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disease control through fertility control: secondary benefits of animal birth control in indian street dogs.we sought to (1) survey sexually intact street dogs for a wide range of diseases in three cities in rajasthan, india and (2) evaluate links between the health of non-treated dogs and both the presence and duration of animal birth control (abc) programs. abc regimes sterilize and vaccinate stray dogs in an attempt to control their population and the spread of rabies. they are commonly suggested to improve the health of those dogs they serve, but here we provide evidence that these benefits also e ...201424239212
detection of brucellosis and leptospirosis in feral pigs in new south wales.to determine the presence and estimate the prevalence of brucella suis, leptospira interrogans serovar pomona (hereafter l. pomona) and leptospira borgpetersenii serovar hardjo (hereafter l. hardjo) in feral pigs culled in new south wales (nsw), australia.201424954403
abortion in cattle due to infection with staphylococcus lugdunensis.an aborted fetus of 7 months gestation, the associated placenta, and a single blood sample from the dam were submitted for diagnostic investigation to the diagnostic laboratory of the lombardy and emilia-romagna experimental zooprophylactic institute in parma, italy. the serum was negative for neospora caninum, coxiella burnetii, chlamydophila abortus, bovine herpesvirus 1 (bhv-1), bovine viral diarrhea virus (bvdv), brucella abortus, and brucella melitensis. fetal tissues and placental cotyledo ...201425292193
the sars coronavirus 3a protein binds calcium in its cytoplasmic domain.the severe acute respiratory syndrome coronavirus (sars-cov) is a positive stranded rna virus with ∼30kb genome. among all open reading frames (orfs) of this virus, the orf3a is the largest, and encodes a protein of 274 amino acids, named as 3a protein. sequence analysis suggests that the orf3a aligned to one calcium pump present in plasmodium falciparum and the enzyme glutamine synthetase found in leptospira interrogans. this sequence similarity was found to be limited only to amino acid residu ...201425116391
biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) from glucose with elevated 3-hydroxyvalerate fraction via combined citramalate and threonine pathway in escherichia coli.the biosynthesis of polyhydroxyalkanoate copolymers in escherichia coli from unrelated carbon sources becomes attractive nowadays. we previously developed a poly(hydroxybutyrate-co-hydroxyvalerte) (phbv) biosynthetic pathway from an unrelated carbon source via threonine metabolic route in e. coli (chen et al., appl environ microbiol 77:4886-4893, 2011). in our study, a citramalate pathway was introduced in recombinant e. coli by cloning a cima gene from leptospira interrogans. by blocking the py ...201424425304
functional and immunological evaluation of two novel proteins of leptospira spp.this work shows the production and characterization of two novel putative lipoproteins encoded by the genes lic10645 and lic10731 identified in the genome sequences of leptospira interrogans. in silico conservation analysis indicated that the proteins are well conserved among pathogenic leptospiral serovars and species. recombinant proteins were obtained in escherichia coli bl21(de3) star plyss strain, purified by metal-affinity chromatography, and used for characterization and immunological eva ...201424162609
interlaboratory and between-specimen comparisons of diagnostic tests for leptospirosis in sheep and cattle.a study was performed to investigate interlaboratory test agreement between a research and a commercial veterinary diagnostic laboratory on blood and urine samples, and to investigate test agreement between blood, urine, and kidney samples (research laboratory) for leptospirosis diagnosis. samples were sourced from 399 sheep and 146 beef cattle from a local abattoir. interlaboratory agreement for real-time quantitative polymerase chain reaction (qpcr) results on urine samples was almost perfect ...201425292194
kinetic and structural characterization of a typical two-cysteine peroxiredoxin from leptospira interrogans exhibiting redox sensitivity.little is known about the mechanisms by which leptospira interrogans, the causative agent of leptospirosis, copes with oxidative stress at the time it establishes persistent infection within its human host. we report the molecular cloning of a gene encoding a 2-cys peroxiredoxin (linahpc) from this bacterium. after bioinformatic analysis we found that linahpc contains the characteristic ggig and yf motifs present in peroxiredoxins that are sensitive to overoxidation (mainly eukaryotic proteins). ...201425236736
serosurvey for selected pathogens in free-ranging american black bears (ursus americanus) in maryland, usa.american black bears (ursus americanus) in maryland, usa, live in forested areas in close proximity to humans and their domestic pets. from 1999 to 2011, we collected 84 serum samples from 63 black bears (18 males; 45 females) in five maryland counties and tested them for exposure to infectious, including zoonotic, pathogens. a large portion of the bears had antibody to canine distemper virus and toxoplasma gondii, many at high titers. prevalences of antibodies to zoonotic agents such as rabies ...201425075540
pathogenic leptospira species acquire factor h and vitronectin via the surface protein lcpa.upon infection, pathogenic leptospira species bind several complement regulators in order to overcome host innate immunity. we previously characterized a 20-kda leptospiral surface protein which interacts with c4b binding protein (c4bp): leptospiral complement regulator-acquiring protein a (lcpa). here we show that lcpa also interacts with human factor h (fh), which remains functionally active once bound to the protein. antibodies directed against short consensus repeat 20 (scr20) inhibited bind ...201425534939
pathogenic leptospira species acquire factor h and vitronectin via the surface protein lcpa.upon infection, pathogenic leptospira species bind several complement regulators in order to overcome host innate immunity. we previously characterized a 20-kda leptospiral surface protein which interacts with c4b binding protein (c4bp): leptospiral complement regulator-acquiring protein a (lcpa). here we show that lcpa also interacts with human factor h (fh), which remains functionally active once bound to the protein. antibodies directed against short consensus repeat 20 (scr20) inhibited bind ...201425534939
thermal control of virulence factors in bacteria: a hot topic.pathogenic bacteria sense environmental cues, including the local temperature, to control the production of key virulence factors. thermal regulation can be achieved at the level of dna, rna or protein and although many virulence factors are subject to thermal regulation, the exact mechanisms of control are yet to be elucidated in many instances. understanding how virulence factors are regulated by temperature presents a significant challenge, as gene expression and protein production are often ...201425494856
chagas' disease: an emergent urban zoonosis. the caracas valley (venezuela) as an epidemiological model.the unprecedented emergence of important public health and veterinary zoonoses is usually a result of exponential population growth and globalization of human activities. i characterized chagas' disease as an emergent zoonosis in the caracas valley (venezuela) due to the following findings: the presence of reservoirs (didelphis marsupialis, rattus rattus) and vectors (panstrongylus geniculatus, panstrongylus rufotuberculatus) infected with trypanosoma cruzi in urbanized or marginalized areas; th ...201425520950
pathogenic landscape of transboundary zoonotic diseases in the mexico-us border along the rio grande.transboundary zoonotic diseases, several of which are vector borne, can maintain a dynamic focus and have pathogens circulating in geographic regions encircling multiple geopolitical boundaries. global change is intensifying transboundary problems, including the spatial variation of the risk and incidence of zoonotic diseases. the complexity of these challenges can be greater in areas where rivers delineate international boundaries and encompass transitions between ecozones. the rio grande serve ...201425453027
sensitive real-time pcr detection of pathogenic leptospira spp. and a comparison of nucleic acid amplification methods for the diagnosis of leptospirosis.bacteria of the genus leptospira, the causative agents of leptospirosis, are categorized into pathogenic and non-pathogenic species. however, the benefit of using a clinical diagnostic that is specific for pathogenic species remains unclear. in this study, we present the development of a real-time pcr (rtpcr) for the detection of pathogenic leptospira (the pathogenic rtpcr), and we perform a comparison of the pathogenic rtpcr with a published assay that detects all leptospira species [the undiff ...201425379890
pasteurella pneumotropica evades the human complement system by acquisition of the complement regulators factor h and c4bp.pasteurella pneumotropica is an opportunist gram negative bacterium responsible for rodent pasteurellosis that affects upper respiratory, reproductive and digestive tracts of mammals. in animal care facilities the presence of p. pneumotropica causes severe to lethal infection in immunodeficient mice, being also a potential source for human contamination. indeed, occupational exposure is one of the main causes of human infection by p. pneumotropica. the clinical presentation of the disease includ ...201425347183
a strange lupus-like malar rash with renal involvement: an angioimmunoblastic t-cell lymphoma - a case report.cutaneous malar rash and kidney involvement has not previously been reported as presenting symptoms of an angioimmunoblastic t-cell lymphoma (aitl). we report a case of a woman with erythematous rash. a pet-ct revealed a lymphadenopathy and splenomegaly. an inguinal lymph node biopsy showed an aitl. there was clinical improvement after prednisone.201425678974
a strange lupus-like malar rash with renal involvement: an angioimmunoblastic t-cell lymphoma - a case report.cutaneous malar rash and kidney involvement has not previously been reported as presenting symptoms of an angioimmunoblastic t-cell lymphoma (aitl). we report a case of a woman with erythematous rash. a pet-ct revealed a lymphadenopathy and splenomegaly. an inguinal lymph node biopsy showed an aitl. there was clinical improvement after prednisone.201425678974
identification of cell-binding adhesins of leptospira interrogans.leptospirosis is a globally distributed bacterial infectious disease caused by pathogenic members of the genus leptospira. infection can lead to illness ranging from mild and non-specific to severe, with jaundice, kidney and liver dysfunction, and widespread endothelial damage. the adhesion of pathogenic leptospira species (spp.), the causative agent of leptospirosis, to host tissue components is necessary for infection and pathogenesis. while it is well-established that extracellular matrix (ec ...201425275630
liver involvement in systemic infection.the liver is often involved in systemic infections, resulting in various types of abnormal liver function test results. in particular, hyperbilirubinemia in the range of 2-10 mg/dl is often seen in patients with sepsis, and several mechanisms for this phenomenon have been proposed. in this review, we summarize how the liver is involved in various systemic infections that are not considered to be primarily hepatotropic. in most patients with systemic infections, treatment for the invading microbe ...201425276279
evolution of the f0f1 atp synthase complex in light of the patchy distribution of different bioenergetic pathways across prokaryotes.bacteria and archaea are characterized by an amazing metabolic diversity, which allows them to persist in diverse and often extreme habitats. apart from oxygenic photosynthesis and oxidative phosphorylation, well-studied processes from chloroplasts and mitochondria of plants and animals, prokaryotes utilize various chemo- or lithotrophic modes, such as anoxygenic photosynthesis, iron oxidation and reduction, sulfate reduction, and methanogenesis. most bioenergetic pathways have a similar general ...201425188293
microbe-specific unconventional t cells induce human neutrophil differentiation into antigen cross-presenting cells.the early immune response to microbes is dominated by the recruitment of neutrophils whose primary function is to clear invading pathogens. however, there is emerging evidence that neutrophils play additional effector and regulatory roles. the present study demonstrates that human neutrophils assume ag cross-presenting functions and suggests a plausible scenario for the local generation of apc-like neutrophils through the mobilization of unconventional t cells in response to microbial metabolite ...201425165152
the cross-talk between spirochetal lipoproteins and immunity.spirochetal diseases such as syphilis, lyme disease, and leptospirosis are major threats to public health. however, the immunopathogenesis of these diseases has not been fully elucidated. spirochetes interact with the host through various structural components such as lipopolysaccharides (lps), surface lipoproteins, and glycolipids. although spirochetal antigens such as lps and glycolipids may contribute to the inflammatory response during spirochetal infections, spirochetes such as treponema pa ...201425071771
adult-onset still's disease presenting as myopericarditis.a 24-year-old man presented to the emergency department with fever, maculopapular rash, myalgia and polyarthralgia, thoracic pain and dry cough, which had been present for 24 h. at the time of observation he had high fever (39°c), maculopapular rash on the torso, arms and legs proximally, axillary adenopathies and pharyngitis. laboratorial data showed elevated inflammation markers (leukocytosis, c reactive protein of 44 mg/dl, erythrocyte sedimentation rate of 120 mm), elevated transaminases, la ...201424898998
a putative regulatory genetic locus modulates virulence in the pathogen leptospira interrogans.limited research has been conducted on the role of transcriptional regulators in relation to virulence in leptospira interrogans, the etiological agent of leptospirosis. here, we identify an l. interrogans locus that encodes a sensor protein, an anti-sigma factor antagonist, and two genes encoding proteins of unknown function. transposon insertion into the gene encoding the sensor protein led to dampened transcription of the other 3 genes in this locus. this lb139 insertion mutant (the lb139(-) ...201424686063
development of a recombinase polymerase amplification assay for the detection of pathogenic leptospira.detection of leptospires based on dna amplification techniques is essential for the early diagnosis of leptospirosis when anti-leptospira antibodies are below the detection limit of most serological tests. in middle and low income countries where leptospirosis is endemic, routine implementation of real-time pcr is financially and technically challenging due to the requirement of expensive thermocycler equipment. in this study we report the development and evaluation of a novel isothermal recombi ...201424814943
abstracts from the 37th annual meeting of the society of general internal medicine, 2014, san diego, ca, usa. 201424737224
molecular architecture of the bacterial flagellar motor in cells.the flagellum is one of the most sophisticated self-assembling molecular machines in bacteria. powered by the proton-motive force, the flagellum rapidly rotates in either a clockwise or counterclockwise direction, which ultimately controls bacterial motility and behavior. escherichia coli and salmonella enterica have served as important model systems for extensive genetic, biochemical, and structural analysis of the flagellum, providing unparalleled insights into its structure, function, and gen ...201424697492
a model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by leptospira interrogans serovar copenhageni.leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus leptospira. more than 500,000 cases of severe leptospirosis are reported annually, with >10% of these being fatal. leptospires can survive for weeks in suitably moist conditions before encountering a new host. reservoir hosts, typically rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. transmission occurs when mucosal surfaces o ...201424626166
b-cell-specific peptides of leptospira interrogans liga for diagnosis of patients with acute leptospirosis.leptospirosis is a reemerging infectious disease that is underdiagnosed and under-recognized due to low-sensitivity and cumbersome serological tests. rapid reliable alternative tests are needed for early diagnosis of the disease. considering the importance of the pathogenesis-associated leptospiral liga protein expressed in vivo, we have evaluated its application in the diagnosis of the acute form of leptospirosis. the c-terminal coding sequence of liga (liga-c) was cloned into pet15b and expres ...201424403522
identification of borrelia species after creation of an in-house maldi-tof ms database.lyme borreliosis (lb) is a multisystemic disease caused by borrelia burgdorferi sensu lato (sl) complex transmitted to humans by ixodes ticks. b. burgdorferi sl complex, currently comprising at least 19 genospecies, includes the main pathogenic species responsible for human disease in europe: b. burgdorferi sensu stricto (ss), b. afzelii, and b. garinii. in this study, for the first time, maldi-tof ms was applied to borrelia spp., supplementing the existing database, limited to the species b. bu ...201424533160
oral immunization with escherichia coli expressing a lipidated form of liga protects hamsters against challenge with leptospira interrogans serovar copenhageni.leptospirosis is a potentially fatal zoonosis transmitted by reservoir host animals that harbor leptospires in their renal tubules and shed the bacteria in their urine. leptospira interrogans serovar copenhageni transmitted from rattus norvegicus to humans is the most prevalent cause of urban leptospirosis. we examined l. interrogans liga, domains 7 to 13 (liga7-13), as an oral vaccine delivered by escherichia coli as a lipidated, membrane-associated protein. the efficacy of the vaccine was eval ...201424478102
the multifunctional role of the pallilysin-associated treponema pallidum protein, tp0750, in promoting fibrinolysis and extracellular matrix component degradation.the mechanisms that facilitate dissemination of the highly invasive spirochaete, treponema pallidum, are incompletely understood. previous studies showed the treponemal metalloprotease pallilysin (tp0751) possesses fibrin clot degradation capability, suggesting a role in treponemal dissemination. in the current study we report characterization of the functionally linked protein tp0750. structural modelling predicts tp0750 contains a von willebrand factor type a (vwfa) domain, a protein-protein i ...201424303899
pyruvate protects pathogenic spirochetes from h2o2 killing.pathogenic spirochetes cause clinically relevant diseases in humans and animals, such as lyme disease and leptospirosis. the causative agent of lyme disease, borrelia burgdorferi, and the causative agent of leptospirosis, leptospria interrogans, encounter reactive oxygen species (ros) during their enzootic cycles. this report demonstrated that physiologically relevant concentrations of pyruvate, a potent h2o2 scavenger, and provided passive protection to b. burgdorferi and l. interrogans against ...201424392147
early diagnosis of leptospirosis.a 25-years old man from zagreb, croatia, was admitted to the university hospital for infectious diseases four days after the onset of symptoms such as fever, intense pain in the calves and anuria. the patient owned a rabbit and, before the onset of the disease, repaired some rubber pipes damaged by rodents. at admission, he had a severe clinical picture with fever, hypotension, jaundice, immobility, and pain in leg muscles. treatment with ceftriaxone was initiated in combination with volume rest ...201425002958
destruction of the hepatocyte junction by intercellular invasion of leptospira causes jaundice in a hamster model of weil's disease.weil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. the mechanisms of jaundice caused by pathogenic leptospira remain unclear. we therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of weil's disease. in this work, we obtained three-dimensional images of infected hamster livers using scanning electron microscop ...201424945433
multiplex nucleic acid amplification test for diagnosis of dengue fever, malaria, and leptospirosis.dengue, leptospirosis, and malaria are among the most common etiologies of systemic undifferentiated febrile illness (ufi) among travelers to the developing world, and these pathogens all have the potential to cause life-threatening illness in returned travelers. the current study describes the development of an internally controlled multiplex nucleic acid amplification test for the detection of dengue virus (denv) and leptospira and plasmodium species, with a specific callout for plasmodium fal ...201424671788
interpretation of microscopic agglutination test for leptospirosis diagnosis and seroprevalence.determination of antibody titer by microscopic agglutination test (mat) has been used as a tool for leptospirosis diagnosis. four fold or greater rise in antibody titers between acute and convalescent sera suggests recent leptospira infection. in addition, results obtained by mat have been used to predict infecting serovars. however, cross reactivity among various leptospira serovars have been reported when patient sera were tested with a battery of leptospira serovars. this study demonstrates c ...201425183074
production and characterization of a polyclonal antibody of anti-rlipl21-igg against leptospira for early detection of acute leptospirosis.leptospirosis is one of the zoonotic diseases in animals and humans throughout the world. lipl21 is one of the important surface-exposed lipoproteins in leptospires and the most effective cross protective immunogenic antigen. it is widely considered as a diagnostic marker for leptospirosis. in this study, we evaluated the serodiagnostic potential of lipl21 protein of leptospira interrogans serovar pomona. we have successfully amplified, cloned, and expressed lipl21 in e. coli and evaluated its s ...201424860824
serodiagnosis of equine leptospirosis by enzyme-linked immunosorbent assay using four recombinant protein markers.leptospirosis, caused by leptospira spp., is one of the most common zoonotic diseases in the world. we tested four recombinant proteins of leptospira interrogans, namely, rlipl21, rloa22, rlipl32, and rligacon4-8, to evaluate their potential for use as antigens for the diagnosis of equine leptospirosis. we employed equine sera (n = 130) that were microscopic agglutination test (mat) negative and sera (n = 176) that were mat positive for the 5 serovars that most commonly cause equine leptospirosi ...201424451330
high-temperature protein g is an essential virulence factor of leptospira interrogans.leptospira interrogans is a global zoonotic pathogen and is the causative agent of leptospirosis, an endemic disease of humans and animals worldwide. there is limited understanding of leptospiral pathogenesis; therefore, further elucidation of the mechanisms involved would aid in vaccine development and the prevention of infection. htpg (high-temperature protein g) is the bacterial homolog to the highly conserved molecular chaperone hsp90 and is important in the stress responses of many bacteria ...201424366253
regional differences of leptospirosis in sri lanka: observations from a flood-associated outbreak in 2011.leptospirosis is known to be an important cause of weather disaster-related infectious disease epidemics. in 2011, an outbreak of leptospirosis occurred in the relatively dry district of anuradhapura, sri lanka where diagnosis was resisted by local practitioners because leptospirosis was not known in the area and the clinical presentation was considered atypical. to identify the causative leptospira associated with this outbreak, we carried out a cross-sectional study. consecutive clinically sus ...201424454971
a homolog of glyceraldehyde-3-phosphate dehydrogenase from riemerella anatipestifer is an extracellular protein and exhibits biological activity.riemerella anatipestifer is the causative agent of septicemia anserum exsudativa in ducks. its pathogenesis and virulence factors are still unclear. the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (gapdh), an anchorless and multifunctional protein on the surface of several pathogenic microorganisms, is involved in virulence and adhesion. whether homologs of gapdh exist, and display similar characteristics in r. anatipestifer (ragapdh) has not been determined. in our research, the ...201425183032
post-translational modification of lipl32 during leptospira interrogans infection.leptospirosis, a re-emerging disease of global importance caused by pathogenic leptospira spp., is considered the world's most widespread zoonotic disease. rats serve as asymptomatic carriers of pathogenic leptospira and are critical for disease spread. in such reservoir hosts, leptospires colonize the kidney, are shed in the urine, persist in fresh water and gain access to a new mammalian host through breaches in the skin.201425356675
hideyo noguchi (1876-1928): distinguished bacteriologist. 201425631898
responses of murine and human macrophages to leptospiral infection: a study using comparative array analysis.leptospirosis is a re-emerging tropical infectious disease caused by pathogenic leptospira spp. the different host innate immune responses are partially related to the different severities of leptospirosis. in this study, we employed transcriptomics and cytokine arrays to comparatively calculate the responses of murine peritoneal macrophages (mpms) and human peripheral blood monocytes (hbms) to leptospiral infection. we uncovered a series of different expression profiles of these two immune cell ...201324130911
pathogenomic inference of virulence-associated genes in leptospira interrogans.leptospirosis is a globally important, neglected zoonotic infection caused by spirochetes of the genus leptospira. since genetic transformation remains technically limited for pathogenic leptospira, a systems biology pathogenomic approach was used to infer leptospiral virulence genes by whole genome comparison of culture-attenuated leptospira interrogans serovar lai with its virulent, isogenic parent. among the 11 pathogen-specific protein-coding genes in which non-synonymous mutations were foun ...201324098822
detection of human leptospirosis as a cause of acute fever by capture elisa using a leptospira interrogans serovar copenhageni (m20) derived antigen.leptospirosis is a potentially lethal zoonosis mainly affecting low-resource tropical countries, including peru and its neighbouring countries. timely diagnosis of leptospirosis is critical but may be challenging in the regions where it is most prevalent. the serodiagnostic gold standard microagglutination test (mat) may be technically prohibitive. our objective in this study was to assess the sensitivity, specificity, and predictive value of an igm antibody capture enzyme-linked immunoassay (ma ...201324053555
adhesins of leptospira interrogans mediate the interaction to fibrinogen and inhibit fibrin clot formation in vitro.we report in this work that leptospira strains, virulent l. interrogans serovar copenhageni, attenuated l. interrogans serovar copenhageni and saprophytic l. biflexa serovar patoc are capable of binding fibrinogen (fg). the interaction of leptospires with fg inhibits thrombin- induced fibrin clot formation that may affect the haemostatic equilibrium. additionally, we show that plasminogen (plg)/plasmin (pla) generation on the surface of leptospira causes degradation of human fg. the data suggest ...201324009788
a call to order at the spirochaetal host-pathogen interface.as the lyme disease spirochaete borrelia burgdorferi shuttles back and forth between arthropod vector and vertebrate host, it encounters vastly different and hostile environments. major mechanisms contributing to the success of this pathogen throughout this complex transmission cycle are phase and antigenic variation of abundant and serotype-defining surface lipoproteins. these peripherally membrane-anchored virulence factors mediate niche-specific interactions with vector/host factors and prote ...201323750784
periplasmic flagellar export apparatus protein, flih, is involved in post-transcriptional regulation of flab, motility and virulence of the relapsing fever spirochete borrelia hermsii.spirochetes are bacteria characterized in part by rotating periplasmic flagella that impart their helical or flat-wave morphology and motility. while most other bacteria rely on a transcriptional cascade to regulate the expression of motility genes, spirochetes employ post-transcriptional mechanism(s) that are only partially known. in the present study, we characterize a spontaneous non-motile mutant of the relapsing fever spirochete borrelia hermsii that was straight, non-motile and deficient i ...201324009690
characterization of three novel adhesins of leptospira interrogans.we report cloning, expression, purification, and characterization of three predicted leptospiral membrane proteins (lic11360, lic11009, and lic11975). in silico analysis and proteinase k accessibility data suggest that these proteins might be surface exposed. we show that proteins encoded by lic11360, lic11009 and lic11975 genes interact with laminin in a dose-dependent and saturable manner. the proteins are referred to as leptospiral surface adhesions 23, 26, and 36 (lsa23, lsa26, and lsa36), r ...201323958908
interaction of leptospira elongation factor tu with plasminogen and complement factor h: a metabolic leptospiral protein with moonlighting activities.the elongation factor tu (ef-tu), an abundant bacterial protein involved in protein synthesis, has been shown to display moonlighting activities. known to perform more than one function at different times or in different places, it is found in several subcellular locations in a single organism, and may serve as a virulence factor in a range of important human pathogens. here we demonstrate that leptospira ef-tu is surface-exposed and performs additional roles as a cell-surface receptor for host ...201324312361
a prime-boost strategy using the novel vaccine candidate, lema, protects hamsters against leptospirosis.toward developing an effective vaccine capable of conferring heterologous protection, the putative lipoprotein lema, which presents an m3 epitope similar to that of listeria, was evaluated as a vaccine candidate in the hamster model of leptospirosis. lema is conserved (>70% pairwise identity) among the pathogenic leptospira spp., indicating its potential in stimulating a cross-protective immune response. using different vaccination strategies, including prime-boost, dna vaccine, and a subunit pr ...201323515012
a gene transfer agent and a dynamic repertoire of secretion systems hold the keys to the explosive radiation of the emerging pathogen bartonella.gene transfer agents (gtas) randomly transfer short fragments of a bacterial genome. a novel putative gta was recently discovered in the mouse-infecting bacterium bartonella grahamii. although gtas are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. here, we present a comparative analysis of 16 bartonella genomes ranging from 1.4 to 2.6 mb in size, including six novel genomes from bartonella isolated from a cow, two moose, two dogs, and a kangaroo. a ...201323555299
essential calcium-binding cluster of leptospira lipl32 protein for inflammatory responses through the toll-like receptor 2 pathway.leptospirosis is the most widespread zoonosis caused by the pathogenic leptospira worldwide. lipl32, a 32-kda lipoprotein, is the most abundant protein on the outer membrane of leptospira and has an atypical poly(asp) motif ((161)dddddgdd(168)). the x-ray crystallographic structure of lipl32 revealed that the calcium-binding cluster of lipl32 includes several essential residues asp(132), thr(133), asp(164), asp(165), and tyr(178). the goals of this study were to determine possible roles of the c ...201323486465
importance of uncharged polar residues and proline in the proximal two-thirds (pro107-ser128) of the highly conserved region of mouse ileal na+-dependent bile acid transporter, slc10a2, in transport activity and cellular expression.slc10a2-mediated reabsorption of bile acids at the distal end of the ileum is the first step in enterohepatic circulation. because bile acids act not only as detergents but also as signaling molecules in lipid metabolism and energy production, slc10a2 is important as the key transporter for understanding the in vivo kinetics of bile acids. slc10a family members and the homologous genes of various species share a highly conserved region corresponding to gly104-pro142 of slc10a2. the functional im ...201323374508
pathogenic and saprophytic leptospira species in water and soils from selected urban sites in peninsular malaysia.leptospira species were studied in water and soils from selected urban sites in malaysia. a total of 151 water (n=121) and soil (n=30) samples were collected from 12 recreational lakes and wet markets. all samples were filtered and inoculated into semi-solid ellinghausen and mccullough modified by johnson and harris (emjh) media supplemented with additional 5-fluorouracil. the cultures were then incubated at 30°c and observed under a dark field microscope with intervals of 10 days. a pcr assay t ...201323363618
cross-sectional study of leptospira seroprevalence in humans, rats, mice, and dogs in a main tropical sea-port city.samples were collected from 128 symptomatic humans, 83 dogs, 49 mice, and 20 rats (rattus rattus: 16; rattus norvegicus: 4) in neighborhoods where human leptospirosis have been reported within the principal sea-port city of colombia. seroprevalences were assessed against 19 pathogenic, 1 intermediate pathogenic, and 1 saprophytic leptospira serogroups. pathogenic leptospira were confirmed using conventional leptospira-specific polymerase chain-reaction and pulsed-field gel electrophoresis analys ...201323149584
impact of crispr immunity on the emergence and virulence of bacterial pathogens.crispr-cas systems protect prokaryotes from viruses and plasmids and function primarily as an adaptive immune system in these organisms. recent discoveries, however, revealed unexpected roles for crispr loci as barriers to horizontal gene transfer and as modulators of gene expression. we review how both of these functions of crispr-cas systems can affect the emergence and virulence of human bacterial pathogens.201324581697
impact of crispr immunity on the emergence and virulence of bacterial pathogens.crispr-cas systems protect prokaryotes from viruses and plasmids and function primarily as an adaptive immune system in these organisms. recent discoveries, however, revealed unexpected roles for crispr loci as barriers to horizontal gene transfer and as modulators of gene expression. we review how both of these functions of crispr-cas systems can affect the emergence and virulence of human bacterial pathogens.201324581697
a multi-part matching strategy for mapping loinc with laboratory terminologies.to address the problem of mapping local laboratory terminologies to logical observation identifiers names and codes (loinc). to study different ontology matching algorithms and investigate how the probability of term combinations in loinc helps to increase match quality and reduce manual effort.201324363318
a multi-part matching strategy for mapping loinc with laboratory terminologies.to address the problem of mapping local laboratory terminologies to logical observation identifiers names and codes (loinc). to study different ontology matching algorithms and investigate how the probability of term combinations in loinc helps to increase match quality and reduce manual effort.201324363318
role for cis-acting rna sequences in the temperature-dependent expression of the multiadhesive lig proteins in leptospira interrogans.the spirochete leptospira interrogans causes a systemic infection that provokes a febrile illness. the putative lipoproteins liga and ligb promote adhesion of leptospira to host proteins, interfere with coagulation, and capture complement regulators. in this study, we demonstrate that the expression level of the liga and ligb proteins was substantially higher when l. interrogans proliferated at 37°c instead of the standard culture temperature of 30°c. the rna comprising the 175-nucleotide 5' unt ...201324013626
leptospira interrogans enolase is secreted extracellularly and interacts with plasminogen.leptospira interrogans is the agent for leptospirosis, an important zoonosis in humans and animals across the globe. surface proteins of invading pathogens, such as l. interrogans, are thought to be responsible for successful microbial persistence in vivo via interaction with specific host components. in particular, a number of invasive infectious agents exploit host proteolytic pathways, such as one involving plasminogen (pg), which aid in efficient pathogen dissemination within the host. here ...201324205133
leptospira interrogans serovar copenhageni harbors two lexa genes involved in sos response.bacteria activate a regulatory network in response to the challenges imposed by dna damage to genetic material, known as the sos response. this system is regulated by the reca recombinase and by the transcriptional repressor lexa. leptospira interrogans is a pathogen capable of surviving in the environment for weeks, being exposed to a great variety of stress agents and yet retaining its ability to infect the host. this study aims to investigate the behavior of l. interrogans serovar copenhageni ...201324098496
diagnostic ophthalmology. anterior uveitis of the right eye. 201324155500
cell extract-containing medium for culture of intracellular fastidious bacteria.the culture of fastidious microorganisms is a critical step in infectious disease studies. as a proof-of-concept experiment, we evaluated an empirical medium containing eukaryotic cell extracts for its ability to support the growth of coxiella burnetii. here, we demonstrate the exponential growth of several bacterial strains, including the c. burnetii nine mile phase i and phase ii strains, and c. burnetii isolates from humans and animals. low-oxygen-tension conditions and the presence of small ...201323740722
leptospiral outer membrane protein lipl41 is not essential for acute leptospirosis but requires a small chaperone protein, lep, for stable expression.leptospirosis is a worldwide zoonosis caused by pathogenic leptospira spp., but knowledge of leptospiral pathogenesis remains limited. however, the development of mutagenesis systems has allowed the investigation of putative virulence factors and their involvement in leptospirosis. lipl41 is the third most abundant lipoprotein found in the outer membranes of pathogenic leptospires and has been considered a putative virulence factor. lipl41 is encoded on the large chromosome 28 bp upstream of a s ...201323690405
a phylogenomic and molecular signature based approach for characterization of the phylum spirochaetes and its major clades: proposal for a taxonomic revision of the phylum.the spirochaetes species cause many important diseases including syphilis and lyme disease. except for their containing a distinctive endoflagella, no other molecular or biochemical characteristics are presently known that are specific for either all spirochaetes or its different families. we report detailed comparative and phylogenomic analyses of protein sequences from spirochaetes genomes to understand their evolutionary relationships and to identify molecular signatures for this group. these ...201323908650
identification of novel adhesins of m. tuberculosis h37rv using integrated approach of multiple computational algorithms and experimental analysis.pathogenic bacteria interacting with eukaryotic host express adhesins on their surface. these adhesins aid in bacterial attachment to the host cell receptors during colonization. a few adhesins such as heparin binding hemagglutinin adhesin (hbha), apa, malate synthase of m. tuberculosis have been identified using specific experimental interaction models based on the biological knowledge of the pathogen. in the present work, we carried out computational screening for adhesins of m. tuberculosis. ...201323922800
bba70 of borrelia burgdorferi is a novel plasminogen-binding protein.the lyme disease spirochete borrelia burgdorferi lacks endogenous, surface-exposed proteases. in order to efficiently disseminate throughout the host and penetrate tissue barriers, borreliae rely on recruitment of host proteases, such as plasmin(ogen). here we report the identification of a novel plasminogen-binding protein, bba70. binding of plasminogen is dose-dependent and is affected by ionic strength. the bba70-plasminogen interaction is mediated by lysine residues, primarily located in a p ...201323861404
aggregate-reactivation activity of the molecular chaperone clpb from ehrlichia chaffeensis.rickettsiale diseases, including human monocytic ehrlichiosis caused by ehrlichia chaffeensis, are the second leading cause of the tick-borne infections in the usa and a growing health concern. little is known about how e. chaffeensis survives the host-induced stress in vertebrate and tick hosts. a molecular chaperone clpb from several microorganisms has been reported to reactivate aggregated proteins in cooperation with the co-chaperones dnak/dnaj/grpe (kje). in this study, we performed the fir ...201323667479
interaction of leptospira interrogans with human proteolytic systems enhances dissemination through endothelial cells and protease levels.we have recently reported the ability of leptospira to capture plasminogen (plg) and generate plasmin (pla) bound on the microbial surface in the presence of exogenous activators. in this work, we examined the effects of leptospiral plg binding for active penetration through the endothelial cell barrier and activation. the results indicate that leptospires with plg association or pla activation have enhanced migration activity through human umbilical vein endothelial cell (huvec) monolayers comp ...201323478319
development of immunochromatography-based methods for detection of leptospiral lipopolysaccharide antigen in urine.leptospirosis is an infectious disease caused by the spirochete bacteria leptospira spp. and is commonly found throughout the world. diagnosis of leptospirosis performed by culture and microscopic agglutination tests is laborious and time-consuming. therefore, we aimed to develop a novel immunochromatography (icg)-based method for detecting leptospira antigen in the urine of patients and animals. we used the 1h6 monoclonal antibody (mab), which is specific to the lipopolysaccharide (lps) that is ...201323467776
the htra protease of borrelia burgdorferi degrades outer membrane protein bmpd and chemotaxis phosphatase chex.borrelia burgdorferi, the spirochaetal agent of lyme disease, codes for a single htra protein, htrabb (bb0104) that is homologous to degp of escherichia coli (41% amino acid identity). htrabb shows physical and biochemical similarities to degp in that it has the trimer as its fundamental unit and can degrade casein via its catalytic serine. recombinant htrabb exhibits proteolytic activity in vitro, while a mutant (htrabbs198a) does not. however, htrabb and degp have some important differences as ...201323565798
structure and activity of the flagellar rotor protein fliy: a member of the chec phosphatase family.fliy is a flagellar rotor protein of the chec phosphatase family.201323532838
lipl32 is a subsurface lipoprotein of leptospira interrogans: presentation of new data and reevaluation of previous studies.the agents of leptospirosis, a zoonosis with worldwide distribution, are pathogenic spirochetes belonging to the genus leptospira. the leptospiral life cycle involves transmission via fresh water and colonization of the renal tubules of their reservoir hosts. infection of accidental hosts, including humans, may result in life-threatening sequelae. bacterial outer membrane proteins (omps), particularly those with surface-exposed regions, play crucial roles in pathogen virulence mechanisms and ada ...201323323152
assessment of real-time pcr assay for detection of rickettsia spp. and rickettsia rickettsii in banked clinical samples.two novel real-time pcr assays were developed for the detection of rickettsia spp. one assay detects all tested rickettsia spp.; the other is specific for rickettsia rickettsii. evaluation using dna from human blood and tissue samples showed both assays to be more sensitive than nested pcr assays currently in use at the cdc.201323135935
the gain and loss of chromosomal integron systems in the treponema species.integron systems are now recognized as important agents of bacterial evolution and are prevalent in most environments. one of the human pathogens known to harbor chromosomal integrons, the treponema spirochetes are the only clade among spirochete species found to carry integrons. with the recent release of many new treponema genomes, we were able to study the distribution of chromosomal integrons in this genus.201323339550
rats, cities, people, and pathogens: a systematic review and narrative synthesis of literature regarding the ecology of rat-associated zoonoses in urban centers.urban norway and black rats (rattus norvegicus and rattus rattus) are the source of a number of pathogens responsible for significant human morbidity and mortality in cities around the world. these pathogens include zoonotic bacteria (leptospira interrogans, yersina pestis, rickettsia typhi, bartonella spp., streptobacillus moniliformis), viruses (seoul hantavirus), and parasites (angiostrongylus cantonensis). a more complete understanding of the ecology of these pathogens in people and rats is ...201323590323
a review of pig pathology in tanzania.the approximately 1.58 million pigs in tanzania represent 3.7% of the national population of quadruped meat-producing animals. pigs are kept mainly by small producers who own 99.5% of the national stock in units that average 3.04 animals (range 2-48). government policy has had little practical application. african swine fever, foot-and-mouth disease and cysticercosis are important diseases. the first two are notifiable diseases under tanzania legislation; the last has widespread distribution and ...201323733144
in vitro assessment of functional properties of lactic acid bacteria isolated from faecal microbiota of healthy dogs for potential use as probiotics.lactic acid bacteria were isolated and identified in the faeces of chinese crested and yorkshire terrier pups and their probiotic features were investigated in vitro. thirty seven isolates were identified as lactobacillus or enterococcus. out of these isolates, 31 were lactic acid bacteria (lab) and belonged to the species lactobacillus reuteri (16/37; 43.3%), lactobacillus animalis (7/37; 18.9%), lactobacillus acidophilus (3/37; 8.1%), lactobacillus sanfranciscensis (2/37; 5.4%), lactobacillus ...201323538205
a survey of rodent-borne pathogens carried by wild rattus spp. in northern vietnam.to examine the prevalence of human pathogens carried by rats in urban areas in hanoi and hai phong, vietnam, we live-trapped 100 rats in january 2011 and screened them for a panel of bacteria and viruses. antibodies against leptospira interrogans (22·0%), seoul virus (14·0%) and rat hepatitis e virus (23·0%) were detected in rats, but antibodies against yersinia pestis were not detected. antibodies against l. interrogans and seoul virus were found only in adult rats. in contrast, antibodies to r ...201323114204
the ompa family of proteins: roles in bacterial pathogenesis and immunity.the ompa family of outer membrane proteins is a group of genetically related, heat-modifiable, surface-exposed, porin proteins that are in high-copy number in the outer membrane of mainly gram-negative bacteria. ompa proteins are characterized by an n-terminal domain that forms an eight-stranded, anti-parallel β barrel, which is embedded in the outer membrane. the c-terminal domain is globular and located in the periplasmic space. escherichia coli ompa is the best characterized of the proteins. ...201322986056
characterization of a bifunctional enzyme with (p)ppgpp-hydrolase/synthase activity in leptospira interrogans.alarmone guanosine 5'-diphosphate (or 5'-triphosphate) 3'-diphosphate [(p)ppgpp] is the key component that globally regulates stringent control in bacteria. there are two homologous enzymes, rela and spot in escherichia coli, which are responsible for fluctuations in (p)ppgpp concentration inside the cell, whereas there exists only a single rela/spot enzyme in gram-positive bacteria. we have identified a bifunctional enzyme with (p)ppgpp-hydrolase/synthase activity in leptospira interrogans. we ...201324111633
genetic and molecular biological characterization of two homologous cher genes from leptospira interrogans.the leptospira interrogans genome encodes two copies of cher genes and each of them is able to complement for the swarming defective phenotype of escherichia coli cher null mutant rp1254 to certain extent, while over-expression of either of them inhibits the swarming of the chemotactic wild-type e. coli strain, rp437. therefore, both cher1 and cher2 ought to bear the methyltransferase activities, although cher1 has only one instead of two conserved basic amino acid residues located on the positi ...201323934012
adhesin activity of leptospira interrogans lipoprotein identified by in vivo and in vitro shotgun phage display.leptospira interrogans causes leptospirosis, one of the most common zoonotic diseases in the world. this pathogenic spirochete is able to bind to extracellular matrix, to express virulent factors and to cause host death. until now, there is no effective human vaccine for the disease. shotgun phage display genomic libraries of l. interrogans were constructed and used for in vivo biopanning in hamsters and screened for ligands able to bind to llc-pk1 epithelial cells. in both panning procedures, c ...201323291183
characterization of lic11207, a novel leptospiral protein that is recognized by human convalescent sera and prevents apoptosis of polymorphonuclear leukocytes.we report the study of a predicted outer-membrane leptospiral protein encoded by the gene lic11207. this protein is conserved in several pathogenic leptospiral strains but is absent in the saprophyte leptospira biflexa. this putative outer-membrane protein has a domain of unknown function (duf) 1565 found in several phylogenetically diverse bacteria and in the archaeon methanosarcina acetivorans. the gene was cloned and expressed in escherichia coli bl21 (si) strain using the expression vector p ...201323092690
contribution of leptospira, neospora caninum and bovine viral diarrhea virus to fetal loss of beef cattle in new zealand.the profitability of beef breeding farms in new zealand depends principally on optimal reproductive performance. the aim of this study was to estimate the impact of four major pathogens, bovine viral diarrhea virus (bvdv), neospora caninum (n. caninum), leptospira borgpetersenii serovar hardjo (hardjo), and leptospira interrogans serovar pomona (pomona), on rates of fetal loss in commercial beef breeding herds. farms reporting fetal loss were recruited, and a blood sample from aborting cows (cas ...201323932894
first isolation of leptospira interrogans from lycalopex griseus (south american gray fox) in argentina shows new mlva genotype.to identify carriers of leptospira spp. in argentina, wild animals were trapped in buenos aires province during three nights, capturing 12 didelphis albiventris (white-eared opossum), six chaetophractus villosus (big hairy armadillo), five lycalopex griseus (south american gray fox), and two conepatus chinga (molina's hog-nosed skunk). all were tested by microscopic agglutination test, and five (two gray foxes, two armadillos, and one skunk) were positive for leptospira interrogans serovars cani ...201323307384
in vivo gene expression and immunoreactivity of leptospira collagenase.pulmonary hemorrhage is an increasing cause of death of leptospirosis patients. bacterial collagenase has been shown to be involved in lung hemorrhage induced by various infectious agents. according to leptospira whole genome study, cola, a gene suggested to code for bacterial collagenase has been identified. we investigated cola gene expression in lung tissues of leptospira infected hamsters. golden syrian hamsters were injected intraperitoneally with leptospira interrogans serovar pyrogenes. t ...201323305770
effect of osmolarity and viscosity on the motility of pathogenic and saprophytic leptospira.the motility of bacteria is an important factor in their infectivity. in this study, the motility of leptospira, a member of the spirochete family that causes a zoonotic disease known as leptospirosis, was analyzed in different viscous or osmotic conditions. motility assays revealed that both pathogenic and saprophytic strains increase their swimming speeds with increasing viscosity. however, only pathogenic leptospira interrogans maintained vigorous motility near physiological osmotic condition ...201323278547
cluster of leptospirosis cases among military personnel in rio de janeiro, brazil.we report two cases of leptospirosis in military personnel in southeastern brazil. the cases were hospitalized following field training exercises, and presented with acute meningoencephalitis, respiratory illnesses, and skin rash. leptospira interrogans serovars icterohaemorrhagiae, hebdomadis, patoc, and cynopteri were identified in the cases by microscopic agglutination test and pcr.201323195639
[renal manifestations of leptospirosis: 88 cases].this prospective study analyzes 173 patients, hospitalized between january 1, 2005, and december 31, 2008, for serologically confirmed leptospirosis. it describes the renal, clinical and laboratory manifestations in 88 (50.8%) of these cases. acute kidney failure was frequent in this group (68 cases = 77.3%). kidney damage was one of the multiple organs affected, with infection and hepatic and hemorrhagic signs predominant.201324001652
[leptospirosis epidemic: 48 cases].the epidemic reported here took place from november 30, 2006, through january 3, 2007, in a rural area of tala-athmane and led to the hospitalization of 48 patients with leptospirosis. it was due to the proximity of homes to two uncontrolled garbage dumps invaded by rodents. all 48 hospitalized cases were confirmed serologically, and more than 60% were serogroup icterohaemorrhagiae. more than 14.5% of the patients were contaminated during occupational exposure. the authors describe the clinical ...201324001651
development of leptospira in vitro potency assays: eu/industry experience and perspectives.nobivac® lepto (msd animal health) is a non-adjuvanted canine leptospirosis vaccine containing inactivated whole cells of leptospira interrogans serogroup canicola serovar portlandvere and l. interrogans serogroup icterohaemorrhagiae serovar copenhageni. the current standard in vivo potency test is a hamster challenge test associated with major drawbacks such as animal suffering and poor reproducibility. here, the quantification of antigenic mass by elisa as a new in vitro potency test is descri ...201323867758
leptospirosis in fox squirrels (sciurus niger) of larimer county, colorado, usa.leptospirosis is a zoonotic disease caused by the bacterium leptospira interrogans. the organism is typically maintained within a geographic region by colonizing renal tubules of carrier animals and shed into the environment in urine. we assessed whether l. interrogans was present in fox squirrels (sciurus niger) in larimer county, colorado, usa, and whether it is associated with disease. twenty-two squirrels were trapped from 29 november 2011 to 15 december 2011 for use in an unrelated study. t ...201323778614
haemoglobin and red cell counts in leptospirosis patients infected with different serovars.the aim of the study was to compare haemoglobin and red cell counts between patients known to be infected with a range of leptospiral serovars.201323740067
chemogenomics profiling of drug targets of peptidoglycan biosynthesis pathway in leptospira interrogans by virtual screening approaches.leptospirosis is a worldwide zoonosis of global concern caused by leptospira interrogans. the availability of ligand libraries has facilitated the search for novel drug targets using chemogenomics approaches, compared with the traditional method of drug discovery, which is time consuming and yields few leads with little intracellular information for guiding target selection. recent subtractive genomics studies have revealed the putative drug targets in peptidoglycan biosynthesis pathways in lept ...201323676922
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