its conversion to plasmin, potentially increasing the fibrinolytic capacity of the fungus, as demonstrated in fibrin degradation assays. The addition of rFBA or anti-rFBA antibodies was capable of reducing the interaction between macrophages and Paracoccidioides, possibly by blocking the binding sites for FBA. These data reveal the possible participation of the FBA in the processes of cell adhesion and tissue invasion/dissemination of Paracoccidioides. These data indicate that Paracoccidioides is a pathogen that has several plasminogen-binding proteins that likely play important roles in pathogen-host interaction. In this context, FBA is a protein that might be involved somehow in the processes of invasion and spread of the fungus during infection.

Bioactive natural products from novel microbial sources.

PubMed

Challinor, Victoria L; Bode, Helge B

2015-09-01

Despite the importance of microbial natural products for human health, only a few bacterial genera have been mined for the new natural products needed to overcome the urgent threat of antibiotic resistance. This is surprising, given that genome sequencing projects have revealed that the capability to produce natural products is not a rare feature among bacteria. Even the bacteria occurring in the human microbiome produce potent antibiotics, and thus potentially are an untapped resource for novel compounds, potentially with new activities. This review highlights examples of bacteria that should be considered new sources of natural products, including anaerobes, pathogens, and symbionts of humans, insects, and nematodes. Exploitation of these producer strains, combined with advances in modern natural product research methodology, has the potential to open the way for a new golden age of microbial therapeutics. © 2015 New York Academy of Sciences.

Apoptotic death of Listeria monocytogenes-infected human macrophages induced by lactoferricin B, a bovine lactoferrin-derived peptide.

PubMed

Longhi, C; Conte, M P; Ranaldi, S; Penta, M; Valenti, P; Tinari, A; Superti, F; Seganti, L

2005-01-01

Listeria monocytogenes, an intracellular facultative food-borne pathogen, was reported to induce apoptosis in vitro and in vivo in a variety of cell types with the exception of murine macrophages. These cells represent the predominant compartment of bacterial multiplication and die as a result of necrosis. In this study we showed that human non-activated and IFN-gamma-activated macrophagic-like (THP-1) cells infected with L. monocytogenes, mainly die by necrosis rather than by an apoptotic process. Two natural products derived from bovine milk, lactoferrin and its derivative peptide lactoferricin B, are capable of regulating the fate of infected human macrophages. Bovine lactoferrin treatment of macrophages protects them from L. monocytogenes-induced death whereas lactoferricin B, its derivative peptide, determines a shifting of the equilibrium from necrosis to apoptosis.

Prevention the spread of norovirus infection on airborne route by using Plasma Assisted Catalytic Technology (PACT) device.

PubMed

Tanaka, Yoshimoto; Fujino, Kan; Larkins, Gerald Andrew; Osawa, Atsushi; Hayashi, Yuji; Taharaguchi, Satoshi

2018-04-30

Zoonosis becomes a popular word. Highly pathogenic influenza virus (HPI), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) recently occurred at around Africa, Meddle-East and South-East Asia area, whose virus is classified as airborne. Sterilization capability was investigated by using chemical reactor of PACT device. Test on airborne infection was carried out by Feline Calicivirus Vaccine (FCV) strain F9, which is also surrogated human norovirus. It was found that PACT device could sterilize instantly FCV when passing through the plasma space of PACT device. Sterilization rate may be more than 99.99% (below the detection limit). This result may be available to sterilize various virus including human norovirus and airborne-infectious microorganisms.

Broad-range lytic bacteriophages that kill Staphylococcus aureus local field strains

PubMed Central

Boncompain, Carina A.; Amadio, Ariel A.; Carrasco, Soledad; Suárez, Cristian A.

2017-01-01

Staphylococcus aureus is a very successful opportunistic pathogen capable of causing a variety of diseases ranging from mild skin infections to life-threatening sepsis, meningitis and pneumonia. Its ability to display numerous virulence mechanisms matches its skill to display resistance to several antibiotics, including β-lactams, underscoring the fact that new anti-S. aureus drugs are urgently required. In this scenario, the utilization of lytic bacteriophages that kill bacteria in a genus -or even species- specific way, has become an attractive field of study. In this report, we describe the isolation, characterization and sequencing of phages capable of killing S. aureus including methicillin resistant (MRSA) and multi-drug resistant S. aureus local strains from environmental, animal and human origin. Genome sequencing and bio-informatics analysis showed the absence of genes encoding virulence factors, toxins or antibiotic resistance determinants. Of note, there was a high similarity between our set of phages to others described in the literature such as phage K. Considering that reported phages were obtained in different continents, it seems plausible that there is a commonality of genetic features that are needed for optimum, broad host range anti-staphylococcal activity of these related phages. Importantly, the high activity and broad host range of one of our phages underscores its promising value to control the presence of S. aureus in fomites, industry and hospital environments and eventually on animal and human skin. The development of a cocktail of the reported lytic phages active against S. aureus–currently under way- is thus, a sensible strategy against this pathogen. PMID:28742812

Variable epitope libraries: new vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response.

PubMed

Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen

2011-07-18

The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

Broad-range lytic bacteriophages that kill Staphylococcus aureus local field strains.

PubMed

Abatángelo, Virginia; Peressutti Bacci, Natalia; Boncompain, Carina A; Amadio, Ariel F; Carrasco, Soledad; Suárez, Cristian A; Morbidoni, Héctor R

2017-01-01

Staphylococcus aureus is a very successful opportunistic pathogen capable of causing a variety of diseases ranging from mild skin infections to life-threatening sepsis, meningitis and pneumonia. Its ability to display numerous virulence mechanisms matches its skill to display resistance to several antibiotics, including β-lactams, underscoring the fact that new anti-S. aureus drugs are urgently required. In this scenario, the utilization of lytic bacteriophages that kill bacteria in a genus -or even species- specific way, has become an attractive field of study. In this report, we describe the isolation, characterization and sequencing of phages capable of killing S. aureus including methicillin resistant (MRSA) and multi-drug resistant S. aureus local strains from environmental, animal and human origin. Genome sequencing and bio-informatics analysis showed the absence of genes encoding virulence factors, toxins or antibiotic resistance determinants. Of note, there was a high similarity between our set of phages to others described in the literature such as phage K. Considering that reported phages were obtained in different continents, it seems plausible that there is a commonality of genetic features that are needed for optimum, broad host range anti-staphylococcal activity of these related phages. Importantly, the high activity and broad host range of one of our phages underscores its promising value to control the presence of S. aureus in fomites, industry and hospital environments and eventually on animal and human skin. The development of a cocktail of the reported lytic phages active against S. aureus-currently under way- is thus, a sensible strategy against this pathogen.

Pan-genome analysis of Aeromonas hydrophila, Aeromonas veronii and Aeromonas caviae indicates phylogenomic diversity and greater pathogenic potential for Aeromonas hydrophila.

PubMed

Ghatak, Sandeep; Blom, Jochen; Das, Samir; Sanjukta, Rajkumari; Puro, Kekungu; Mawlong, Michael; Shakuntala, Ingudam; Sen, Arnab; Goesmann, Alexander; Kumar, Ashok; Ngachan, S V

2016-07-01

Aeromonas species are important pathogens of fishes and aquatic animals capable of infecting humans and other animals via food. Due to the paucity of pan-genomic studies on aeromonads, the present study was undertaken to analyse the pan-genome of three clinically important Aeromonas species (A. hydrophila, A. veronii, A. caviae). Results of pan-genome analysis revealed an open pan-genome for all three species with pan-genome sizes of 9181, 7214 and 6884 genes for A. hydrophila, A. veronii and A. caviae, respectively. Core-genome: pan-genome ratio (RCP) indicated greater genomic diversity for A. hydrophila and interestingly RCP emerged as an effective indicator to gauge genomic diversity which could possibly be extended to other organisms too. Phylogenomic network analysis highlighted the influence of homologous recombination and lateral gene transfer in the evolution of Aeromonas spp. Prediction of virulence factors indicated no significant difference among the three species though analysis of pathogenic potential and acquired antimicrobial resistance genes revealed greater hazards from A. hydrophila. In conclusion, the present study highlighted the usefulness of whole genome analyses to infer evolutionary cues for Aeromonas species which indicated considerable phylogenomic diversity for A. hydrophila and hitherto unknown genomic evidence for pathogenic potential of A. hydrophila compared to A. veronii and A. caviae.

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

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...

High Incidence of Pathogenic Streptococcus agalactiae ST485 Strain in Pregnant/Puerperal Women and Isolation of Hyper-Virulent Human CC67 Strain

PubMed Central

Li, Liping; Wang, Rui; Huang, Yan; Huang, Ting; Luo, Fuguang; Huang, Weiyi; Yang, Xiuying; Lei, Aiying; Chen, Ming; Gan, Xi

2018-01-01

Group B streptococcus (GBS) is the major pathogen causing diseases in neonates, pregnant/puerperal women, cows and fish. Recent studies have shown that GBS may be infectious across hosts and some fish GBS strain might originate from human. The purpose of this study is to investigate the genetic relationship of CC103 strains that recently emerged in cows and humans, and explore the pathogenicity of clinical GBS isolates from human to tilapia. Ninety-two pathogenic GBS isolates were identified from 19 patients with different diseases and their evolution and pathogenicity to tilapia were analyzed. The multilocus sequence typing revealed that clonal complex (CC) 103 strain was isolated from 21.74% (20/92) of patients and ST485 strain was from 14.13% (13/92) patients with multiple diseases including neonates. Genomic evolution analysis showed that both bovine and human CC103 strains alternately form independent evolutionary branches. Three CC67 isolates carried gbs2018-C gene and formed one evolutionary branch with ST61 and ST67 strains that specifically infect dairy cows. Studies of interspecies transmission to tilapia found that 21/92 (22.83%) isolates including all ST23 isolates were highly pathogenic to tilapia and demonstrated that streptococci could break through the blood-brain barrier into brain tissue. In conclusions, CC103 strains are highly prevalent among pathogenic GBS from humans and have evolved into the highly pathogenic ST485 strains specifically infecting humans. The CC67 strains isolated from cows are able to infect humans through evolutionary events of acquiring CC17-specific type C gbs2018 gene and others. Human-derived ST23 pathogenic GBS strains are highly pathogenic to tilapia. PMID:29467722

Interaction of an opportunistic fungus Purpureocillium lilacinum with human macrophages and dendritic cells.

PubMed

Peixoto, Mariana Lima Perazzini; Santos, Dilvani Oliveira; Souza, Ivy de Castro Campos de; Neri, Eloah Christina Lyrio; Sequeira, Danielly Correa Moreira de; De Luca, Paula Mello; Borba, Cíntia de Moraes

2014-01-01

Purpureocillium lilacinum is emerging as a causal agent of hyalohyphomycosis that is refractory to antifungal drugs; however, the pathogenic mechanisms underlying P. lilacinum infection are not understood. In this study, we investigated the interaction of P. lilacinum conidia with human macrophages and dendritic cells in vitro. Spores of a P. lilacinum clinical isolate were obtained by chill-heat shock. Mononuclear cells were isolated from eight healthy individuals. Monocytes were separated by cold aggregation and differentiated into macrophages by incubation for 7 to 10 days at 37°C or into dendritic cells by the addition of the cytokines human granulocyte-macrophage colony stimulating factor and interleukin-4. Conidial suspension was added to the human cells at 1:1, 2:1, and 5:1 (conidia:cells) ratios for 1h, 6h, and 24h, and the infection was evaluated by Giemsa staining and light microscopy. After 1h interaction, P. lilacinum conidia were internalized by human cells and after 6h contact, some conidia became inflated. After 24h interaction, the conidia produced germ tubes and hyphae, leading to the disruption of macrophage and dendritic cell membranes. The infection rate analyzed after 6h incubation of P. lilacinum conidia with cells at 2:1 and 1:1 ratios was 76.5% and 25.5%, respectively, for macrophages and 54.3% and 19.5%, respectively, for cultured dendritic cells. P. lilacinum conidia are capable of infecting and destroying both macrophages and dendritic cells, clearly demonstrating the ability of this pathogenic fungus to invade human phagocytic cells.

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.

'Order from disorder sprung': recognition and regulation in the immune system

NASA Astrophysics Data System (ADS)

Mak, Tak W.

2003-06-01

Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen threat is resolved. Once Paradise has been regained, memory cells remain in the body to sharply reduce the impact of a second exposure to a pathogen. Vaccination programs take advantage of this capacity of the human immune system for immunological memory, sparing millions the suffering associated with disease scourges. Thus does the order of the immune response spring from the disorder of pathogen attacks, and thus is Paradise preserved.

'Order from disorder sprung': recognition and regulation in the immune system.

PubMed

Mak, Tak W

2003-06-15

Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen threat is resolved. Once Paradise has been regained, memory cells remain in the body to sharply reduce the impact of a second exposure to a pathogen. Vaccination programs take advantage of this capacity of the human immune system for immunological memory, sparing millions the suffering associated with disease scourges. Thus does the order of the immune response spring from the disorder of pathogen attacks, and thus is Paradise preserved.

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

Potential of Bacillus spp produces siderophores insuppressing thewilt disease of banana plants

NASA Astrophysics Data System (ADS)

Kesaulya, H.; Hasinu, J. V.; Tuhumury, G. NC

2018-01-01

In nature, different types of siderophore such as hydroxymate, catecholets and carboxylate, are produced by different bacteria. Bacillus spp were isolated from potato rhizospheric soil can produce siderophore of both catecholets and salicylate type with different concentrations. Various strains of Bacillus spp were tested for pathogen inhibition capability in a dual culture manner. The test results showed the ability of inhibition of pathogen isolated from banana wilt disease. From the result tested were found Bacillus niabensis Strain PT-32-1, Bacillus subtilis Strain SWI16b, Bacillus subtilis Strain HPC21, Bacillus mojavensis Strain JCEN3, and Bacillus subtilis Strain HPC24 showed different capabilities in suppressing pathogen.

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...

The Food Production Environment and the Development of Antimicrobial Resistance in Human Pathogens of Animal Origin.

PubMed

Lekshmi, Manjusha; Ammini, Parvathi; Kumar, Sanath; Varela, Manuel F

2017-03-14

Food-borne pathogens are a serious human health concern worldwide, and the emergence of antibiotic-resistant food pathogens has further confounded this problem. Once-highly-efficacious antibiotics are gradually becoming ineffective against many important pathogens, resulting in severe treatment crises. Among several reasons for the development and spread of antimicrobial resistance, their overuse in animal food production systems for purposes other than treatment of infections is prominent. Many pathogens of animals are zoonotic, and therefore any development of resistance in pathogens associated with food animals can spread to humans through the food chain. Human infections by antibiotic-resistant pathogens such as Campylobacter spp., Salmonella spp., Escherichia coli and Staphylococcus aureus are increasing. Considering the human health risk due to emerging antibiotic resistance in food animal-associated bacteria, many countries have banned the use of antibiotic growth promoters and the application in animals of antibiotics critically important in human medicine. Concerted global efforts are necessary to minimize the use of antimicrobials in food animals in order to control the development of antibiotic resistance in these systems and their spread to humans via food and water.

The Anopheles innate immune system in the defense against malaria infection

PubMed Central

Clayton, April M.; Dong, Yuemei; Dimopoulos, George

2014-01-01

The multifaceted innate immune system of insects is capable of fighting infection by a variety of pathogens including those causing human malaria. Malaria transmission by the Anopheles mosquito depends on the Plasmodium parasite’s successful completion of its lifecycle in the insect vector, a process that involves interactions with several tissues and cell types as well as with the mosquito’s innate immune system. This review will discuss our current understanding of the Anopheles mosquito’s innate immune responses against the malaria parasite Plasmodium and the influence of the insect’s intestinal microbiota on parasite infection. PMID:23988482

Potent Inhibitors of the Hepatitis C Virus NS3 Protease: Design and Synthesis of Macrocyclic Substrate-Based [beta]-Strand Mimics

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

Goudreau, Nathalie; Brochu, Christian; Cameron, Dale R.

2008-06-30

The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring {beta}-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.

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.

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

Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species.

PubMed

Paulussen, Caroline; Hallsworth, John E; Álvarez-Pérez, Sergio; Nierman, William C; Hamill, Philip G; Blain, David; Rediers, Hans; Lievens, Bart

2017-03-01

Fungi of the genus Aspergillus are widespread in the environment. Some Aspergillus species, most commonly Aspergillus fumigatus, may lead to a variety of allergic reactions and life-threatening systemic infections in humans. Invasive aspergillosis occurs primarily in patients with severe immunodeficiency, and has dramatically increased in recent years. There are several factors at play that contribute to aspergillosis, including both fungus and host-related factors such as strain virulence and host pulmonary structure/immune status, respectively. The environmental tenacity of Aspergilllus, its dominance in diverse microbial communities/habitats, and its ability to navigate the ecophysiological and biophysical challenges of host infection are attributable, in large part, to a robust stress-tolerance biology and exceptional capacity to generate cell-available energy. Aspects of its stress metabolism, ecology, interactions with diverse animal hosts, clinical presentations and treatment regimens have been well-studied over the past years. Here, we synthesize these findings in relation to the way in which some Aspergillus species have become successful opportunistic pathogens of human- and other animal hosts. We focus on the biophysical capabilities of Aspergillus pathogens, key aspects of their ecophysiology and the flexibility to undergo a sexual cycle or form cryptic species. Additionally, recent advances in diagnosis of the disease are discussed as well as implications in relation to questions that have yet to be resolved. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

A Sensitive and Rapid Method to Determin the Adhesion Capacity of Probiotics and Pathogenic Microorganisms to Human Gastrointestinal Mucins.

PubMed

Ringot-Destrez, Bélinda; D'Alessandro, Zéa; Lacroix, Jean-Marie; Mercier-Bonin, Muriel; Léonard, Renaud; Robbe-Masselot, Catherine

2018-05-29

Mucus is the habitat for the microorganisms, bacteria and yeast that form the commensal flora. Mucins, the main macromolecules of mucus, and more specifically, the glycans that cover them, play essential roles in microbial gastrointestinal colonization. Probiotics and pathogens must also colonize mucus to have lasting positive or deleterious effects. The question of which mucin-harboured glycan motifs favour the adhesion of specific microorganisms remains very poorly studied. In the current study, a simple test based on the detection of fluorescent-labeled microorganisms raised against microgram amounts of mucins spotted on nitrocellulose was developed. The adhesion of various probiotic, commensal and pathogenic microorganisms was evaluated on a panel of human purified gastrointestinal mucins and compared with that of commercially available pig gastric mucins (PGM) and of mucins secreted by the colonic cancer cell line HT29-MTX. The latter two proved to be very poor indicators of adhesion capacity on intestinal mucins. Our results show that the nature of the sialylated cores of O -glycans, determined by MALDI MS-MS analysis, potentially enables sialic acid residues to modulate the adhesion of microorganisms either positively or negatively. Other identified factors affecting the adhesion propensity were O -glycan core types and the presence of blood group motifs. This test should help to select probiotics with enhanced adhesion capabilities as well as deciphering the role of specific mucin glycotopes on microbial adhesion.

Identification of pathogenic fungi with an optoelectronic nose

PubMed Central

Zhang, Yinan; Askim, Jon R.; Zhong, Wenxuan; Orlean, Peter; Suslick, Kenneth S.

2014-01-01

Human fungal infections have gained recent notoriety following contamination of pharmaceuticals in the compounding process. Such invasive infections are a more serious global problem, especially for immunocompromised patients. While superficial fungal infections are common and generally curable, invasive fungal infections are often life-threatening and much harder to diagnose and treat. Despite the increasing awareness of the situation’s severity, currently available fungal diagnostic methods cannot always meet diagnostic needs, especially for invasive fungal infections. Volatile organic compounds produced by fungi provide an alternative diagnostic approach for identification of fungal strains. We report here an optoelectronic nose based on a disposable colorimetric sensor array capable of rapid differentiation and identification of pathogenic fungi based on their metabolic profiles of emitted volatiles. The sensor arrays were tested with 12 human pathogenic fungal strains grown on standard agar medium. Array responses were monitored with an ordinary flatbed scanner. All fungal strains gave unique composite responses within 3 hours and were correctly clustered using hierarchical cluster analysis. A standard jackknifed linear discriminant analysis gave a classification accuracy of 94% for 155 trials. Tensor discriminant analysis, which takes better advantage of the high dimensionality of the sensor array data, gave a classification accuracy of 98.1%. The sensor array is also able to observe metabolic changes in growth patterns upon the addition of fungicides, and this provides a facile screening tool for determining fungicide efficacy for various fungal strains in real time. PMID:24570999

A Quaternary Mechanism Enables the Complex Biological Functions of Octameric Human UDP-glucose Pyrophosphorylase, a Key Enzyme in Cell Metabolism

PubMed Central

Führing, Jana Indra; Cramer, Johannes Thomas; Schneider, Julia; Baruch, Petra; Gerardy-Schahn, Rita; Fedorov, Roman

2015-01-01

In mammals, UDP-glucose pyrophosphorylase (UGP) is the only enzyme capable of activating glucose-1-phosphate (Glc-1-P) to UDP-glucose (UDP-Glc), a metabolite located at the intersection of virtually all metabolic pathways in the mammalian cell. Despite the essential role of its product, the molecular basis of UGP function is poorly understood. Here we report the crystal structure of human UGP in complex with its product UDP-Glc. Beyond providing first insight into the active site architecture, we describe the substrate binding mode and intermolecular interactions in the octameric enzyme that are crucial to its activity. Importantly, the quaternary mechanism identified for human UGP in this study may be common for oligomeric sugar-activating nucleotidyltransferases. Elucidating such mechanisms is essential for understanding nucleotide sugar metabolism and opens the perspective for the development of drugs that specifically inhibit simpler organized nucleotidyltransferases in pathogens. PMID:25860585

Proteomic analysis of Aspergillus fumigatus - clinical implications.

PubMed

Moloney, Nicola M; Owens, Rebecca A; Doyle, Sean

2016-07-01

Aspergillus fumigatus is a ubiquitous saprophytic fungus capable of producing small airborne spores, which are frequently inhaled by humans. In healthy individuals, the fungus is rapidly cleared by innate mechanisms, including immune cells. However, in individuals with impaired lung function or immunosuppression the spores can germinate and prompt severe allergic responses, and disease with limited or extensive invasiveness. The traits that make A. fumigatus a successful colonizer and pathogen of humans are multi-factorial. Thus, a global investigative approach is required to elucidate the mechanisms utilized by the fungus to cause disease. Expert commentary: In doing so, a better understanding of disease pathology can be achieved with improved therapeutic/diagnostic solutions, thereby improving patient outcome. Proteomic analysis permits such investigations and recent work has yielded insight into these mechanisms.

Apheresis for Collection of Ebola Convalescent Plasma in Liberia

PubMed Central

Brown, Jerry F.; Rowe, Kathleen; Zacharias, Peter; van Hasselt, James; Dye, John M.; Wohl, David A.; Fischer, William A.; Cunningham, Coleen K.; Thielman, Nathan M.; Hoover, David L.

2017-01-01

Purpose This report describes initiation of apheresis capability in Liberia, Africa to support a clinical trial of convalescent plasma therapy for Ebola Virus Disease. Methods A bloodmobile was outfitted in the United States as a four-bed apheresis unit with capabilities including pathogen reduction, electronic blood establishment computer system, designated areas for donor counseling and laboratory testing, and onboard electrical power generation. After air transport to Liberia, the bloodmobile was positioned at ELWA Hospital, Monrovia, and connected to the hospital’s power grid. Liberian staff were trained to conduct donor screening, which included questionnaire and onsite blood typing and transfusion transmitted infection (TTI) testing, and plasma collection and processing. Results The bloodmobile was operational within three weeks after arrival of the advance team. Of 101 donors who passed the pre-screening questionnaire, 32 were deferred. Twenty-eight of 99 tested survivors were deferred for positive transfusion transmitted infection (TTI) tests; 21 were positive for hepatitis B, hepatitis C, or human immunodeficiency virus. The majority of donors had type O blood; all but one were Rh positive. Forty-three survivors donated at least once; 89 apheresis attempts resulted in 81 successful collections. Conclusions Apheresis capability was emergently established in Liberia to support an efficacy trial of Ebola Convalescent Plasma. Extensive cooperation among multinational team members, engineers, logisticians and blood safety technical personnel at the operational site was required to surmount challenges to execution posed by logistical factors. The high proportion of positive TTI tests supported the use of a pathogen reduction system to enhance product safety. PMID:27393614

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.

A genetic and pathologic study of a DENV2 clinical isolate capable of inducing encephalitis and hematological disturbances in immunocompetent mice.

PubMed

Amorim, Jaime Henrique; Pereira Bizerra, Raíza Sales; dos Santos Alves, Rúbens Prince; Sbrogio-Almeida, Maria Elisabete; Levi, José Eduardo; Capurro, Margareth Lara; de Souza Ferreira, Luís Carlos

2012-01-01

Dengue virus (DENV) is the causative agent of dengue fever (DF), a mosquito-borne illness endemic to tropical and subtropical regions. There is currently no effective drug or vaccine formulation for the prevention of DF and its more severe forms, i.e., dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There are two generally available experimental models for the study of DENV pathogenicity as well as the evaluation of potential vaccine candidates. The first model consists of non-human primates, which do not develop symptoms but rather a transient viremia. Second, mouse-adapted virus strains or immunocompromised mouse lineages are utilized, which display some of the pathological features of the infection observed in humans but may not be relevant to the results with regard to the wild-type original virus strains or mouse lineages. In this study, we describe a genetic and pathological study of a DENV2 clinical isolate, named JHA1, which is naturally capable of infecting and killing Balb/c mice and reproduces some of the symptoms observed in DENV-infected subjects. Sequence analyses demonstrated that the JHA1 isolate belongs to the American genotype group and carries genetic markers previously associated with neurovirulence in mouse-adapted virus strains. The JHA1 strain was lethal to immunocompetent mice following intracranial (i.c.) inoculation with a LD(50) of approximately 50 PFU. Mice infected with the JHA1 strain lost weight and exhibited general tissue damage and hematological disturbances, with similarity to those symptoms observed in infected humans. In addition, it was demonstrated that the JHA1 strain shares immunological determinants with the DENV2 NGC reference strain, as evaluated by cross-reactivity of anti-envelope glycoprotein (domain III) antibodies. The present results indicate that the JHA1 isolate may be a useful tool in the study of DENV pathogenicity and will help in the evaluation of anti-DENV vaccine formulations as well as potential therapeutic approaches.

Microgravity as a biological tool to examine host-pathogen interactions and to guide development of therapeutics and preventatives that target pathogenic bacteria.

PubMed

Higginson, Ellen E; Galen, James E; Levine, Myron M; Tennant, Sharon M

2016-11-01

Space exploration programs have long been interested in the effects of spaceflight on biology. This research is important not only in its relevance to future deep space exploration, but also because it has allowed investigators to ask questions about how gravity impacts cell behavior here on Earth. In the 1980s, scientists designed and built the first rotating wall vessel, capable of mimicking the low shear environment found in space. This vessel has since been used to investigate growth of both microorganisms and human tissue cells in low shear modeled microgravity conditions. Bacterial behavior has been shown to be altered both in space and under simulated microgravity conditions. In some cases, bacteria appear attenuated, whereas in others virulence is enhanced. This has consequences not only for manned spaceflight, but poses larger questions about the ability of bacteria to sense the world around them. By using the microgravity environment as a tool, we can exploit this phenomenon in the search for new therapeutics and preventatives against pathogenic bacteria for use both in space and on Earth. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2018-04-03

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

Members of a new subgroup of Streptococcus anginosus harbor virulence related genes previously observed in Streptococcus pyogenes.

PubMed

Babbar, Anshu; Kumar, Venkatesan Naveen; Bergmann, René; Barrantes, Israel; Pieper, Dietmar H; Itzek, Andreas; Nitsche-Schmitz, D Patric

2017-04-01

Conventionally categorized as commensals, the Streptococci of the species S. anginosus are facultative human pathogens that are difficult to diagnose and often overlooked. Furthermore, detailed investigation and diagnosis of S. anginosus infections is hampered by unexplored taxonomy and widely elusive molecular pathogenesis. To explore their pathogenic potential, S. anginosus isolates collected from patients of two geographical locations (Vellore, India and Leipzig, Germany) were subjected to multi-locus sequence analysis (MLSA). This analysis revealed the potential presence of a new distinct clade of the species S. anginosus, tentatively termed here as genomosubspecies vellorensis. A complementary PCR-based screening for S. pyogenes virulence factor as well as antibiotic resistance genes revealed not only the presence of superantigen- and extracellular DNase coding genes identical to corresponding genes of S. pyogenes, but also of erythromycin and tetracycline resistance genes in the genomes of the analyzed S. anginosus isolates, thus posing a matter of significant health concern. Identification of new pathogenic S. anginosus strains capable of causing difficult to treat infections may pose additional challenges to the diagnosis and treatment of Streptococcus based infections. Copyright © 2017 Elsevier GmbH. All rights reserved.

The National Ebola Training and Education Center: Preparing the United States for Ebola and Other Special Pathogens.

PubMed

Kratochvil, Christopher J; Evans, Laura; Ribner, Bruce S; Lowe, John J; Harvey, Melissa Cole; Hunt, Richard C; Tumpey, Abbigail J; Fagan, Ryan P; Schwedhelm, Michelle M; Bell, Sonia; Maher, John; Kraft, Colleen S; Cagliuso, Nicholas V; Vanairsdale, Sharon; Vasa, Angela; Smith, Philip W

The National Ebola Training and Education Center (NETEC) was established in 2015 in response to the 2014-2016 Ebola virus disease outbreak in West Africa. The US Department of Health and Human Services office of the Assistant Secretary for Preparedness and Response and the US Centers for Disease Control and Prevention sought to increase the competency of healthcare and public health workers, as well as the capability of healthcare facilities in the United States, to deliver safe, efficient, and effective care to patients infected with Ebola and other special pathogens nationwide. NYC Health + Hospitals/Bellevue, Emory University, and the University of Nebraska Medical Center/Nebraska Medicine were awarded this cooperative agreement, based in part on their experience in safely and successfully evaluating and treating patients with Ebola virus disease in the United States. In 2016, NETEC received a supplemental award to expand on 3 initial primary tasks: (1) develop metrics and conduct peer review assessments; (2) develop and provide educational materials, resources, and tools, including exercise design templates; (3) provide expert training and technical assistance; and, to add a fourth task, create a special pathogens clinical research network.

Antibiotic Resistance Determinants in a Pseudomonas putida Strain Isolated from a Hospital

PubMed Central

Duque, Estrella; Fernández, Matilde; Molina-Santiago, Carlos; Roca, Amalia; Porcel, Mario; de la Torre, Jesús; Segura, Ana; Plesiat, Patrick; Jeannot, Katy; Ramos, Juan-Luis

2014-01-01

Environmental microbes harbor an enormous pool of antibiotic and biocide resistance genes that can impact the resistance profiles of animal and human pathogens via horizontal gene transfer. Pseudomonas putida strains are ubiquitous in soil and water but have been seldom isolated from humans. We have established a collection of P. putida strains isolated from in-patients in different hospitals in France. One of the isolated strains (HB3267) kills insects and is resistant to the majority of the antibiotics used in laboratories and hospitals, including aminoglycosides, ß-lactams, cationic peptides, chromoprotein enediyne antibiotics, dihydrofolate reductase inhibitors, fluoroquinolones and quinolones, glycopeptide antibiotics, macrolides, polyketides and sulfonamides. Similar to other P. putida clinical isolates the strain was sensitive to amikacin. To shed light on the broad pattern of antibiotic resistance, which is rarely found in clinical isolates of this species, the genome of this strain was sequenced and analysed. The study revealed that the determinants of multiple resistance are both chromosomally-borne as well as located on the pPC9 plasmid. Further analysis indicated that pPC9 has recruited antibiotic and biocide resistance genes from environmental microorganisms as well as from opportunistic and true human pathogens. The pPC9 plasmid is not self-transmissible, but can be mobilized by other bacterial plasmids making it capable of spreading antibiotic resistant determinants to new hosts. PMID:24465371

Gold nanoparticles synthesized by Brassica oleracea (Broccoli) acting as antimicrobial agents against human pathogenic bacteria and fungi

NASA Astrophysics Data System (ADS)

Piruthiviraj, Prakash; Margret, Anita; Krishnamurthy, Poornima Priyadharsani

2016-04-01

Production of antimicrobial agents through the synthesis of gold nanoparticles using green technology has been extensively made consistent by various researchers; yet, this study uses the flower bud's aqueous extracts of Brassica oleracea (Broccoli) as a reducing agent for chloroauric acid (1 mM). After 30 min of incubation, synthesis of gold nanoparticles (AuNps) was observed by a change in extract color from pale yellow to purple color. Synthesis of AuNps was confirmed in UV-visible spectroscopy at the range of approximately 560 nm. The SEM analysis showed the average nanoparticles size of 12-22 nm. The antimicrobial activity of AuNps was analyzed by subjecting it to human pathogenic bacteria (Gram-positive Staphylococcus aureus and Gram-negative Klebsiella pneumonia) and fungi (Aspergillus flavus, Aspergillus niger and Candida albicans) using disc diffusion method. The broccoli-synthesized AuNps showed the efficient antibacterial and antifungal activity of above-mentioned microbes. It was confirmed that AuNps have the best antimicrobial agent compared to the standard antibiotics (Gentamicin and Fluconazole). When the concentrations of AuNps were increased (10, 25, and 50 µg/ml), the sensitivity zone also increased for all the tested microbes. The synthesized AuNps are capable of rendering high antimicrobial efficacy and, hence, have a great potential in the preparation of drugs used against major bacterial and fungal diseases in humans.

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

Production of monoclonal antibody inhibiting dipeptidylaminopeptidase IV activity of Porphyromonas gingivalis.

PubMed

Teshirogi, K; Hayakawa, M; Ikemi, T; Abiko, Y

2003-06-01

Porphyromonas gingivalis is a Gram-negative anaerobic bacterial species implicated as an important pathogen in the development of adult periodontitis. We previously cloned a gene encoding dipeptydilaminopeptidase IV (DAPIV) from P. gingivalis. In the present study, for immunological diagnosis and development of passive immunization, we produced a mouse monoclonal antibody (MAb) capable of inhibiting the DAPIV activity of P. gingivalis using highly purified recombinant DAPIV as an immunogen. The constructed MAb, designated as MAb-Pg-DAP-1, significantly inhibited DAPIV activity in P. gingivalis, as well as slightly inhibited that in other gram-negative bacteria such as Porphyromonas endodontalis and Prevotella loesheii, whereas no inhibition was seen in the gram-positive bacteria Streptococcus mutans and Actinomyces viscosus. Furthermore, the MAb did not inhibit DAPIV enzyme activity in human serum. This novel MAb may be useful for the development of immunological diagnosis capability and in passive immunization.

Antimicrobial Peptides from Fruits and Their Potential Use as Biotechnological Tools—A Review and Outlook

PubMed Central

Meneguetti, Beatriz T.; Machado, Leandro dos Santos; Oshiro, Karen G. N.; Nogueira, Micaella L.; Carvalho, Cristiano M. E.; Franco, Octávio L.

2017-01-01

Bacterial resistance is a major threat to plant crops, animals and human health, and over the years this situation has increasingly spread worldwide. Due to their many bioactive compounds, plants are promising sources of antimicrobial compounds that can potentially be used in the treatment of infections caused by microorganisms. As well as stem, flowers and leaves, fruits have an efficient defense mechanism against pests and pathogens, besides presenting nutritional and functional properties due to their multifunctional molecules. Among such compounds, the antimicrobial peptides (AMPs) feature different antimicrobials that are capable of disrupting the microbial membrane and of acting in binding to intra-cytoplasmic targets of microorganisms. They are therefore capable of controlling or halting the growth of microorganisms. In summary, this review describes the major classes of AMPs found in fruits, their possible use as biotechnological tools and prospects for the pharmaceutical industry and agribusiness. PMID:28119671

Highly pathogenic avian H5N8 influenza viruses: should we be concerned?

PubMed

Tate, M D

2018-01-01

Avian influenza A viruses pose a constant threat to global human health as sporadic infections continue to occur with associated high mortality rates. To date, a number of avian influenza virus subtypes have infected humans, including H5N1, H7N9, H9N2 and H7N7. The majority of 'bird flu' cases are thought to have arisen from direct contact with infected poultry, particularly in live markets in Asia. 1 While human cases of the H5N8 subtype have not been documented as yet, there is the potential that H5N8 viruses could acquire mutations which favour infection of human cells. There is also the possibility that novel viruses with a tropism for human cells could be generated if H5N8 should reassasort with other circulating avian viruses, such as those of the H5N1 subtype. The emergence of a novel H5N8 virus with the capability of infecting humans could have drastic consequences to global health.

Reduced Set of Virulence Genes Allows High Accuracy Prediction of Bacterial Pathogenicity in Humans

PubMed Central

Iraola, Gregorio; Vazquez, Gustavo; Spangenberg, Lucía; Naya, Hugo

2012-01-01

Although there have been great advances in understanding bacterial pathogenesis, there is still a lack of integrative information about what makes a bacterium a human pathogen. The advent of high-throughput sequencing technologies has dramatically increased the amount of completed bacterial genomes, for both known human pathogenic and non-pathogenic strains; this information is now available to investigate genetic features that determine pathogenic phenotypes in bacteria. In this work we determined presence/absence patterns of different virulence-related genes among more than finished bacterial genomes from both human pathogenic and non-pathogenic strains, belonging to different taxonomic groups (i.e: Actinobacteria, Gammaproteobacteria, Firmicutes, etc.). An accuracy of 95% using a cross-fold validation scheme with in-fold feature selection is obtained when classifying human pathogens and non-pathogens. A reduced subset of highly informative genes () is presented and applied to an external validation set. The statistical model was implemented in the BacFier v1.0 software (freely available at ), that displays not only the prediction (pathogen/non-pathogen) and an associated probability for pathogenicity, but also the presence/absence vector for the analyzed genes, so it is possible to decipher the subset of virulence genes responsible for the classification on the analyzed genome. Furthermore, we discuss the biological relevance for bacterial pathogenesis of the core set of genes, corresponding to eight functional categories, all with evident and documented association with the phenotypes of interest. Also, we analyze which functional categories of virulence genes were more distinctive for pathogenicity in each taxonomic group, which seems to be a completely new kind of information and could lead to important evolutionary conclusions. PMID:22916122

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

QUANTITATIVE ASSESSMENT OF PATHOGENS IN DRINKING WATER

EPA Science Inventory

The project has been summarized in a series of peer-reviewed published papers as outlined in the Publication section of this report. Pathogens capable of causing waterborne diseases include bacteria, protozoa, and viruses. Fecal indicator bacteria are the primary microorganisms u...

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

PubMed

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

2018-05-01

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

Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation.

PubMed

Gerstein, Aleeza C; Fu, Man Shun; Mukaremera, Liliane; Li, Zhongming; Ormerod, Kate L; Fraser, James A; Berman, Judith; Nielsen, Kirsten

2015-10-13

Cryptococcus neoformans is a major life-threatening fungal pathogen. In response to the stress of the host environment, C. neoformans produces large polyploid titan cells. Titan cell production enhances the virulence of C. neoformans, yet whether the polyploid aspect of titan cells is specifically influential remains unknown. We show that titan cells were more likely to survive and produce offspring under multiple stress conditions than typical cells and that even their normally sized daughters maintained an advantage over typical cells in continued exposure to stress. Although polyploid titan cells generated haploid daughter cell progeny upon in vitro replication under nutrient-replete conditions, titan cells treated with the antifungal drug fluconazole produced fluconazole-resistant diploid and aneuploid daughter cells. Interestingly, a single titan mother cell was capable of generating multiple types of aneuploid daughter cells. The increased survival and genomic diversity of titan cell progeny promote rapid adaptation to new or high-stress conditions. The ability to adapt to stress is a key element for survival of pathogenic microbes in the host and thus plays an important role in pathogenesis. Here we investigated the predominantly haploid human fungal pathogen Cryptococcus neoformans, which is capable of ploidy and cell size increases during infection through production of titan cells. The enlarged polyploid titan cells are then able to rapidly undergo ploidy reduction to generate progeny with reduced ploidy and/or aneuploidy. Under stressful conditions, titan cell progeny have a growth and survival advantage over typical cell progeny. Understanding how titan cells enhance the rate of cryptococcal adaptation under stress conditions may assist in the development of novel drugs aimed at blocking ploidy transitions. Copyright © 2015 Gerstein et al.

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...

Preliminary survey of antibiotic-resistant fecal indicator bacteria and pathogenic Escherichia coli from river-water samples collected in Oakland County, Michigan, 2003

USGS Publications Warehouse

Fogarty, Lisa R.; Duris, Joseph W.; Aichele, Stephen S.

2005-01-01

A preliminary study was done in Oakland County, Michigan, to determine the concentration of fecal indicator bacteria (fecal coliform bacteria and enterococci), antibiotic resistance patterns of these two groups, and the presence of potentially pathogenic Escherichia coli (E. coli). For selected sites, specific members of these groups [E. coli, Enterococcus faecium (E. faecium) and Enterococcus faecalis (E. faecalis)] were isolated and tested for levels of resistance to specific antibiotics used to treat human infections by pathogens in these groups and for their potential to transfer these resistances. In addition, water samples from all sites were tested for indicators of potentially pathogenic E. coli by three assays: a growth-based assay for sorbitol-negative E. coli, an immunological assay for E. coli O157, and a molecular assay for three virulence and two serotype genes. Samples were also collected from two non-urbanized sites outside of Oakland County. Results from the urbanized Oakland County area were compared to those from these two non-urbanized sites. Fecal indicator bacteria concentrations exceeded State of Michigan recreational water-quality standards and (or) recommended U.S. Environmental Protection Agency (USEPA) standards in samples from all but two Oakland County sites. Multiple-antibiotic-resistant fecal coliform bacteria were found at all sites, including two reference sites from outside the county. Two sites (Stony Creek and Paint Creek) yielded fecal coliform isolates resistant to all tested antibiotics. Patterns indicative of extended-spectrum-β-lactamase (ESBL)- producing fecal coliform bacteria were found at eight sites in Oakland County and E. coli resistant to clinically significant antibiotics were recovered from the River Rouge, Clinton River, and Paint Creek. Vancomycin-resistant presumptive enterococci were found at six sites in Oakland County and were not found at the reference sites. Evidence of acquired antibiotic resistances was detected in bacteria from multiple sites in Oakland County but not detected in bacteria from the reference sites. Integrons capable of transferring resistance were detected in isolates from the River Rouge and Clinton River. E. faecium and E. faecalis identified in samples collected from Kearsley Creek and Evans Ditch were resistant to high levels of vancomycin and carried transferable genes responsible for resistance. Several sites in Oakland County had indicators of pathogenic E. coli in August and (or) September 2003. Two samples from the Clinton River in August tested positive for all three E. coli O157 tests. Both the August and September samples from one River Rouge site were positive for the immunological and molecular assay for E. coli O157. A combination of virulence genes commonly associated with human illness was detected at five sites in August and seven sites in September. Antibiotic-resistance profiles of clinical concern along with genes capable of transferring the resistance were found at several sites throughout Oakland County; samples from many of these sites also contained potentially pathogenic E. coli.

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.

Biocontrol agents promote growth of potato pathogens, depending on environmental conditions.

PubMed

Cray, Jonathan A; Connor, Mairéad C; Stevenson, Andrew; Houghton, Jonathan D R; Rangel, Drauzio E N; Cooke, Louise R; Hallsworth, John E

2016-05-01

There is a pressing need to understand and optimize biological control so as to avoid over-reliance on the synthetic chemical pesticides that can damage environmental and human health. This study focused on interactions between a novel biocontrol-strain, Bacillus sp. JC12GB43, and potato-pathogenic Phytophthora and Fusarium species. In assays carried out in vitro and on the potato tuber, the bacterium was capable of near-complete inhibition of pathogens. This Bacillus was sufficiently xerotolerant (water activity limit for growth = 0.928) to out-perform Phytophthora infestans (~0.960) and challenge Fusarium coeruleum (~0.847) and Fusarium sambucinum (~0.860) towards the lower limits of their growth windows. Under some conditions, however, strain JC12GB43 stimulated proliferation of the pathogens: for instance, Fusarium coeruleum growth-rate was increased under chaotropic conditions in vitro (132 mM urea) by >100% and on tubers (2-M glycerol) by up to 570%. Culture-based assays involving macromolecule-stabilizing (kosmotropic) compatible solutes provided proof-of-principle that the Bacillus may provide kosmotropic metabolites to the plant pathogen under conditions that destabilize macromolecular systems of the fungal cell. Whilst unprecedented, this finding is consistent with earlier reports that fungi can utilize metabolites derived from bacterial cells. Unless the antimicrobial activities of candidate biocontrol strains are assayed over a full range of field-relevant parameters, biocontrol agents may promote plant pathogen infections and thereby reduce crop yields. These findings indicate that biocontrol activity, therefore, ought to be regarded as a mode-of-behaviour (dependent on prevailing conditions) rather than an inherent property of a bacterial strain. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Hidden Population Structure and Cross-species Transmission of Whipworms (Trichuris sp.) in Humans and Non-human Primates in Uganda

PubMed Central

Ghai, Ria R.; Simons, Noah D.; Chapman, Colin A.; Omeja, Patrick A.; Davies, T. Jonathan; Ting, Nelson; Goldberg, Tony L.

2014-01-01

Background Whipworms (Trichuris sp.) are a globally distributed genus of parasitic helminths that infect a diversity of mammalian hosts. Molecular methods have successfully resolved porcine whipworm, Trichuris suis, from primate whipworm, T. trichiura. However, it remains unclear whether T. trichiura is a multi-host parasite capable of infecting a wide taxonomic breadth of primate hosts or a complex of host specific parasites that infect one or two closely related hosts. Methods and Findings We examined the phylogenetic structure of whipworms in a multi-species community of non-human primates and humans in Western Uganda, using both traditional microscopy and molecular methods. A newly developed nested polymerase chain reaction (PCR) method applied to non-invasively collected fecal samples detected Trichuris with 100% sensitivity and 97% specificity relative to microscopy. Infection rates varied significantly among host species, from 13.3% in chimpanzees (Pan troglodytes) to 88.9% in olive baboons (Papio anubis). Phylogenetic analyses based on nucleotide sequences of the Trichuris internal transcribed spacer regions 1 and 2 of ribosomal DNA revealed three co-circulating Trichuris groups. Notably, one group was detected only in humans, while another infected all screened host species, indicating that whipworms from this group are transmitted among wild primates and humans. Conclusions and Significance Our results suggest that the host range of Trichuris varies by taxonomic group, with some groups showing host specificity, and others showing host generality. In particular, one Trichuris taxon should be considered a multi-host pathogen that is capable of infecting wild primates and humans. This challenges past assumptions about the host specificity of this and similar helminth parasites and raises concerns about animal and human health. PMID:25340752

Hidden population structure and cross-species transmission of whipworms (Trichuris sp.) in humans and non-human primates in Uganda.

PubMed

Ghai, Ria R; Simons, Noah D; Chapman, Colin A; Omeja, Patrick A; Davies, T Jonathan; Ting, Nelson; Goldberg, Tony L

2014-10-01

Whipworms (Trichuris sp.) are a globally distributed genus of parasitic helminths that infect a diversity of mammalian hosts. Molecular methods have successfully resolved porcine whipworm, Trichuris suis, from primate whipworm, T. trichiura. However, it remains unclear whether T. trichiura is a multi-host parasite capable of infecting a wide taxonomic breadth of primate hosts or a complex of host specific parasites that infect one or two closely related hosts. We examined the phylogenetic structure of whipworms in a multi-species community of non-human primates and humans in Western Uganda, using both traditional microscopy and molecular methods. A newly developed nested polymerase chain reaction (PCR) method applied to non-invasively collected fecal samples detected Trichuris with 100% sensitivity and 97% specificity relative to microscopy. Infection rates varied significantly among host species, from 13.3% in chimpanzees (Pan troglodytes) to 88.9% in olive baboons (Papio anubis). Phylogenetic analyses based on nucleotide sequences of the Trichuris internal transcribed spacer regions 1 and 2 of ribosomal DNA revealed three co-circulating Trichuris groups. Notably, one group was detected only in humans, while another infected all screened host species, indicating that whipworms from this group are transmitted among wild primates and humans. Our results suggest that the host range of Trichuris varies by taxonomic group, with some groups showing host specificity, and others showing host generality. In particular, one Trichuris taxon should be considered a multi-host pathogen that is capable of infecting wild primates and humans. This challenges past assumptions about the host specificity of this and similar helminth parasites and raises concerns about animal and human health.

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.

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.

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

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

Cary,; Bruce, R; Stubben, Christopher J

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

Multiplex detection of respiratory pathogens

DOEpatents

McBride, Mary [Brentwood, CA; Slezak, Thomas [Livermore, CA; Birch, James M [Albany, CA

2012-07-31

Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

Molecular epidemiology of Giardia and Cryptosporidium infections.

PubMed

Thompson, R C A; Ash, A

2016-06-01

Giardia and Cryptosporidium are ubiquitous enteric protozoan pathogens of vertebrates. Although recognised as the aetiological agents of disease in humans and domestic animals for many years, fundamental questions concerning their ecology have been unresolved. Molecular tools have helped to better understand their genetic diversity and in so doing have helped to resolve questions about their transmission patterns and associated impacts on public health. However, the value of molecular tools is often complicated by questions concerning their applications, interpretation of results and terminology. Taxonomic issues have, until recently, made it difficult to determine the epidemiology of infections with both Giardia and Cryptosporidium. Similarly, improved understanding of their respective phylogenetic relationships has helped to resolve questions about zoonotic potential and distribution in wildlife. In the case of Cryptosporidium, imaging technologies have complemented phylogenetic studies in demonstrating the parasite's affinities with gregarine protozoa and have further supported its extracellular developmental capability and potential role as an environmental pathogen. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Quorum Quenching Agents: Resources for Antivirulence Therapy

PubMed Central

Tang, Kaihao; Zhang, Xiao-Hua

2014-01-01

The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy. PMID:24886865

Isolation, characterization and chromatography based purification of antibacterial compound isolated from rare endophytic actinomycetes Micrococcus yunnanensis.

PubMed

Ranjan, Ravi; Jadeja, Vasantba

2017-10-01

Endophytic actinomycetes are considered as one of the relatively unexplored potential sources in search of antibiotic producer against antibiotic resistant pathogens. A potent strain isolated from Catharanthus roseus that displays antibacterial potential against antibiotic resistant human pathogen Staphylococcus aureus was characterized and designated as Micrococcus yunnanensis strain rsk5. Rsk5 is capable of producing optimum antibacterial metabolites on starch casein medium at 30 °C, pH 5 and 2% NaCl condition. The crude antibacterial agent was extracted from fermentation broth by ethyl acetate and separated by TLC using chloroform-methanol (24:1, v/v) solvent system with R f value of 0.26. It was partially purified by flash chromatography, followed by HPLC and analyzed by ultraviolet visible spectrophotometer to get absorption maxima at 208.4 nm. The ESI-MS spectra showed molecular ion peaks at m / z 472.4 [M-H], which does not match with any known antibacterial compound.

Analysis of a food-borne fungal pathogen outbreak: virulence and genome of a Mucor circinelloides isolate from yogurt.

PubMed

Lee, Soo Chan; Billmyre, R Blake; Li, Alicia; Carson, Sandra; Sykes, Sean M; Huh, Eun Young; Mieczkowski, Piotr; Ko, Dennis C; Cuomo, Christina A; Heitman, Joseph

2014-07-08

Food-borne pathogens are ongoing problems, and new pathogens are emerging. The impact of fungi, however, is largely underestimated. Recently, commercial yogurts contaminated with Mucor circinelloides were sold, and >200 consumers became ill with nausea, vomiting, and diarrhea. Mucoralean fungi cause the fatal fungal infection mucormycosis, whose incidence has been continuously increasing. In this study, we isolated an M. circinelloides strain from a yogurt container, and multilocus sequence typing identified the strain as Mucor circinelloides f. circinelloides. M. circinelloides f. circinelloides is the most virulent M. circinelloides subspecies and is commonly associated with human infections, whereas M. circinelloides f. lusitanicus and M. circinelloides f. griseocyanus are less common causes of infection. Whole-genome analysis of the yogurt isolate confirmed it as being close to the M. circinelloides f. circinelloides subgroup, with a higher percentage of divergence with the M. circinelloides f. lusitanicus subgroup. In mating assays, the yogurt isolate formed sexual zygospores with the (-) M. circinelloides f. circinelloides tester strain, which is congruent with its sex locus encoding SexP, the (+) mating type sex determinant. The yogurt isolate was virulent in murine and wax moth larva host systems. In a murine gastromucormycosis model, Mucor was recovered from fecal samples of infected mice for up to 10 days, indicating that Mucor can survive transit through the GI tract. In interactions with human immune cells, M. circinelloides f. lusitanicus induced proinflammatory cytokines but M. circinelloides f. circinelloides did not, which may explain the different levels of virulence in mammalian hosts. This study demonstrates that M. circinelloides can spoil food products and cause gastrointestinal illness in consumers and may pose a particular risk to immunocompromised patients. Importance: The U.S. FDA reported that yogurt products were contaminated with M. circinelloides, a mucoralean fungal pathogen, and >200 consumers complained of symptoms, including vomiting, nausea, and diarrhea. The manufacturer voluntarily withdrew the affected yogurt products from the market. Compared to other food-borne pathogens, including bacteria, viruses, and parasites, less focus has been placed on the risk of fungal pathogens. This study evaluates the potential risk from the food-borne fungal pathogen M. circinelloides that was isolated from the contaminated commercial yogurt. We successfully cultured an M. circinelloides isolate and found that the isolate belongs to the species M. circinelloides f. circinelloides, which is often associated with human infections. In murine and insect host models, the isolate was virulent. While information disseminated in the popular press would suggest this fungal contaminant poses little or no risk to consumers, our results show instead that it is capable of causing significant infections in animals. Copyright © 2014 Lee et al.

The design of a microfluidic biochip for the rapid, multiplexed detection of foodborne pathogens by surface plasmon resonance imaging

NASA Astrophysics Data System (ADS)

Zordan, Michael D.; Grafton, Meggie M. G.; Park, Kinam; Leary, James F.

2010-02-01

The rapid detection of foodborne pathogens is increasingly important due to the rising occurrence of contaminated food supplies. We have previously demonstrated the design of a hybrid optical device that has the capability to perform realtime surface plasmon resonance (SPR) and epi-fluorescence imaging. We now present the design of a microfluidic biochip consisting of a two-dimensional array of functionalized gold spots. The spots on the array have been functionalized with capture peptides that specifically bind E. coli O157:H7 or Salmonella enterica. This array is enclosed by a PDMS microfluidic flow cell. A magnetically pre-concentrated sample is injected into the biochip, and whole pathogens will bind to the capture array. The previously constructed optical device is being used to detect the presence and identity of captured pathogens using SPR imaging. This detection occurs in a label-free manner, and does not require the culture of bacterial samples. Molecular imaging can also be performed using the epi-fluorescence capabilities of the device to determine pathogen state, or to validate the identity of the captured pathogens using fluorescently labeled antibodies. We demonstrate the real-time screening of a sample for the presence of E. coli O157:H7 and Salmonella enterica. Additionally the mechanical properties of the microfluidic flow cell will be assessed. The effect of these properties on pathogen capture will be examined.

DNA Mutations Mediate Microevolution between Host-Adapted Forms of the Pathogenic Fungus Cryptococcus neoformans

PubMed Central

Magditch, Denise A.; Liu, Tong-Bao; Xue, Chaoyang; Idnurm, Alexander

2012-01-01

The disease cryptococcosis, caused by the fungus Cryptococcus neoformans, is acquired directly from environmental exposure rather than transmitted person-to-person. One explanation for the pathogenicity of this species is that interactions with environmental predators select for virulence. However, co-incubation of C. neoformans with amoeba can cause a “switch” from the normal yeast morphology to a pseudohyphal form, enabling fungi to survive exposure to amoeba, yet conversely reducing virulence in mammalian models of cryptococcosis. Like other human pathogenic fungi, C. neoformans is capable of microevolutionary changes that influence the biology of the organism and outcome of the host-pathogen interaction. A yeast-pseudohyphal phenotypic switch also happens under in vitro conditions. Here, we demonstrate that this morphological switch, rather than being under epigenetic control, is controlled by DNA mutation since all pseudohyphal strains bear mutations within genes encoding components of the RAM pathway. High rates of isolation of pseudohyphal strains can be explained by the physical size of RAM pathway genes and a hypermutator phenotype of the strain used in phenotypic switching studies. Reversion to wild type yeast morphology in vitro or within a mammalian host can occur through different mechanisms, with one being counter-acting mutations. Infection of mice with RAM mutants reveals several outcomes: clearance of the infection, asymptomatic maintenance of the strains, or reversion to wild type forms and progression of disease. These findings demonstrate a key role of mutation events in microevolution to modulate the ability of a fungal pathogen to cause disease. PMID:23055925

Novel aptamer-linked nanoconjugate approach for detection of waterborne bacterial pathogens: an update

NASA Astrophysics Data System (ADS)

Singh, Gulshan; Manohar, Murli; Adegoke, Anthony Ayodeji; Stenström, Thor Axel; Shanker, Rishi

2017-01-01

The lack of microbiologically safe water in underdeveloped nations is the prime cause of infectious disease outbreaks. The need for the specific identification and detection of microorganisms encourages the development of advanced, rapid, sensitive and highly specific methods for the monitoring of pathogens and management of potential risk to human health. The rapid molecular assays based on detection of specific molecular signatures offer advantages over conventional methods in terms of specificity and sensitivity but require complex instrumentation and skilled personnel. Nanotechnology is an emerging area and provides a robust approach for the identification of pathogenic microorganism utilizing the peculiar properties of nanomaterials, i.e. small size (1-100 nm) and large surface area. This emerging technology promises to fulfill the urgent need of a novel strategy to enhance the bacterial identification and quantitation in the environment. In this context, the peculiar properties of gold nanoparticles, their plasmonic shifts, and changes in magnetic properties have been utilized for the simple and cost-effective detection of bacterial nucleic acids, antigens and toxins with quite improved sensitivity. One of the promising leads to develop an advance detection method might be the coupling of nucleic acid aptamers (capable of interacting specifically with bacteria, protozoa, and viruses) with nanomaterials. Such aptamer-nano conjugate can be used for the specific recognition of infectious agents in different environmental matrices. This review summarizes the application of nanotechnology in the area of pathogen detection and discusses the prospects of coupling nucleic acid aptamers with nanoparticles for the specific detection of targeted pathogens.

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

Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus

USDA-ARS?s Scientific Manuscript database

Disease pathways form overlapping networks, and hub proteins represent attractive targets for broad-spectrum drugs. Using bacterial toxins as a proof of concept, we describe a new approach of discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pa...

There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes.

PubMed

Marcinkiewicz, Ashley L; Kraiczy, Peter; Lin, Yi-Pin

2017-01-01

Lyme disease and relapsing fever are caused by various Borrelia species. Lyme disease borreliae , the most common vector-borne pathogens in both the U.S. and Europe, are transmitted by Ixodes ticks and disseminate from the site of tick bites to tissues leading to erythema migrans skin rash, arthritis, carditis, and neuroborreliosis. Relapsing fever borreliae , carried by ticks and lice, trigger reoccurring fever episodes. Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system. The complement system acts as an important innate immune defense mechanism in humans and vertebrates. Upon activation, the cleaved complement components form complexes on the pathogen surface to eventually promote bacteriolysis. The complement system is negatively modulated by a number of functionally diverse regulators to avoid tissue damage. To evade and inhibit the complement system, spirochetes are capable of binding complement components and regulators. Complement inhibition results in bacterial survival in serum (serum resistance) and is thought to promote bloodstream survival, which facilitates spirochete dissemination and disease manifestations. In this review, we discuss current methodologies to elucidate the mechanisms of Borrelia spp. that promote serum resistance and bloodstream survival, as well as novel methods to study factors responsible for bloodstream survival of Lyme disease borreliae that can be applied to relapsing fever borreliae . Understanding the mechanisms these pathogens utilize to evade the complement system will ultimately aid in the development of novel therapeutic strategies and disease prevention to improve human health.

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

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.

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

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.

Neonatal innate TLR-mediated responses are distinct from those of adults.

PubMed

Kollmann, Tobias R; Crabtree, Juliet; Rein-Weston, Annie; Blimkie, Darren; Thommai, Francis; Wang, Xiu Yu; Lavoie, Pascal M; Furlong, Jeff; Fortuno, Edgardo S; Hajjar, Adeline M; Hawkins, Natalie R; Self, Steven G; Wilson, Christopher B

2009-12-01

The human neonate and infant are unduly susceptible to infection with a wide variety of microbes. This susceptibility is thought to reflect differences from adults in innate and adaptive immunity, but the nature of these differences is incompletely characterized. The innate immune response directs the subsequent adaptive immune response after integrating information from TLRs and other environmental sensors. We set out to provide a comprehensive analysis defining differences in response to TLR ligation between human neonates and adults. In response to most TLR ligands, neonatal innate immune cells, including monocytes and conventional and plasmacytoid dendritic cells produced less IL-12p70 and IFN-alpha (and consequently induced less IFN-gamma), moderately less TNF-alpha, but as much or even more IL-1beta, IL-6, IL-23, and IL-10 than adult cells. At the single-cell level, neonatal innate cells generally were less capable of producing multiple cytokines simultaneously, i.e., were less polyfunctional. Overall, our data suggest a robust if not enhanced capacity of the neonate vs the adult white-blood cell TLR-mediated response to support Th17- and Th2-type immunity, which promotes defense against extracellular pathogens, but a reduced capacity to support Th1-type responses, which promote defense against intracellular pathogens.

Toxoplasma gondii, source to sea: higher contribution of domestic felids to terrestrial parasite loading despite lower infection prevalence.

PubMed

Vanwormer, Elizabeth; Conrad, Patricia A; Miller, Melissa A; Melli, Ann C; Carpenter, Tim E; Mazet, Jonna A K

2013-09-01

Environmental transmission of Toxoplasma gondii, a global zoonotic parasite, adversely impacts human and animal health. Toxoplasma is a significant cause of mortality in threatened Southern sea otters, which serve as sentinels for disease threats to people and animals in coastal environments. As wild and domestic felids are the only recognized hosts capable of shedding Toxoplasma oocysts into the environment, otter infection suggests land-to-sea pathogen transmission. To assess relative contributions to terrestrial parasite loading, we evaluated infection and shedding among managed and unmanaged feral domestic cats, mountain lions, and bobcats in coastal California, USA. Infection prevalence differed among sympatric felids, with a significantly lower prevalence for managed feral cats (17%) than mountain lions, bobcats, or unmanaged feral cats subsisting on wild prey (73-81%). A geographic hotspot of infection in felids was identified near Monterey Bay, bordering a high-risk site for otter infection. Increased odds of oocyst shedding were detected in bobcats and unmanaged feral cats. Due to their large populations, pet and feral domestic cats likely contribute more oocysts to lands bordering the sea otter range than native wild felids. Continued coastal development may influence felid numbers and distribution, increase terrestrial pathogens in freshwater runoff, and alter disease dynamics at the human-animal-environment interface.

MORPHOLOGICAL AND PATHOGENIC VARIATIONS IN TREPONEMA PALLIDUM

PubMed Central

Noguchi, Hideyo

1912-01-01

When many cultures of Treponema pallidum, whether obtained from the testicular lesions produced in rabbits or directly from human cases of syphilis, are compared, certain definite differences in morphological character become apparent. The different specimens can be divided into thicker and thinner forms or types, and an average or normal form or type. The last is the common or most frequent variety, but the other two occur with sufficient frequency and retain their characters with such constancy as to constitute distinct varieties. Indeed, two of the varieties—the average and the thinner—occurred in association in a chancre and were separated afterwards in cultures. The gross cultural properties of the three varieties present no points of distinction. The lesions caused in the testicle of the rabbit differ according to the variety inoculated, and consist either of a diffuse or of a nodular orchitis. This is a highly important distinction, and if, in the study of a still larger number of specimens of pallida, it is maintained, it is capable of throwing light on certain important clinical features of the human syphilitic disease. The thinner variety of Treponema pallidum resembles in morphology Treponema microdentium, from which it is unmistakably distinguished by cultural characters. The morphological and pathogenic variations in cultures of the pallidum may constitute racial differences within the species. PMID:19867516

Apheresis for collection of Ebola convalescent plasma in Liberia.

PubMed

Brown, Jerry F; Rowe, Kathleen; Zacharias, Peter; van Hasselt, James; Dye, John M; Wohl, David A; Fischer, William A; Cunningham, Coleen K; Thielman, Nathan M; Hoover, David L

2017-06-01

This report describes initiation of apheresis capability in Liberia, Africa to support a clinical trial of convalescent plasma therapy for Ebola Virus Disease. A bloodmobile was outfitted in the United States as a four-bed apheresis unit with capabilities including pathogen reduction, electronic blood establishment computer system, designated areas for donor counseling and laboratory testing, and onboard electrical power generation. After air transport to Liberia, the bloodmobile was positioned at ELWA Hospital, Monrovia, and connected to the hospital's power grid. Liberian staff were trained to conduct donor screening, which included questionnaire and onsite blood typing and transfusion transmitted infection (TTI) testing, and plasma collection and processing. The bloodmobile was operational within 3 weeks after arrival of the advance team. Of 101 donors who passed the pre-screening questionnaire, 32 were deferred. Twenty-eight of ninty-nine tested survivors were deferred for positive transfusion transmitted infection (TTI) tests; twenty-one were positive for hepatitis B, hepatitis C, or human immunodeficiency virus. The majority of donors had type O blood; all but one were Rh positive. Forty-three survivors donated at least once; eighty-nine apheresis attempts resulted in eighty-one successful collections. Apheresis capability was emergently established in Liberia to support an efficacy trial of Ebola Convalescent Plasma. Extensive cooperation among multinational team members, engineers, logisticians, and blood safety technical personnel at the operational site was required to surmount challenges to execution posed by logistical factors. The high proportion of positive TTI tests supported the use of a pathogen reduction system to enhance product safety. J. Clin. Apheresis 32:175-181, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

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 influenza is more effective than avian influenza at antiviral suppression in airway cells.

PubMed

Hsu, Alan Chen-Yu; Barr, Ian; Hansbro, Philip M; Wark, Peter A

2011-06-01

Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.

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.

Microbial small molecules - weapons of plant subversion.

PubMed

Stringlis, Ioannis A; Zhang, Hao; Pieterse, Corné M J; Bolton, Melvin D; de Jonge, Ronnie

2018-05-25

Covering: up to 2018 Plants live in close association with a myriad of microbes that are generally harmless. However, the minority of microbes that are pathogens can severely impact crop quality and yield, thereby endangering food security. By contrast, beneficial microbes provide plants with important services, such as enhanced nutrient uptake and protection against pests and diseases. Like pathogens, beneficial microbes can modulate host immunity to efficiently colonize the nutrient-rich niches within and around the roots and aerial tissues of a plant, a phenomenon mirroring the establishment of commensal microbes in the human gut. Numerous ingenious mechanisms have been described by which pathogenic and beneficial microbes in the plant microbiome communicate with their host, including the delivery of immune-suppressive effector proteins and the production of phytohormones, toxins and other bioactive molecules. Plants signal to their associated microbes via exudation of photosynthetically fixed carbon sources, quorum-sensing mimicry molecules and selective secondary metabolites such as strigolactones and flavonoids. Molecular communication thus forms an integral part of the establishment of both beneficial and pathogenic plant-microbe relations. Here, we review the current knowledge on microbe-derived small molecules that can act as signalling compounds to stimulate plant growth and health by beneficial microbes on the one hand, but also as weapons for plant invasion by pathogens on the other. As an exemplary case, we used comparative genomics to assess the small molecule biosynthetic capabilities of the Pseudomonas genus; a genus rich in both plant pathogenic and beneficial microbes. We highlight the biosynthetic potential of individual microbial genomes and the population at large, providing evidence for the hypothesis that the distinction between detrimental and beneficial microbes is increasingly fading. Knowledge on the biosynthesis and molecular activity of microbial small molecules will aid in the development of successful biological agents boosting crop resiliency in a sustainable manner and could also provide scientific routes to pathogen inhibition or eradication.

Making vaccines "on demand": a potential solution for emerging pathogens and biodefense?

PubMed

De Groot, Anne S; Einck, Leo; Moise, Leonard; Chambers, Michael; Ballantyne, John; Malone, Robert W; Ardito, Matthew; Martin, William

2013-09-01

The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of "novel pathogens" such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process-from genome to gene sequence, ready to insert in a DNA plasmid-can now be accomplished in less than 24 h. While these vaccines are by no means "standard," the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard.

Microbial minimalism: genome reduction in bacterial pathogens.

PubMed

Moran, Nancy A

2002-03-08

When bacterial lineages make the transition from free-living or facultatively parasitic life cycles to permanent associations with hosts, they undergo a major loss of genes and DNA. Complete genome sequences are providing an understanding of how extreme genome reduction affects evolutionary directions and metabolic capabilities of obligate pathogens and symbionts.

Random T-DNA mutagenesis identifies a Cu-Zn-superoxide dismutase gene as a virulence factor of Sclerotinia sclerotiorum

USDA-ARS?s Scientific Manuscript database

The Ascomycetous fungus Sclerotinia sclerotiorum is a devastating pathogen capable of infecting more than 400 plant species including many economically important crops. In order to gain a better mechanistic understanding of its non-specific host-pathogen interactions, random mutagenesis through Agro...

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

A Novel Protective Vaccine Antigen from the Core Escherichia coli Genome

PubMed Central

Moriel, Danilo G.; Tan, Lendl; Goh, Kelvin G. K.; Ipe, Deepak S.; Lo, Alvin W.; Peters, Kate M.

2016-01-01

ABSTRACT Escherichia coli is a versatile pathogen capable of causing intestinal and extraintestinal infections that result in a huge burden of global human disease. The diversity of E. coli is reflected by its multiple different pathotypes and mosaic genome composition. E. coli strains are also a major driver of antibiotic resistance, emphasizing the urgent need for new treatment and prevention measures. Here, we used a large data set comprising 1,700 draft and complete genomes to define the core and accessory genome of E. coli and demonstrated the overlapping relationship between strains from different pathotypes. In combination with proteomic investigation, this analysis revealed core genes that encode surface-exposed or secreted proteins that represent potential broad-coverage vaccine antigens. One of these antigens, YncE, was characterized as a conserved immunogenic antigen able to protect against acute systemic infection in mice after vaccination. Overall, this work provides a genomic blueprint for future analyses of conserved and accessory E. coli genes. The work also identified YncE as a novel antigen that could be exploited in the development of a vaccine against all pathogenic E. coli strains—an important direction given the high global incidence of infections caused by multidrug-resistant strains for which there are few effective antibiotics. IMPORTANCE E. coli is a multifaceted pathogen of major significance to global human health and an important contributor to increasing antibiotic resistance. Given the paucity of therapies still effective against multidrug-resistant pathogenic E. coli strains, novel treatment and prevention strategies are urgently required. In this study, we defined the core and accessory components of the E. coli genome by examining a large collection of draft and completely sequenced strains available from public databases. This data set was mined by employing a reverse-vaccinology approach in combination with proteomics to identify putative broadly protective vaccine antigens. One such antigen was identified that was highly immunogenic and induced protection in a mouse model of bacteremia. Overall, our study provides a genomic and proteomic framework for the selection of novel vaccine antigens that could mediate broad protection against pathogenic E. coli. PMID:27904885

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.

Detection of Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, and Powassan Virus in Ticks by a Multiplex Real-Time Reverse Transcription-PCR Assay

PubMed Central

Tagliafierro, Teresa; Cucura, D. Moses; Rochlin, Ilia; Sameroff, Stephen; Lipkin, W. Ian

2017-01-01

ABSTRACT Ixodes scapularis ticks are implicated in transmission of Anaplasma phagocytophilum, Borrelia burgdorferi, Borrelia miyamotoi, Babesia microti, and Powassan virus. We describe the establishment and implementation of the first multiplex real-time PCR assay with the capability to simultaneously detect and differentiate all five pathogens in a single reaction. The application of this assay for analysis of ticks at sites in New York and Connecticut revealed a high prevalence of B. microti in ticks from Suffolk County, NY. These findings are consistent with reports of a higher incidence of babesiosis from clinicians managing the care of patients with tick-borne diseases in this region. IMPORTANCE The understanding of pathogen prevalence is an important factor in the determination of human risks for tick-borne diseases and can help guide diagnosis and treatment. The implementation of our assay addresses a critical need in surveillance of tick-borne diseases, through generation of a comprehensive assessment of pathogen prevalence in I. scapularis. Our finding of a high frequency of ticks infected with Babesia microti in Suffolk County, NY, implicates this agent as a probable frequent cause of non-Lyme tick-borne disease in this area. PMID:28435891

Detection of Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, and Powassan Virus in Ticks by a Multiplex Real-Time Reverse Transcription-PCR Assay.

PubMed

Tokarz, Rafal; Tagliafierro, Teresa; Cucura, D Moses; Rochlin, Ilia; Sameroff, Stephen; Lipkin, W Ian

2017-01-01

Ixodes scapularis ticks are implicated in transmission of Anaplasma phagocytophilum , Borrelia burgdorferi , Borrelia miyamotoi , Babesia microti , and Powassan virus. We describe the establishment and implementation of the first multiplex real-time PCR assay with the capability to simultaneously detect and differentiate all five pathogens in a single reaction. The application of this assay for analysis of ticks at sites in New York and Connecticut revealed a high prevalence of B. microti in ticks from Suffolk County, NY. These findings are consistent with reports of a higher incidence of babesiosis from clinicians managing the care of patients with tick-borne diseases in this region. IMPORTANCE The understanding of pathogen prevalence is an important factor in the determination of human risks for tick-borne diseases and can help guide diagnosis and treatment. The implementation of our assay addresses a critical need in surveillance of tick-borne diseases, through generation of a comprehensive assessment of pathogen prevalence in I. scapularis . Our finding of a high frequency of ticks infected with Babesia microti in Suffolk County, NY, implicates this agent as a probable frequent cause of non-Lyme tick-borne disease in this area.

Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates.

PubMed

Bolton, Diane L; Santra, Sampa; Swett-Tapia, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Mach, Linh; Naim, Hussein; Kozlowski, Pamela A; Lifton, Michelle; Goudsmit, Jaap; Letvin, Norman; Roederer, Mario; Radošević, Katarina

2012-09-07

Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag immunization alone elicited robust measles-specific humoral and cellular responses, but failed to elicit transgene (Gag)-specific immune responses, following aerosol or intratracheal/intramuscular delivery. However, when administered as a priming vaccine to a heterologous boost with recombinant adenovirus serotype 5 expressing the same transgene, rMV-Gag significantly enhanced Gag-specific T lymphocyte responses following rAd5 immunization. Gag-specific humoral responses were not enhanced, however, which may be due to either the transgene or the vector. Cellular response priming by rMV against the transgene was highly effective even when using a suboptimal dose of rAd5 for the boost. These data demonstrate feasibility of using rMV as a priming component of heterologous prime-boost vaccine regimens for pathogens requiring strong cellular responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of Chlorine Exposure on the Survival and Antibiotic Gene Expression of Multidrug Resistant Acinetobacter baumannii in Water

PubMed Central

Karumathil, Deepti Prasad; Yin, Hsin-Bai; Kollanoor-Johny, Anup; Venkitanarayanan, Kumar

2014-01-01

Acinetobacter baumannii is a multidrug resistant pathogen capable of causing a wide spectrum of clinical conditions in humans. Acinetobacter spp. is ubiquitously found in different water sources. Chlorine being the most commonly used disinfectant in water, the study investigated the effect of chlorine on the survival of A. baumannii in water and transcription of genes conferring antibiotic resistance. Eight clinical isolates of A. baumannii, including a fatal meningitis isolate (ATCC 17978) (~108 CFU/mL) were separately exposed to free chlorine concentrations (0.2, 1, 2, 3 and 4 ppm) with a contact time of 30, 60, 90 and 120 second. The surviving pathogen counts at each specified contact time were determined using broth dilution assay. In addition, real-time quantitative PCR (RT-qPCR) analysis of the antibiotic resistance genes (efflux pump genes and those encoding resistance to specific antibiotics) of three selected A. baumannii strains following exposure to chlorine was performed. Results revealed that all eight A. baumannii isolates survived the tested chlorine levels during all exposure times (p > 0.05). Additionally, there was an up-regulation of all or some of the antibiotic resistance genes in A. baumannii, indicating a chlorine-associated induction of antibiotic resistance in the pathogen. PMID:24514427

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...

Challenges and priorities for modelling livestock health and pathogens in the context of climate change

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

Özkan, Şeyda

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire basedmore » exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change. - Highlights: • Experts identified challenges for health and pathogen modelling under climate change. • Eighteen key challenges and associated research priorities were identified. • Increasing capacity will require improved organisation and sharing knowledge. • Better communication across the diverse topics and approaches in this field is needed.« less

Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents.

PubMed

Baldridge, Jory R; McGowan, Patrick; Evans, Jay T; Cluff, Christopher; Mossman, Sally; Johnson, David; Persing, David

2004-07-01

Toll-like receptor (TLR) agonists are being developed for use as vaccine adjuvants and as stand-alone immunomodulators because of their ability to stimulate innate and adaptive immune responses. Among the most thoroughly studied TLR agonists are the lipid A molecules that target the TLR4 complex. One promising candidate, monophosphoryl lipid A, which is a derivative of lipid A from Salmonella minnesota, has proven to be safe and effective as a vaccine adjuvant in > 120,000 human doses. A new class of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates (AGPs), have been engineered specifically to target human TLR4 and are showing promise as vaccine adjuvants and as monotherapeutic agents capable of eliciting nonspecific protection against a wide range of infectious pathogens. In this review, the authors provide an update of the preclinical and clinical experiences with the TLR4 agonists, MPL (Corixa Corporation) adjuvant and the AGPs.

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

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.

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.

Prevalence of tick-borne haemoparasites in small ruminants in Turkey and diagnostic sensitivity of single-PCR and RLB.

PubMed

Bilgic, Huseyin Bilgin; Bakırcı, Serkan; Kose, Onur; Unlu, Ahmet Hakan; Hacılarlıoglu, Selin; Eren, Hasan; Weir, William; Karagenc, Tulin

2017-04-27

Tick-borne haemoparasitic diseases (TBHDs), caused by Theileria, Babesia, Anaplasma and Ehrlichia, are common in regions of the world where the distributions of host, pathogen and vector overlap. Many of these diseases threaten livestock production and some also represent a concern to human public health. The primary aim of this study was to determine the prevalence of the above-mentioned pathogens in a large number of blood samples (n = 1979) collected from sheep (n = 1727) and goats (n = 252) in Turkey. A secondary aim was to assess the diagnostic sensitivity of a number of species-specific polymerase chain reaction (PCR) tests and the reverse line blotting (RLB) assay. DNA samples were screened using species-specific PCR for the presence of Theileria ovis, Theileria sp. MK, T. lestoquardi, T. uilenbergi, T. luwenshuni, Babesia ovis, Anaplasma ovis and A. phagocytophilum while RLB was undertaken to test for the presence of all known Theileria, Babesia, Anaplasma and Ehrlichia species. The diagnostic sensitivity of these two approaches was then compared in terms of their ability to detect single species and mixed infections. Overall, 84 and 74.43% of the small ruminants sampled were identified as hosting one or more pathogen(s) by species-specific PCR and RLB respectively. The presence of Theileria sp. OT1, T. luwenshuni and T. uilenbergi in Turkey was revealed for the first time while the presence of Babesia motasi, B. crassa and T. separata in Turkish small ruminants was confirmed using molecular methods. A high prevalence of mixed infection was evident, with PCR and RLB approaches indicating that 52.24 and 35.42% of animals were co-infected with multiple species, respectively. More than 80% of the mixed infections contained T. ovis and/or A. ovis. The RLB approach was found to be capable of detecting mixed infections with species such as Theileria sp. OT1, Theileria sp. OT3, T. separata, B. crassa and Babesia spp. The results indicated that pathogens causing TBHDs are highly prevalent in sheep and goats in Turkey. The diagnostic sensitivity of species-specific single PCR was generally higher than that of RLB. However, the latter approach was still capable of identifying a high proportion of individuals containing mixed-species infections. The use of species-specific single PCR is recommended to accurately estimate pathogen prevalence and to identify co-infected hosts.

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.

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.

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.

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

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...

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

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.

Challenges and priorities for modelling livestock health and pathogens in the context of climate change.

PubMed

Özkan, Şeyda; Vitali, Andrea; Lacetera, Nicola; Amon, Barbara; Bannink, André; Bartley, Dave J; Blanco-Penedo, Isabel; de Haas, Yvette; Dufrasne, Isabelle; Elliott, John; Eory, Vera; Fox, Naomi J; Garnsworthy, Phil C; Gengler, Nicolas; Hammami, Hedi; Kyriazakis, Ilias; Leclère, David; Lessire, Françoise; Macleod, Michael; Robinson, Timothy P; Ruete, Alejandro; Sandars, Daniel L; Shrestha, Shailesh; Stott, Alistair W; Twardy, Stanislaw; Vanrobays, Marie-Laure; Ahmadi, Bouda Vosough; Weindl, Isabelle; Wheelhouse, Nick; Williams, Adrian G; Williams, Hefin W; Wilson, Anthony J; Østergaard, Søren; Kipling, Richard P

2016-11-01

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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.

Staphylococcus aureus utilizes host-derived lipoprotein particles as sources of exogenous fatty acids.

PubMed

Delekta, Phillip C; Shook, John C; Lydic, Todd A; Mulks, Martha H; Hammer, Neal D

2018-03-26

Methicillin-resistant Staphylococcus aureus (MRSA) is a threat to global health. Consequently, much effort has focused on the development of new antimicrobials that target novel aspects of S. aureus physiology. Fatty acids are required to maintain cell viability, and bacteria synthesize fatty acids using the type II fatty acid synthesis pathway (FASII). FASII is significantly different from human fatty acid synthesis, underscoring the therapeutic potential of inhibiting this pathway. However, many Gram-positive pathogens incorporate exogenous fatty acids, bypassing FASII inhibition and leaving the clinical potential of FASII inhibitors uncertain. Importantly, the source(s) of fatty acids available to pathogens within the host environment remains unclear. Fatty acids are transported throughout the body by lipoprotein particles in the form of triglycerides and esterified cholesterol. Thus, lipoproteins, such as low-density lipoprotein (LDL) represent a potentially rich source of exogenous fatty acids for S. aureus during infection. We sought to test the ability of LDLs to serve as a fatty acid source for S. aureus and show that cells cultured in the presence of human LDLs demonstrate increased tolerance to the FASII inhibitor, triclosan. Using mass spectrometry, we observed that host-derived fatty acids present in the LDLs are incorporated into the staphylococcal membrane and that tolerance to triclosan is facilitated by the fatty acid kinase A, FakA, and Geh, a triacylglycerol lipase. Finally, we demonstrate that human LDLs support the growth of S. aureus fatty acid auxotrophs. Together, these results suggest that human lipoprotein particles are a viable source of exogenous fatty acids for S. aureus during infection. IMPORTANCE Inhibition of bacterial fatty acid synthesis is a promising approach to combating infections caused by S. aureus and other human pathogens. However, S. aureus incorporates exogenous fatty acids into its phospholipid bilayer. Therefore, the clinical utility of targeting bacterial fatty acid synthesis is debated. Moreover, the fatty acid reservoir(s) exploited by S. aureus are not well understood. Human low-density lipoprotein particles represent a particularly abundant in vivo source of fatty acids and are present in tissues S. aureus colonizes. Herein, we establish that S. aureus is capable of utilizing the fatty acids present in low-density lipoproteins to bypass both chemical and genetic inhibition of fatty acid synthesis. These findings imply that S. aureus targets LDLs as a source of fatty acids during pathogenesis. Copyright © 2018 American Society for Microbiology.

Advanced Vaccine Candidates for Lassa Fever

PubMed Central

Lukashevich, Igor S.

2012-01-01

Lassa virus (LASV) is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF). LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever) with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered. PMID:23202493

Advanced vaccine candidates for Lassa fever.

PubMed

Lukashevich, Igor S

2012-10-29

Lassa virus (LASV) is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF). LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever) with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

Are We Prepared in Case of a Possible Smallpox-Like Disease Emergence?

PubMed Central

Olson, Victoria A.; Shchelkunov, Sergei N.

2017-01-01

Smallpox was the first human disease to be eradicated, through a concerted vaccination campaign led by the World Health Organization. Since its eradication, routine vaccination against smallpox has ceased, leaving the world population susceptible to disease caused by orthopoxviruses. In recent decades, reports of human disease from zoonotic orthopoxviruses have increased. Furthermore, multiple reports of newly identified poxviruses capable of causing human disease have occurred. These facts raise concerns regarding both the opportunity for these zoonotic orthopoxviruses to evolve and become a more severe public health issue, as well as the risk of Variola virus (the causative agent of smallpox) to be utilized as a bioterrorist weapon. The eradication of smallpox occurred prior to the development of the majority of modern virological and molecular biological techniques. Therefore, there is a considerable amount that is not understood regarding how this solely human pathogen interacts with its host. This paper briefly recounts the history and current status of diagnostic tools, vaccines, and anti-viral therapeutics for treatment of smallpox disease. The authors discuss the importance of further research to prepare the global community should a smallpox-like virus emerge.

Tech Transfer Webinar: Amoeba Cysts as Natural Containers for the Transport and Storage of Pathogens

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

El-Etr, Sahar

2014-10-08

Sahar El-Etr, Biomedical Scientist at the Lawrence Livermore National Laboratory, shares a unique method for transporting clinical samples from the field to a laboratory. The use of amoeba as “natural” containers for pathogens was utilized to develop the first living system for the transport and storage of pathogens. The amoeba system works at ambient temperature for extended periods of time—capabilities currently not available for biological sample transport.

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

New perspective on functional capabilities of microbiome associated with spacecraft assembly facilities

NASA Astrophysics Data System (ADS)

Vaishampayan, Parag

2016-07-01

In compliance with Planetary Protection policy, NASA monitors the total microbial burden of spacecraft and associated environments as a means for minimizing forward contamination. Despite numerous characterizations of microbial populations in spacecraft assembly cleanrooms, understanding the metabolic traits responsible for their persistence and survival remains a significant challenge. The principal objective of this study is to establish functional traits by exploring the entire gene content (metagenome) of the cleanroom microbial community. DNA-based techniques are incapable of distinguishing viable microorganisms from dead microbial cells in samples. Consequently, metagenomic analyses based on total environmental DNA extracts do not render a meaningful understanding of the metabolic and/or functional characteristics of living microorganisms in cleanrooms. A molecular viability marker was applied to samples collected from a cleanroom facility, and subsequent metagenomic sequencing experiments showed considerable differences between the resulting viable-only and total microbiomes. Nevertheless, analyses of sequence abundance suggested that the viable microbiome was influenced by both the human microbiome and the ambient ecosystem external to the facility, which resulted in a complex community profile. Also detected were the first viral signatures ever retrieved from a cleanroom facility: the genomes of human cyclovirus 7078A and Propionibacterium phage P14.4. We also wanted to evaluate if the strict cleaning and decontamination procedures selectively favor survival and growth of hardy microrganisms, such as pathogens. Three geographically distinct cleanrooms were sampled during the assembly of three NASA spacecraft: Dawn, Phoenix, and Mars Science Laboratory. Potential pathogens and their corresponding virulence factors were present in all the samples. Decreased microbial and pathogenic diversity during spacecraft assembly, compared to before and after, indicates that decontamination and preventative measures were effective and well implemented. The findings presented here, as well as the innovative methods that enabled their discovery, promise to have profound implications for the design and interpretation of ongoing and future studies in cleanrooms, indoor environments, and potential future human missions to Mars.

Differential compartmentalization of Streptococcus pyogenes virulence factors and host protein binding properties as a mechanism for host adaptation.

PubMed

Kilsgård, Ola; Karlsson, Christofer; Malmström, Erik; Malmström, Johan

2016-11-01

Streptococcus pyogenes is an important human pathogen responsible for substantial morbidity and mortality worldwide. Although S. pyogenes is a strictly human pathogen with no other known animal reservoir, several murine infection models exist to explore different aspects of the bacterial pathogenesis. Inoculating mice with wild-type S. pyogenes strains can result in the generation of new bacterial phenotypes that are hypervirulent compared to the original inoculum. In this study, we used a serial mass spectrometry based proteomics strategy to investigate if these hypervirulent strains have an altered distribution of virulence proteins across the intracellular, surface associated and secreted bacterial compartments and if any change in compartmentalization can alter the protein-protein interaction network between bacteria and host proteins. Quantitative analysis of the S. pyogenes surface and secreted proteomes revealed that animal passaged strains are associated with significantly higher amount of virulence factors on the bacterial surface and in the media. This altered virulence factor compartmentalization results in increased binding of several mouse plasma proteins to the bacterial surface, a trend that was consistent for mouse plasma from several different mouse strains. In general, both the wild-type strain and animal passaged strain were capable of binding high amounts of human plasma proteins. However, compared to the non-passaged strains, the animal passaged strains displayed an increased ability to bind mouse plasma proteins, in particular for M protein binders, indicating that the increased affinity for mouse blood plasma proteins is a consequence of host adaptation of this pathogen to a new host. In conclusion, plotting the total amount of virulence factors against the total amount of plasma proteins associated to the bacterial surface could clearly separate out animal passaged strains from wild type strains indicating a virulence model that could predict the virulence of a S. pyogenes strain in mice and which could be used to identify key aspects of this bacteria's pathogenesis. Copyright © 2016 Elsevier GmbH. All rights reserved.

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig.

PubMed

Tungatt, Katie; Dolton, Garry; Morgan, Sophie B; Attaf, Meriem; Fuller, Anna; Whalley, Thomas; Hemmink, Johanneke D; Porter, Emily; Szomolay, Barbara; Montoya, Maria; Hammond, John A; Miles, John J; Cole, David K; Townsend, Alain; Bailey, Mick; Rizkallah, Pierre J; Charleston, Bryan; Tchilian, Elma; Sewell, Andrew K

2018-05-01

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens.

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig

PubMed Central

Morgan, Sophie B.; Attaf, Meriem; Szomolay, Barbara; Miles, John J.; Townsend, Alain; Bailey, Mick; Charleston, Bryan; Tchilian, Elma

2018-01-01

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens. PMID:29772011

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

PubMed Central

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

2017-01-01

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

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.

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

Advances in direct T-cell alloreactivity: function, avidity, biophysics and structure.

PubMed

Smith, C; Miles, J J; Khanna, R

2012-01-01

Although T-cell-based adaptive immunity plays a crucial role in protection against infectious pathogens and uncontrolled outgrowth of malignant cells, a large portion of these T cells are also capable of responding to allogeneic HLA molecules, violating the paradigm of self-major histocompatibility complex (MHC) restriction. Recent studies have provided insights into the mechanisms by which these T cells recognize allogeneic targets. The role of antiviral T cells in direct alloreactivity through peptide-dependent molecular mimicry and alternate peptide-MHC docking modes has emerged as major models for the human alloresponse. Here, we review in depth recent advances in this field and discuss how molecular interactions between T cells and HLA molecules drive the activation of these effector cells and its potential implications for alloreactivity in human transplantation. ©Copyright 2011 American Society of Transplantation and the American Society of Transplant Surgeons.

DETECTION OF AEROSOLIZED BACTERIA IN EXPIRED AIR SAMPLES FROM ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

PubMed

Burke, Sophie M; Vogelnest, Larry; Thompson, Paul; Tovey, Euan R; Williamson, Peter

2017-06-01

Elephant-mediated transmission of tuberculosis is assumed to be similar to human models, which state close and prolonged contact with an infected individual is required for transmission. Although considered a risk factor for infection, several case studies have reported that close contact with an elephant is not always necessary for transmission, and the role of aerosolized bacteria remains unclear. To investigate aerosol-mediated transmission of pathogenic bacteria from elephants, a method for the detection of aerosols using an adapted sampling system was developed. A commensal bacterium was isolated from the upper respiratory tract of elephants ( Elephas maximus ) and was used as a proxy organism to detect aerosolized droplets in the sampling system. It was found that elephants are capable of producing aerosolized bacterial particles of a size small enough to remain airborne for prolonged periods and penetrate the lower regions of the human respiratory tract.

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...

Protective Effect of Vaginal Lactobacillus paracasei CRL 1289 against Urogenital Infection Produced by Staphylococcus aureus in a Mouse Animal Model

PubMed Central

Zárate, Gabriela; Santos, Viviana; Nader-Macias, María Elena

2007-01-01

Urogenital infections of bacterial origin have a high incidence among the world female population at reproductive age. Lactobacilli, the predominant microorganisms of the healthy vaginal microbiota, have shown a protective effect against the colonization and overgrowth of urogenital pathogens that increased the interest for including them into probiotics products assigned to restore the urogenital balance. In the present work, we determined in a mouse animal model the capability of Lactobacillus paracasei CRL 1289, a human vaginal strain with probiotic properties, to prevent the vaginal colonization of a uropathogenic strain of Staphylococcus aureus. Six-week-old female BALB/c mice, synchronized in their estral cycle, were intravaginally inoculated with two doses of 109 lactobacilli before challenging them with a single dose of 105 or 107 CFU of S. aureus. The vaginal colonization of both microorganisms and the effect on the vaginal structure were determined at 2, 5, and 7 days after pathogen inoculation. Control mice and those challenged only with the pathogen showed an insignificant lactobacilli population, whereas 105 lactobacilli/mL of vaginal homogenate were recovered at 2 days after challenge from the L. paracasei CRL 1289 and the probiotic + pathogen groups, decreasing this number on the following days. The treatment with L. paracasei CRL 1289 decreased significantly the number of staphylococci recovered at 2 and 5 days when mice were challenged only with 105 CFU of pathogen. The inoculation of S. aureus produced a remarkable inflammatory response and structural alterations in the vaginal mucosa that decreases in a significant manner when the mice were protected with L. paracasei CRL 1289. The results obtained suggest that this particular Lactobacillus strain could prevent the onset of urogenital infections by interfering with the epithelial colonization by uropathogenic S. aureus. PMID:17485818

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.

[The detection of occurrence rate of genes coding capability to form pili binding in auto-strains of Escherichia coli].

PubMed

Ivanova, E I; Popkova, S M; Dzhioev, Iu P; Rakova, E B; Dolgikh, V V; Savel'kaeva, M V; Nemchenko, U M; Bukharova, E V; Serdiuk, L V

2015-01-01

E. coli is a commensal of intestine of the vertebrata. The exchange of genetic material of different types of bacteria between themselves and with other representatives of family of Enterobacteriaceae in intestinal ecosystem results in development of types of normal colibacillus with genetic characteristics of pathogenicity that can serve as a theoretical substantiation to attribute such strains to pathobionts. The entero-pathogenic colibacillus continues be an important cause of diarrhea in children in developing countries. The gene responsible for formation of pili binding is a necessary condition for virulence of entero-pathogenic colibacillus. The polymerase chain reaction was applied to examine 316 strains of different types of E. coli (normal, with weak enzyme activity and hemolytic activity) isolated from healthy children and children with functional disorders of gastro-intestinal tract for presence of genes coding capability to form pill binding. The presence of this gene in different biochemical types of E. coli permits to establish the fact of formation of reservoir of pathogenicity in indigent microbiota of intestinal biocenosis.

Long-term exposure to antibiotics has caused accumulation of resistance determinants in the gut microbiota of honeybees.

PubMed

Tian, Baoyu; Fadhil, Nibal H; Powell, J Elijah; Kwong, Waldan K; Moran, Nancy A

2012-10-30

Antibiotic treatment can impact nontarget microbes, enriching the pool of resistance genes available to pathogens and altering community profiles of microbes beneficial to hosts. The gut microbiota of adult honeybees, a distinctive community dominated by eight bacterial species, provides an opportunity to examine evolutionary responses to long-term treatment with a single antibiotic. For decades, American beekeepers have routinely treated colonies with oxytetracycline for control of larval pathogens. Using a functional metagenomic screen of bacteria from Maryland bees, we detected a high incidence of tetracycline/oxytetracycline resistance. This resistance is attributable to known resistance loci for which nucleotide sequences and flanking mobility genes were nearly identical to those from human pathogens and from bacteria associated with farm animals. Surveys using diagnostic PCR and sequencing revealed that gut bacteria of honeybees from diverse localities in the United States harbor eight tetracycline resistance loci, including efflux pump genes (tetB, tetC, tetD, tetH, tetL, and tetY) and ribosome protection genes (tetM and tetW), often at high frequencies. Isolates of gut bacteria from Connecticut bees display high levels of tetracycline resistance. Resistance genes were ubiquitous in American samples, though rare in colonies unexposed for 25 years. In contrast, only three resistance loci, at low frequencies, occurred in samples from countries not using antibiotics in beekeeping and samples from wild bumblebees. Thus, long-term antibiotic treatment has caused the bee gut microbiota to accumulate resistance genes, drawn from a widespread pool of highly mobile loci characterized from pathogens and agricultural sites. We found that 50 years of using antibiotics in beekeeping in the United States has resulted in extensive tetracycline resistance in the gut microbiota. These bacteria, which form a distinctive community present in healthy honeybees worldwide, may function in protecting bees from disease and in providing nutrition. In countries that do not use antibiotics in beekeeping, bee gut bacteria contained far fewer resistance genes. The tetracycline resistance that we observed in American samples reflects the capture of mobile resistance genes closely related to those known from human pathogens and agricultural sites. Thus, long-term treatment to control a specific pathogen resulted in the accumulation of a stockpile of resistance capabilities in the microbiota of a healthy gut. This stockpile can, in turn, provide a source of resistance genes for pathogens themselves. The use of novel antibiotics in beekeeping may disrupt bee health, adding to the threats faced by these pollinators.

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.

Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

PubMed Central

O’Kell, Allison L.; Wasserfall, Clive; Catchpole, Brian; Davison, Lucy J.; Hess, Rebecka S.; Kushner, Jake A.

2017-01-01

Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy. Also similar to human type 1 diabetes, the canonical canine disorder appears to be increasing in prevalence. Whereas islet architecture in rodents is distinctly different from humans, canine pancreatic endocrine cell distribution is more similar. Differences in breed susceptibility alongside associations with MHC and other canine immune response genes parallel that of different ethnic groups within the human population, a potential benefit over NOD mice. The impact of environment on disease development also favors canine over rodent models. Herein, we consider the potential for canine diabetes to provide valuable insights for human type 1 diabetes in terms of pancreatic histopathology, impairment of β-cell function and mass, islet inflammation (i.e., insulitis), and autoantibodies specific for β-cell antigens. PMID:28533295

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.

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.

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.

Tech Transfer Webinar: Amoeba Cysts as Natural Containers for the Transport and Storage of Pathogens

ScienceCinema

El-Etr, Sahar

2018-01-16

Sahar El-Etr, Biomedical Scientist at the Lawrence Livermore National Laboratory, shares a unique method for transporting clinical samples from the field to a laboratory. The use of amoeba as “natural” containers for pathogens was utilized to develop the first living system for the transport and storage of pathogens. The amoeba system works at ambient temperature for extended periods of time—capabilities currently not available for biological sample transport.

Clinical relevance of the ESKAPE pathogens.

PubMed

Pendleton, Jack N; Gorman, Sean P; Gilmore, Brendan F

2013-03-01

In recent years, the Infectious Diseases Society of America has highlighted a faction of antibiotic-resistant bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) - acronymically dubbed 'the ESKAPE pathogens' - capable of 'escaping' the biocidal action of antibiotics and mutually representing new paradigms in pathogenesis, transmission and resistance. This review aims to consolidate clinically relevant background information on the ESKAPE pathogens and provide a contemporary summary of bacterial resistance, alongside pertinent microbiological considerations necessary to face the mounting threat of antimicrobial resistance.

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.

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.

Escherichia coli global gene expression in urine from women with urinary tract infection.

PubMed

Hagan, Erin C; Lloyd, Amanda L; Rasko, David A; Faerber, Gary J; Mobley, Harry L T

2010-11-11

Murine models of urinary tract infection (UTI) have provided substantial data identifying uropathogenic E. coli (UPEC) virulence factors and assessing their expression in vivo. However, it is unclear how gene expression in these animal models compares to UPEC gene expression during UTI in humans. To address this, we used a UPEC strain CFT073-specific microarray to measure global gene expression in eight E. coli isolates monitored directly from the urine of eight women presenting at a clinic with bacteriuria. The resulting gene expression profiles were compared to those of the same E. coli isolates cultured statically to exponential phase in pooled, sterilized human urine ex vivo. Known fitness factors, including iron acquisition and peptide transport systems, were highly expressed during human UTI and support a model in which UPEC replicates rapidly in vivo. While these findings were often consistent with previous data obtained from the murine UTI model, host-specific differences were observed. Most strikingly, expression of type 1 fimbrial genes, which are among the most highly expressed genes during murine experimental UTI and encode an essential virulence factor for this experimental model, was undetectable in six of the eight E. coli strains from women with UTI. Despite the lack of type 1 fimbrial expression in the urine samples, these E. coli isolates were generally capable of expressing type 1 fimbriae in vitro and highly upregulated fimA upon experimental murine infection. The findings presented here provide insight into the metabolic and pathogenic profile of UPEC in urine from women with UTI and represent the first transcriptome analysis for any pathogenic E. coli during a naturally occurring infection in humans.

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.

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

Drug-resistant human Staphylococcus aureus in sanctuary apes pose a threat to endangered wild ape populations.

PubMed

Schaumburg, Frieder; Mugisha, Lawrence; Peck, Bruce; Becker, Karsten; Gillespie, Thomas R; Peters, Georg; Leendertz, Fabian H

2012-12-01

Reintroduction of sanctuary apes to natural habitat is considered an important tool for conservation; however, reintroduction has the potential to endanger resident wild apes through the introduction of human pathogens. We found a high prevalence of drug-resistant, human-associated lineages of Staphylococcus aureus in sanctuary chimpanzees (Pan troglodytes) from Zambia and Uganda. This pathogen is associated with skin and soft tissue diseases and severe invasive infections (i.e. pneumonia and septicemia). Colonization by this bacterium is difficult to clear due to frequent recolonization. In addition to its pathogenic potential, human-related S. aureus can serve as an indicator organism for the transmission of other potential pathogens like pneumococci or mycobacteria. Plans to reintroduce sanctuary apes should be reevaluated in light of the high risk of introducing human-adapted S. aureus into wild ape populations where treatment is impossible. © 2012 Wiley Periodicals, Inc.

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.

Phage and Yeast Display.

PubMed

Sheehan, Jared; Marasco, Wayne A

2015-02-01

Despite the availability of antimicrobial drugs, the continued development of microbial resistance--established through escape mutations and the emergence of resistant strains--limits their clinical utility. The discovery of novel, therapeutic, monoclonal antibodies (mAbs) offers viable clinical alternatives in the treatment and prophylaxis of infectious diseases. Human mAb-based therapies are typically nontoxic in patients and demonstrate high specificity for the intended microbial target. This specificity prevents negative impacts on the patient microbiome and avoids driving the resistance of nontarget species. The in vitro selection of human antibody fragment libraries displayed on phage or yeast surfaces represents a group of well-established technologies capable of generating human mAbs. The advantage of these forms of microbial display is the large repertoire of human antibody fragments present during a single selection campaign. Furthermore, the in vitro selection environments of microbial surface display allow for the rapid isolation of antibodies--and their encoding genes--against infectious pathogens and their toxins that are impractical within in vivo systems, such as murine hybridomas. This article focuses on the technologies of phage display and yeast display, as these strategies relate to the discovery of human mAbs for the treatment and vaccine development of infectious diseases.

Medication of production animals--cure of malfunctioning animals or production systems?

PubMed

Chrièl, Mariann; Dietz, Hans Henrik

2003-01-01

Medication is used in all intensive animal productions. However, the increasing problems with resistant bacteria in all animal productions and in humans are supported by a number of reports. Special attention is given to the risk for transmitting food-borne (multi) resistant zoonotic agents to humans due to failure in antibiotic treatment resulting in lower cure rates or higher case fatality rates. The use of medication in humans per se is capable of selecting for resistance in human pathogens. Nevertheless, the amount of used medication/antimicrobials in treatment of Danish production animals goes far beyond the amount used for human consumption. The increase in consumption has not been followed by a similarly increased mortality, e.g. illustrated by the number of rendered animals, increased use of injection medicine for veterinary treatments of diseased animals, or increased number of remarks on the carcasses from the slaughterhouses. Medication in animal production is facing its limits and relevant economic alternatives have to be developed. The strategy for the future must concentrate on using medication only for clinically diseased animals and not as a strategic treatment of the whole herd in order to maximise growth and camouflage of suboptimal production systems and insufficient management.

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.

Agaricus blazei hot water extract shows anti quorum sensing activity in the nosocomial human pathogen Pseudomonas aeruginosa.

PubMed

Soković, Marina; Ćirić, Ana; Glamočlija, Jasmina; Nikolić, Miloš; van Griensven, Leo J L D

2014-04-03

The edible mushroom Agaricus blazei Murill is known to induce protective immunomodulatory action against a variety of infectious diseases. In the present study we report potential anti-quorum sensing properties of A. blazei hot water extract. Quorum sensing (QS) plays an important role in virulence, biofilm formation and survival of many pathogenic bacteria, including the Gram negative Pseudomonas aeruginosa, and is considered as a novel and promising target for anti-infectious agents. In this study, the effect of the sub-MICs of Agaricus blazei water extract on QS regulated virulence factors and biofilm formation was evaluated against P. aeruginosa PAO1. Sub-MIC concentrations of the extract which did not kill P. aeruginosa nor inhibited its growth, demonstrated a statistically significant reduction of virulence factors of P. aeruginosa, such as pyocyanin production, twitching and swimming motility. The biofilm forming capability of P. aeruginosa was also reduced in a concentration-dependent manner at sub-MIC values. Water extract of A. blazei is a promising source of antiquorum sensing and antibacterial compounds.

Antimicrobial polymers.

PubMed

Jain, Anjali; Duvvuri, L Sailaja; Farah, Shady; Beyth, Nurit; Domb, Abraham J; Khan, Wahid

2014-12-01

Better health is basic requirement of human being, but the rapid growth of harmful pathogens and their serious health effects pose a significant challenge to modern science. Infections by pathogenic microorganisms are of great concern in many fields such as medical devices, drugs, hospital surfaces/furniture, dental restoration, surgery equipment, health care products, and hygienic applications (e.g., water purification systems, textiles, food packaging and storage, major or domestic appliances etc.) Antimicrobial polymers are the materials having the capability to kill/inhibit the growth of microbes on their surface or surrounding environment. Recently, they gained considerable interest for both academic research and industry and were found to be better than their small molecular counterparts in terms of enhanced efficacy, reduced toxicity, minimized environmental problems, resistance, and prolonged lifetime. Hence, efforts have focused on the development of antimicrobial polymers with all desired characters for optimum activity. In this Review, an overview of different antimicrobial polymers, their mechanism of action, factors affecting antimicrobial activity, and application in various fields are given. Recent advances and the current clinical status of these polymers are also discussed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Research Contributing to Improvements in Controlling Florida's Mosquitoes and Mosquito-borne Diseases.

PubMed

Tabachnick, Walter J

2016-09-28

Research on mosquitoes and mosquito-borne diseases has contributed to improvements in providing effective, efficient, and environmentally proper mosquito control. Florida has benefitted from several research accomplishments that have increased the state's mosquito control capabilities. Research with Florida's mosquitoes has resulted in the development of ecologically sound management of mosquito impoundments on Florida's east coast. This strategy, called Rotational Impoundment Management (RIM), has improved the ability to target the delivery of pesticides and has helped to reduce non-target effects and environmental damage. Research has led to the development of an arbovirus surveillance system which includes sentinel chicken surveillance, real time use of environmental contributing factors like meteorology and hydrology to target mosquito control, as well as public health efforts to mitigate disease outbreaks to areas with risk of disease. These research driven improvements have provided substantial benefits to all of Florida. More research is needed to meet the future challenges to reduce emerging pathogens like Zika virus and the consequences of environmental changes like global climate change that are likely to influence the effects of mosquito-borne pathogens on human health and well-being.

Serratia marcescens Is Able to Survive and Proliferate in Autophagic-Like Vacuoles inside Non-Phagocytic Cells

PubMed Central

Colombo, María Isabel; García Véscovi, Eleonora

2011-01-01

Serratia marcescens is an opportunistic human pathogen that represents a growing problem for public health, particularly in hospitalized or immunocompromised patients. However, little is known about factors and mechanisms that contribute to S. marcescens pathogenesis within its host. In this work, we explore the invasion process of this opportunistic pathogen to epithelial cells. We demonstrate that once internalized, Serratia is able not only to persist but also to multiply inside a large membrane-bound compartment. This structure displays autophagic-like features, acquiring LC3 and Rab7, markers described to be recruited throughout the progression of antibacterial autophagy. The majority of the autophagic-like vacuoles in which Serratia resides and proliferates are non-acidic and have no degradative properties, indicating that the bacteria are capable to either delay or prevent fusion with lysosomal compartments, altering the expected progression of autophagosome maturation. In addition, our results demonstrate that Serratia triggers a non-canonical autophagic process before internalization. These findings reveal that S. marcescens is able to manipulate the autophagic traffic, generating a suitable niche for survival and proliferation inside the host cell. PMID:21901159

Vibrio vulnificus: death on the half shell. A personal journey with the pathogen and its ecology.

PubMed

Oliver, James D

2013-05-01

Vibrio vulnificus is an estuarine bacterium which occurs in high numbers in filter-feeding molluscan shellfish, such as oysters. In individuals with certain underlying diseases, ingestion of the bacterium, e.g., in raw or undercooked oysters, can lead to a rapid and extremely fatal infection. Indeed, this one bacterium is responsible for 95 % of all seafood-borne deaths. In addition, the bacterium is capable of entering a preexisting lesion or cut obtained during coastal recreational activities, resulting in potentially fatal wound infections. This brief review, which comprised a presentation made at the Gordon Research Conference on "Oceans and Human Health," reflects over 35 years of research on this bacterium in the author's laboratory. It describes some of the known virulence factors and why males account for ca 85 % of all V. vulnificus cases. It notes the two genotypes now known to exist and how this pathogen enters a dormant, "viable but nonculturable" state during the winter months. Finally, the review discusses how global warming may be causing worldwide increases in the frequency and geographical extent of Vibrio infections.

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

The Role of 2,4-diacetylphloroglucinol- and phenazine-1-carboxylic acid-producing Pseudomonas spp. in Natural Protection of Wheat from Soilborne Pathogens

USDA-ARS?s Scientific Manuscript database

Fluorescent Pseudomonas isolated from the rhizosphere of diverse plants have been studied as biocontrol agents of soilborne pathogens worldwide. Certain strains of these bacteria are capable of exerting a variety of mechanisms of plant growth promotion and protection, including the production of the...

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.

Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor.

PubMed

Qi, Wenbao; Jia, Weixin; Liu, Di; Li, Jing; Bi, Yuhai; Xie, Shumin; Li, Bo; Hu, Tao; Du, Yingying; Xing, Li; Zhang, Jiahao; Zhang, Fuchun; Wei, Xiaoman; Eden, John-Sebastian; Li, Huanan; Tian, Huaiyu; Li, Wei; Su, Guanming; Lao, Guangjie; Xu, Chenggang; Xu, Bing; Liu, Wenjun; Zhang, Guihong; Ren, Tao; Holmes, Edward C; Cui, Jie; Shi, Weifeng; Gao, George F; Liao, Ming

2018-01-15

Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant. IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed the molecular features and compared the relative characteristics of one H7N9 LPAIV and two H7N9 HPAIVs isolated from chickens and two human-origin H7N9 HPAIVs in chicken and mouse models. We found that all HPAIVs both are highly pathogenic and have valid transmissibility in chickens. Strikingly, the human-origin viruses were more highly pathogenic than the avian-origin viruses in mice, and dynamic mutations were confirmed by NGS and Sanger sequencing. Our findings offer important insight into the origin, adaptation, pathogenicity, and transmissibility of these viruses to both poultry and mammals. Copyright © 2018 American Society for Microbiology.

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.

Electron beam inactivation of selected microbial pathogens and indicator organisms in aerobically and anaerobically digested sewage sludge.

PubMed

Praveen, Chandni; Jesudhasan, Palmy R; Reimers, Robert S; Pillai, Suresh D

2013-09-01

Microbial pathogens in municipal sewage sludges need to be inactivated prior to environmental disposal. The efficacy of high energy (10 MeV) e-beam irradiation to inactivate a variety of selected microbial pathogens and indicator organisms in aerobically and anaerobically digested sewage sludge was evaluated. Both bacterial and viral pathogens and indicator organisms are susceptible to e-beam irradiation. However, as expected there was a significant difference in their respective e-beam irradiation sensitivity. Somatic coliphages, bacterial endospores and enteric viruses were more resistant compared to bacterial pathogens. The current US EPA mandated 10 kGy minimum dose was capable of achieving significant reduction of both bacterial and viral pathogens. Somatic coliphages can be used as a microbial indicator for monitoring e-beam processes in terms of pathogen inactivation in sewage sludges. Copyright © 2013 Elsevier Ltd. All rights reserved.

Beijing Sublineages of Mycobacterium tuberculosis Differ in Pathogenicity in the Guinea Pig

PubMed Central

Shanley, Crystal A.; Ackart, David; Jarlsberg, Leah G.; Shang, Shaobin; Obregon-Henao, Andres; Harton, Marisabel; Basaraba, Randall J.; Henao-Tamayo, Marcela; Barrozo, Joyce C.; Rose, Jordan; Kawamura, L. Masae; Coscolla, Mireia; Fofanov, Viacheslav Y.; Koshinsky, Heather; Gagneux, Sebastien; Hopewell, Philip C.; Ordway, Diane J.; Orme, Ian M.

2012-01-01

The Beijing family of Mycobacterium tuberculosis strains is part of lineage 2 (also known as the East Asian lineage). In clinical studies, we have observed that isolates from the sublineage RD207 of lineage 2 were more readily transmitted among humans. To investigate the basis for this difference, we tested representative strains with the characteristic Beijing spoligotype from four of the five sublineages of lineage 2 in the guinea pig model and subjected these strains to comparative whole-genome sequencing. The results of these studies showed that all of the clinical strains were capable of growing and causing lung pathology in guinea pigs after low-dose aerosol exposure. Differences between the abilities of the four sublineages to grow in the lungs of these animals were not overt, but members of RD207 were significantly more pathogenic, resulting in severe lung damage. The RD207 strains also induced much higher levels of markers associated with regulatory T cells and showed a significant loss of activated T cells in the lungs over the course of the infections. Whole-genome sequencing of the strains revealed mutations specific for RD207 which may explain this difference. Based on these data, we hypothesize that the sublineages of M. tuberculosis are associated with distinct pathological and clinical phenotypes and that these differences influence the transmissibility of particular M. tuberculosis strains in human populations. PMID:22718126

Syndromic surveillance for West Nile virus using raptors in rehabilitation.

PubMed

Ana, Alba; Perez Andrés, M; Julia, Ponder; Pedro, Puig; Arno, Wünschmann; Kimberly, Vander Waal; Julio, Alvarez; Michelle, Willette

2017-11-29

Wildlife rehabilitation centers routinely gather health-related data from diverse species. Their capability to signal the occurrence of emerging pathogens and improve traditional surveillance remains largely unexplored. This paper assessed the utility for syndromic surveillance of raptors admitted to The Raptor Center (TRC) to signal circulation of West Nile Virus (WNV) in Minnesota between 1990 and 2014. An exhaustive descriptive analysis using grouping time series structures and models of interrupted times series was conducted for indicator subsets. A total of 13,080 raptors were monitored. The most representative species were red-tailed hawks, great horned owls, Cooper's hawks, American kestrels and bald eagles. Results indicated that temporal patterns of accessions at the TRC changed distinctively after the incursion of WNV in 2002. The frequency of hawks showing WNV-like signs increased almost 3 times during July and August, suggesting that monitoring of hawks admitted to TRC with WNV-like signs could serve as an indicator of WNV circulation. These findings were also supported by the results of laboratory diagnosis. This study demonstrates that monitoring of data routinely collected by wildlife rehabilitation centers has the potential to signal the spread of pathogens that may affect wild, domestic animals and humans, thus supporting the early detection of disease incursions in a region and monitoring of disease trends. Ultimately, data collected in rehabilitation centers may provide insights to efficiently allocate financial and human resources on disease prevention and surveillance.

Highly selective trapping of enteropathogenic E. coli on Fabry-Pérot sensor mirrors.

PubMed

Ivanova, Elena P; Truong, Vi Khanh; Gervinskas, Gediminas; Mitik-Dineva, Natasa; Day, Daniel; Jones, Robert T; Crawford, Russell J; Juodkazis, Saulius

2012-05-15

Untreated recycled water, such as sewage and graywater, will almost always contain a wide range of agents that are likely to present risks to human health, including chemicals and pathogenic microorganisms. The microbial hazards, such as large numbers of enteric pathogens that can cause gastroenteric illness if ingested, are the main cause of concern for human health. The presence of the enteropathogenic Escherichia coli (EPEC) serotype is of particular concern, as this group of bacteria is responsible for causing severe infant and travelers' diarrhea, gastroenteritis and hemolytic uremic syndrome. A biosensing system based on an optical Fabry-Pérot (FP) cavity, capable of directly detecting the presence of EPEC within 5 min, has been developed using a simple micro-thin double-sided adhesive tape and two semi-transparent FP mirror plates. The system utilizes a poly(methyl methacrylate) (PMMA) or glass substrates sputtered by 40-nm-thick gold thin films serving as FP mirrors. Mirrors have been activated using 0.1M mercaptopropionic acid, influencing an immobilization density of the translocated intimin receptor (TIR) of 100 ng/cm(2). The specificity of recognition was confirmed by exposing TIR functionalized surfaces to four taxonomically related and/or distantly related bacterial strains. It was found that the TIR-functionalized surfaces did not show any bacterial capture for these other bacterial strains within a 15 min incubation period. Copyright © 2012 Elsevier B.V. All rights reserved.

The phenotype and function of preterm infant monocytes: implications for susceptibility to infection.

PubMed

de Jong, Emma; Strunk, Tobias; Burgner, David; Lavoie, Pascal M; Currie, Andrew

2017-09-01

The extreme vulnerability of preterm infants to invasive microbial infections has been attributed to "immature" innate immune defenses. Monocytes are important innate immune sentinel cells critical in the defense against infection in blood. They achieve this via diverse mechanisms that include pathogen recognition receptor- and inflammasome-mediated detection of microbes, migration into infected tissues, and differentiation into Mϕs and dendritic cells, initiation of the inflammatory cascade by free radicals and cytokine/chemokine production, pathogen clearance by phagocytosis and intracellular killing, and the removal of apoptotic cells. Relatively little is known about these cells in preterm infants, especially about how their phenotype adapts to changes in the microbial environment during the immediate postnatal period. Overall, preterm monocytes exhibit attenuated proinflammatory cytokine responses following stimulation by whole bacterial or specific microbial components in vitro. These attenuated cytokine responses cannot be explained by a lack of intracellular signaling events downstream of pattern recognition receptors. This hyporesponsiveness also contrasts with mature, term-like phagocytosis capabilities detectable even in the most premature infant. Finally, human data on the effects of fetal chorioamnionitis on monocyte biology are incomplete and inconsistent. In this review, we present an integrated view of human studies focused on monocyte functions in preterm infants. We discuss how a developmental immaturity of these cells may contribute to preterm infants' susceptibility to infections. © Society for Leukocyte Biology.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-15

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

Sexual Reproduction of Human Fungal Pathogens

PubMed Central

Heitman, Joseph; Carter, Dee A.; Dyer, Paul S.; Soll, David R.

2014-01-01

We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce findings on other species associated with human infections. In particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. Rather than being asexual, mitotic, and largely clonal, as was thought to be prevalent as recently as a decade ago, we now appreciate that the vast majority of pathogenic fungi have retained extant sexual, or parasexual, cycles. In some examples, sexual and parasexual unions of pathogenic fungi involve closely related individuals, generating diversity in the population but with more restricted recombination than expected from fertile, sexual, outcrossing and recombining populations. In other cases, species and isolates participate in global outcrossing populations with the capacity for considerable levels of gene flow. These findings illustrate general principles of eukaryotic pathogen emergence with relevance for other fungi, parasitic eukaryotic pathogens, and both unicellular and multicellular eukaryotic organisms. PMID:25085958

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.

Human Milk Glycoproteins Protect Infants Against Human Pathogens

PubMed Central

Liu, Bo

2013-01-01

Abstract Breastfeeding protects the neonate against pathogen infection. Major mechanisms of protection include human milk glycoconjugates functioning as soluble receptor mimetics that inhibit pathogen binding to the mucosal cell surface, prebiotic stimulation of gut colonization by favorable microbiota, immunomodulation, and as a substrate for bacterial fermentation products in the gut. Human milk proteins are predominantly glycosylated, and some biological functions of these human milk glycoproteins (HMGPs) have been reported. HMGPs range in size from 14 kDa to 2,000 kDa and include mucins, secretory immunoglobulin A, bile salt-stimulated lipase, lactoferrin, butyrophilin, lactadherin, leptin, and adiponectin. This review summarizes known biological roles of HMGPs that may contribute to the ability of human milk to protect neonates from disease. PMID:23697737

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

Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?

PubMed

Burnouf, Thierry; Strunk, Dirk; Koh, Mickey B C; Schallmoser, Katharina

2016-01-01

The essential physiological role of platelets in wound healing and tissue repair builds the rationale for the use of human platelet derivatives in regenerative medicine. Abundant growth factors and cytokines stored in platelet granules can be naturally released by thrombin activation and clotting or artificially by freeze/thaw-mediated platelet lysis, sonication or chemical treatment. Human platelet lysate prepared by the various release strategies has been established as a suitable alternative to fetal bovine serum as culture medium supplement, enabling efficient propagation of human cells under animal serum-free conditions for a multiplicity of applications in advanced somatic cell therapy and tissue engineering. The rapidly increasing number of studies using platelet derived products for inducing human cell proliferation and differentiation has also uncovered a considerable variability of human platelet lysate preparations which limits comparability of results. The main variations discussed herein encompass aspects of donor selection, preparation of the starting material, the possibility for pooling in plasma or additive solution, the implementation of pathogen inactivation and consideration of ABO blood groups, all of which can influence applicability. This review outlines the current knowledge about human platelet lysate as a powerful additive for human cell propagation and highlights its role as a prevailing supplement for human cell culture capable to replace animal serum in a growing spectrum of applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel management of urinary tract infections.

PubMed

Storm, Douglas W; Patel, Ashay S; Koff, Stephen A; Justice, Sheryl S

2011-07-01

To highlight observations that have suggested the need for changing the conventional approach to the evaluation and management of urinary tract infections (UTIs) and vesicoureteral reflux in children and examine new alternative approaches to prevention of UTI and renal scarring based on research into host-pathogen interaction. Recent studies have questioned the traditional approach of using prophylactic antibiotics to prevent recurrence of UTI and development of renal scarring in children with vesicoureteral reflux. Ongoing research on host-pathogen interactions reveals a promising capability to analyze virulence factors in bacteria causing UTIs in children, identify highly virulent bacteria capable of causing pyelonephritis and renal injury, and to selectively target the gastrointestinal reservoirs of these bacteria for elimination using probiotics. Promising experimental studies correlating bacterial virulence with pattern of UTI and identification and characterization of a newly available probiotic capable of eradicating uropathogenic bacteria make targeted probiotic prevention of renal injury-inducing UTIs a potential therapeutic reality.

Fungi that Infect Humans.

PubMed

Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R

2017-06-01

Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides ; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients- Candida , Pneumocystis , and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.

Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum*

PubMed Central

Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

2012-01-01

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858

Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

PubMed

Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T

2012-09-28

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

Highly Pathogenic Avian Influenza H5N6 Viruses Exhibit Enhanced Affinity for Human Type Sialic Acid Receptor and In-Contact Transmission in Model Ferrets

PubMed Central

Sun, Honglei; Pu, Juan; Wei, Yandi; Sun, Yipeng; Hu, Jiao; Liu, Litao; Xu, Guanlong; Gao, Weihua; Li, Chong; Zhang, Xuxiao; Huang, Yinhua; Chang, Kin-Chow; Liu, Xiufan

2016-01-01

ABSTRACT Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans. IMPORTANCE Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored. PMID:27122581

Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for In Vivo Fitness and Virulence

PubMed Central

Li, Guiling; Liang, Zhuowen; Wang, Xiatai; Yang, Yonghong; Shao, Zhujun; Li, Machao; Ma, Yueyun; Qu, Fen; Morrison, Donald A.

2016-01-01

Natural genetic transformation of Streptococcus pneumoniae, an important human pathogen, mediates horizontal gene transfer for the development of drug resistance, modulation of carriage and virulence traits, and evasion of host immunity. Transformation frequency differs greatly among pneumococcal clinical isolates, but the molecular basis and biological importance of this interstrain variability remain unclear. In this study, we characterized the transformation frequency and other associated phenotypes of 208 S. pneumoniae clinical isolates representing at least 30 serotypes. While the vast majority of these isolates (94.7%) were transformable, the transformation frequency differed by up to 5 orders of magnitude between the least and most transformable isolates. The strain-to-strain differences in transformation frequency were observed among many isolates producing the same capsule types, indicating no general association between transformation frequency and serotype. However, a statistically significant association was observed between the levels of transformation and colonization fitness/virulence in the hypertransformable isolates. Although nontransformable mutants of all the selected hypertransformable isolates were significantly attenuated in colonization fitness and virulence in mouse infection models, such mutants of the strains with relatively low transformability had no or marginal fitness phenotypes under the same experimental settings. This finding strongly suggests that the pneumococci with high transformation capability are “addicted” to a “hypertransformable” state for optimal fitness in the human host. This work has thus provided an intriguing hint for further investigation into how the competence system impacts the fitness, virulence, and other transformation-associated traits of this important human pathogen. PMID:27068094

Disease induction by human microbial pathogens in plant-model systems: potential, problems and prospects.

PubMed

van Baarlen, Peter; van Belkum, Alex; Thomma, Bart P H J

2007-02-01

Relatively simple eukaryotic model organisms such as the genetic model weed plant Arabidopsis thaliana possess an innate immune system that shares important similarities with its mammalian counterpart. In fact, some human pathogens infect Arabidopsis and cause overt disease with human symptomology. In such cases, decisive elements of the plant's immune system are likely to be targeted by the same microbial factors that are necessary for causing disease in humans. These similarities can be exploited to identify elementary microbial pathogenicity factors and their corresponding targets in a green host. This circumvents important cost aspects that often frustrate studies in humans or animal models and, in addition, results in facile ethical clearance.

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

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.

Novel utilization of the outer membrane proteins for the identification and differentiation of pathogenic versus nonpathogenic microbial strains using mass spectrometry-based proteomics approach

NASA Astrophysics Data System (ADS)

Jabbour, Rabih E.; Wade, Mary; Deshpande, Samir V.; McCubbin, Patrick; Snyder, A. Peter; Bevilacqua, Vicky

2012-06-01

Mass spectrometry based proteomic approaches are showing promising capabilities in addressing various biological and biochemical issues. Outer membrane proteins (OMPs) are often associated with virulence in gram-negative pathogens and could prove to be excellent model biomarkers for strain level differentiation among bacteria. Whole cells and OMP extracts were isolated from pathogenic and non-pathogenic strains of Francisella tularensis, Burkholderia thailandensis, and Burkholderia mallei. OMP extracts were compared for their ability to differentiate and delineate the correct database organism to an experimental sample and for the degree of dissimilarity to the nearest-neighbor database strains. This study addresses the comparative experimental proteome analyses of OMPs vs. whole cell lysates on the strain-level discrimination among gram negative pathogenic and non-pathogenic strains.

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

PubMed

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

2009-09-27

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

Challenges and Strategies for Proteome Analysis of the Interaction of Human Pathogenic Fungi with Host Immune Cells.

PubMed

Krüger, Thomas; Luo, Ting; Schmidt, Hella; Shopova, Iordana; Kniemeyer, Olaf

2015-12-14

Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.

Foodborne pathogen detection using hyperspectral imaging

USDA-ARS?s Scientific Manuscript database

Foodborne pathogens can cause various diseases and even death when humans consume foods contaminated with microbial pathogens. Traditional culture-based direct plating methods are still the “gold standard” for presumptive-positive pathogen screening. Although considerable research has been devoted t...

Biohazard potential of putative Martian organisms during missions to Mars.

PubMed

Warmflash, David; Larios-Sanz, Maia; Jones, Jeffrey; Fox, George E; McKay, David S

2007-04-01

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 the 1970s have been generally interpreted as inconclusive for surface organisms, and attributed to active but nonbiological chemistries, the possibility of native surface life has never been ruled out completely. 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 future human landing sites harbor extant life forms. If native life were found to exist, it would be problematic to determine whether any of its species might present a medical danger 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 biohazard protection. A survey of terrestrial pathogens was conducted with special emphasis on those whose evolution has not depended on the presence of animal hosts. The history of the development and implementation of Apollo anti-contamination protocol and recommendations of the National Research Council's 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 therefore theoretically possible on Mars. Although remote, 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 probability of human pathogens on Mars, while low, is not zero. Still, 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, it is recommended that EVA (extravehicular activity) suits be decontaminated when astronauts enter surface habitats upon returning from field activity and that biosafety protocols 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 mission to Mars, and this and the surface biosafety program should be integral to human expeditions from the earliest stages of the mission planning.

Pathogenic features of heterotrophic plate count bacteria from drinking-water boreholes.

PubMed

Horn, Suranie; Pieters, Rialet; Bezuidenhout, Carlos

2016-12-01

Evidence suggests that heterotrophic plate count (HPC) bacteria may be hazardous to humans with weakened health. We investigated the pathogenic potential of HPC bacteria from untreated borehole water, consumed by humans, for: their haemolytic properties, the production of extracellular enzymes such as DNase, proteinase, lipase, lecithinase, hyaluronidase and chondroitinase, the effect simulated gastric fluid has on their survival, as well as the bacteria's antibiotic-susceptible profile. HuTu-80 cells acted as model for the human intestine and were exposed to the HPC isolates to determine their effects on the viability of the cells. Several HPC isolates were α- or β-haemolytic, produced two or more extracellular enzymes, survived the SGF treatment, and showed resistance against selected antibiotics. The isolates were also harmful to the human intestinal cells to varying degrees. A novel pathogen score was calculated for each isolate. Bacillus cereus had the highest pathogen index: the pathogenicity of the other bacteria declined as follows: Aeromonas taiwanensis > Aeromonas hydrophila > Bacillus thuringiensis > Alcaligenes faecalis > Pseudomonas sp. > Bacillus pumilus > Brevibacillus sp. > Bacillus subtilis > Bacillus sp. These results demonstrated that the prevailing standards for HPCs in drinking water may expose humans with compromised immune systems to undue risk.

Complete Genome Sequence of Pseudomonas fluorescens LBUM636, a Strain with Biocontrol Capabilities against Late Blight of Potato

PubMed Central

Morrison, Christopher K.; Novinscak, Amy; Gadkar, Vijay J.; Joly, David L.

2016-01-01

Herein provided is the full-genome sequence of Pseudomonas fluorescens LBUM636. This strain is a plant growth-promoting rhizobacterium (PGPR) which produces phenazine-1-carboxylic acid, an antibiotic involved in the biocontrol of numerous plant pathogens, including late blight of potato caused by the plant pathogen Phytophthora infestans. PMID:27231373

The ecology of emerging infectious diseases in migratory birds: an assessment of the role of climate change and priorities for future research.

PubMed

Fuller, Trevon; Bensch, Staffan; Müller, Inge; Novembre, John; Pérez-Tris, Javier; Ricklefs, Robert E; Smith, Thomas B; Waldenström, Jonas

2012-03-01

Pathogens that are maintained by wild birds occasionally jump to human hosts, causing considerable loss of life and disruption to global commerce. Preliminary evidence suggests that climate change and human movements and commerce may have played a role in recent range expansions of avian pathogens. Since the magnitude of climate change in the coming decades is predicted to exceed climatic changes in the recent past, there is an urgent need to determine the extent to which climate change may drive the spread of disease by avian migrants. In this review, we recommend actions intended to mitigate the impact of emergent pathogens of migratory birds on biodiversity and public health. Increased surveillance that builds upon existing bird banding networks is required to conclusively establish a link between climate and avian pathogens and to prevent pathogens with migratory bird reservoirs from spilling over to humans.

Evolution of Bordetellae from Environmental Microbes to Human Respiratory Pathogens: Amoebae as a Missing Link.

PubMed

Taylor-Mulneix, Dawn L; Hamidou Soumana, Illiassou; Linz, Bodo; Harvill, Eric T

2017-01-01

The genus Bordetella comprises several bacterial species that colonize the respiratory tract of mammals. It includes B. pertussis , a human-restricted pathogen that is the causative agent of Whooping Cough. In contrast, the closely related species B. bronchiseptica colonizes a broad range of animals as well as immunocompromised humans. Recent metagenomic studies have identified known and novel bordetellae isolated from different environmental sources, providing a new perspective on their natural history. Using phylogenetic analysis, we have shown that human and animal pathogenic bordetellae have most likely evolved from ancestors that originated from soil and water. Our recent study found that B. bronchiseptica can evade amoebic predation and utilize Dictyostelium discoideum as an expansion and transmission vector, which suggests that the evolutionary pressure to evade the amoebic predator enabled the rise of bordetellae as respiratory pathogens. Interactions with amoeba may represent the starting point for bacterial adaptation to eukaryotic cells. However, as bacteria evolve and adapt to a novel host, they can become specialized and restricted to a specific host. B. pertussis is known to colonize and cause infection only in humans, and this specialization to a closed human-to-human lifecycle has involved genome reduction and the loss of ability to utilize amoeba as an environmental reservoir. The discoveries from studying the interaction of Bordetella species with amoeba will elicit a better understanding of the evolutionary history of these and other important human pathogens.

The virulence of human pathogenic fungi: notes from the South of France.

PubMed

Reedy, Jennifer L; Bastidas, Robert J; Heitman, Joseph

2007-08-16

The Second FEBS Advanced Lecture Course on Human Fungal Pathogens: Molecular Mechanisms of Host-Pathogen Interactions and Virulence, organized by Christophe d'Enfert (Institut Pasteur, France), Anita Sil (UCSF, USA), and Steffen Rupp (Fraunhofer, IGB, Germany), occurred May 2007 in La Colle sur Loup, France. Here we review the advances presented and the current state of knowledge in key areas of fungal pathogenesis.

Comparative Genomic Analysis of Pathogenic and Probiotic Enterococcus faecalis Isolates, and Their Transcriptional Responses to Growth in Human Urine

PubMed Central

Snipen, Lars; Nes, Ingolf F.; Brede, Dag A.

2010-01-01

Urinary tract infection (UTI) is the most common infection caused by enterococci, and Enterococcus faecalis accounts for the majority of enterococcal infections. Although a number of virulence related traits have been established, no comprehensive genomic or transcriptomic studies have been conducted to investigate how to distinguish pathogenic from non-pathogenic E. faecalis in their ability to cause UTI. In order to identify potential genetic traits or gene regulatory features that distinguish pathogenic from non-pathogenic E. faecalis with respect to UTI, we have performed comparative genomic analysis, and investigated growth capacity and transcriptome profiling in human urine in vitro. Six strains of different origins were cultivated and all grew readily in human urine. The three strains chosen for transcriptional analysis showed an overall similar response with respect to energy and nitrogen metabolism, stress mechanism, cell envelope modifications, and trace metal acquisition. Our results suggest that citrate and aspartate are significant for growth of E. faecalis in human urine, and manganese appear to be a limiting factor. The majority of virulence factors were either not differentially regulated or down-regulated. Notably, a significant up-regulation of genes involved in biofilm formation was observed. Strains from different origins have similar capacity to grow in human urine. The overall similar transcriptional responses between the two pathogenic and the probiotic strain suggest that the pathogenic potential of a certain E. faecalis strain may to a great extent be determined by presence of fitness and virulence factors, rather than the level of expression of such traits. PMID:20824220

Improved understanding of factors driving methicillin-resistant Staphylococcus aureus epidemic waves

PubMed Central

Chatterjee, Som S; Otto, Michael

2013-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the most important causes of nosocomial infections worldwide. Since the global spread of MRSA in the 1960s, MRSA strains have evolved with increased pathogenic potential. Notably, some strains are now capable of causing persistent infections not only in hospitalized patients but also in healthy individuals in the community. Furthermore, MRSA is increasingly associated with infections among livestock-associated workers, primarily because of transmission from animals to humans. Moreover, many MRSA strains have gained resistance to most available antibiotics. In this review, we will present current knowledge on MRSA epidemiology and discuss new endeavors being undertaken to understand better the molecular and epidemiological underpinnings of MRSA outbreaks. PMID:23861600

In Vitro Assessment of the Probiotic Potential of Lactococcus lactis LMG 7930 against Ruminant Mastitis-Causing Pathogens.

PubMed

Armas, Federica; Camperio, Cristina; Marianelli, Cinzia

2017-01-01

Mastitis in dairy ruminants is considered to be the most expensive disease to farmers worldwide. Recently, the intramammary infusion of lactic acid bacteria has emerged as a potential new alternative to antibiotics for preventing and treating bovine mastitis. In this study we have investigated in vitro the probiotic potential of Lactococcus lactis LMG 7930, a food-grade and nisin-producing strain, against mastitis-causing pathogens. We have characterized its carbohydrate fermentation and antibiotic susceptibility profiles, cell surface properties and antimicrobial activity, as well as its capabilities to adhere to and inhibit the invasion of pathogens into the bovine mammary epithelial cell line BME-UV1d. We found that L. lactis LMG 7930 was sensitive to tested drugs, according to the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), and showed an improved carbohydrate fermentation capacity compared to starter strains. Moreover, the strain exhibited antagonistic properties towards many of the pathogens tested. It presented medium surface hydrophobicity, a low basic property and no electron acceptor capability. It showed low auto-aggregation and no co-aggregation abilities towards any of the tested pathogens. The strain was one of the most adhesive to bovine mammary epithelial cells among tested bacteria, but its internalisation was low. The strain did not affect significantly pathogen invasion; however, a trend to decrease internalization of some pathogens tested was observed. In conclusion, our results suggest that this strain might be a promising candidate for the development of new strategies of mastitis control in ruminants. Future investigations are needed to evaluate its safety and efficacy under field conditions.

Survival after pathogen exposure in group-living insects: don't forget the stress of social isolation!

PubMed

Kohlmeier, P; Holländer, K; Meunier, J

2016-09-01

A major cost of group-living is its inherent risk of pathogen infection. To limit this risk, many group-living animals have developed the capability to prophylactically boost their immune system in the presence of group members and/or to mount collective defences against pathogens. These two phenomena, called density-dependent prophylaxis and social immunity, respectively, are often used to explain why, in group-living species, individuals survive better in groups than in isolation. However, this survival difference may also reflect an alternative and often overlooked process: a cost of social isolation on individuals' capability to fight against infections. Here, we disentangled the effects of density-dependent prophylaxis, social immunity and stress of social isolation on the survival after pathogen exposure in group-living adults of the European earwig Forficula auricularia. By manipulating the presence of group members both before and after pathogen exposure, we demonstrated that the cost of being isolated after infection, but not the benefits of social immunity or density-dependent prophylaxis, explained the survival of females. Specifically, females kept constantly in groups or constantly isolated had higher survival rates than females that were first in groups and then isolated after infection. Our results also showed that this cost of social isolation was absent in males and that social isolation did not reduce the survival of noninfected individuals. Overall, this study gives a new perspective on the role of pathogens in social evolution, as it suggests that an apparently nonadaptive, personal immune process may promote the maintenance of group-living under pathogenic environments. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

In Vitro Assessment of the Probiotic Potential of Lactococcus lactis LMG 7930 against Ruminant Mastitis-Causing Pathogens

PubMed Central

Armas, Federica; Camperio, Cristina

2017-01-01

Mastitis in dairy ruminants is considered to be the most expensive disease to farmers worldwide. Recently, the intramammary infusion of lactic acid bacteria has emerged as a potential new alternative to antibiotics for preventing and treating bovine mastitis. In this study we have investigated in vitro the probiotic potential of Lactococcus lactis LMG 7930, a food-grade and nisin-producing strain, against mastitis-causing pathogens. We have characterized its carbohydrate fermentation and antibiotic susceptibility profiles, cell surface properties and antimicrobial activity, as well as its capabilities to adhere to and inhibit the invasion of pathogens into the bovine mammary epithelial cell line BME-UV1d. We found that L. lactis LMG 7930 was sensitive to tested drugs, according to the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), and showed an improved carbohydrate fermentation capacity compared to starter strains. Moreover, the strain exhibited antagonistic properties towards many of the pathogens tested. It presented medium surface hydrophobicity, a low basic property and no electron acceptor capability. It showed low auto-aggregation and no co-aggregation abilities towards any of the tested pathogens. The strain was one of the most adhesive to bovine mammary epithelial cells among tested bacteria, but its internalisation was low. The strain did not affect significantly pathogen invasion; however, a trend to decrease internalization of some pathogens tested was observed. In conclusion, our results suggest that this strain might be a promising candidate for the development of new strategies of mastitis control in ruminants. Future investigations are needed to evaluate its safety and efficacy under field conditions. PMID:28068371

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.

Alzheimer's Disease: APP, Gamma Secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and Their Relationships with Herpes Simplex, C. Pneumoniae, Other Suspect Pathogens, and the Immune System

PubMed Central

Carter, Chris

2011-01-01

Alzheimer's disease susceptibility genes, APP and gamma-secretase, are involved in the herpes simplex life cycle, and that of other suspect pathogens (C. pneumoniae, H. pylori, C. neoformans, B. burgdorferri, P. gingivalis) or immune defence. Such pathogens promote beta-amyloid deposition and tau phosphorylation and may thus be causative agents, whose effects are conditioned by genes. The antimicrobial effects of beta-amyloid, the localisation of APP/gamma-secretase in immunocompetent dendritic cells, and gamma secretase cleavage of numerous pathogen receptors suggest that this network is concerned with pathogen disposal, effects which may be abrogated by the presence of beta-amyloid autoantibodies in the elderly. These autoantibodies, as well as those to nerve growth factor and tau, also observed in Alzheimer's disease, may well be antibodies to pathogens, due to homology between human autoantigens and pathogen proteins. NGF or tau antibodies promote beta-amyloid deposition, neurofibrillary tangles, or cholinergic neuronal loss, and, with other autoantibodies, such as anti-ATPase, are potential agents of destruction, whose formation is dictated by sequence homology between pathogen and human proteins, and thus by pathogen strain and human genes. Pathogen elimination in the ageing population and removal of culpable autoantibodies might reduce the incidence and offer hope for a cure in this affliction. PMID:22254144

Novel Insights into Cell Entry of Emerging Human Pathogenic Arenaviruses.

PubMed

Fedeli, Chiara; Moreno, Héctor; Kunz, Stefan

2018-06-22

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

Sequestration and Scavenging of Iron in Infection

PubMed Central

Parrow, Nermi L.; Fleming, Robert E.

2013-01-01

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

Structural analysis of malaria-parasite lysyl-tRNA synthetase provides a platform for drug development.

PubMed

Khan, Sameena; Garg, Ankur; Camacho, Noelia; Van Rooyen, Jason; Kumar Pole, Anil; Belrhali, Hassan; Ribas de Pouplana, Lluis; Sharma, Vinay; Sharma, Amit

2013-05-01

Aminoacyl-tRNA synthetases are essential enzymes that transmit information from the genetic code to proteins in cells and are targets for antipathogen drug development. Elucidation of the crystal structure of cytoplasmic lysyl-tRNA synthetase from the malaria parasite Plasmodium falciparum (PfLysRS) has allowed direct comparison with human LysRS. The authors' data suggest that PfLysRS is dimeric in solution, whereas the human counterpart can also adopt tetrameric forms. It is shown for the first time that PfLysRS is capable of synthesizing the signalling molecule Ap4a (diadenosine tetraphosphate) using ATP as a substrate. The PfLysRS crystal structure is in the apo form, such that binding to ATP will require rotameric changes in four conserved residues. Differences in the active-site regions of parasite and human LysRSs suggest the possibility of exploiting PfLysRS for selective inhibition. These investigations on PfLysRS further validate malarial LysRSs as attractive antimalarial targets and provide new structural space for the development of inhibitors that target pathogen LysRSs selectively.

Anti-pathogenic and probiotic attributes of Lactobacillus salivarius and Lactobacillus plantarum strains isolated from feces of Algerian infants and adults.

PubMed

Ait Seddik, Hamza; Bendali, Farida; Cudennec, Benoit; Drider, Djamel

2017-04-01

Sixty-seven (67) lactic acid bacteria (LAB) isolates belonging to Lactobacillus genus were isolated from human feces and tested for their auto-aggregation and cell surface hydrophobicity in order to establish their adhesion capabilities, a prerequisite for probiotic selection. Strains with the upmost auto-aggregation and cell surface hydrophobicity scores were identified by MALDI-TOF spectrometry and 16S rDNA sequencing as Lactobacillus plantarum (p25lb1 and p98lb1) and Lactobacillus salivarius (p85lb1 and p104lb1). These strains were also able to adhere to human epithelial colorectal adenocarcinoma Caco-2 cells, with percentages ranging from 4.68 to 9.59%. They displayed good survival under conditions mimicking the gastrointestinal environment and remarkably impeded adhesion and invasion of human Caco-2 by Listeria monocytogenes and Enteropathogenic Escherichia coli. It should also be noted that Lb. plantarum p98lb1 was able to reduce in vitro cholesterol concentration by about 32%, offering an additional health attribute. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Effect of Intermediate Hosts on Emerging Zoonoses.

PubMed

Cui, Jing-An; Chen, Fangyuan; Fan, Shengjie

2017-08-01

Most emerging zoonotic pathogens originate from animals. They can directly infect humans through natural reservoirs or indirectly through intermediate hosts. As a bridge, an intermediate host plays different roles in the transmission of zoonotic pathogens. In this study, we present three types of pathogen transmission to evaluate the effect of intermediate hosts on emerging zoonotic diseases in human epidemics. These types are identified as follows: TYPE 1, pathogen transmission without an intermediate host for comparison; TYPE 2, pathogen transmission with an intermediate host as an amplifier; and TYPE 3, pathogen transmission with an intermediate host as a vessel for genetic variation. In addition, we established three mathematical models to elucidate the mechanisms underlying zoonotic disease transmission according to these three types. Stability analysis indicated that the existence of intermediate hosts increased the difficulty of controlling zoonotic diseases because of more difficult conditions to satisfy for the disease to die out. The human epidemic would die out under the following conditions: TYPE 1: [Formula: see text] and [Formula: see text]; TYPE 2: [Formula: see text], [Formula: see text], and [Formula: see text]; and TYPE 3: [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] Simulation with similar parameters demonstrated that intermediate hosts could change the peak time and number of infected humans during a human epidemic; intermediate hosts also exerted different effects on controlling the prevalence of a human epidemic with natural reservoirs in different periods, which is important in addressing problems in public health. Monitoring and controlling the number of natural reservoirs and intermediate hosts at the right time would successfully manage and prevent the prevalence of emerging zoonoses in humans.

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.

Metagenomic analysis of planktonic microbial consortia from a non-tidal urban-impacted segment of James River

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

Brown, Bonnie L.; LePrell, Rebecca V.; Franklin, Rima B.

Knowledge of the diversity and ecological function of the microbial consortia of James River in Virginia, USA, is essential to developing a more complete understanding of the ecology of this model river system. Metagenomic analysis of James River's planktonic microbial community was performed for the first time using an unamplified genomic library and a 16S rDNA amplicon library prepared and sequenced by Ion PGM and MiSeq, respectively. From the 0.46-Gb WGS library (GenBank:SRR1146621; MG-RAST:4532156.3), 4 x 10 6 reads revealed >3 x 10 6 genes, 240 families of prokaryotes, and 155 families of eukaryotes. From the 0.68-Gb 16S library (GenBank:SRR2124995;more » MG-RAST:4631271.3; EMB:2184), 4 x 10 6 reads revealed 259 families of eubacteria. Results of the WGS and 16S analyses were highly consistent and indicated that more than half of the bacterial sequences were Proteobacteria, predominantly Comamonadaceae. The most numerous genera in this group were Acidovorax (including iron oxidizers, nitrotolulene degraders, and plant pathogens), which accounted for 10 % of assigned bacterial reads. Polaromonas were another 6 % of all bacterial reads, with many assignments to groups capable of degrading polycyclic aromatic hydrocarbons. Albidiferax (iron reducers) and Variovorax (biodegraders of a variety of natural biogenic compounds as well as anthropogenic contaminants such as polycyclic aromatic hydrocarbons and endocrine disruptors) each accounted for an additional 3% of bacterial reads. Comparison of these data to other publically-available aquatic metagenomes revealed that this stretch of James River is highly similar to the upper Mississippi River, and that these river systems are more similar to aquaculture and sludge ecosystems than they are to lakes or to a pristine section of the upper Amazon River. Altogether, these analyses exposed previously unknown aspects of microbial biodiversity, documented the ecological responses of microbes to urban effects, and revealed the noteworthy presence of 22 human-pathogenic bacterial genera (e.g., Enterobacteriaceae, pathogenic Pseudomonadaceae, and ‘Vibrionales') and 6 pathogenic eukaryotic genera (e.g., Trypanosomatidae and Vahlkampfiidae). This information about pathogen diversity may be used to promote human epidemiological studies, enhance existing water quality monitoring efforts, and increase awareness of the possible health risks associated with recreational use of James River.« less

Metagenomic analysis of planktonic microbial consortia from a non-tidal urban-impacted segment of James River

DOE PAGES

Brown, Bonnie L.; LePrell, Rebecca V.; Franklin, Rima B.; ...

2015-09-19

Knowledge of the diversity and ecological function of the microbial consortia of James River in Virginia, USA, is essential to developing a more complete understanding of the ecology of this model river system. Metagenomic analysis of James River's planktonic microbial community was performed for the first time using an unamplified genomic library and a 16S rDNA amplicon library prepared and sequenced by Ion PGM and MiSeq, respectively. From the 0.46-Gb WGS library (GenBank:SRR1146621; MG-RAST:4532156.3), 4 x 10 6 reads revealed >3 x 10 6 genes, 240 families of prokaryotes, and 155 families of eukaryotes. From the 0.68-Gb 16S library (GenBank:SRR2124995;more » MG-RAST:4631271.3; EMB:2184), 4 x 10 6 reads revealed 259 families of eubacteria. Results of the WGS and 16S analyses were highly consistent and indicated that more than half of the bacterial sequences were Proteobacteria, predominantly Comamonadaceae. The most numerous genera in this group were Acidovorax (including iron oxidizers, nitrotolulene degraders, and plant pathogens), which accounted for 10 % of assigned bacterial reads. Polaromonas were another 6 % of all bacterial reads, with many assignments to groups capable of degrading polycyclic aromatic hydrocarbons. Albidiferax (iron reducers) and Variovorax (biodegraders of a variety of natural biogenic compounds as well as anthropogenic contaminants such as polycyclic aromatic hydrocarbons and endocrine disruptors) each accounted for an additional 3% of bacterial reads. Comparison of these data to other publically-available aquatic metagenomes revealed that this stretch of James River is highly similar to the upper Mississippi River, and that these river systems are more similar to aquaculture and sludge ecosystems than they are to lakes or to a pristine section of the upper Amazon River. Altogether, these analyses exposed previously unknown aspects of microbial biodiversity, documented the ecological responses of microbes to urban effects, and revealed the noteworthy presence of 22 human-pathogenic bacterial genera (e.g., Enterobacteriaceae, pathogenic Pseudomonadaceae, and ‘Vibrionales') and 6 pathogenic eukaryotic genera (e.g., Trypanosomatidae and Vahlkampfiidae). This information about pathogen diversity may be used to promote human epidemiological studies, enhance existing water quality monitoring efforts, and increase awareness of the possible health risks associated with recreational use of James River.« less

Metagenomic analysis of planktonic microbial consortia from a non-tidal urban-impacted segment of James River.

PubMed

Brown, Bonnie L; LePrell, Rebecca V; Franklin, Rima B; Rivera, Maria C; Cabral, Francine M; Eaves, Hugh L; Gardiakos, Vicki; Keegan, Kevin P; King, Timothy L

2015-01-01

Knowledge of the diversity and ecological function of the microbial consortia of James River in Virginia, USA, is essential to developing a more complete understanding of the ecology of this model river system. Metagenomic analysis of James River's planktonic microbial community was performed for the first time using an unamplified genomic library and a 16S rDNA amplicon library prepared and sequenced by Ion PGM and MiSeq, respectively. From the 0.46-Gb WGS library (GenBank:SRR1146621; MG-RAST:4532156.3), 4 × 10(6) reads revealed >3 × 10(6) genes, 240 families of prokaryotes, and 155 families of eukaryotes. From the 0.68-Gb 16S library (GenBank:SRR2124995; MG-RAST:4631271.3; EMB:2184), 4 × 10(6) reads revealed 259 families of eubacteria. Results of the WGS and 16S analyses were highly consistent and indicated that more than half of the bacterial sequences were Proteobacteria, predominantly Comamonadaceae. The most numerous genera in this group were Acidovorax (including iron oxidizers, nitrotolulene degraders, and plant pathogens), which accounted for 10 % of assigned bacterial reads. Polaromonas were another 6 % of all bacterial reads, with many assignments to groups capable of degrading polycyclic aromatic hydrocarbons. Albidiferax (iron reducers) and Variovorax (biodegraders of a variety of natural biogenic compounds as well as anthropogenic contaminants such as polycyclic aromatic hydrocarbons and endocrine disruptors) each accounted for an additional 3 % of bacterial reads. Comparison of these data to other publically-available aquatic metagenomes revealed that this stretch of James River is highly similar to the upper Mississippi River, and that these river systems are more similar to aquaculture and sludge ecosystems than they are to lakes or to a pristine section of the upper Amazon River. Taken together, these analyses exposed previously unknown aspects of microbial biodiversity, documented the ecological responses of microbes to urban effects, and revealed the noteworthy presence of 22 human-pathogenic bacterial genera (e.g., Enterobacteriaceae, pathogenic Pseudomonadaceae, and 'Vibrionales') and 6 pathogenic eukaryotic genera (e.g., Trypanosomatidae and Vahlkampfiidae). This information about pathogen diversity may be used to promote human epidemiological studies, enhance existing water quality monitoring efforts, and increase awareness of the possible health risks associated with recreational use of James River.

Emerging pathogens in the fish farming industry and sequencing-based pathogen discovery.

PubMed

Tengs, Torstein; Rimstad, Espen

2017-10-01

The use of large scale DNA/RNA sequencing has become an integral part of biomedical research. Reduced sequencing costs and the availability of efficient computational resources has led to a revolution in how problems concerning genomics and transcriptomics are addressed. Sequencing-based pathogen discovery represents one example of how genetic data can now be used in ways that were previously considered infeasible. Emerging pathogens affect both human and animal health due to a multitude of factors, including globalization, a shifting environment and an increasing human population. Fish farming represents a relevant, interesting and challenging system to study emerging pathogens. This review summarizes recent progress in pathogen discovery using sequence data, with particular emphasis on viruses in Atlantic salmon (Salmo salar). Copyright © 2017 Elsevier Ltd. All rights reserved.

Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis

PubMed Central

Rohmer, Laurence; Hocquet, Didier; Miller, Samuel I.

2011-01-01

It is interesting to speculate that the evolutionary drive of microbes to develop pathogenic characteristics was to access the nutrient resources that animals provided. Environments in animals that pathogens colonize have also driven the evolution of new bacterial characteristics to maximize these new nutritional opportunities. This review focuses on genomic and functional aspects of pathogen metabolism that allow efficient utilization of nutrient resources provided by animals. Similar to genes encoding specific virulence traits, some genes encoding metabolic functions have been horizontally acquired by pathogens to provide a selective advantage in host tissues. Selective advantage in host tissues can also be gained in some circumstances by loss of function due to mutations that alter metabolic capabilities. Greater understanding of bacterial metabolism within host tissues should be important for increased understanding of host-pathogen interactions and the development of future therapeutic strategies. PMID:21600774

Droplet microfluidics for amplification-free genetic detection of single cells.

PubMed

Rane, Tushar D; Zec, Helena C; Puleo, Chris; Lee, Abraham P; Wang, Tza-Huei

2012-09-21

In this article we present a novel droplet microfluidic chip enabling amplification-free detection of single pathogenic cells. The device streamlines multiple functionalities to carry out sample digitization, cell lysis, probe-target hybridization for subsequent fluorescent detection. A peptide nucleic acid fluorescence resonance energy transfer probe (PNA beacon) is used to detect 16S rRNA present in pathogenic cells. Initially the sensitivity and quantification abilities of the platform are tested using a synthetic target mimicking the actual expression level of 16S rRNA in single cells. The capability of the device to perform "sample-to-answer" pathogen detection of single cells is demonstrated using E. coli as a model pathogen.

[MAIT cells in autoimmunity].

PubMed

Miyake, Sachiko

2012-01-01

Mucosal associated invariant T (MAIT) cells are restricted by a nonpolymorphic MHC-related molecule-1 (MR1), and express an invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. MAIT cells are selected in the thymus, but, interestingly, MAIT cells require B cells as well as commensal flora for their peripheral expansion. Bourhis et al demonstrated that MAIT cells display antimicrobial capacity. Both human and mouse MAIT cells have been shown to be activated by Escherichia coli-infected antigen presenting cells in an MR1-dependent manner. MAIT cells show a protective role against Mycobacteriu abscessus or E. coli infections in mice. Human MAIT cells are capable of producing IFNγ and IL-17 and are found in Mycobacterium tuberculosis-infected lung tissues. Thus, MAIT cells play an antimicrobial function under these infectious conditions. MAIT cells play a protective role against autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), whereas they play a pathogenic role in murine models of arthritis. In patients with autoimmune diseases, the frequency of MAIT cells in peripheral blood was significantly reduced. The frequency of MAIT cells reflected the disease activity in MS patients, suggesting the involvement of MAIT cells in the regulation of autoimmune diseases.

Salmonella enterica suppresses Pectobacterium carotovorum subsp. carotovorum population and soft rot progression by acidifying the microaerophilic environment.

PubMed

Kwan, Grace; Charkowski, Amy O; Barak, Jeri D

2013-02-12

Although enteric human pathogens are usually studied in the context of their animal hosts, a significant portion of their life cycle occurs on plants. Plant disease alters the phyllosphere, leading to enhanced growth of human pathogens; however, the impact of human pathogens on phytopathogen biology and plant health is largely unknown. To characterize the interaction between human pathogens and phytobacterial pathogens in the phyllosphere, we examined the interactions between Pectobacterium carotovorum subsp. carotovorum and Salmonella enterica or Escherichia coli O157:H7 with regard to bacterial populations, soft rot progression, and changes in local pH. The presence of P. carotovorum subsp. carotovorum enhanced the growth of both S. enterica and E. coli O157:H7 on leaves. However, in a microaerophilic environment, S. enterica reduced P. carotovorum subsp. carotovorum populations and soft rot progression by moderating local environmental pH. Reduced soft rot was not due to S. enterica proteolytic activity. Limitations on P. carotovorum subsp. carotovorum growth, disease progression, and pH elevation were not observed on leaves coinoculated with E. coli O157:H7 or when leaves were coinoculated with S. enterica in an aerobic environment. S. enterica also severely undermined the relationship between the phytobacterial population and disease progression of a P. carotovorum subsp. carotovorum budB mutant defective in the 2,3-butanediol pathway for acid neutralization. Our results show that S. enterica and E. coli O157:H7 interact differently with the enteric phytobacterial pathogen P. carotovorum subsp. carotovorum. S. enterica inhibition of soft rot progression may conceal a rapidly growing human pathogen population. Whereas soft rotted produce can alert consumers to the possibility of food-borne pathogens, healthy-looking produce may entice consumption of contaminated vegetables. Salmonella enterica and Escherichia coli O157:H7 may use plants to move between animal and human hosts. Their populations are higher on plants cocolonized with the common bacterial soft rot pathogen Pectobacterium carotovorum subsp. carotovorum, turning edible plants into a risk factor for human disease. We inoculated leaves with P. carotovorum subsp. carotovorum and S. enterica or E. coli O157:H7 to study the interactions between these bacteria. While P. carotovorum subsp. carotovorum enhanced the growth of both S. enterica and E. coli O157:H7, these human pathogens affected P. carotovorum subsp. carotovorum fundamentally differently. S. enterica reduced P. carotovorum subsp. carotovorum growth and acidified the environment, leading to less soft rot on leaves; E. coli O157:H7 had no such effects. As soft rot signals a food safety risk, the reduction of soft rot symptoms in the presence of S. enterica may lead consumers to eat healthy-looking but S. enterica-contaminated produce.

Experimental Reservoirs of Human Pathogens: The Vibrio Cholerae Paradigm (7th Annual SFAF Meeting, 2012)

ScienceCinema

Colwell, Rita

2018-05-14

Rita Colwell on "Experimental Reservoirs of Human Pathogens: The Vibrio cholerae paradigm" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

MICROBES, MONITORING AND HUMAN HEALTH

EPA Science Inventory

There are about 20,000 wastewater treatment plants in the United States. These plants discharge about 50 trillion gallons of wastewater daily into the nation's surface waters. Most wastewater contains human feces, which are a potential source of microbial pathogens. Pathogens ...

Experimental Reservoirs of Human Pathogens: The Vibrio Cholerae Paradigm (7th Annual SFAF Meeting, 2012)

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

Colwell, Rita

Rita Colwell on "Experimental Reservoirs of Human Pathogens: The Vibrio cholerae paradigm" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

Agricultural pathogen decontamination technology-reducing the threat of infectious agent spread.

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

Betty, Rita G.; Bieker, Jill Marie; Tucker, Mark David

Outbreaks of infectious agricultural diseases, whether natural occurring or introduced intentionally, could have catastrophic impacts on the U.S. economy. Examples of such agricultural pathogens include foot and mouth disease (FMD), avian influenza (AI), citrus canker, wheat and soy rust, etc. Current approaches to mitigate the spread of agricultural pathogens include quarantine, development of vaccines for animal diseases, and development of pathogen resistant crop strains in the case of plant diseases. None of these approaches is rapid, and none address the potential persistence of the pathogen in the environment, which could lead to further spread of the agent and damage aftermore » quarantine is lifted. Pathogen spread in agricultural environments commonly occurs via transfer on agricultural equipment (transportation trailers, tractors, trucks, combines, etc.), having components made from a broad range of materials (galvanized and painted steel, rubber tires, glass and Plexiglas shields, etc), and under conditions of heavy organic load (mud, soil, feces, litter, etc). A key element of stemming the spread of an outbreak is to ensure complete inactivation of the pathogens in the agricultural environment and on the equipment used in those environments. Through the combination of enhanced agricultural pathogen decontamination chemistry and a validated inactivation verification methodology, important technologies for incorporation as components of a robust response capability will be enabled. Because of the potentially devastating economic impact that could result from the spread of infectious agricultural diseases, the proposed capability components will promote critical infrastructure protection and greater border and food supply security. We investigated and developed agricultural pathogen decontamination technologies to reduce the threat of infectious-agent spread, and thus enhance agricultural biosecurity. Specifically, enhanced detergency versions of the patented Sandia decontamination chemistry were developed and tested against a few surrogate pathogens under conditions of relatively heavy organic load. Tests were conducted on surfaces commonly found in agricultural environments. Wide spectrum decontamination efficacy, low corrosivity, and biodegradability issues were addressed in developing an enhanced detergency formulation. A method for rapid assessment of loss of pathogenic activity (inactivation) was also assessed. This enhanced technology will enable rapid assessment of contamination following an intentional event, and will also be extremely useful in routine assessment of agricultural environments. The primary effort during the second year was progress towards a demonstration of both decontamination and viral inactivation technologies of Foot and Mouth virus (FMDv) using the modified SNL chemistry developed through this project. Lab studies using a surrogate virus (bovine enterovirus) were conducted using DF200, modified DF200 chemistry, and decontaminants currently recommended for use in heavily loaded organic, agricultural environments (VirkonS, 10% bleach, sodium hydroxide and citric acid). Tests using actual FMD virus will be performed at the Department of Homeland Security's Plum Island facilities in the fall of 2005. Success and the insight gained from this project will lead to enhanced response capability, which will benefit agencies such as USDA, DHS, DOD, and the agricultural industry.« less

Setosphaeria rostrata: Insights from the sequenced genome of Setosphaeria turcica.

PubMed

Wu, Dongliang; Turgeon, B Gillian

2013-12-01

Exserohilum rostratum, also known as Setosphaeria rostrata caused an outbreak of meningitis in 2012. S. rostrata is known as a minor pathogen of grasses and a member of the Dothideomycetes, a group that includes saprobes as well as mild to aggressive plant pathogens. A few taxa in this group, such as E. rostratum and Cochliobolus lunatus (Curvularia lunata) can be human pathogens, in favorable circumstances. Fortunately, human disease caused by E. rostratum is rare. However, the increasing number of formerly inconsequential fungi surfacing as significant pathogens demands efforts to identify determinants of crossover pathogenicity in general, and S. rostrata in particular. Very few genetic and molecular data are available for S. rostrata. The first genome sequence for any species in the genus Setosphaeria (Setosphaeria turcica) was published this year. The literature to date related to virulence determinants of S. rostrata and S. turcica to plants and a summary of S. turcica genome features that may inform future studies with the human pathogen, S. rostrata, are presented. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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

PubMed Central

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

2013-01-01

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

New relationships among the sudden oak death pathogen, bark and ambrosia beetles, and fungi colonizing coast live oaks

Treesearch

Nadir Erbilgin; Brice A. McPherson; Pierluigi Bonello; David L. Wood; Andrew J. Nelson

2008-01-01

Sudden oak death (SOD) has had devastating effects on several oak species in many California coastal forests. Phytophthora ramorum has been identified as the primary causal agent of sudden oak death. While the pathogen may be capable of killing mature trees, it is likely that in nature opportunistic organisms play significant roles in the decline and...

Novel methods for pathogen control in livestock preharvest: An update

USDA-ARS?s Scientific Manuscript database

Pathogenic bacteria are found asymptomatically within and on food animals, which often results in pathogen entry into the food chain, causing human illnesses. Slaughter and processing plants do an outstanding job in reducing pathogen contamination through the use of intervention strategies after sl...

Pathogen reduction in human plasma using an ultrashort pulsed laser

USDA-ARS?s Scientific Manuscript database

Pathogen reduction is an ideal 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, and they introduce chemicals with concerns of side effects which prevent...

Statistical Physics of T-Cell Development and Pathogen Specificity

NASA Astrophysics Data System (ADS)

Košmrlj, Andrej; Kardar, Mehran; Chakraborty, Arup K.

2013-04-01

In addition to an innate immune system that battles pathogens in a nonspecific fashion, higher organisms, such as humans, possess an adaptive immune system to combat diverse (and evolving) microbial pathogens. Remarkably, the adaptive immune system mounts pathogen-specific responses, which can be recalled upon reinfection with the same pathogen. It is difficult to see how the adaptive immune system can be preprogrammed to respond specifically to a vast and unknown set of pathogens. Although major advances have been made in understanding pertinent molecular and cellular phenomena, the precise principles that govern many aspects of an immune response are largely unknown. We discuss complementary approaches from statistical mechanics and cell biology that can shed light on how key components of the adaptive immune system, T cells, develop to enable pathogen-specific responses against many diverse pathogens. The mechanistic understanding that emerges has implications for how host genetics may influence the development of T cells with differing responses to the human immunodeficiency virus (HIV) infection.

Humans and Cattle: A Review of Bovine Zoonoses

PubMed Central

Cardwell, Diana M.; Moeller, Robert B.; Gray, Gregory C.

2014-01-01

Abstract Infectious disease prevention and control has been among the top public health objectives during the last century. However, controlling disease due to pathogens that move between animals and humans has been challenging. Such zoonotic pathogens have been responsible for the majority of new human disease threats and a number of recent international epidemics. Currently, our surveillance systems often lack the ability to monitor the human–animal interface for emergent pathogens. Identifying and ultimately addressing emergent cross-species infections will require a “One Health” approach in which resources from public veterinary, environmental, and human health function as part of an integrative system. Here we review the epidemiology of bovine zoonoses from a public health perspective. PMID:24341911

Xenosurveillance reflects traditional sampling techniques for the identification of human pathogens: A comparative study in West Africa

PubMed Central

Fakoli, Lawrence S.; Bolay, Kpehe; Bolay, Fatorma K.; Diclaro, Joseph W.; Brackney, Doug E.; Stenglein, Mark D.; Ebel, Gregory D.

2018-01-01

Background Novel surveillance strategies are needed to detect the rapid and continuous emergence of infectious disease agents. Ideally, new sampling strategies should be simple to implement, technologically uncomplicated, and applicable to areas where emergence events are known to occur. To this end, xenosurveillance is a technique that makes use of blood collected by hematophagous arthropods to monitor and identify vertebrate pathogens. Mosquitoes are largely ubiquitous animals that often exist in sizable populations. As well, many domestic or peridomestic species of mosquitoes will preferentially take blood-meals from humans, making them a unique and largely untapped reservoir to collect human blood. Methodology/Principal findings We sought to take advantage of this phenomenon by systematically collecting blood-fed mosquitoes during a field trail in Northern Liberia to determine whether pathogen sequences from blood engorged mosquitoes accurately mirror those obtained directly from humans. Specifically, blood was collected from humans via finger-stick and by aspirating bloodfed mosquitoes from the inside of houses. Shotgun metagenomic sequencing of RNA and DNA derived from these specimens was performed to detect pathogen sequences. Samples obtained from xenosurveillance and from finger-stick blood collection produced a similar number and quality of reads aligning to two human viruses, GB virus C and hepatitis B virus. Conclusions/Significance This study represents the first systematic comparison between xenosurveillance and more traditional sampling methodologies, while also demonstrating the viability of xenosurveillance as a tool to sample human blood for circulating pathogens. PMID:29561834

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.

Xenosurveillance reflects traditional sampling techniques for the identification of human pathogens: A comparative study in West Africa.

PubMed

Fauver, Joseph R; Weger-Lucarelli, James; Fakoli, Lawrence S; Bolay, Kpehe; Bolay, Fatorma K; Diclaro, Joseph W; Brackney, Doug E; Foy, Brian D; Stenglein, Mark D; Ebel, Gregory D

2018-03-01

Novel surveillance strategies are needed to detect the rapid and continuous emergence of infectious disease agents. Ideally, new sampling strategies should be simple to implement, technologically uncomplicated, and applicable to areas where emergence events are known to occur. To this end, xenosurveillance is a technique that makes use of blood collected by hematophagous arthropods to monitor and identify vertebrate pathogens. Mosquitoes are largely ubiquitous animals that often exist in sizable populations. As well, many domestic or peridomestic species of mosquitoes will preferentially take blood-meals from humans, making them a unique and largely untapped reservoir to collect human blood. We sought to take advantage of this phenomenon by systematically collecting blood-fed mosquitoes during a field trail in Northern Liberia to determine whether pathogen sequences from blood engorged mosquitoes accurately mirror those obtained directly from humans. Specifically, blood was collected from humans via finger-stick and by aspirating bloodfed mosquitoes from the inside of houses. Shotgun metagenomic sequencing of RNA and DNA derived from these specimens was performed to detect pathogen sequences. Samples obtained from xenosurveillance and from finger-stick blood collection produced a similar number and quality of reads aligning to two human viruses, GB virus C and hepatitis B virus. This study represents the first systematic comparison between xenosurveillance and more traditional sampling methodologies, while also demonstrating the viability of xenosurveillance as a tool to sample human blood for circulating pathogens.

Highly Pathogenic Avian Influenza H5N6 Viruses Exhibit Enhanced Affinity for Human Type Sialic Acid Receptor and In-Contact Transmission in Model Ferrets.

PubMed

Sun, Honglei; Pu, Juan; Wei, Yandi; Sun, Yipeng; Hu, Jiao; Liu, Litao; Xu, Guanlong; Gao, Weihua; Li, Chong; Zhang, Xuxiao; Huang, Yinhua; Chang, Kin-Chow; Liu, Xiufan; Liu, Jinhua

2016-07-15

Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans. Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Antimicrobial and biocompatible properties of nanomaterials.

PubMed

Ul-Islam, M; Shehzad, A; Khan, S; Khattak, W A; Ullah, M W; Park, J K

2014-01-01

The rapid development of drug-resistant characteristics in pathogenic viral, bacterial, and fungal species and the consequent spread of infectious diseases are currently receiving serious attention. Indeed, there is a pressing demand to explore novel materials and develop new strategies that can address these issues of serious concern. Nanomaterials are currently proving to be the most capable therapeutic agents to cope with such hazards. The exceptional physiochemical properties and impressive antimicrobial capabilities of nanoparticles have provoked their utilization in biomedical fields. Nanomaterials of both organic and inorganic nature have shown the capabilities of disrupting microbial cells through different mechanisms. Along with the direct influence on the microbial cell membrane, DNA and proteins, these nanomaterials produce reactive oxygen species (ROS) that damage cell components and viruses. Currently, a serious hazard associated with these antimicrobial nanomaterials is their toxicity to human and animal cells. Extensive studies have reported the dose, time, and cell-dependent toxicology of various nanomaterials, and some have shown excellent biocompatible properties. Nevertheless, there is still debate regarding the use of nanomaterials for medical applications. Therefore, in this review, the antimicrobial activities of various nanomaterials with details of their acting mechanisms were compiled. The relative toxic and biocompatible behavior of nanomaterials emphasized in this study provides information pertaining to their practical applicability in medical fields.

Identification of potentially human-pathogenic Enterocytozoon bieneusi genotypes in various birds.

PubMed

Lobo, Maria Luísa; Xiao, Lihua; Cama, Vitaliano; Magalhães, Nuno; Antunes, Francisco; Matos, Olga

2006-11-01

Enterocytozoon bieneusi was detected in 24 of 83 samples from birds of the orders Columbiformes, Passeriformes, and Psittaciformes. It was identical to or closely related to the Peru6 genotype, which was previously found in humans in Peru. Thus, various birds can be a significant source of environmental contamination by potentially human-pathogenic E. bieneusi.

From Exit to Entry: Long-term Survival and Transmission of Salmonella

PubMed Central

Waldner, Landon L.; MacKenzie, Keith D.; Köster,, Wolfgang; White, Aaron P.

2012-01-01

Salmonella spp. are a leading cause of human infectious disease worldwide and pose a serious health concern. While we have an improving understanding of pathogenesis and the host-pathogen interactions underlying the infection process, comparatively little is known about the survival of pathogenic Salmonella outside their hosts. This review focuses on three areas: (1) in vitro evidence that Salmonella spp. can survive for long periods of time under harsh conditions; (2) observations and conclusions about Salmonella persistence obtained from human outbreaks; and (3) new information revealed by genomic- and population-based studies of Salmonella and related enteric pathogens. We highlight the mechanisms of Salmonella persistence and transmission as an essential part of their lifecycle and a prerequisite for their evolutionary success as human pathogens. PMID:25436767

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.

Microbe Profile: Mycobacterium tuberculosis: Humanity's deadly microbial foe.

PubMed

Gordon, Stephen V; Parish, Tanya

2018-04-01

Mycobacterium tuberculosis is an expert and deadly pathogen, causing the disease tuberculosis (TB) in humans. It has several notable features: the ability to enter non-replicating states for long periods and cause latent infection; metabolic remodelling during chronic infection; a thick, waxy cell wall; slow growth rate in culture; and intrinsic drug resistance and antibiotic tolerance. As a pathogen, M. tuberculosis has a complex relationship with its host, is able to replicate inside macrophages, and expresses diverse immunomodulatory molecules. M. tuberculosis currently causes over 1.8 million deaths a year, making it the world's most deadly human pathogen.

Generic aspects of the airborne spread of human pathogens indoors and emerging air decontamination technologies.

PubMed

Ijaz, M Khalid; Zargar, Bahram; Wright, Kathryn E; Rubino, Joseph R; Sattar, Syed A

2016-09-02

Indoor air can be an important vehicle for a variety of human pathogens. This review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. The following groups of human pathogens are covered because of their known or potential airborne spread: vegetative bacteria (staphylococci and legionellae), fungi (Aspergillus, Penicillium, and Cladosporium spp and Stachybotrys chartarum), enteric viruses (noro- and rotaviruses), respiratory viruses (influenza and coronaviruses), mycobacteria (tuberculous and nontuberculous), and bacterial spore formers (Clostridium difficile and Bacillus anthracis). An overview of methods for experimentally generating and recovering airborne human pathogens is included, along with a discussion of factors that influence microbial survival in indoor air. Available guidelines from the U.S. Environmental Protection Agency and other global regulatory bodies for the study of airborne pathogens are critically reviewed with particular reference to microbial surrogates that are recommended. Recent developments in experimental facilities to contaminate indoor air with microbial aerosols are presented, along with emerging technologies to decontaminate indoor air under field-relevant conditions. Furthermore, the role that air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings is discussed. Copyright © 2016. Published by Elsevier Inc.

Slaughterhouse pigs are a major reservoir of Streptococcus suis serotype 2 capable of causing human infection in southern Vietnam.

PubMed

Ngo, Thi Hoa; Tran, Thi Bich Chieu; Tran, Thi Thu Nga; Nguyen, Van Dung; Campbell, James; Pham, Hong Anh; Huynh, Huu Tho; Nguyen, Van Vinh Chau; Bryant, Juliet E; Tran, Tinh Hien; Farrar, Jeremy; Schultsz, Constance

2011-03-28

Streptococcus suis is a pathogen of major economic significance to the swine industry and is increasingly recognized as an emerging zoonotic agent in Asia. In Vietnam, S. suis is the leading cause of bacterial meningitis in adult humans. Zoonotic transmission is most frequently associated with serotype 2 strains and occupational exposure to pigs or consumption of infected pork. To gain insight into the role of pigs for human consumption as a reservoir for zoonotic infection in southern Vietnam, we determined the prevalence and diversity of S. suis carriage in healthy slaughterhouse pigs. Nasopharyngeal tonsils were sampled from pigs at slaughterhouses serving six provinces in southern Vietnam and Ho Chi Minh City area from September 2006 to November 2007. Samples were screened by bacterial culture. Isolates of S. suis were serotyped and characterized by multi locus sequence typing (MLST) and pulse field gel electrophoresis (PFGE). Antibiotic susceptibility profiles and associated genetic resistance determinants, and the presence of putative virulence factors were determined. 41% (222/542) of pigs carried S. suis of one or multiple serotypes. 8% (45/542) carried S. suis serotype 2 which was the most common serotype found (45/317 strains, 14%). 80% of serotype 2 strains belonged to the MLST clonal complex 1,which was previously associated with meningitis cases in Vietnam and outbreaks of severe disease in China in 1998 and 2005. These strains clustered with representative strains isolated from patients with meningitis in PFGE analysis, and showed similar antimicrobial resistance and virulence factor profiles. Slaughterhouse pigs are a major reservoir of S. suis serotype 2 capable of causing human infection in southern Vietnam. Strict hygiene at processing facilities, and health education programs addressing food safety and proper handling of pork should be encouraged.

The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas.

PubMed

Kurthkoti, Krishna; Amin, Hamel; Marakalala, Mohlopheni J; Ghanny, Saleena; Subbian, Selvakumar; Sakatos, Alexandra; Livny, Jonathan; Fortune, Sarah M; Berney, Michael; Rodriguez, G Marcela

2017-08-15

This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies. IMPORTANCE One-third of the world population may harbor persistent M. tuberculosis , causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain M. tuberculosis persistence in infected individuals. Iron is an essential nutrient for M. tuberculosis growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which M. tuberculosis likely experiences drastic Fe deprivation and, second, that Fe-starved M. tuberculosis is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in M. tuberculosis and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent M. tuberculosis , which can be exploited for the design of new antitubercular therapies. Copyright © 2017 Kurthkoti et al.

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.

Insights into the evolution of pathogenicity of Escherichia coli from genomic analysis of intestinal E. coli of Marmota himalayana in Qinghai–Tibet plateau of China

PubMed Central

Lu, Shan; Jin, Dong; Wu, Shusheng; Yang, Jing; Lan, Ruiting; Bai, Xiangning; Liu, Sha; Meng, Qiong; Yuan, Xuejiao; Zhou, Juan; Pu, Ji; Chen, Qiang; Dai, Hang; Hu, Yuanyuan; Xiong, Yanwen; Ye, Changyun; Xu, Jianguo

2016-01-01

Escherichia coli is both of a widespread harmless gut commensal and a versatile pathogen of humans. Domestic animals are a well-known reservoir for pathogenic E. coli. However, studies of E. coli populations from wild animals that have been separated from human activities had been very limited. Here we obtained 580 isolates from intestinal contents of 116 wild Marmot Marmota himalayana from Qinghai–Tibet plateau, China, with five isolates per animal. We selected 125 (hereinafter referred to as strains) from the 580 isolates for genome sequencing, based on unique pulse field gel electrophoresis patterns and at least one isolate per animal. Whole genome sequence analysis revealed that all 125 strains carried at least one and the majority (79.2%) carried multiple virulence genes based on the analysis of 22 selected virulence genes. In particular, the majority of the strains carried virulence genes from different pathovars as potential 'hybrid pathogens'. The alleles of eight virulence genes from the Marmot E. coli were found to have diverged earlier than all known alleles from human and other animal E. coli. Phylogenetic analysis of the 125 Marmot E. coli genomes and 355 genomes selected from 1622 human and other E. coli strains identified two new phylogroups, G and H, both of which diverged earlier than the other phylogroups. Eight of the 12 well-known pathogenic E. coli lineages were found to share a most recent common ancestor with one or more Marmot E. coli strains. Our results suggested that the intestinal E. coli of the Marmots contained a diverse virulence gene pool and is potentially pathogenic to humans. These findings provided a new understanding of the evolutionary origin of pathogenic E. coli. PMID:27924811

Insights into the evolution of pathogenicity of Escherichia coli from genomic analysis of intestinal E. coli of Marmota himalayana in Qinghai-Tibet plateau of China.

PubMed

Lu, Shan; Jin, Dong; Wu, Shusheng; Yang, Jing; Lan, Ruiting; Bai, Xiangning; Liu, Sha; Meng, Qiong; Yuan, Xuejiao; Zhou, Juan; Pu, Ji; Chen, Qiang; Dai, Hang; Hu, Yuanyuan; Xiong, Yanwen; Ye, Changyun; Xu, Jianguo

2016-12-07

Escherichia coli is both of a widespread harmless gut commensal and a versatile pathogen of humans. Domestic animals are a well-known reservoir for pathogenic E. coli. However, studies of E. coli populations from wild animals that have been separated from human activities had been very limited. Here we obtained 580 isolates from intestinal contents of 116 wild Marmot Marmota himalayana from Qinghai-Tibet plateau, China, with five isolates per animal. We selected 125 (hereinafter referred to as strains) from the 580 isolates for genome sequencing, based on unique pulse field gel electrophoresis patterns and at least one isolate per animal. Whole genome sequence analysis revealed that all 125 strains carried at least one and the majority (79.2%) carried multiple virulence genes based on the analysis of 22 selected virulence genes. In particular, the majority of the strains carried virulence genes from different pathovars as potential 'hybrid pathogens'. The alleles of eight virulence genes from the Marmot E. coli were found to have diverged earlier than all known alleles from human and other animal E. coli. Phylogenetic analysis of the 125 Marmot E. coli genomes and 355 genomes selected from 1622 human and other E. coli strains identified two new phylogroups, G and H, both of which diverged earlier than the other phylogroups. Eight of the 12 well-known pathogenic E. coli lineages were found to share a most recent common ancestor with one or more Marmot E. coli strains. Our results suggested that the intestinal E. coli of the Marmots contained a diverse virulence gene pool and is potentially pathogenic to humans. These findings provided a new understanding of the evolutionary origin of pathogenic E. coli.

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

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

USGS Publications Warehouse

Givens, Carrie E.; Kolpin, Dana W.; Borchardt, Mark A.; Duris, Joseph W.; Moorman, Thomas B.; Spencer, Susan K.

2016-01-01

Manure application is a source of pathogens to the environment. Through overland runoff and tile drainage, zoonotic pathogens can contaminate surface water and streambed sediment and could affect both wildlife and human health. This study examined the environmental occurrence of gene markers for livestock-related bacterial, protozoan, and viral pathogens and antibiotic resistance in surface waters within the South Fork Iowa River basin before and after periods of swine manure application on agricultural land. Increased concentrations of indicator bacteria after manure application exceeding Iowa's state bacteria water quality standards suggest that swine manure contributes to diminished water quality and may pose a risk to human health. Additionally, the occurrence of HEV and numerous bacterial pathogen genes for Escherichia coli, Enterococcus spp., Salmonella sp., and Staphylococcus aureus in both manure samples and in corresponding surface water following periods of manure application suggests a potential role for swine in the spreading of zoonotic pathogens to the surrounding environment. During this study, several zoonotic pathogens were detected including Shiga-toxin producing E. coli, Campylobacter jejuni, pathogenic enterococci, and S. aureus; all of which can pose mild to serious health risks to swine, humans, and other wildlife. This research provides the foundational understanding required for future assessment of the risk to environmental health from livestock-related zoonotic pathogen exposures in this region. This information could also be important for maintaining swine herd biosecurity and protecting the health of wildlife near swine facilities.

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

Pathogenic flora composition and overview of the trends used for bacterial pathogenicity identifications.

PubMed

Orji, Frank Anayo; Ugbogu, Ositadinma Chinyere; Ugbogu, Eziuche Amadike; Barbabosa-Pliego, Alberto; Monroy, Jose Cedillo; Elghandour, Mona M M Y; Salem, Abdelfattah Z M

2018-05-05

Over 250 species of resident flora in the class of bacteria are known to be associated with humans. These conventional flora compositions is often determined by factors which may not be limited to genetics, age, sex, stress and nutrition of humans. Man is constantly in contact with bacteria through media such as air, water, soil and food. This paper reviews the concept of bacterial pathogenesis from the sequential point of colonization to tissue injury. The paper in addition to examination of the factors which enhance virulence in bacterial pathogens also x-rayed the concept of pathogenicity islands and the next generation approaches or rather current trends/methods used in the bacterial pathogenicity investigations. In terms of pathogenicity which of course is the capacity to cause disease in animals, requires that the attacking bacterial strain is virulent, and has ability to bypass the host immune defensive mechanisms. In order to achieve or exhibit pathogenicity, the virulence factors required by microorganisms include capsule, pigments, enzymes, iron acquisition through siderophores. Bacterial Pathogenicity Islands as a distinct concept in bacterial pathogenesis are just loci on the chromosome or extra chromosomal units which are acquired by horizontal gene transfer within pathogens in a microbial community or biofilm. In the area of laboratory investigations, bacterial pathogenesis was initially carried out using culture dependent approaches, which can only detect about 1% of human and veterinary-important pathogens. However, in the recent paradigms shift, the use of proteomics, metagenomics, phylogenetic tree analyses, spooligotyping, and finger printing etc. have made it possible that 100% of the bacterial pathogens in nature can be extensively studied. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pathogen Specific, IRF3-Dependent Signaling and Innate Resistance to Human Kidney Infection

PubMed Central

Fischer, Hans; Lutay, Nataliya; Ragnarsdóttir, Bryndís; Yadav, Manisha; Jönsson, Klas; Urbano, Alexander; Al Hadad, Ahmed; Rämisch, Sebastian; Storm, Petter; Dobrindt, Ulrich; Salvador, Ellaine; Karpman, Diana; Jodal, Ulf; Svanborg, Catharina

2010-01-01

The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease susceptibility. We describe here a new, IRF3-dependent signaling pathway that is critical for distinguishing pathogens from normal flora at the mucosal barrier. Following uropathogenic E. coli infection, Irf3−/− mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice. TLR4 signaling was initiated after ceramide release from glycosphingolipid receptors, through TRAM, CREB, Fos and Jun phosphorylation and p38 MAPK-dependent mechanisms, resulting in nuclear translocation of IRF3 and activation of IRF3/IFNβ-dependent antibacterial effector mechanisms. This TLR4/IRF3 pathway of pathogen discrimination was activated by ceramide and by P-fimbriated E. coli, which use ceramide-anchored glycosphingolipid receptors. Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers. IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3−/− mice. Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response. PMID:20886096

Overview of measles and mumps vaccine: origin, present, and future of vaccine production.

PubMed

Betáková, T; Svetlíková, D; Gocník, M

2013-01-01

Measles and mumps are common viral childhood diseases that can cause serious complications. Vaccination remains the most efficient way to control the spread of these viruses. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblast or primary dog kidney cell substrates, is no longer sufficient. This limitation can be overcome by utilizing other recognized cell substrates such as Madin Darby Canine Kidney (MDCK), Chinese Hamster Ovary (CHO), Vero (monkey origin) cells, MRC-5 (human diploid) or as an alternative, introducing new cell substrates of human or avian origin. A very important factor in vaccine production is the safety and immunogenicity of the final vaccine, where the proper choice of cell substrate used for virus propagation is made. All substrates used in vaccine production must be fully characterized to avoid the contamination of hidden unknown pathogens which is difficult to achieve in primary cell substrates.

Genomics and the making of yeast biodiversity.

PubMed

Hittinger, Chris Todd; Rokas, Antonis; Bai, Feng-Yan; Boekhout, Teun; Gonçalves, Paula; Jeffries, Thomas W; Kominek, Jacek; Lachance, Marc-André; Libkind, Diego; Rosa, Carlos A; Sampaio, José Paulo; Kurtzman, Cletus P

2015-12-01

Yeasts are unicellular fungi that do not form fruiting bodies. Although the yeast lifestyle has evolved multiple times, most known species belong to the subphylum Saccharomycotina (syn. Hemiascomycota, hereafter yeasts). This diverse group includes the premier eukaryotic model system, Saccharomyces cerevisiae; the common human commensal and opportunistic pathogen, Candida albicans; and over 1000 other known species (with more continuing to be discovered). Yeasts are found in every biome and continent and are more genetically diverse than angiosperms or chordates. Ease of culture, simple life cycles, and small genomes (∼10-20Mbp) have made yeasts exceptional models for molecular genetics, biotechnology, and evolutionary genomics. Here we discuss recent developments in understanding the genomic underpinnings of the making of yeast biodiversity, comparing and contrasting natural and human-associated evolutionary processes. Only a tiny fraction of yeast biodiversity and metabolic capabilities has been tapped by industry and science. Expanding the taxonomic breadth of deep genomic investigations will further illuminate how genome function evolves to encode their diverse metabolisms and ecologies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Working Toward a Healthy Planet

NASA Technical Reports Server (NTRS)

Maynard, Nancy G.

2003-01-01

Using information from NASA s Earth Science Public Health Applications Program, Dr. Maynard will address how remote sensing data and associated technologies can be used toward a better understanding of the links among human health, the environment and weather/climate - and, how this increased understanding plus improved information sharing can empower local health and environmental decision-makers to better predict climate-related health problems, take preventive measures, and improve response actions. Remotely-sensed data and observations are providing powerful new tools for addressing climate and environment-related human health problems through increased capabilities for monitoring and surveillance of parameters useful to such problems as infectious and vector-borne diseases, air and water quality, harmful algal blooms, UV radiation, contaminant and pathogen transport in air and water, and thermal stress. NASA s multi-disciplinary scientific team is demonstrating how satellites from their unique vantage point in space can serve as sentinels for weather, climate, and health problems through studies on asthma, malaria, Rift Valley Fever, Asian and African dust, and West Nile Virus

Salmonella enterica Suppresses Pectobacterium carotovorum subsp. carotovorum Population and Soft Rot Progression by Acidifying the Microaerophilic Environment

PubMed Central

Kwan, Grace; Charkowski, Amy O.; Barak, Jeri D.

2013-01-01

ABSTRACT Although enteric human pathogens are usually studied in the context of their animal hosts, a significant portion of their life cycle occurs on plants. Plant disease alters the phyllosphere, leading to enhanced growth of human pathogens; however, the impact of human pathogens on phytopathogen biology and plant health is largely unknown. To characterize the interaction between human pathogens and phytobacterial pathogens in the phyllosphere, we examined the interactions between Pectobacterium carotovorum subsp. carotovorum and Salmonella enterica or Escherichia coli O157:H7 with regard to bacterial populations, soft rot progression, and changes in local pH. The presence of P. carotovorum subsp. carotovorum enhanced the growth of both S. enterica and E. coli O157:H7 on leaves. However, in a microaerophilic environment, S. enterica reduced P. carotovorum subsp. carotovorum populations and soft rot progression by moderating local environmental pH. Reduced soft rot was not due to S. enterica proteolytic activity. Limitations on P. carotovorum subsp. carotovorum growth, disease progression, and pH elevation were not observed on leaves coinoculated with E. coli O157:H7 or when leaves were coinoculated with S. enterica in an aerobic environment. S. enterica also severely undermined the relationship between the phytobacterial population and disease progression of a P. carotovorum subsp. carotovorum budB mutant defective in the 2,3-butanediol pathway for acid neutralization. Our results show that S. enterica and E. coli O157:H7 interact differently with the enteric phytobacterial pathogen P. carotovorum subsp. carotovorum. S. enterica inhibition of soft rot progression may conceal a rapidly growing human pathogen population. Whereas soft rotted produce can alert consumers to the possibility of food-borne pathogens, healthy-looking produce may entice consumption of contaminated vegetables. PMID:23404399

REAL-TIME PCR DETECTION OF THREE HUMAN-PATHOGENIC SPECIES FROM THE MICROSPORIDIAL GENUS ENCEPHALITOZOON

EPA Science Inventory

Three microsporidial species from the genus Encephalitozoon, E. hellem, E. cuniculi and E. intestinalis, have emerged as important opportunistic pathogens of humans affecting organ transplant recipients, AIDS patients, and other immunocompromised patients. Even though these thre...

Heat Inactivation of Human Pathogens on Catfish

USDA-ARS?s Scientific Manuscript database

In the National Advisory Committee on Microbiological Criteria for Food (NACMCF) determined that the cooking (time/temperature) for finfish would be different than for meat products and identified a need for time/temperature requirements to assure the thermal inactivation of the human pathogens: Sa...

Meeting Regulatory Requirements And Moving To Class A (Presentation)

EPA Science Inventory

The United States' regulations for the management of sewage sludge were designed to protect human health from infectious disease causing organisms by minimizing the contact of humans with pathogenic microorganisms. This paper reviews the pathogens that may be found in sewage slu...

Meeting Regulatory Requirements And Moving To Class A

EPA Science Inventory

The United States' regulations for the management of sewage sludge were designed to protect human health from infectious disease causing organisms by minimizing the contact of humans with pathogenic microorganisms. This paper reviews the pathogens that may be found in sewage slu...

Hydrologic, land cover and seasonal patterns of waterborne pathogens in great lakes tributaries

USDA-ARS?s Scientific Manuscript database

Great Lakes tributaries deliver waterborne pathogens from a host of sources. To examine the hydrologic, land cover, and seasonal variability of waterborne pathogens, protozoa (2), pathogenic bacteria (4) and human (8) and bovine (8) viruses from eight rivers were monitored in the Great Lakes watersh...

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

The bacterial microbiome of dermacentor andersoni ticks influences pathogen susceptibility

USDA-ARS?s Scientific Manuscript database

Ticks are of medical and veterinary importance due to their ability to transmit pathogens to humans and animals. The Rocky Mountain wood tick, Dermacentor andersoni, is a vector of a number of pathogens, including Anaplasma marginale, which is the most widespread tick-borne pathogen of livestock. Al...

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

USDA-ARS?s Scientific Manuscript database

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

Meat Science and Muscle Biology Symposium: Ecological and dietary impactors of foodborne pathogens and methods to reduce fecal shedding in cattle.

PubMed

Callaway, T R; Edrington, T S; Nisbet, D J

2014-04-01

Pathogenic bacteria can live asymptomatically within and on cattle and can enter the food chain but also can be transmitted to humans by fecal or direct animal contact. Reducing pathogenic bacterial incidence and populations within live cattle represents an important step in improving food safety. A broad range of preslaughter intervention strategies are being developed, which can be loosely classified as 1) directly antipathogen strategies, 2) competitive enhancement strategies (that use the microbiome's competitive nature against pathogens), and 3) animal management strategies. Included within these broad categories are such diverse methods as vaccination against foodborne pathogens, probiotics and prebiotics, bacterial viruses (i.e., bacteriophages), sodium chlorate feeding, and dietary and management changes that specifically alter the microbiome. The simultaneous application of 1 or more preharvest strategies has the potential to reduce human foodborne illnesses by erecting multiple hurdles preventing entry into humans. However, economic factors that govern producer profitability must be kept in mind while improving food safety.

Pathogenic strains of Yersinia enterocolitica isolated from domestic dogs (Canis familiaris) belonging to farmers are of the same subtype as pathogenic Y. enterocolitica strains isolated from humans and may be a source of human infection in Jiangsu Province, China.

PubMed

Wang, Xin; Cui, Zhigang; Wang, Hua; Tang, Liuying; Yang, Jinchuan; Gu, Ling; Jin, Dong; Luo, Longze; Qiu, Haiyan; Xiao, Yuchun; Xiong, Haiping; Kan, Biao; Xu, Jianguo; Jing, Huaiqi

2010-05-01

We isolated 326 Yersinia enterocolitica strains from 5,919 specimens from patients with diarrhea at outpatient clinics, livestock, poultry, wild animals, insect vectors, food, and the environment in the cities of Nantong and Xuzhou in Jiangsu Province, China, from 2004 to 2008. The results showed that the 12 pathogenic strains were of the O:3 serotype. Six strains were isolated from domestic dogs (Canis familiaris) belonging to farmers and were found to be the primary carriers of pathogenic Y. enterocolitica strains, especially in Xuzhou. Pulsed-field gel electrophoresis analysis of the pathogenic strains from dogs belonging to farmers showed that they shared the same patterns as strains from diarrhea patients isolated in 1994. This indicates that the strains from domestic dogs have a close correlation with the strains causing human infections.

Pathogenic Strains of Yersinia enterocolitica Isolated from Domestic Dogs (Canis familiaris) Belonging to Farmers Are of the Same Subtype as Pathogenic Y. enterocolitica Strains Isolated from Humans and May Be a Source of Human Infection in Jiangsu Province, China ▿ ‡

PubMed Central

Wang, Xin; Cui, Zhigang; Wang, Hua; Tang, Liuying; Yang, Jinchuan; Gu, Ling; Jin, Dong; Luo, Longze; Qiu, Haiyan; Xiao, Yuchun; Xiong, Haiping; Kan, Biao; Xu, Jianguo; Jing, Huaiqi

2010-01-01

We isolated 326 Yersinia enterocolitica strains from 5,919 specimens from patients with diarrhea at outpatient clinics, livestock, poultry, wild animals, insect vectors, food, and the environment in the cities of Nantong and Xuzhou in Jiangsu Province, China, from 2004 to 2008. The results showed that the 12 pathogenic strains were of the O:3 serotype. Six strains were isolated from domestic dogs (Canis familiaris) belonging to farmers and were found to be the primary carriers of pathogenic Y. enterocolitica strains, especially in Xuzhou. Pulsed-field gel electrophoresis analysis of the pathogenic strains from dogs belonging to farmers showed that they shared the same patterns as strains from diarrhea patients isolated in 1994. This indicates that the strains from domestic dogs have a close correlation with the strains causing human infections. PMID:20181899

Investigation of Listeria, Salmonella, and toxigenic Escherichia coli in various pet foods.

PubMed

Nemser, Sarah M; Doran, Tara; Grabenstein, Michael; McConnell, Terri; McGrath, Timothy; Pamboukian, Ruiqing; Smith, Angele C; Achen, Maya; Danzeisen, Gregory; Kim, Sun; Liu, Yong; Robeson, Sharon; Rosario, Grisel; McWilliams Wilson, Karen; Reimschuessel, Renate

2014-09-01

The Veterinary Laboratory Investigation and Response Network (Vet-LIRN), in collaboration with the Food Emergency Response Network (FERN) and its Microbiology Cooperative Agreement Program (MCAP) laboratories, conducted a study to evaluate the prevalence of selected microbial organisms in various types of pet foods. The goal of this blinded study was to help the Center for Veterinary Medicine prioritize potential future pet food-testing efforts. The study also increased the FERN laboratories' screening capabilities for foodborne pathogens in animal feed matrices, since such pathogens may also be a significant health risk to consumers who come into contact with pet foods. Six U.S. Food and Drug Administration FERN MCAP laboratories analyzed approximately 1056 samples over 2 years. Laboratories tested for Salmonella, Listeria, Escherichia coli O157:H7 enterohemorrhagic E. coli, and Shiga toxin-producing strains of E. coli (STEC). Dry and semimoist dog and cat foods purchased from local stores were tested during Phase 1. Raw dog and cat foods, exotic animal feed, and jerky-type treats purchased through the Internet were tested in Phase 2. Of the 480 dry and semimoist samples, only 2 tested positive: 1 for Salmonella and 1 for Listeria greyii. However, of the 576 samples analyzed during Phase 2, 66 samples were positive for Listeria (32 of those were Listeria monocytogenes) and 15 samples positive for Salmonella. These pathogens were isolated from raw foods and jerky-type treats, not the exotic animal dry feeds. This study showed that raw pet foods may harbor food safety pathogens, such as Listeria monocytogenes and Salmonella. Consumers should handle these products carefully, being mindful of the potential risks to human and animal health.

Wild eel microbiome reveals that skin mucus of fish could be a natural niche for aquatic mucosal pathogen evolution.

PubMed

Carda-Diéguez, Miguel; Ghai, Rohit; Rodríguez-Valera, Francisco; Amaro, Carmen

2017-12-21

Fish skin mucosal surfaces (SMS) are quite similar in composition and function to some mammalian MS and, in consequence, could constitute an adequate niche for the evolution of mucosal aquatic pathogens in natural environments. We aimed to test this hypothesis by searching for metagenomic and genomic evidences in the SMS-microbiome of a model fish species (Anguilla Anguilla or eel), from different ecosystems (four natural environments of different water salinity and one eel farm) as well as the water microbiome (W-microbiome) surrounding the host. Remarkably, potentially pathogenic Vibrio monopolized wild eel SMS-microbiome from natural ecosystems, Vibrio anguillarum/Vibrio vulnificus and Vibrio cholerae/Vibrio metoecus being the most abundant ones in SMS from estuary and lake, respectively. Functions encoded in the SMS-microbiome differed significantly from those in the W-microbiome and allowed us to predict that successful mucus colonizers should have specific genes for (i) attachment (mainly by forming biofilms), (ii) bacterial competence and communication, and (iii) resistance to mucosal innate immunity, predators (amoeba), and heavy metals/drugs. In addition, we found several mobile genetic elements (mainly integrative conjugative elements) as well as a series of evidences suggesting that bacteria exchange DNA in SMS. Further, we isolated and sequenced a V. metoecus strain from SMS. This isolate shares pathogenicity islands with V. cholerae O1 from intestinal infections that are absent in the rest of sequenced V. metoecus strains, all of them from water and extra-intestinal infections. We have obtained metagenomic and genomic evidence in favor of the hypothesis on the role of fish mucosal surfaces as a specialized habitat selecting microbes capable of colonizing and persisting on other comparable mucosal surfaces, e.g., the human intestine.

Investigation of Listeria, Salmonella, and Toxigenic Escherichia coli in Various Pet Foods

PubMed Central

Doran, Tara; Grabenstein, Michael; McConnell, Terri; McGrath, Timothy; Pamboukian, Ruiqing; Smith, Angele C.; Achen, Maya; Danzeisen, Gregory; Kim, Sun; Liu, Yong; Robeson, Sharon; Rosario, Grisel; McWilliams Wilson, Karen; Reimschuessel, Renate

2014-01-01

Abstract The Veterinary Laboratory Investigation and Response Network (Vet-LIRN), in collaboration with the Food Emergency Response Network (FERN) and its Microbiology Cooperative Agreement Program (MCAP) laboratories, conducted a study to evaluate the prevalence of selected microbial organisms in various types of pet foods. The goal of this blinded study was to help the Center for Veterinary Medicine prioritize potential future pet food–testing efforts. The study also increased the FERN laboratories' screening capabilities for foodborne pathogens in animal feed matrices, since such pathogens may also be a significant health risk to consumers who come into contact with pet foods. Six U.S. Food and Drug Administration FERN MCAP laboratories analyzed approximately 1056 samples over 2 years. Laboratories tested for Salmonella, Listeria, Escherichia coli O157:H7 enterohemorrhagic E. coli, and Shiga toxin–producing strains of E. coli (STEC). Dry and semimoist dog and cat foods purchased from local stores were tested during Phase 1. Raw dog and cat foods, exotic animal feed, and jerky-type treats purchased through the Internet were tested in Phase 2. Of the 480 dry and semimoist samples, only 2 tested positive: 1 for Salmonella and 1 for Listeria greyii. However, of the 576 samples analyzed during Phase 2, 66 samples were positive for Listeria (32 of those were Listeria monocytogenes) and 15 samples positive for Salmonella. These pathogens were isolated from raw foods and jerky-type treats, not the exotic animal dry feeds. This study showed that raw pet foods may harbor food safety pathogens, such as Listeria monocytogenes and Salmonella. Consumers should handle these products carefully, being mindful of the potential risks to human and animal health. PMID:24824368

Combined use of vancomycin-modified Ag-coated magnetic nanoparticles and secondary enhanced nanoparticles for rapid surface-enhanced Raman scattering detection of bacteria.

PubMed

Wang, Chongwen; Gu, Bing; Liu, Qiqi; Pang, Yuanfeng; Xiao, Rui; Wang, Shengqi

2018-01-01

Pathogenic bacteria have always been a significant threat to human health. The detection of pathogens needs to be rapid, accurate, and convenient. We present a sensitive surface-enhanced Raman scattering (SERS) biosensor based on the combination of vancomycin-modified Ag-coated magnetic nanoparticles (Fe 3 O 4 @Ag-Van MNPs) and Au@Ag nanoparticles (NPs) that can effectively capture and discriminate bacterial pathogens from solution. The high-performance Fe 3 O 4 @Ag MNPs were modified with vancomycin and used as bacteria capturer for magnetic separation and enrichment. The modified MNPS were found to exhibit strong affinity with a broad range of Gram-positive and Gram-negative bacteria. After separating and rinsing bacteria, Fe 3 O 4 @Ag-Van MNPs and Au@Ag NPs were synergistically used to construct a very large number of hot spots on bacteria cells, leading to ultrasensitive SERS detection. The dominant merits of our dual enhanced strategy included high bacterial-capture efficiency (>65%) within a wide pH range (pH 3.0-11.0), a short assay time (<30 min), and a low detection limit (5×10 2 cells/mL). Moreover, the spiked tests show that this method is still valid in milk and blood samples. Owing to these capabilities, the combined system enabled the sensitive and specific discrimination of different pathogens in complex solution, as verified by its detection of Gram-positive bacterium Escherichia coli , Gram-positive bacterium Staphylococcus aureus , and methicillin-resistant S. aureus . This method has great potential for field applications in food safety, environmental monitoring, and infectious disease diagnosis.

Combined use of vancomycin-modified Ag-coated magnetic nanoparticles and secondary enhanced nanoparticles for rapid surface-enhanced Raman scattering detection of bacteria

PubMed Central

Pang, Yuanfeng; Xiao, Rui; Wang, Shengqi

2018-01-01

Background Pathogenic bacteria have always been a significant threat to human health. The detection of pathogens needs to be rapid, accurate, and convenient. Methods We present a sensitive surface-enhanced Raman scattering (SERS) biosensor based on the combination of vancomycin-modified Ag-coated magnetic nanoparticles (Fe3O4@Ag-Van MNPs) and Au@Ag nanoparticles (NPs) that can effectively capture and discriminate bacterial pathogens from solution. The high-performance Fe3O4@Ag MNPs were modified with vancomycin and used as bacteria capturer for magnetic separation and enrichment. The modified MNPS were found to exhibit strong affinity with a broad range of Gram-positive and Gram-negative bacteria. After separating and rinsing bacteria, Fe3O4@Ag-Van MNPs and Au@Ag NPs were synergistically used to construct a very large number of hot spots on bacteria cells, leading to ultrasensitive SERS detection. Results The dominant merits of our dual enhanced strategy included high bacterial-capture efficiency (>65%) within a wide pH range (pH 3.0–11.0), a short assay time (<30 min), and a low detection limit (5×102 cells/mL). Moreover, the spiked tests show that this method is still valid in milk and blood samples. Owing to these capabilities, the combined system enabled the sensitive and specific discrimination of different pathogens in complex solution, as verified by its detection of Gram-positive bacterium Escherichia coli, Gram-positive bacterium Staphylococcus aureus, and methicillin-resistant S. aureus. Conclusion This method has great potential for field applications in food safety, environmental monitoring, and infectious disease diagnosis. PMID:29520142

Wild canids as sentinels of ecological health: a conservation medicine perspective

PubMed Central

Aguirre, A Alonso

2009-01-01

The extinction of species across the globe is accelerating, directly or indirectly due to human activities. Biological impoverishment, habitat fragmentation, climate change, increasing toxification, and the rapid global movement of people and other living organisms have worked synergistically to diminish ecosystem function. This has resulted in unprecedented levels of disease emergence, driven by human-induced environmental degradation, which poses a threat to the survival and health of biodiversity. The emerging discipline of conservation medicine addresses these concerns through the following entities: humans; global climate; habitat destruction and alteration; biodiversity, including wildlife populations; domestic animals; and pathogens, parasites and pollutants. Furthermore, conservation medicine focuses on explicit linkages between these entities. As a crisis discipline, the usefulness of conservation medicine ultimately will depend on its applicability to solving problems. The perspectives and scientific findings of conservation medicine provide input into biomedical education; and policy and management of ecosystems, habitats and imperiled species. A sentinel species is one that has presented itself, or has been selected, to provide insight into the state (health) of an ecosystem, based on user-defined (e.g., researchers, conservationists or policymakers) objectives (e.g., disease, parasites, toxics, climate change, habitat destruction), coupled with the utility and vulnerability of this species to the perceived stress. The scientific information generated by the sentinel species should empower stakeholders and decision-makers to take mitigative action or support predictive capabilities; the "utility" of the species selected should consider its value and relevance to conservationists and to society at large (e.g., education and outreach; social sciences). Wild canids may serve as excellent sentinel species of emerging canine vector-borne diseases. Several canine vector-borne diseases or antibodies to these pathogens have been identified in wild canids including visceral leishmaniosis, Lyme disease, heartworm, hepatozoonosis and anaplasmosis to name a few. These reports are relatively recent as they relate to wildlife-domestic animal interactions, globalisation, translocations, habitat fragmentation and climate change. These pathogens and their relationship to wild canids are described herein. Further research needs to be performed to elucidate the role of the 36 extant species of wild canids in the epidemiology of canine vector-borne diseases. PMID:19426446

Wild canids as sentinels of ecological health: a conservation medicine perspective.

PubMed

Aguirre, A Alonso

2009-03-26

The extinction of species across the globe is accelerating, directly or indirectly due to human activities. Biological impoverishment, habitat fragmentation, climate change, increasing toxification, and the rapid global movement of people and other living organisms have worked synergistically to diminish ecosystem function. This has resulted in unprecedented levels of disease emergence, driven by human-induced environmental degradation, which poses a threat to the survival and health of biodiversity. The emerging discipline of conservation medicine addresses these concerns through the following entities: humans; global climate; habitat destruction and alteration; biodiversity, including wildlife populations; domestic animals; and pathogens, parasites and pollutants. Furthermore, conservation medicine focuses on explicit linkages between these entities. As a crisis discipline, the usefulness of conservation medicine ultimately will depend on its applicability to solving problems. The perspectives and scientific findings of conservation medicine provide input into biomedical education; and policy and management of ecosystems, habitats and imperiled species. A sentinel species is one that has presented itself, or has been selected, to provide insight into the state (health) of an ecosystem, based on user-defined (e.g., researchers, conservationists or policymakers) objectives (e.g., disease, parasites, toxics, climate change, habitat destruction), coupled with the utility and vulnerability of this species to the perceived stress. The scientific information generated by the sentinel species should empower stakeholders and decision-makers to take mitigative action or support predictive capabilities; the "utility" of the species selected should consider its value and relevance to conservationists and to society at large (e.g., education and outreach; social sciences). Wild canids may serve as excellent sentinel species of emerging canine vector-borne diseases. Several canine vector-borne diseases or antibodies to these pathogens have been identified in wild canids including visceral leishmaniosis, Lyme disease, heartworm, hepatozoonosis and anaplasmosis to name a few. These reports are relatively recent as they relate to wildlife-domestic animal interactions, globalisation, translocations, habitat fragmentation and climate change. These pathogens and their relationship to wild canids are described herein. Further research needs to be performed to elucidate the role of the 36 extant species of wild canids in the epidemiology of canine vector-borne diseases.

Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.

PubMed

Stenland, Christopher J; Lee, Douglas C; Brown, Paul; Petteway, Stephen R; Rubenstein, Richard

2002-11-01

Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrP(vCJD)), human sporadic CJD (PrP(sCJD)) and Gerstmann-Sträussler-Scheinker (PrP(GSS)) syndrome was compared to the partitioning of hamster scrapie (PrP(Sc)) in three plasma protein purification steps. Sheep scrapie (PrP(Sc)) was similarly evaluated. The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrP(vCJD), human PrP(sCJD), human PrP(GSS), sheep PrP(Sc), and hamster 263K PrP(Sc). The partitioning of the pathogenic form of the PrP was analyzed. Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrP(Sc). A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (> or = 3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.

F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability.

PubMed

Kang, Jingjing; Gao, Jie; Yao, Wenwu; Kang, Lin; Gao, Shan; Yang, Hao; Ji, Bin; Li, Ping; Liu, Jing; Yao, Jiahao; Xin, Wenwen; Zhao, Baohua; Wang, Jinglin

2017-07-03

Epsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETX F199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETX F199E was almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca 2+ release from intracellular Ca 2+ stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETX F199E as a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins.

F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability

PubMed Central

Kang, Jingjing; Gao, Jie; Yao, Wenwu; Kang, Lin; Gao, Shan; Yang, Hao; Ji, Bin; Li, Ping; Liu, Jing; Yao, Jiahao; Xin, Wenwen; Zhao, Baohua; Wang, Jinglin

2017-01-01

ABSTRACT Epsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETXF199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETXF199E was almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca2+ release from intracellular Ca2+ stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETXF199E as a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins. PMID:28304231

Features of Two New Proteins with OmpA-Like Domains Identified in the Genome Sequences of Leptospira interrogans

PubMed Central

Teixeira, Aline F.; de Morais, Zenaide M.; Kirchgatter, Karin; Romero, Eliete C.; Vasconcellos, Silvio A.; Nascimento, Ana Lucia T. O.

2015-01-01

Leptospirosis is an acute febrile disease caused by pathogenic spirochetes of the genus Leptospira. It is considered an important re-emerging infectious disease that affects humans worldwide. The knowledge about the mechanisms by which pathogenic leptospires invade and colonize the host remains limited since very few virulence factors contributing to the pathogenesis of the disease have been identified. Here, we report the identification and characterization of two new leptospiral proteins with OmpA-like domains. The recombinant proteins, which exhibit extracellular matrix-binding properties, are called Lsa46 - LIC13479 and Lsa77 - LIC10050 (Leptospiral surface adhesins of 46 and 77 kDa, respectively). Attachment of Lsa46 and Lsa77 to laminin was specific, dose dependent and saturable, with KD values of 24.3 ± 17.0 and 53.0 ± 17.5 nM, respectively. Lsa46 and Lsa77 also bind plasma fibronectin, and both adhesins are plasminogen (PLG)-interacting proteins, capable of generating plasmin (PLA) and as such, increase the proteolytic ability of leptospires. The proteins corresponding to Lsa46 and Lsa77 are present in virulent L. interrogans L1-130 and in saprophyte L. biflexa Patoc 1 strains, as detected by immunofluorescence. The adhesins are recognized by human leptospirosis serum samples at the onset and convalescent phases of the disease, suggesting that they are expressed during infection. Taken together, our data could offer valuable information to the understanding of leptospiral pathogenesis. PMID:25849456

Evidence for retrovirus and paramyxovirus infection of multiple bat species in china.

PubMed

Yuan, Lihong; Li, Min; Li, Linmiao; Monagin, Corina; Chmura, Aleksei A; Schneider, Bradley S; Epstein, Jonathan H; Mei, Xiaolin; Shi, Zhengli; Daszak, Peter; Chen, Jinping

2014-05-16

Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the 103 vertebrate viral contigs, 79 displayed low identity (<70%) to known viruses including human viruses at the amino acid level, suggesting that these belong to novel and genetically divergent viruses. Overall, the most frequently identified viruses, particularly in bats from the family Hipposideridae, were retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans.

Evidence for Retrovirus and Paramyxovirus Infection of Multiple Bat Species in China

PubMed Central

Yuan, Lihong; Li, Min; Li, Linmiao; Monagin, Corina; Chmura, Aleksei A.; Schneider, Bradley S.; Epstein, Jonathan H.; Mei, Xiaolin; Shi, Zhengli; Daszak, Peter; Chen, Jinping

2014-01-01

Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the 103 vertebrate viral contigs, 79 displayed low identity (<70%) to known viruses including human viruses at the amino acid level, suggesting that these belong to novel and genetically divergent viruses. Overall, the most frequently identified viruses, particularly in bats from the family Hipposideridae, were retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans. PMID:24841387

An overview of dissolved organic carbon in groundwater and implications for drinking water safety

NASA Astrophysics Data System (ADS)

Regan, S.; Hynds, P.; Flynn, R.

2017-06-01

Dissolved organic carbon (DOC) is composed of a diverse array of compounds, predominantly humic substances, and is a near ubiquitous component of natural groundwater, notwithstanding climatic extremes such as arid and hyper-arid settings. Despite being a frequently measured parameter of groundwater quality, the complexity of DOC composition and reaction behaviour means that links between concentration and human health risk are difficult to quantify and few examples are reported in the literature. Measured concentrations from natural/unpolluted groundwater are typically below 4 mg C/l, whilst concentrations above these levels generally indicate anthropogenic influences and/or contamination issues and can potentially compromise water safety. Treatment processes are effective at reducing DOC concentrations, but refractory humic substance reaction with chlorine during the disinfection process produces suspected carcinogenic disinfectant by-products (DBPs). However, despite engineered artificial recharge systems being commonly used to remove DOC from recycled treated wastewaters, little research has been conducted on the presence of DBPs in potable groundwater systems. In recent years, the capacity to measure the influence of organic matter on colloidal contaminants and its influence on the mobility of pathogenic microorganisms has aided understanding of transport processes in aquifers. Additionally, advances in polymerase chain reaction techniques used for the detection, identification, and quantification of waterborne pathogens, provide a method to confidently investigate the behaviour of DOC and its effect on contaminant transfer in aquifers. This paper provides a summary of DOC occurrence in groundwater bodies and associated issues capable of indirectly affecting human health.

Green synthesis, antimicrobial and cytotoxic effects of silver nanoparticles using Eucalyptus chapmaniana leaves extract.

PubMed

Sulaiman, Ghassan Mohammad; Mohammed, Wasnaa Hatif; Marzoog, Thorria Radam; Al-Amiery, Ahmed Abdul Amir; Kadhum, Abdul Amir H; Mohamad, Abu Bakar

2013-01-01

To synthesize silver nanopaticles from leaves extract of Eucalyptus chapmaniana (E. chapmaniana) and test the antimicrobial of the nanoparticles against different pathogenic bacteria, yeast and its toxicity against human acute promyelocytic leukemia (HL-60) cell line. Ten milliliter of leaves extract was mixed with 90 mL of 0.01 mmol/mL or 0.02 mmol/mL aqueous AgNO3 and exposed to sun light for 1 h. A change from yellowish to reddish brown color was observed. Characterization using UV-vis spectrophotometery and X-ray diffraction analysis were performed. Antimicrobial activity against six microorganisms was tested using well diffusion method and cytoxicity test using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole was obtained on the human leukemia cell line (HL-60). UV-vis spectral analysis showed silver surface plasmon resonance band at 413 nm. X-ray diffraction showed that the particles were crystalline in nature with face centered cubic structure of the bulk silver with broad beaks at 38.50° and 44.76°. The synthesized silver nanoparticles efficiently inhibited various pathogenic organisms and reduced viability of the HL-60 cells in a dose-dependent manner. It has been demonstrated that the extract of E. chapmaniana leaves are capable of producing silver nanoparticles extracellularly and the Ag nanoparticles are quite stable in solution. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial and anticancer activity of these particles.

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

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.

Coinfections acquired from ixodes ticks.

PubMed

Swanson, Stephen J; Neitzel, David; Reed, Kurt D; Belongia, Edward A

2006-10-01

The pathogens that cause Lyme disease (LD), human anaplasmosis, and babesiosis can coexist in Ixodes ticks and cause human coinfections. Although the risk of human coinfection differs by geographic location, the true prevalence of coinfecting pathogens among Ixodes ticks remains largely unknown for the majority of geographic locations. The prevalence of dually infected Ixodes ticks appears highest among ticks from regions of North America and Europe where LD is endemic, with reported prevalences of < or =28%. In North America and Europe, the majority of tick-borne coinfections occur among humans with diagnosed LD. Humans coinfected with LD and babesiosis appear to have more intense, prolonged symptoms than those with LD alone. Coinfected persons can also manifest diverse, influenza-like symptoms, and abnormal laboratory test results are frequently observed. Coinfecting pathogens might alter the efficiency of transmission, cause cooperative or competitive pathogen interactions, and alter disease severity among hosts. No prospective studies to assess the immunologic effects of coinfection among humans have been conducted, but animal models demonstrate that certain coinfections can modulate the immune response. Clinicians should consider the likelihood of coinfection when pursuing laboratory testing or selecting therapy for patients with tick-borne illness.

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.

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

PubMed

Tabachnick, W J

2010-03-15

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

A retrospective cross-sectional quantitative molecular approach in biological samples from patients with syphilis.

PubMed

Pinto, Miguel; Antelo, Minia; Ferreira, Rita; Azevedo, Jacinta; Santo, Irene; Borrego, Maria José; Gomes, João Paulo

2017-03-01

Syphilis is the sexually transmitted disease caused by Treponema pallidum, a pathogen highly adapted to the human host. As a multistage disease, syphilis presents distinct clinical manifestations that pose different implications for diagnosis. Nevertheless, the inherent factors leading to diverse disease progressions are still unknown. We aimed to assess the association between treponemal loads and dissimilar disease outcomes, to better understand syphilis. We retrospectively analyzed 309 DNA samples distinct anatomic sites associated with particular syphilis manifestations. All samples had previously tested positive by a PCR-based diagnostic kit. An absolute quantitative real-time PCR procedure was used to precisely quantify the number of treponemal and human cells to determine T. pallidum loads in each sample. In general, lesion exudates presented the highest T. pallidum loads in contrast with blood-derived samples. Within the latter, a higher dispersion of T. pallidum quantities was observed for secondary syphilis. T. pallidum was detected in substantial amounts in 37 samples of seronegative individuals and in 13 cases considered as syphilis-treated. No association was found between treponemal loads and serological results or HIV status. This study suggests a scenario where syphilis may be characterized by: i) heterogeneous and high treponemal loads in primary syphilis, regardless of the anatomic site, reflecting dissimilar duration of chancres development and resolution; ii) high dispersion of bacterial concentrations in secondary syphilis, potentially suggesting replication capability of T. pallidum while in the bloodstream; and iii) bacterial evasiveness, either to the host immune system or antibiotic treatment, while remaining hidden in privileged niches. This work highlights the importance of using molecular approaches to study uncultivable human pathogens, such as T. pallidum, in the infection process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Short- and Long-Term Clinical Outcomes in Rhesus Monkeys Inoculated with a Highly Pathogenic Chimeric Simian/Human Immunodeficiency Virus

PubMed Central

Endo, Yasuyuki; Igarashi, Tatsuhiko; Nishimura, Yoshiaki; Buckler, Charles; Buckler-White, Alicia; Plishka, Ronald; Dimitrov, Dimiter S.; Martin, Malcolm A.

2000-01-01

A highly pathogenic simian/human immunodeficiency virus (SHIV), SHIVDH12R, isolated from a rhesus macaque that had been treated with anti-human CD8 monoclonal antibody at the time of primary infection with the nonpathogenic, molecularly cloned SHIVDH12, induced marked and rapid CD4+ T cell loss in all rhesus macaques intravenously inoculated with 1.0 50% tissue culture infective dose (TCID50) to 4.1 × 105 TCID50s of virus. Animals inoculated with 650 TCID50s of SHIVDH12R or more experienced irreversible CD4+ T lymphocyte depletion and developed clinical disease requiring euthanasia between weeks 12 and 23 postinfection. In contrast, the CD4+ T-cell numbers in four of five monkeys receiving 25 TCID50s of SHIVDH12R or less stabilized at low levels, and these surviving animals produced antibodies capable of neutralizing SHIVDH12R. In the fifth monkey, no recovery from the CD4+ T cell decline occurred, and the animal had to be euthanized. Viral RNA levels, subsequent to the initial peak of infection but not at peak viremia, correlated with the virus inoculum size and the eventual clinical course. Both initial infection rate constants, k, and decay constants, d, were determined, but only the latter were statistically correlated to clinical outcome. The attenuating effects of reduced inoculum size were also observed when virus was inoculated by the mucosal route. Because the uncloned SHIVDH12R stock possessed the genetic properties of a lentivirus quasispecies, we were able to assess the evolution of the input virus swarm in animals surviving the acute infection by monitoring the emergence of neutralization escape viral variants. PMID:10888632

Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase

PubMed Central

Reglinski, Mark; Calay, Damien; Siggins, Matthew K.; Mason, Justin C.; Botto, Marina; Sriskandan, Shiranee

2017-01-01

The complement cascade is crucial for clearance and control of invading pathogens, and as such is a key target for pathogen mediated host modulation. C3 is the central molecule of the complement cascade, and plays a vital role in opsonization of bacteria and recruitment of neutrophils to the site of infection. Streptococcal species have evolved multiple mechanisms to disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), a C5a inactivating enzyme, is widely conserved. Here we demonstrate for the first time that pyogenic streptococcal species are capable of cleaving C3, and identify C3 and C3a as novel substrates for the streptococcal ScpA, which are functionally inactivated as a result of cleavage 7 amino acids upstream of the natural C3 convertase. Cleavage of C3a by ScpA resulted in disruption of human neutrophil activation, phagocytosis and chemotaxis, while cleavage of C3 generated abnormally-sized C3a and C3b moieties with impaired function, in particular reducing C3 deposition on the bacterial surface. Despite clear effects on human complement, expression of ScpA reduced clearance of group A streptococci in vivo in wildtype and C5 deficient mice, and promoted systemic bacterial dissemination in mice that lacked both C3 and C5, suggesting an additional complement-independent role for ScpA in streptococcal pathogenesis. ScpA was shown to mediate streptococcal adhesion to both human epithelial and endothelial cells, consistent with a role in promoting bacterial invasion within the host. Taken together, these data show that ScpA is a multi-functional virulence factor with both complement-dependent and independent roles in streptococcal pathogenesis. PMID:28806402

Serratia Infections: from Military Experiments to Current Practice

PubMed Central

Mahlen, Steven D.

2011-01-01

Summary: Serratia species, in particular Serratia marcescens, are significant human pathogens. S. marcescens has a long and interesting taxonomic, medical experimentation, military experimentation, and human clinical infection history. The organisms in this genus, particularly S. marcescens, were long thought to be nonpathogenic. Because S. marcescens was thought to be a nonpathogen and is usually red pigmented, the U.S. military conducted experiments that attempted to ascertain the spread of this organism released over large areas. In the process, members of both the public and the military were exposed to S. marcescens, and this was uncovered by the press in the 1970s, leading to U.S. congressional hearings. S. marcescens was found to be a certain human pathogen by the mid-1960s. S. marcescens and S. liquefaciens have been isolated as causative agents of numerous outbreaks and opportunistic infections, and the association of these organisms with point sources such as medical devices and various solutions given to hospitalized patients is striking. Serratia species appear to be common environmental organisms, and this helps to explain the large number of nosocomial infections due to these bacteria. Since many nosocomial infections are caused by multiply antibiotic-resistant strains of S. marcescens, this increases the danger to hospitalized patients, and hospital personnel should be vigilant in preventing nosocomial outbreaks due to this organism. S. marcescens, and probably other species in the genus, carries several antibiotic resistance determinants and is also capable of acquiring resistance genes. S. marcescens and S. liquefaciens are usually identified well in the clinical laboratory, but the other species are rare enough that laboratory technologists may not recognize them. 16S rRNA gene sequencing may enable better identification of some of the less common Serratia species. PMID:21976608

Serratia infections: from military experiments to current practice.

PubMed

Mahlen, Steven D

2011-10-01

Serratia species, in particular Serratia marcescens, are significant human pathogens. S. marcescens has a long and interesting taxonomic, medical experimentation, military experimentation, and human clinical infection history. The organisms in this genus, particularly S. marcescens, were long thought to be nonpathogenic. Because S. marcescens was thought to be a nonpathogen and is usually red pigmented, the U.S. military conducted experiments that attempted to ascertain the spread of this organism released over large areas. In the process, members of both the public and the military were exposed to S. marcescens, and this was uncovered by the press in the 1970s, leading to U.S. congressional hearings. S. marcescens was found to be a certain human pathogen by the mid-1960s. S. marcescens and S. liquefaciens have been isolated as causative agents of numerous outbreaks and opportunistic infections, and the association of these organisms with point sources such as medical devices and various solutions given to hospitalized patients is striking. Serratia species appear to be common environmental organisms, and this helps to explain the large number of nosocomial infections due to these bacteria. Since many nosocomial infections are caused by multiply antibiotic-resistant strains of S. marcescens, this increases the danger to hospitalized patients, and hospital personnel should be vigilant in preventing nosocomial outbreaks due to this organism. S. marcescens, and probably other species in the genus, carries several antibiotic resistance determinants and is also capable of acquiring resistance genes. S. marcescens and S. liquefaciens are usually identified well in the clinical laboratory, but the other species are rare enough that laboratory technologists may not recognize them. 16S rRNA gene sequencing may enable better identification of some of the less common Serratia species.

Bat–man disease transmission: zoonotic pathogens from wildlife reservoirs to human populations

PubMed Central

Allocati, N; Petrucci, A G; Di Giovanni, P; Masulli, M; Di Ilio, C; De Laurenzi, V

2016-01-01

Bats are natural reservoir hosts and sources of infection of several microorganisms, many of which cause severe human diseases. Because of contact between bats and other animals, including humans, the possibility exists for additional interspecies transmissions and resulting disease outbreaks. The purpose of this article is to supply an overview on the main pathogens isolated from bats that have the potential to cause disease in humans. PMID:27551536

Commercial strain-derived clinical Saccharomyces cerevisiae can evolve new phenotypes without higher pathogenicity.

PubMed

Pfliegler, Walter P; Boros, Enikő; Pázmándi, Kitti; Jakab, Ágnes; Zsuga, Imre; Kovács, Renátó; Urbán, Edit; Antunovics, Zsuzsa; Bácsi, Attila; Sipiczki, Matthias; Majoros, László; Pócsi, István

2017-11-01

Saccharomyces cerevisiae is one of the most important microbes in food industry, but there is growing evidence on its potential pathogenicity as well. Its status as a member of human mycobiome is still not fully understood. In this study, we characterize clinical S. cerevisiae isolates from Hungarian hospitals along with commercial baking and probiotic strains, and determine their phenotypic parameters, virulence factors, interactions with human macrophages, and pathogenicity. Four of the clinical isolates could be traced back to commercial strains based on genetic fingerprinting. Our observations indicate that the commercial-derived clinical isolates have evolved new phenotypes and show similar, or in two cases, significantly decreased pathogenicity. Furthermore, immunological experiments revealed that the variability in human primary macrophage activation after coincubation with yeasts is largely donor and not isolate dependent. Isolates in this study offer an interesting insight into the potential microevolution of probiotic and food strains in human hosts. These commensal yeasts display various changes in their phenotypes, indicating that the colonization of the host does not necessarily impose a selective pressure toward higher virulence/pathogenicity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

PubMed Central

Luczo, Jasmina M.; Stambas, John; Durr, Peter A.; Michalski, Wojtek P.

2015-01-01

Summary The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio‐economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host‐pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:26467906

Pathogenicity of Shigella in chickens.

PubMed

Shi, Run; Yang, Xia; Chen, Lu; Chang, Hong-tao; Liu, Hong-ying; Zhao, Jun; Wang, Xin-wei; Wang, Chuan-qing

2014-01-01

Shigellosis in chickens was first reported in 2004. This study aimed to determine the pathogenicity of Shigella in chickens and the possibility of cross-infection between humans and chickens. The pathogenicity of Shigella in chickens was examined via infection of three-day-old SPF chickens with Shigella strain ZD02 isolated from a human patient. The virulence and invasiveness were examined by infection of the chicken intestines and primary chicken intestinal epithelial cells. The results showed Shigella can cause death via intraperitoneal injection in SPF chickens, but only induce depression via crop injection. Immunohistochemistry and transmission electron microscopy revealed the Shigella can invade the intestinal epithelia. Immunohistochemistry of the primary chicken intestinal epithelial cells infected with Shigella showed the bacteria were internalized into the epithelial cells. Electron microscopy also confirmed that Shigella invaded primary chicken intestinal epithelia and was encapsulated by phagosome-like membranes. Our data demonstrate that Shigella can invade primary chicken intestinal epithelial cells in vitro and chicken intestinal mucosa in vivo, resulting in pathogenicity and even death. The findings suggest Shigella isolated from human or chicken share similar pathogenicity as well as the possibility of human-poultry cross-infection, which is of public health significance.

Pathogenicity of Shigella in Chickens

PubMed Central

Chen, Lu; Chang, Hong-tao; Liu, Hong-ying; Zhao, Jun; Wang, Xin-wei; Wang, Chuan-qing

2014-01-01

Shigellosis in chickens was first reported in 2004. This study aimed to determine the pathogenicity of Shigella in chickens and the possibility of cross-infection between humans and chickens. The pathogenicity of Shigella in chickens was examined via infection of three-day-old SPF chickens with Shigella strain ZD02 isolated from a human patient. The virulence and invasiveness were examined by infection of the chicken intestines and primary chicken intestinal epithelial cells. The results showed Shigella can cause death via intraperitoneal injection in SPF chickens, but only induce depression via crop injection. Immunohistochemistry and transmission electron microscopy revealed the Shigella can invade the intestinal epithelia. Immunohistochemistry of the primary chicken intestinal epithelial cells infected with Shigella showed the bacteria were internalized into the epithelial cells. Electron microscopy also confirmed that Shigella invaded primary chicken intestinal epithelia and was encapsulated by phagosome-like membranes. Our data demonstrate that Shigella can invade primary chicken intestinal epithelial cells in vitro and chicken intestinal mucosa in vivo, resulting in pathogenicity and even death. The findings suggest Shigella isolated from human or chicken share similar pathogenicity as well as the possibility of human-poultry cross-infection, which is of public health significance. PMID:24949637

Origin, Migration Routes and Worldwide Population Genetic Structure of the Wheat Yellow Rust Pathogen Puccinia striiformis f.sp. tritici

PubMed Central

Ali, Sajid; Gladieux, Pierre; Leconte, Marc; Gautier, Angélique; Justesen, Annemarie F.; Hovmøller, Mogens S.; Enjalbert, Jérôme; de Vallavieille-Pope, Claude

2014-01-01

Analyses of large-scale population structure of pathogens enable the identification of migration patterns, diversity reservoirs or longevity of populations, the understanding of current evolutionary trajectories and the anticipation of future ones. This is particularly important for long-distance migrating fungal pathogens such as Puccinia striiformis f.sp. tritici (PST), capable of rapid spread to new regions and crop varieties. Although a range of recent PST invasions at continental scales are well documented, the worldwide population structure and the center of origin of the pathogen were still unknown. In this study, we used multilocus microsatellite genotyping to infer worldwide population structure of PST and the origin of new invasions based on 409 isolates representative of distribution of the fungus on six continents. Bayesian and multivariate clustering methods partitioned the set of multilocus genotypes into six distinct genetic groups associated with their geographical origin. Analyses of linkage disequilibrium and genotypic diversity indicated a strong regional heterogeneity in levels of recombination, with clear signatures of recombination in the Himalayan (Nepal and Pakistan) and near-Himalayan regions (China) and a predominant clonal population structure in other regions. The higher genotypic diversity, recombinant population structure and high sexual reproduction ability in the Himalayan and neighboring regions suggests this area as the putative center of origin of PST. We used clustering methods and approximate Bayesian computation (ABC) to compare different competing scenarios describing ancestral relationship among ancestral populations and more recently founded populations. Our analyses confirmed the Middle East-East Africa as the most likely source of newly spreading, high-temperature-adapted strains; Europe as the source of South American, North American and Australian populations; and Mediterranean-Central Asian populations as the origin of South African populations. Although most geographic populations are not markedly affected by recent dispersal events, this study emphasizes the influence of human activities on recent long-distance spread of the pathogen. PMID:24465211

Immuno capture PCR for rapid and sensitive identification of pathogenic Bacillus anthracis.

PubMed

Makam, Shivakiran S; Majumder, Saugata; Kingston, Joseph J; Urs, Radhika M; Tuteja, Urmil; Sripathi, Murali H; Batra, Harsh V

2013-12-01

Immuno capture PCR (IPCR) is a technique capable of detecting the pathogens with high specificity and sensitivity. Rapid and accurate detection of Bacillus anthracis was achieved using anti-EA1 antibodies to capture the cells and two primer sets targeting the virulence factors of the pathogen i.e., protective antigen (pag) and capsule (cap) in an IPCR format. Monoclonal antibodies specific to B. anthracis were generated against extractable antigen 1 protein and used as capture antibody onto 96 well polystyrene plates. Following the binding of the pathogen, the DNA extraction was carried out in the well itself and further processed for PCR assay. We compared IPCR described here with conventional duplex PCR using the same primers and sandwich ELISA using the monoclonal antibodies developed in the present study. IPCR was capable of detecting as few as 10 and 100 cfu ml⁻¹ of bacterial cells and spores, respectively. IPCR was found to be 2-3 logs more sensitive than conventional duplex PCR and the sandwich ELISA. The effect of other bacteria and any organic materials on IPCR was also analyzed and found that this method was robust with little change in the sensitivity in the presence of interfering agents. Moreover, we could demonstrate a simple process of microwave treatment for spore disruption which otherwise are resistant to chemical treatments. Also, the IPCR could clearly distinguish the pathogenic and nonpathogenic strains of B. anthracis in the same assay. This can help in saving resources on unnecessary decontamination procedures during false alarms.

Behavior of Yersinian enteriocolitica in foods

USDA-ARS?s Scientific Manuscript database

Yersinia enterocolitica, a zoonotic pathogen that causes yersiniosis in humans and animals, is discussed. The prevalence in foods and infection of this pathogen to humans and animals was investigated, and most of the biochemical tests used to biogroup Y. enterocolitica stated. In this study, the pos...

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome

PubMed Central

Ferlaino, Michael; Rogers, Mark F.; Shihab, Hashem A.; Mort, Matthew; Cooper, David N.; Gaunt, Tom R.; Campbell, Colin

2018-01-01

Background Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. Results We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. Conclusions FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome. PMID:28985712

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome.

PubMed

Ferlaino, Michael; Rogers, Mark F; Shihab, Hashem A; Mort, Matthew; Cooper, David N; Gaunt, Tom R; Campbell, Colin

2017-10-06

Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome.

Human milk inactivates pathogens individually, additively, and synergistically.

PubMed

Isaacs, Charles E

2005-05-01

Breast-feeding can reduce the incidence and the severity of gastrointestinal and respiratory infections in the suckling neonate by providing additional protective factors to the infant's mucosal surfaces. Human milk provides protection against a broad array of infectious agents through redundancy. Protective factors in milk can target multiple early steps in pathogen replication and target each step with more than one antimicrobial compound. The antimicrobial activity in human milk results from protective factors working not only individually but also additively and synergistically. Lipid-dependent antimicrobial activity in milk results from the additive activity of all antimicrobial lipids and not necessarily the concentration of one particular lipid. Antimicrobial milk lipids and peptides can work synergistically to decrease both the concentrations of individual compounds required for protection and, as importantly, greatly reduce the time needed for pathogen inactivation. The more rapidly pathogens are inactivated the less likely they are to establish an infection. The total antimicrobial protection provided by human milk appears to be far more than can be elucidated by examining protective factors individually.

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

PubMed Central

de la Fuente, José; Antunes, Sandra; Bonnet, Sarah; Cabezas-Cruz, Alejandro; Domingos, Ana G.; Estrada-Peña, Agustín; Johnson, Nicholas; Kocan, Katherine M.; Mansfield, Karen L.; Nijhof, Ard M.; Papa, Anna; Rudenko, Nataliia; Villar, Margarita; Alberdi, Pilar; Torina, Alessandra; Ayllón, Nieves; Vancova, Marie; Golovchenko, Maryna; Grubhoffer, Libor; Caracappa, Santo; Fooks, Anthony R.; Gortazar, Christian; Rego, Ryan O. M.

2017-01-01

Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases. PMID:28439499

Mycobacterium tuberculosis: Success through dormancy

PubMed Central

Gengenbacher, Martin; Kaufmann, Stefan H. E.

2012-01-01

Tuberculosis (TB) remains a major health threat, killing near to 2 million individuals around this globe, annually. The sole vaccine developed almost a century ago, provides limited protection only during childhood. After decades without the introduction of new antibiotics, several candidates are currently undergoing clinical investigation. Curing TB requires prolonged combination chemotherapy with several drugs. Moreover, monitoring the success of therapy is questionable due to the lack of reliable biomarkers. To substantially improve the situation, a detailed understanding of the crosstalk between human host and the pathogen Mycobacterium tuberculosis (Mtb) is vital. Principally, Mtb’s enormous success is based on three capacities: First, reprogramming of macrophages after primary infection/phagocytosis in order to prevent its own destruction; second, initiating the formation of well-organized granulomas, comprising different immune cells to create a confined environment for the host–pathogen standoff; third, the capability to shut down its own central metabolism, terminate replication and thereby transit into a stage of dormancy rendering itself extremely resistant to host defense and drug treatment. Here we review the molecular mechanisms underlying these processes, draw conclusions in a working model of mycobacterial dormancy and highlight gaps in our understanding to be addressed in future research. PMID:22320122

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

PubMed

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

2015-09-01

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

Research Contributing to Improvements in Controlling Florida’s Mosquitoes and Mosquito-Borne Diseases

PubMed Central

Tabachnick, Walter J.

2016-01-01

Research on mosquitoes and mosquito-borne diseases has contributed to improvements in providing effective, efficient, and environmentally proper mosquito control. Florida has benefitted from several research accomplishments that have increased the state’s mosquito control capabilities. Research with Florida’s mosquitoes has resulted in the development of ecologically sound management of mosquito impoundments on Florida’s east coast. This strategy, called Rotational Impoundment Management (RIM), has improved the ability to target the delivery of pesticides and has helped to reduce non-target effects and environmental damage. Research has led to the development of an arbovirus surveillance system which includes sentinel chicken surveillance, real time use of environmental contributing factors like meteorology and hydrology to target mosquito control, as well as public health efforts to mitigate disease outbreaks to areas with risk of disease. These research driven improvements have provided substantial benefits to all of Florida. More research is needed to meet the future challenges to reduce emerging pathogens like Zika virus and the consequences of environmental changes like global climate change that are likely to influence the effects of mosquito-borne pathogens on human health and well-being. PMID:27690112

An investigation of virulence factors of Legionella pneumophila environmental isolates.

PubMed

Arslan-Aydoğdu, Elif Özlem; Kimiran, Ayten

Nine Legionella pneumophila strains isolated from cooling towers and a standard strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1) were analyzed and compared in terms of motility, flagella structure, ability to form biofilms, enzymatic activities (hemolysin, nucleases, protease, phospholipase A, phospholipase C, acid phosphatase, alkaline phosphatase and lipase), hemagglutination capabilities, and pathogenicity in various host cells (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human peripheral monocytes). All the isolates of bacteria appeared to be motile and polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of virulence factors, isolate 4 was found to be the most pathogenic strain, while 6 out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7) were more virulent than the ATCC 33152 strain. The different bacterial strains exhibited differences in properties such as adhesion, penetration and reproduction in the hosts, and preferred host type. To our knowledge, this is the first study to compare the virulence of environmental L. pneumophila strains isolated in Turkey, and it provides important information relevant for understanding the epidemiology of L. pneumophila. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Comparative innate immune interactions of human and bovine secretory IgA with pathogenic and non-pathogenic bacteria.

PubMed

Hodgkinson, Alison J; Cakebread, Julie; Callaghan, Megan; Harris, Paul; Brunt, Rachel; Anderson, Rachel C; Armstrong, Kelly M; Haigh, Brendan

2017-03-01

Secretory IgA (SIgA) from milk contributes to early colonization and maintenance of commensal/symbiotic bacteria in the gut, as well as providing defence against pathogens. SIgA binds bacteria using specific antigenic sites or non-specifically via its glycans attached to α-heavy-chain and secretory component. In our study, we tested the hypothesis that human and bovine SIgA have similar innate-binding activity for bacteria. SIgAs, isolated from human and bovine milk, were incubated with a selection of commensal, pathogenic and probiotic bacteria. Using flow cytometry, we measured numbers of bacteria binding SIgA and their level of SIgA binding. The percentage of bacteria bound by human and bovine SIgA varied from 30 to 90% depending on bacterial species and strains, but was remarkably consistent between human and bovine SIgA. The level of SIgA binding per bacterial cell was lower for those bacteria that had a higher percentage of SIgA-bound bacteria, and higher for those bacteria that had lower percentage of SIgA-bound bacteria. Overall, human and bovine SIgA interacted with bacteria in a comparable way. This contributes to longer term research about the potential benefits of bovine SIgA for human consumers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Allovahlkampfia spelaea Causing Keratitis in Humans

PubMed Central

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

2016-01-01

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

Antibacterial efficacy of the seed extracts of Melia azedarach against some hospital isolated human pathogenic bacterial strains

PubMed Central

Khan, Abdul Viqar; Ahmed, Qamar Uddin; Mir, M Ramzan; Shukla, Indu; Khan, Athar Ali

2011-01-01

Objective To investigate the antibacterial potential of the polar and non-polar extracts of the seeds of Melia azedarach (M. azedarach) L. (Meliaceae) against eighteen hospital isolated human pathogenic bacterial strains. Methods Petrol, benzene, ethyl acetate, methanol, and aqueous extracts at five different concentrations (1, 2, 5, 10 and 15 mg/mL) were evaluated. Disk diffusion method was followed to evaluate the antibacterial efficacy. Results All extracts of the seeds demonstrated significant antibacterial activity against tested pathogens. Among all extracts, ethyl acetate extract revealed the highest inhibition comparatively. The present study also favored the traditional uses reported earlier. Conclusions Results of this study strongly confirm that the seed extracts of M. azedarach could be effective antibiotics, both in controlling gram-positive and gram-negative human pathogenic infections. PMID:23569812

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

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.

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.

Functionalized Nanopipettes: A Sensitive Tool for Pathogen Detection

NASA Astrophysics Data System (ADS)

Actis, P.; Jejelowo, O.; Pourmand, N.

2010-04-01

Nanopipette technology is capable of detecting and functional analyzing biomolecules. Preliminary experiments are demonstrating the sensitivity and selectivity of the technique with specific proteins targeting environmental toxins.

Cryptococcus: from environmental saprophyte to global pathogen

PubMed Central

May, Robin C.; Stone, Neil R.H.; Wiesner, Darin L.; Bicanic, Tihana; Nielsen, Kirsten

2016-01-01

Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development. PMID:26685750

Cryptococcus: from environmental saprophyte to global pathogen.

PubMed

May, Robin C; Stone, Neil R H; Wiesner, Darin L; Bicanic, Tihana; Nielsen, Kirsten

2016-02-01

Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development.

Global and local environmental changes as drivers of Buruli ulcer emergence.

PubMed

Combe, Marine; Velvin, Camilla Jensen; Morris, Aaron; Garchitorena, Andres; Carolan, Kevin; Sanhueza, Daniel; Roche, Benjamin; Couppié, Pierre; Guégan, Jean-François; Gozlan, Rodolphe Elie

2017-04-26

Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus confounding the understanding of pathogen transmission pathways from wildlife reservoirs to humans. The emergence of these pathogens in human populations has frequently been associated with global changes, such as socio-economic, climate or biodiversity modifications, by allowing generalist pathogens to invade and persist in new ecological niches, infect new host species, and thus change the nature of transmission pathways. Using the case of Buruli ulcer disease, we review how land-use changes, climatic patterns and biodiversity alterations contribute to disease emergence in many parts of the world. Here we clearly show that Mycobacterium ulcerans is an environmental pathogen characterized by multi-host transmission dynamics and that its infectious pathways to humans rely on the local effects of global environmental changes. We show that the interplay between habitat changes (for example, deforestation and agricultural land-use changes) and climatic patterns (for example, rainfall events), applied in a local context, can lead to abiotic environmental changes and functional changes in local biodiversity that favor the pathogen's prevalence in the environment and may explain disease emergence.

Translocation of cell-penetrating peptides into Candida fungal pathogens.

PubMed

Gong, Zifan; Karlsson, Amy J

2017-09-01

Cell-penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF) 3 K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration-dependent manner, and an additional peptide (TP-10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF) 3 K, and TP-10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens. © 2017 The Protein Society.

Vaccine Adjuvants: from 1920 to 2015 and Beyond

PubMed Central

Di Pasquale, Alberta; Preiss, Scott; Tavares Da Silva, Fernanda; Garçon, Nathalie

2015-01-01

The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190

The spatial profiles and metabolic capabilities of microbial populations impact the growth of antibiotic-resistant mutants

PubMed Central

Kaushik, Karishma S.; Ratnayeke, Nalin; Katira, Parag; Gordon, Vernita D.

2015-01-01

Antibiotic resistance adversely affects clinical and public health on a global scale. Using the opportunistic human pathogen Pseudomonas aeruginosa, we show that increasing the number density of bacteria, on agar containing aminoglycoside antibiotics, can non-monotonically impact the survival of antibiotic-resistant mutants. Notably, at high cell densities, mutant survival is inhibited. A wide range of bacterial species can inhibit antibiotic-resistant mutants. Inhibition results from the metabolic breakdown of amino acids, which results in alkaline by-products. The consequent increase in pH acts in conjunction with aminoglycosides to mediate inhibition. Our work raises the possibility that the manipulation of microbial population structure and nutrient environment in conjunction with existing antibiotics could provide therapeutic approaches to combat antibiotic resistance. PMID:25972434

Methods for molecular surveillance of influenza.

PubMed

Wang, Ruixue; Taubenberger, Jeffery K

2010-05-01

Molecular-based techniques for detecting influenza viruses have become an integral component of human and animal surveillance programs in the last two decades. The recent pandemic of the swine-origin influenza A virus (H1N1) and the continuing circulation of highly pathogenic avian influenza A virus (H5N1) further stress the need for rapid and accurate identification and subtyping of influenza viruses for surveillance, outbreak management, diagnosis and treatment. There has been remarkable progress on the detection and molecular characterization of influenza virus infections in clinical, mammalian, domestic poultry and wild bird samples in recent years. The application of these techniques, including reverse transcriptase-PCR, real-time PCR, microarrays and other nucleic acid sequencing-based amplifications, have greatly enhanced the capability for surveillance and characterization of influenza viruses.

Pathogenesis of group A streptococcal infections.

PubMed

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

2012-05-01

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

Airborne transmission of highly pathogenic influenza virus during processing of infected poultry

USDA-ARS?s Scientific Manuscript database

Human infections with H5N1 highly pathogenic avian influenza (HPAI) virus occur following exposure to virus-infected poultry, often during the slaughter processes. Infectious virus within bioaerosols was detected during laboratory-simulated processing of asymptomatic chickens infected with human- (c...

Draft Genome Sequence of the Serratia rubidaea CIP 103234T Reference Strain, a Human-Opportunistic Pathogen.

PubMed

Bonnin, Rémy A; Girlich, Delphine; Imanci, Dilek; Dortet, Laurent; Naas, Thierry

2015-11-19

We provide here the first genome sequence of a Serratia rubidaea isolate, a human-opportunistic pathogen. This reference sequence will permit a comparison of this species with others of the Serratia genus. Copyright © 2015 Bonnin et al.

Vector-borne Infections

PubMed Central

Ben Beard, C.

2011-01-01

Infections with vector-borne pathogens are a major source of emerging diseases. The ability of vectors to bridge spatial and ecologic gaps between animals and humans increases opportunities for emergence. Small adaptations of a pathogen to a vector can have profound effects on the rate of transmission to humans. PMID:21529382

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...

Biofilm formation by Salmonella Enteritidis and Salmonella Typhimurium isolated from avian sources is partially related with their in vivo pathogenicity.

PubMed

Borges, Karen Apellanis; Furian, Thales Quedi; de Souza, Sara Neves; Menezes, Rafaela; de Lima, Diane Alves; Fortes, Flávia Bornancini Borges; Salle, Carlos Tadeu Pippi; Moraes, Hamilton Luiz Souza; Nascimento, Vladimir Pinheiro

2018-03-22

Salmonella Enteritidis and Salmonella Typhimurium are among the most prevalent serotypes isolated from salmonellosis outbreaks and poultry. Salmonella spp. have the capacity to form biofilms on several surfaces, which can favour survival in hostile environments, such as slaughterhouses. Salmonella strains present differences in pathogenicity. However, there is little information regarding the pathogenicity of S. Enteritidis and S. Typhimurium isolated from avian sources and their relationship to biofilm production. The aim of this study was to use a novel pathogenicity index and a biofilm production assay to evaluate their relationships within these serotypes. In addition, we detected the presence of the spiA and agfA genes in these strains. Biofilm formation was investigated at two temperatures (37 °C and 28 °C) using microtiter plate assay, and the results were compared with the individual pathogenicity index of each strain. PCR was used to detect spiA and agfA, virulence genes associated with biofilm production. S. Enteritidis and S. Typhimurium strains were capable of producing biofilm at 37 °C and 28 °C. Sixty-two percent and 59.5% of S. Enteritidis and 73.8% and 46.2% of S. Typhimurium produced biofilm at 37 °C and 28 °C, respectively. Biofilm production at 37 °C was significantly higher in both serotypes. Only S. Enteritidis was capable of adhering strongly at both temperatures. Biofilm production was related to pathogenicity index only at 28 °C for S. Enteritidis. spiA and agfA were found in almost all strains and were not statistically associated with biofilm production. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Streptococcus iniae, a Human and Animal Pathogen: Specific Identification by the Chaperonin 60 Gene Identification Method

PubMed Central

Goh, Swee Han; Driedger, David; Gillett, Sandra; Low, Donald E.; Hemmingsen, Sean M.; Amos, Mayben; Chan, David; Lovgren, Marguerite; Willey, Barbara M.; Shaw, Carol; Smith, John A.

1998-01-01

It was recently reported that Streptococcus iniae, a bacterial pathogen of aquatic animals, can cause serious disease in humans. Using the chaperonin 60 (Cpn60) gene identification method with reverse checkerboard hybridization and chemiluminescent detection, we identified correctly each of 12 S. iniae samples among 34 aerobic gram-positive isolates from animal and clinical human sources. PMID:9650992

[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.

Integrated pest management and allocation of control efforts for vector-borne diseases

USGS Publications Warehouse

Ginsberg, H.S.

2001-01-01

Applications of various control methods were evaluated to determine how to integrate methods so as to minimize the number of human cases of vector-borne diseases. These diseases can be controlled by lowering the number of vector-human contacts (e.g., by pesticide applications or use of repellents), or by lowering the proportion of vectors infected with pathogens (e.g., by lowering or vaccinating reservoir host populations). Control methods should be combined in such a way as to most efficiently lower the probability of human encounter with an infected vector. Simulations using a simple probabilistic model of pathogen transmission suggest that the most efficient way to integrate different control methods is to combine methods that have the same effect (e.g., combine treatments that lower the vector population; or combine treatments that lower pathogen prevalence in vectors). Combining techniques that have different effects (e.g., a technique that lowers vector populations with a technique that lowers pathogen prevalence in vectors) will be less efficient than combining two techniques that both lower vector populations or combining two techniques that both lower pathogen prevalence, costs being the same. Costs of alternative control methods generally differ, so the efficiency of various combinations at lowering human contact with infected vectors should be estimated at available funding levels. Data should be collected from initial trials to improve the effects of subsequent interventions on the number of human cases.

Origin, Spread and Demography of the Mycobacterium tuberculosis Complex

PubMed Central

Wirth, Thierry; Hildebrand, Falk; Allix-Béguec, Caroline; Wölbeling, Florian; Kubica, Tanja; Kremer, Kristin; van Soolingen, Dick; Rüsch-Gerdes, Sabine; Locht, Camille; Brisse, Sylvain; Meyer, Axel

2008-01-01

The evolutionary timing and spread of the Mycobacterium tuberculosis complex (MTBC), one of the most successful groups of bacterial pathogens, remains largely unknown. Here, using mycobacterial tandem repeat sequences as genetic markers, we show that the MTBC consists of two independent clades, one composed exclusively of M. tuberculosis lineages from humans and the other composed of both animal and human isolates. The latter also likely derived from a human pathogenic lineage, supporting the hypothesis of an original human host. Using Bayesian statistics and experimental data on the variability of the mycobacterial markers in infected patients, we estimated the age of the MTBC at 40,000 years, coinciding with the expansion of “modern” human populations out of Africa. Furthermore, coalescence analysis revealed a strong and recent demographic expansion in almost all M. tuberculosis lineages, which coincides with the human population explosion over the last two centuries. These findings thus unveil the dynamic dimension of the association between human host and pathogen populations. PMID:18802459

Identification of DNA Methyltransferase Genes in Human Pathogenic Bacteria by Comparative Genomics.

PubMed

Brambila-Tapia, Aniel Jessica Leticia; Poot-Hernández, Augusto Cesar; Perez-Rueda, Ernesto; Rodríguez-Vázquez, Katya

2016-06-01

DNA methylation plays an important role in gene expression and virulence in some pathogenic bacteria. In this report, we describe DNA methyltransferases (MTases) present in human pathogenic bacteria and compared them with related species, which are not pathogenic or less pathogenic, based in comparative genomics. We performed a search in the KEGG database of the KEGG database orthology groups associated with adenine and cytosine DNA MTase activities (EC: 2.1.1.37, EC: 2.1.1.113 and EC: 2.1.1.72) in 37 human pathogenic species and 18 non/less pathogenic relatives and performed comparisons of the number of these MTases sequences according to their genome size, the DNA MTase type and with their non-less pathogenic relatives. We observed that Helicobacter pylori and Neisseria spp. presented the highest number of MTases while ten different species did not present a predicted DNA MTase. We also detected a significant increase of adenine MTases over cytosine MTases (2.19 vs. 1.06, respectively, p < 0.001). Adenine MTases were the only MTases associated with restriction modification systems and DNA MTases associated with type I restriction modification systems were more numerous than those associated with type III restriction modification systems (0.84 vs. 0.17, p < 0.001); additionally, there was no correlation with the genome size and the total number of DNA MTases, indicating that the number of DNA MTases is related to the particular evolution and lifestyle of specific species, regulating the expression of virulence genes in some pathogenic bacteria.

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

Production of cross-kingdom oxylipins by pathogenic fungi: An update on their role in development and pathogenicity.

PubMed

Fischer, Gregory J; Keller, Nancy P

2016-03-01

Oxylipins are a class of molecules derived from the incorporation of oxygen into polyunsaturated fatty acid substrates through the action of oxygenases. While extensively investigated in the context of mammalian immune responses, over the last decade it has become apparent that oxylipins are a common means of communication among and between plants, animals, and fungi to control development and alter host-microbe interactions. In fungi, some oxylipins are derived nonenzymatically while others are produced by lipoxygenases, cyclooxygenases, and monooxygenases with homology to plant and human enzymes. Recent investigations of numerous plant and human fungal pathogens have revealed oxylipins to be involved in the establishment and progression of disease. This review highlights oxylipin production by pathogenic fungi and their role in fungal development and pathogen/host interactions.

Hybrid selection for sequencing pathogen genomes from clinical samples

PubMed Central

2011-01-01

We have adapted a solution hybrid selection protocol to enrich pathogen DNA in clinical samples dominated by human genetic material. Using mock mixtures of human and Plasmodium falciparum malaria parasite DNA as well as clinical samples from infected patients, we demonstrate an average of approximately 40-fold enrichment of parasite DNA after hybrid selection. This approach will enable efficient genome sequencing of pathogens from clinical samples, as well as sequencing of endosymbiotic organisms such as Wolbachia that live inside diverse metazoan phyla. PMID:21835008

Advanced DNA-Based Point-of-Care Diagnostic Methods for Plant Diseases Detection.

PubMed

Lau, Han Yih; Botella, Jose R

2017-01-01

Diagnostic technologies for the detection of plant pathogens with point-of-care capability and high multiplexing ability are an essential tool in the fight to reduce the large agricultural production losses caused by plant diseases. The main desirable characteristics for such diagnostic assays are high specificity, sensitivity, reproducibility, quickness, cost efficiency and high-throughput multiplex detection capability. This article describes and discusses various DNA-based point-of care diagnostic methods for applications in plant disease detection. Polymerase chain reaction (PCR) is the most common DNA amplification technology used for detecting various plant and animal pathogens. However, subsequent to PCR based assays, several types of nucleic acid amplification technologies have been developed to achieve higher sensitivity, rapid detection as well as suitable for field applications such as loop-mediated isothermal amplification, helicase-dependent amplification, rolling circle amplification, recombinase polymerase amplification, and molecular inversion probe. The principle behind these technologies has been thoroughly discussed in several review papers; herein we emphasize the application of these technologies to detect plant pathogens by outlining the advantages and disadvantages of each technology in detail.

Advanced DNA-Based Point-of-Care Diagnostic Methods for Plant Diseases Detection

PubMed Central

Lau, Han Yih; Botella, Jose R.

2017-01-01

Diagnostic technologies for the detection of plant pathogens with point-of-care capability and high multiplexing ability are an essential tool in the fight to reduce the large agricultural production losses caused by plant diseases. The main desirable characteristics for such diagnostic assays are high specificity, sensitivity, reproducibility, quickness, cost efficiency and high-throughput multiplex detection capability. This article describes and discusses various DNA-based point-of care diagnostic methods for applications in plant disease detection. Polymerase chain reaction (PCR) is the most common DNA amplification technology used for detecting various plant and animal pathogens. However, subsequent to PCR based assays, several types of nucleic acid amplification technologies have been developed to achieve higher sensitivity, rapid detection as well as suitable for field applications such as loop-mediated isothermal amplification, helicase-dependent amplification, rolling circle amplification, recombinase polymerase amplification, and molecular inversion probe. The principle behind these technologies has been thoroughly discussed in several review papers; herein we emphasize the application of these technologies to detect plant pathogens by outlining the advantages and disadvantages of each technology in detail. PMID:29375588

Control of extraintestinal foodborne pathogens using intervention technologies

USDA-ARS?s Scientific Manuscript database

In recent years it has become apparent that emerging foodborne pathogens including Extraintestinal Pathogenic Escherichia coli (ExPEC), Staphylococcus saprophyticus, and Klebsiella pneumoniae are associated with human health conditions such as inflammatory bowel disease (IBD), ulcerative colitis (UC...

Rational Design of Pathogen-Mimicking Amphiphilic Materials as Nanoadjuvants

NASA Astrophysics Data System (ADS)

Ulery, Bret D.; Petersen, Latrisha K.; Phanse, Yashdeep; Kong, Chang Sun; Broderick, Scott R.; Kumar, Devender; Ramer-Tait, Amanda E.; Carrillo-Conde, Brenda; Rajan, Krishna; Wannemuehler, Michael J.; Bellaire, Bryan H.; Metzger, Dennis W.; Narasimhan, Balaji

2011-12-01

An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The value of using polyanhydride nanovaccines was demonstrated by the induction of long-lived protection against a lethal challenge of Yersinia pestis following a single administration ten months earlier. This approach has the tantalizing potential to catalyze the development of next generation vaccines against diseases caused by emerging and re-emerging pathogens.

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...

Thermal and non-thermal surface treatments of fresh cantaloupes and other melons for inactivating human pathogens

USDA-ARS?s Scientific Manuscript database

Outbreaks of salmonellosis by Salmonella Poona and listeriosis by Listeria monocytogenes have been associated with the consumption of cantaloupes. Commercial washing processes for cantaloupes are limited in their ability to inactivate and/or remove this human pathogen. Our objective was to develop...

Laser system for identification, tracking, and control of flying insects

USDA-ARS?s Scientific Manuscript database

Flying insects are common vectors for transmission of pathogens and inflict significant harm on humans in large parts of the developing world. Besides the direct impact to humans, these pathogens also cause harm to crops and result in agricultural losses. Here, we present a laser-based system that c...

Inactivating Methicillin Resistant Staphylococcus aureus (MRSA) and Other Pathogens by Bacteriocins OR-7 and E 50-52.

USDA-ARS?s Scientific Manuscript database

Worldwide, reports document the increasing frequency of methicillin resistant Staphylococcus aureus (MRSA) infections. Other human pathogens are recognized as unresponsive to antibiotics of last resort. These previously treatable infections now account for increased numbers of human disease and de...

Enterovirus strain and type-specific differences in growth kinetics and virus-induced cell destruction in human pancreatic duct epithelial HPDE cells.

PubMed

Smura, Teemu; Natri, Olli; Ylipaasto, Petri; Hellman, Marika; Al-Hello, Haider; Piemonti, Lorenzo; Roivainen, Merja

2015-12-02

Enterovirus infections have been suspected to be involved in the development of type 1 diabetes. However, the pathogenetic mechanism of enterovirus-induced type 1 diabetes is not known. Pancreatic ductal cells are closely associated with pancreatic islets. Therefore, enterovirus infections in ductal cells may also affect beta-cells and be involved in the induction of type 1 diabetes. The aim of this study was to assess the ability of different enterovirus strains to infect, replicate and produce cytopathic effect in human pancreatic ductal cells. Furthermore, the viral factors that affect these capabilities were studied. The pancreatic ductal cells were highly susceptible to enterovirus infections. Both viral growth and cytolysis were detected for several enterovirus serotypes. However, the viral growth and capability to induce cytopathic effect (cpe) did not correlate completely. Some of the virus strains replicated in ductal cells without apparent cpe. Furthermore, there were strain-specific differences in the growth kinetics and the ability to cause cpe within some serotypes. Viral adaptation experiments were carried out to study the potential genetic determinants behind these phenotypic differences. The blind-passage of non-lytic CV-B6-Schmitt strain in HPDE-cells resulted in lytic phenotype and increased progeny production. This was associated with the substitution of a single amino acid (K257E) in the virus capsid protein VP1 and the viral ability to use decay accelerating factor (DAF) as a receptor. This study demonstrates considerable plasticity in the cell tropism, receptor usage and cytolytic properties of enteroviruses and underlines the strong effect of single or few amino acid substitutions in cell tropism and lytic capabilities of a given enterovirus. Since ductal cells are anatomically close to pancreatic islets, the capability of enteroviruses to infect and destroy pancreatic ductal cells may also implicate in respect to enterovirus induced type 1 diabetes. In addition, the capability for rapid adaptation to different cell types suggests that, on occasion, enterovirus strains with different pathogenetic properties may arise from less pathogenic ancestors. Copyright © 2015 Elsevier B.V. All rights reserved.

Conservation of Erwinia amylovora pathogenicity-relevant genes among Erwinia genomes.

PubMed

Borruso, Luigimaria; Salomone-Stagni, Marco; Polsinelli, Ivan; Schmitt, Armin Otto; Benini, Stefano

2017-12-01

The Erwinia genus comprises species that are plant pathogens, non-pathogen, epiphytes, and opportunistic human pathogens. Within the genus, Erwinia amylovora ranks among the top 10 plant pathogenic bacteria. It causes the fire blight disease and is a global threat to commercial apple and pear production. We analyzed the presence/absence of the E. amylovora genes reported to be important for pathogenicity towards Rosaceae within various Erwinia strains genomes. This simple bottom-up approach, allowed us to correlate the analyzed genes to pathogenicity, host specificity, and make useful considerations to drive targeted studies.

Microbial Vertical Transmission during Human Pregnancy.

PubMed

Arora, Nitin; Sadovsky, Yoel; Dermody, Terence S; Coyne, Carolyn B

2017-05-10

Congenital infections with pathogens such as Zika virus, Toxoplasma gondii, Listeria monocytogenes, Treponema pallidium, parvovirus, HIV, varicella zoster virus, Rubella, Cytomegalovirus, and Herpesviruses are a major cause of morbidity and mortality worldwide. Despite the devastating impact of microbial infections on the developing fetus, relatively little is known about how pathogens associated with congenital disease breach the placental barrier to transit vertically during human pregnancy. In this Review, we focus on transplacental transmission of pathogens during human gestation. We introduce the structure of the human placenta and describe the innate mechanisms by which the placenta restricts microbial access to the intrauterine compartment. Based on current knowledge, we also discuss the potential pathways employed by microorganisms to overcome the placental barrier and prospects for the future. Copyright © 2017 Elsevier Inc. All rights reserved.