Publications

stray dogs as reservoirs of the zoonotic agents leptospira interrogans, trypanosoma cruzi, and aspergillus spp. in an urban area of chiapas in southern mexico.	this investigation determined the presence and prevalence of the zoonotic agents leptospira interrogans, trypanosoma cruzi, and aspergillus spp. in the stray dog population (a total of 224 stray dogs) in an urban area of southern mexico. blood serum samples were taken from all dogs, and root hair samples were taken from dogs with skin lesions and partial alopecia. igg antibodies for l. interrogans from 10 serovars were detected using the microscopic agglutination test. immunofluorescence antibod ...	2010	19514808
detection of leptospira in urine using anti-leptospira-coated gold nanoparticles.	serological assays for antibody detection have been widely used for leptospirosis diagnosis. however, antibody is usually undetectable during the first week after infection. detection of leptospira dna can be done by pcr but this technique requires special equipments and the cost is still relatively high. here we demonstrate that gold nanoparticles can be used to facilitate leptospira detection. gold nanoparticles were coated with rabbit antibody specific to leptospira interrogans serovar bratis ...	2011	20015548
plasmids with a chromosome-like role in rhizobia.	replicon architecture in bacteria is commonly comprised of one indispensable chromosome and several dispensable plasmids. this view has been enriched by the discovery of additional chromosomes, identified mainly by localization of rrna and/or trna genes, and also by experimental demonstration of their requirement for cell growth. the genome of rhizobium etli cfn42 is constituted by one chromosome and six large plasmids, ranging in size from 184 to 642 kb. five of the six plasmids are dispensable ...	2011	21217003
cross-protective immunity against leptospirosis elicited by a live, attenuated lipopolysaccharide mutant.	leptospira species cause leptospirosis, a zoonotic disease found worldwide. current vaccines against leptospirosis provide protection only against closely related serovars.	2011	21220775
characterization of the immunogenic and antigenic potential of putative lipoproteins from leptospira interrogans.	the search for a vaccine capable of conferring heterologous protection, through the identification of conserved and cross-protective antigens, remains an ongoing priority in leptospirosis research. in the present study, an in silico analysis was used to identify potentially protective lipoproteins from leptospira interrogans serovar copenhageni. eight putative lipoproteins were selected (lic10009, lic10054, lic10091, lic11058, lic11567, lic13059, lic13305, and lic20172), cloned and expressed in ...	2011	21221970
fulminant leptospirosis (weil's disease) in an urban setting as an overlooked cause of multiorgan failure: a case report.		2011	21235739
patterns and regulation of ribosomal rna transcription in borrelia burgdorferi.	borrelia burgdorferi contains one 16s and two tandem sets of 23s-5s ribosomal (r) rna genes whose patterns of transcription and regulation are unknown but are likely to be critical for survival and persistence in its hosts.	2011	21251259
characterization of conserved combined t and b cell epitopes in leptospira interrogans major outer membrane proteins ompl1 and lipl41.	leptospira interrogans are bacterial pathogens of animal that cause zoonotic infections in human. outer membrane proteins of leptospire are among the most effective antigens which can stimulate remarkable immune responses during the infection processes, and thus are currently considered leading candidate vaccine antigens. the objective of the present study is to predict and confirm major combined b and t cell epitopes of leptospiral outer membrane proteins ompl1 and lipl41, as well as to evaluat ...	2011	21269437
functional analysis of borrelia burgdorferi uvra in dna damage protection.	bacterial pathogens face constant challenges from dna-damaging agents generated by host phagocytes. although borrelia burgdorferi appears to have much fewer dna repair enzymes than pathogens with larger genomes, it does contain homologues of uvra and uvrb (subunits a and b of excinuclease abc). as a first step to exploring the physiologic function of uvra(bbu) and its possible role in survival in the host in the face of dna-damaging agents, a partially deleted uvra mutant was isolated by targete ...	2011	21272060
structures of domains i and iv from ybbr are representative of a widely distributed protein family.	ybbr domains are widespread throughout eubacteria and are expressed as monomeric units, linked in tandem repeats or cotranslated with other domains. although the precise role of these domains remains undefined, the location of the multiple ybbr domain-encoding ybbr gene in the bacillus subtilis glmm operon and its previous identification as a substrate for a surfactin-type phosphopantetheinyl transferase suggests a role in cell growth, division, and virulence. to further characterize the ybbr do ...	2011	21154411
structures of domains i and iv from ybbr are representative of a widely distributed protein family.	ybbr domains are widespread throughout eubacteria and are expressed as monomeric units, linked in tandem repeats or cotranslated with other domains. although the precise role of these domains remains undefined, the location of the multiple ybbr domain-encoding ybbr gene in the bacillus subtilis glmm operon and its previous identification as a substrate for a surfactin-type phosphopantetheinyl transferase suggests a role in cell growth, division, and virulence. to further characterize the ybbr do ...	2011	21154411
increased immunogenicity to lipl32 of leptospira interrogans when expressed as a fusion protein with the cholera toxin b subunit.	leptospirosis is one of the most widespread zoonosis in the world. the development of a recombinant leptospira vaccine remains a challenge. in this study, we cloned the leptospira interrogans open reading frame (orf) coding the external membrane protein lipl32, an immunodominant antigen found in all pathogenic leptospira, downstream of the highly immunogenic cholera toxin b subunit (ctb) orf. expression and assembly of the ctb-lipl32 fusion protein into oligomeric structures of pentameric size w ...	2011	20721666
evaluation of the use of selective pcr amplification of lps biosynthesis genes for molecular typing of leptospira at the serovar level.	leptospirosis is an important epidemic zoonosis worldwide. currently, there are more than 250 leptospira pathogenic serovars known that can potentially infect humans. conventional classification of leptospires with the serovar as the basic taxon, based on serological recognition of lipopolysaccharide (lps) composition does not correlate well with species determination, based on general genomic features. here, we investigate the selective amplification of polymorphic regions from the lps biosynth ...	2011	20721667
genotyping of leptospira interrogans strains from argentina by multiple-locus variable-number tandem repeat analysis (mlva).	leptospirosis outbreaks occur regularly in argentina and other south american countries, but little is known about their epidemiological relationships. application of new molecular tools, such as the multiple-locus variable-number tandem repeat analysis (mlva) is limited by scant available data on regional strains. we have analyzed the genetic diversity of a collection of 31 strains of leptospira interrogans isolated in argentina during the past five decades from humans and animals, including a ...	2011	20674025
an outbreak of severe leptospirosis in capuchin (cebus) monkeys.	naturally acquired acute leptospirosis in monkeys is uncommon. this study reports an outbreak of severe leptospirosis among 52 capuchin (cebus) monkeys that had been rescued from homes and housed in a wildlife rehabilitation center in colombia in 2007. case confirmation consisted of leptospira isolation followed by a polymerase chain reaction targeting the lipl32 gene. the attack and mortality rates were 71% and 27%, respectively. sixteen cases were confirmed. necropsy revealed diffuse jaundice ...	2011	20554228
putting structure into context: fitting of atomic models into electron microscopic and electron tomographic reconstructions.	a complete understanding of complex dynamic cellular processes such as cell migration or cell adhesion requires the integration of atomic level structural information into the larger cellular context. while direct atomic-level information at the cellular level remains inaccessible, electron microscopy, electron tomography and their associated computational image processing approaches have now matured to a point where sub-cellular structures can be imaged in three dimensions at the nanometer scal ...	2011	22152946
putting structure into context: fitting of atomic models into electron microscopic and electron tomographic reconstructions.	a complete understanding of complex dynamic cellular processes such as cell migration or cell adhesion requires the integration of atomic level structural information into the larger cellular context. while direct atomic-level information at the cellular level remains inaccessible, electron microscopy, electron tomography and their associated computational image processing approaches have now matured to a point where sub-cellular structures can be imaged in three dimensions at the nanometer scal ...	2011	22152946
investment in rapid growth shapes the evolutionary rates of essential proteins.	proteins evolve at very different rates and, most notably, at rates inversely proportional to the level at which they are produced. the relative frequency of highly expressed proteins in the proteome, and thus their impact on the cell budget, increases steeply with growth rate. the maximal growth rate is a key life-history trait reflecting trade-offs between rapid growth and other fitness components. we show that the maximal growth rate is weakly affected by genetic drift. the negative correlati ...	2011	22135464
bridging the gap between validation and implementation of non-animal veterinary vaccine potency testing methods.	in recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. following validation, these tests are slowly being accepted for use by international regulatory authorities. because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing ...	2011	26486625
proteogenomic analysis of bacteria and archaea: a 46 organism case study.	experimental evidence is increasingly being used to reassess the quality and accuracy of genome annotation. proteomics data used for this purpose, called proteogenomics, can alleviate many of the problematic areas of genome annotation, e.g. short protein validation and start site assignment. we performed a proteogenomic analysis of 46 genomes spanning eight bacterial and archaeal phyla across the tree of life. these diverse datasets facilitated the development of a robust approach for proteogeno ...	2011	22114679
generic comparison of protein inference engines.	protein identifications, instead of peptide-spectrum matches, constitute the biologically relevant result of shotgun proteomics studies. how to appropriately infer and report protein identifications has triggered a still ongoing debate. this debate has so far suffered from the lack of appropriate performance measures that allow us to objectively assess protein inference approaches. this study describes an intuitive, generic and yet formal performance measure and demonstrates how it enables exper ...	2011	22057310
generic comparison of protein inference engines.	protein identifications, instead of peptide-spectrum matches, constitute the biologically relevant result of shotgun proteomics studies. how to appropriately infer and report protein identifications has triggered a still ongoing debate. this debate has so far suffered from the lack of appropriate performance measures that allow us to objectively assess protein inference approaches. this study describes an intuitive, generic and yet formal performance measure and demonstrates how it enables exper ...	2011	22057310
toll-like receptors and myocardial inflammation.	toll-like receptors (tlrs) are a member of the innate immune system. tlrs detect invading pathogens through the pathogen-associated molecular patterns (pamps) recognition and play an essential role in the host defense. tlrs can also sense a large number of endogenous molecules with the damage-associated molecular patterns (damps) that are produced under various injurious conditions. animal studies of the last decade have demonstrated that tlr signaling contributes to the pathogenesis of the crit ...	2011	21977329
leptospirosis as frequent cause of acute febrile illness in southern sri lanka.	to determine the proportion of fevers caused by leptospirosis, we obtained serum specimens and epidemiologic and clinical data from patients in galle, sri lanka, march-october 2007. immunoglobulin m elisa was performed on paired serum specimens to diagnose acute (seroconversion or 4-fold titer rise) or past (titer without rise) leptospirosis and seroprevalence (acute). we compared (individually) the diagnostic yield of acute-phase specimens and clinical impression with paired specimens for acute ...	2011	21888794
leptospirosis among hospitalized febrile patients in northern tanzania.	we enrolled consecutive febrile admissions to two hospitals in moshi, tanzania. confirmed leptospirosis was defined as a ≥ 4-fold increase in microscopic agglutination test (mat) titer; probable leptospirosis as reciprocal mat titer ≥ 800; and exposure to pathogenic leptospires as titer ≥ 100. among 870 patients enrolled in the study, 453 (52.1%) had paired sera available, and 40 (8.8%) of these met the definition for confirmed leptospirosis. of 832 patients with ≥ 1 serum sample available, 30 ( ...	2011	21813847
similar structures but different roles - an updated perspective on tlr structures.	toll-like receptors (tlrs) are pattern recognition receptors that recognize conserved structures in pathogens, trigger innate immune responses, and prime antigen-specific adaptive immunity. elucidation of crystal structures of tlrs interacting with their ligands such as tlr1-2 with triacylated lipopeptide, tlr2-6 with diacylated lipopeptide, tlr4-md-2 with lps, and tlr3 with double-stranded rna (dsrna) have enabled an understanding of the initiation of tlr signaling. agonistic ligands such as lp ...	2011	21845181
production of reactive oxygen (h2o2) and nitrogen (no) intermediates and tnf-α in mice genetically selected for high (h) and low (l) antibody response and experimentally infected with leptospira serovar pomona.	the aim of the present study was to evaluate the activity of macrophages, and the production of tnf-α and antibodies against experimental infection by leptospira serovar pomona in mice genetically selected for high (h) or low (l) humoral immune response. to evaluate macrophagic activity, peritoneal and splenic lavages were performed for determination of oxygen (h2o2) and nitrogen (no) intermediates. the production of the tumor necrosis factor (tnf-α) was investigated through bioassays in serum a ...	2011	24031688
outpatient follow-up of patients hospitalized for acute leptospirosis.	the outcome of leptospirosis after the resolution of acute disease, either spontaneously or after treatment, is not well described. the aim of this study was to assess the possible sequelae of acute leptospirosis after hospital discharge.	2011	21616696
trapping conformational states along ligand-binding dynamics of peptide deformylase: the impact of induced fit on enzyme catalysis.	for several decades, molecular recognition has been considered one of the most fundamental processes in biochemistry. for enzymes, substrate binding is often coupled to conformational changes that alter the local environment of the active site to align the reactive groups for efficient catalysis and to reach the transition state. adaptive substrate recognition is a well-known concept; however, it has been poorly characterized at a structural level because of its dynamic nature. here, we provide ...	2011	21629676
sporadic urban leptospirosis.	severe leptospirosis (weil syndrome) was diagnosed in an otherwise healthy environmental worker in baltimore alleys in late november 2010. he developed multiple organ failure but responded to antibiotic therapy and experienced a full recovery within 4 weeks. his diagnosis was confirmed by a rise in indirect hemagglutinin titer (acute 0, convalescent 400). the subject had close contact with baltimore alley rats; a similar epidemiologic exposure and location reported in an outbreak 15 years ago.	2011	23882321
chemical analysis of single cells.		2011	21500835
directed networks reveal genomic barriers and dna repair bypasses to lateral gene transfer among prokaryotes.	lateral gene transfer (lgt) plays a major role in prokaryote evolution with only a few genes that are resistant to it; yet the nature and magnitude of barriers to lateral transfer are still debated. here, we implement directed networks to investigate donor-recipient events of recent lateral gene transfer among 657 sequenced prokaryote genomes. for 2,129,548 genes investigated, we detected 446,854 recent lateral gene transfer events through nucleotide pattern analysis. among these, donor-recipien ...	2011	21270172
ataqs: a computational software tool for high throughput transition optimization and validation for selected reaction monitoring mass spectrometry.	since its inception, proteomics has essentially operated in a discovery mode with the goal of identifying and quantifying the maximal number of proteins in a sample. increasingly, proteomic measurements are also supporting hypothesis-driven studies, in which a predetermined set of proteins is consistently detected and quantified in multiple samples. selected reaction monitoring (srm) is a targeted mass spectrometric technique that supports the detection and quantification of specific proteins in ...	2011	21414234
pathogenesis of leptospirosis: the influence of genomics.	leptospirosis is the most widespread zoonosis worldwide and is caused by serovars of pathogenic leptospira species. the understanding of leptospiral pathogenesis lags far behind that of many other bacterial pathogens. current research is thus directed at identification of leptospiral virulence factors. saprophytic leptospira species are environmental organisms that never cause disease. comparative genomics of pathogens and saprophytes has allowed the identification of more than 900 genes unique ...	2011	21440384
development of transcriptional fusions to assess leptospira interrogans promoter activity.	leptospirosis is a zoonotic infectious disease that affects both humans and animals. the existing genetic tools for leptospira spp. have improved our understanding of the biology of this spirochete as well as the interaction of pathogenic leptospires with the mammalian host. however, new tools are necessary to provide novel and useful information to the field.	2011	21445252
a unique genotype of leptospira interrogans serovar pomona type kennewicki is associated with equine abortion.	although serologic data indicate horses in n. america are exposed to a variety of leptospiral serovars, abortion is almost always associated with leptospira interrogans serovar pomona type kennewicki. a variety of wildlife including raccoons, white tailed deer, striped skunks, opossums, and red and grey foxes have been shown to host serovar pomona and have therefore been suspect as sources of infection for pregnant mares. the aim of the present study was to examine genetic diversity in serovar p ...	2011	21450416
accuracy of loop-mediated isothermal amplification for diagnosis of human leptospirosis in thailand.	there is a lack of diagnostic tests for leptospirosis in technology-restricted settings. we developed loop-mediated isothermal amplification (lamp) specific for the 16s ribosomal rna gene (rrs) of pathogenic and intermediate group leptospira species. the lower limit of detection was 10 genomic equivalents/reaction, and analytical specificity was high; we observed positive reactions for pathogenic/intermediate groups and negative reactions for non-pathogenic leptospira species and other bacterial ...	2011	21460019
exposure to infectious agents in dogs in remote coastal british columbia: possible sentinels of diseases in wildlife and humans.	ranked among the top threats to conservation worldwide, infectious disease is of particular concern for wild canids because domestic dogs (canis familiaris) may serve as sources and reservoirs of infection. on british columbia's largely undeveloped but rapidly changing central and north coasts, little is known about diseases in wolves (canis lupus) or other wildlife. however, several threats exist for transfer of diseases among unvaccinated dogs and wolves. to gain baseline data on infectious ag ...	2011	21461190
surface-associated hsp60 chaperonin of leptospira interrogans serovar autumnalis n2 strain as an immunoreactive protein.	the present study has been formulated in order to detect an immunoreactive protein whose identification can play a major role in the early diagnosis of disease. the identified protein will be produced by recombinant methods and used for the recombinant protein based elisa. a comparison was made between the developed method and the gold standard mat test to evaluate the serodiagnosis potential of the protein. the protein profile, immunoblot and maldi-tof analysis was carried out to identify the i ...	2011	21468684
comparison of real-time pcr assays for detection of pathogenic leptospira spp. in blood and identification of variations in target sequences.	leptospirosis is considered an underdiagnosed disease. although several pcr-based methods are currently in use, there is little information on their comparability. in this study, four quantitative real-time pcr (qpcr) assays (sybr green and taqman chemistries) targeting the secy, lfb1, and lipl32 genes were evaluated as diagnostic assays. in our hands, these assays can detect between 10(2) and 10(3) bacteria/ml of pure culture, whole-blood, plasma, and serum samples. in three independent experim ...	2011	21471336
rnie: genome-wide prediction of bacterial intrinsic terminators.	bacterial rho-independent terminators (rits) are important genomic landmarks involved in gene regulation and terminating gene expression. in this investigation we present rnie, a probabilistic approach for predicting rits. the method is based upon covariance models which have been known for many years to be the most accurate computational tools for predicting homology in structural non-coding rnas. we show that rnie has superior performance in model species from a spectrum of bacterial phyla. fu ...	2011	21478170
potent innate immune response to pathogenic leptospira in human whole blood.	leptospirosis is caused by pathogenic spirochetes of the genus leptospira. the bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. in general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. not much is known about the innate immune response to leptospires during haematogenous dissemination. previous work showed that a human thp-1 cell line recognized heat-killed leptospires a ...	2011	21483834
[leptospirosis outbreak in calves from corrientes province, argentina].	leptospirosis is an infectious disease resulting in significant economic losses in livestock production. this disease causes abortion, embryo death, death of calves within the first few days of life and mastitis. we report a leptospirosis outbreak in calf growing and fattening. histopathological and hemoparasite studies, immunofluorescence, and bacterial cultures were performed. a strain of leptospira interrogans serovar pomona was isolated from samples collected from dead calves.	2011	21491066
[ultramicroscopic alterations in placental tissue from infected animals with leptospira interrogans serovar pomona].		2011	21491071
role of inducible nitric oxide synthase in the pathogenesis of experimental leptospirosis.	nitric oxide (no) produced by inducible nitric oxide synthase (inos) is a radical effector molecule of the innate immune system that can directly inhibit pathogen replication. in order to study subsequent inos kidney expression in experimental leptospirosis, golden syrian hamsters and c3h/hej mice were infected intraperitoneally with 10(2) or 10(7) virulent leptospira interrogans serovar copenhageni (lic) strain fiocruz l1-130. results showed increased levels of inos mrna and protein in kidneys ...	2011	21497651
fourteen-genome comparison identifies dna markers for severe-disease-associated strains of clostridium difficile.	clostridium difficile is a common cause of infectious diarrhea in hospitalized patients. a severe and increased incidence of c. difficile infection (cdi) is associated predominantly with the nap1 strain; however, the existence of other severe-disease-associated (sda) strains and the extensive genetic diversity across c. difficile complicate reliable detection and diagnosis. comparative genome analysis of 14 sequenced genomes, including those of a subset of nap1 isolates, allowed the assessment o ...	2011	21508155
proteomic analyses of nucleoid-associated proteins in escherichia coli, pseudomonas aeruginosa, bacillus subtilis, and staphylococcus aureus.	the bacterial nucleoid contains several hundred kinds of nucleoid-associated proteins (naps), which play critical roles in genome functions such as transcription and replication. several naps, such as hu and h-ns in escherichia coli, have so far been identified.	2011	21541338
serosurvey of leptospirosis and investigation of a possible novel serovar arborea in farmed deer in new zealand.	to investigate the prevalence of leptospira spp. and possible novel serovar arborea infection in farmed deer in new zealand.	2011	21541888
passive immunization with leptospira lps-specific agglutinating but not non-agglutinating monoclonal antibodies protect guinea pigs from fatal pulmonary hemorrhages induced by serovar copenhageni challenge.	leptospira interrogans serovar copenhageni causes pulmonary hemorrhages with respiratory failure, a major cause of death in leptospirosis patients. protective immunity to leptospira is known to correlate with the production of leptospiral lipopolysaccharide (l-lps)-specific agglutinating antibodies. we generated l-lps-specific mouse monoclonal antibodies (mabs) and investigated if these mabs can protect guinea pigs against fatal pulmonary hemorrhages caused by serovar copenhageni. the mabs l8h4 ...	2011	21549788
development of a dna microarray for detection and identification of legionella pneumophila and ten other pathogens in drinking water.	the safety and accessibility of drinking water are major concerns throughout the world. consumption of water contaminated with infectious agents, toxic chemicals or radiological hazards represents a significant health risk and is strongly associated with mortality. therefore, we have developed an oligonucleotide-based microarray using the sequences of 16s-23s rdna internal transcribed spacer regions (its) and the gyrase subunit b gene (gyrb) found in the most prevalent and devastating waterborne ...	2011	21276629
prevalence and carrier status of leptospirosis in smallholder dairy cattle and peridomestic rodents in kandy, sri lanka.	leptospirosis is an important bacterial zoonotic disease globally and one of the notifiable diseases in sri lanka. other than human leptospirosis, little information is available on leptospirosis in domestic and feral animals in sri lanka. thus, this study attempted to determine the prevalence and carrier status of leptospirosis in smallholder dairy cattle and peridomestic rodents to understand the impact of the disease on public health in kandy, sri lanka. cattle and rodent samples were collect ...	2011	21284522
the role of fruit bats in the transmission of pathogenic leptospires in australia.	although antileptospiral antibodies and leptospiral dna have been detected in australian fruit bats, the role of such bats as infectious hosts for the leptospires found in rodents and humans remains unconfirmed. a cohort-design, replicated survey was recently conducted in far north queensland, australia, to determine if the abundance and leptospiral status of rodents were affected by association with colonies of fruit bats (pteropus conspicillatus spp.) via rodent contact with potentially infect ...	2011	21294951
serum tnf-a, stnfr1, il-6, il-8 and il-10 levels in weil's syndrome.	studies on cytokine levels in weil's syndrome are lacking. in this study, tnf-a, stnfr1, il-6, il-8 and il-10 levels were measured in 44 serum samples of patients diagnosed with leptospira interrogans serovar icterohaemorrhagiae infection. tnf-a levels linked with pulmonary hemorrhagic implications, while elevated stnfr1 and il-10 levels linked with fatal cases. il-6 and il-8 did not seem to affect the outcome of the disease. immune response pattern in weil's syndrome bears resemblance to other ...	2011	21316985
adenosine deaminase activity in serum, erythrocytes and lymphocytes of rats infected with leptospira icterohaemorrhagiae.	leptospirosis is a systemic disease of humans and domestic animals, mainly dogs, cattle and swine. the course of human leptospirosis varies from mild to severe fatal forms and the most severe form of human leptospirosis is principally caused by leptospira interrogans serovar icterohaemorrhagiae (l. icterohaemorrhagiae). the enzyme adenosine deaminase (ada) plays an important role in the production and differentiation of blood cells. the aim of this study was to evaluate the activity of ada in se ...	2011	21320715
validation of assays to monitor immune responses in the syrian golden hamster (mesocricetus auratus).	the syrian golden hamster (mesocricetus auratus) is a valuable but under-utilized animal model for studies of human viral pathogens such as bunyaviruses, arenaviruses, flaviviruses, henipaviruses, and sars-coronavirus. a lack of suitable reagents and specific assays for monitoring host responses has limited the use of this animal model to clinical observations, pathology and humoral immune responses. the objective of this study was to establish and validate assays to monitor host immune response ...	2011	21334343
the multifunctional ligb adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic leptospira interrogans.	leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as leptospira interrogans. the mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is ...	2011	21347378
leptospirosis serodiagnosis by elisa based on recombinant outer membrane protein.	the outer membrane protein lipl21, lipl32, lipl41 and loa22 of leptospira interrogans serovar copenhageni were previously revealed by immunoproteomic analysis, using sera from acute phase infection in a guinea pig. the full-length dna of each protein was then cloned from the same serovar and expressed in prset vector. the obtained molecular weight (mw) of recombinant proteins rlipl21, rlipl32 and rloa22 were slightly higher than the mw predicted from nucleotide sequences of each inserted gene, w ...	2011	21353274
host-pathogen interactions made transparent with the zebrafish model.	the zebrafish holds much promise as a high-throughput drug screening model for immune-related diseases, including inflammatory and infectious diseases and cancer. this is due to the excellent possibilities for in vivo imaging in combination with advanced tools for genomic and large scale mutant analysis. the context of the embryo's developing immune system makes it possible to study the contribution of different immune cell types to disease progression. furthermore, due to the temporal separatio ...	2011	21366518
plasmodium immunomics.	the plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. the plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ∼5300 putative proteins. no malaria vaccine has yet been licensed. many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. vaccine efforts to ...	2011	20816843
plasmodium immunomics.	the plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. the plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ∼5300 putative proteins. no malaria vaccine has yet been licensed. many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. vaccine efforts to ...	2011	20816843
innate immune responses to systemic acinetobacter baumannii infection in mice: neutrophils, but not il-17, mediate host resistance.	acinetobacter baumannii is a nosocomial pathogen with a high prevalence of multiply drug resistant strains, causing pneumonia and sepsis. the current studies further develop a systemic mouse model of this infection and characterize selected innate immune responses to the organism. five clinical isolates, with varying degrees of antibiotic resistance, were assessed for virulence in two mouse strains, and between male and female mice, using intraperitoneal infection. nearly a 1000-fold difference ...	2011	21576323
attenuated nephritis in inducible nitric oxide synthase-knockout c57bl/6 mice and pulmonary haemorrhage in cb17 scid and recombination activating gene 1-knockout c57bl/6 mice infected with leptospira interrogans.	the aims of this study were to investigate the frequency of pulmonary haemorrhage (ph) in mice unable to produce functional b- and t-lymphocytes and to explore the effect of an inducible nitric oxide synthase (inos) knockout (ko) on the frequency/severity of interstitial nephritis in vivo. we studied the outcome of infection by the virulent leptospira interrogans serovar copenhageni strain cop. the animals used were inos-ko mice; recombination activating gene 1 ko (rag1-ko); cb17 severe combined ...	2011	21576342
survival of a pathogenic leptospira serovar in response to combined in vitro ph and temperature stresses.	leptospira interrogans is a zoonotic pathogen hosted commensally by many mammalian species. on the western pacific island of american samoa a seroprevalence survey conducted in 2004 indicated that 17% of subjects tested had been exposed to several leptospira serovars, including l. interogans icterohaemorrhagiae. resource management agencies promoted improved animal waste management practices, including composting, to reduce the risk of water contamination and human exposure from small pig husban ...	2011	21592682
seasonality of human leptospirosis in reunion island (indian ocean) and its association with meteorological data.	leptospirosis is a disease which occurs worldwide but particularly affects tropical areas. transmission of the disease is dependent on its excretion by reservoir animals and the presence of moist environment which allows the survival of the bacteria.	2011	21655257
heterologous expression of pathogen-specific genes liga and ligb in the saprophyte leptospira biflexa confers enhanced adhesion to cultured cells and fibronectin.	in comparison to other bacterial pathogens, our knowledge of the molecular basis of the pathogenesis of leptospirosis is extremely limited. an improved understanding of leptospiral pathogenetic mechanisms requires reliable tools for functional genetic analysis. leptospiral immunoglobulin-like (lig) proteins are surface proteins found in pathogenic leptospira, but not in saprophytes. here, we describe a system for heterologous expression of the leptospira interrogans genes liga and ligb in the sa ...	2011	21658265
highly virulent leptospira borgpetersenii strain characterized in the hamster model.	abstract. a recent study by our group reported the isolation and partial serological and molecular characterization of four leptospira borgpetersenii serogroup ballum strains. here, we reproduced experimental leptospirosis in golden syrian hamsters (mesocricetus auratus) and carried out standardization of lethal dose 50% (ld50) of one of these strains (4e). clinical disease features and histopathologic analyses of tissue lesions were also observed. as results, strain 4e induced lethality in the ...	2011	21813846
in vitro evidence for immune evasion activity by human plasmin associated to pathogenic leptospira interrogans.	leptospirosis is a widespread re-emerging zoonosis of human and veterinary concern. it has been shown that virulent leptospires protect themselves against the host's innate immune system, a strategy that allows the bacteria to reach immunologically safe environments. although extensive studies on host-pathogen interactions have been performed, little is known on how leptospires deal with host immune attack. in a previous work, we demonstrated the ability of leptospires to bind human plasminogen ...	2011	21802507
structural and sequence analysis of imelysin-like proteins implicated in bacterial iron uptake.	imelysin-like proteins define a superfamily of bacterial proteins that are likely involved in iron uptake. members of this superfamily were previously thought to be peptidases and were included in the merops family m75. we determined the first crystal structures of two remotely related, imelysin-like proteins. the psychrobacter arcticus structure was determined at 2.15 å resolution and contains the canonical imelysin fold, while higher resolution structures from the gut bacteria bacteroides ovat ...	2011	21799754
discovery of an orthoreovirus in the aborted fetus of a steller sea lion (eumetopias jubatus).	an aborted mid-gestational male steller sea lion fetus with an attached placenta was recovered on the floor of an open floating capture trap located off norris rock near denman island, british columbia. viral culture of the placenta demonstrated cytopathic effect. although no specific signal was obtained in microarray experiments using rna obtained from viral culture, elution and sequence analysis revealed the presence of a reovirus. complete genome pyrosequencing led to the identification of an ...	2011	21795475
a sensitive and specific igm-elisa for the serological diagnosis of human leptospirosis using a rlipl32/1-lipl21-ompl1/2 fusion protein.	to construct a lipl32/1-lipl21-ompl1/2 fusion gene and its prokaryotic expression system, and to establish an enzyme-linked immunosorbent assay (elisa) using the rlipl32/1-lipl21-ompl1/2 fusion antigen of leptospira interrogans for sensitive and specific detection of igm in the serum of patients with leptospirosis.	2011	21784316
quantification of mrna and protein and integration with protein turnover in a bacterium.	biological function and cellular responses to environmental perturbations are regulated by a complex interplay of dna, rna, proteins and metabolites inside cells. to understand these central processes in living systems at the molecular level, we integrated experimentally determined abundance data for mrna, proteins, as well as individual protein half-lives from the genome-reduced bacterium mycoplasma pneumoniae. we provide a fine-grained, quantitative analysis of basic intracellular processes un ...	2011	21772259
absolute quantification of microbial proteomes at different states by directed mass spectrometry.	over the past decade, liquid chromatography coupled with tandem mass spectrometry (lc-ms/ms) has evolved into the main proteome discovery technology. up to several thousand proteins can now be reliably identified from a sample and the relative abundance of the identified proteins can be determined across samples. however, the remeasurement of substantially similar proteomes, for example those generated by perturbation experiments in systems biology, at high reproducibility and throughput remains ...	2011	21772258
characterization of novel ompa-like protein of leptospira interrogans that binds extracellular matrix molecules and plasminogen.	leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease of human and veterinary concern. the identification of novel proteins that mediate host-pathogen interactions is important for understanding the bacterial pathogenesis as well as to identify protective antigens that would help fight the disease. we describe in this work the cloning, expression, purification and characterization of three predicted leptospiral membrane proteins, lic10258, lic12880 (lp30) and lic12 ...	2011	21755014
elucidation of a novel vibrio cholerae lipid a secondary hydroxy-acyltransferase and its role in innate immune recognition.	similar to most gram-negative bacteria, the outer leaflet of the outer membrane of vibrio cholerae is comprised of lipopolysaccharide. previous reports have proposed that v. cholerae serogroups o1 and o139 synthesize structurally different lipid a domains, which anchor lipopolysaccharide within the outer membrane. in the current study, intact lipid a species of v. cholerae o1 and o139 were analysed by mass spectrometry. we demonstrate that v. cholerae serogroups associated with human disease syn ...	2011	21752109
immuno-fluorescence assay of leptospiral surface-exposed proteins.	bacterial surface proteins are involved in direct contact with host cells and in uptake of nutrients from the environment (1). for this reason, cellular localization can provide insights into the functional role of bacterial proteins. surface localization of bacterial proteins is a key step towards identification of virulence factors involved in mechanisms of pathogenicity. methods for fractionating leptospiral membranes (2-5) may be selective for a certain class of outer-membrane proteins (omps ...	2011	21750491
leptospira interrogans encodes an rok family glucokinase involved in a cryptic glucose utilization pathway.	although leptospira interrogans is unable to utilize glucose as its carbon/energy source, the la_1437 gene of l. interrogans serovar lai potentially encodes a group iii glucokinase (glk). the l. interrogans glk (liglk) heterogeneously expressed in escherichia coli was purified and proved to be a homodimeric enzyme with its specific activity of 12.3 ┬▒ 0.6 u/mg x protein determined under an improved assay condition (ph 9.0, 50 ┬░ c), 7.5-fold higher than that assayed under the previously used con ...	2011	21705346
[the ompa-like protein loa22 from leptospira interrogans serovar lai induces apoptosis in a549 via ca2+ signal pathway].	to study the effect of loa22 mature peptide on the apoptosis of a549 to explore the mechanism of pulmonary impairment in severe forms of leptospirosis.	2011	21826986
incorporation of real-time pcr into routine public health surveillance of culture negative bacterial meningitis in s+úo paulo, brazil.	real-time (rt)-pcr increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. we validated a multiplex rt-pcr assay for streptococcus pneumoniae, neisseria meningitidis, and haemophilus influenzae in brazil. risk factors for being culture-negative, rt-pcr positive were determined. the sensitivity of rt-pcr in cerebrospinal fluid (csf) was 100% (95% confidence limits, 96.0%-100%) for n. meningitidis, 97.8% (85.5%-99.9%) fo ...	2011	21731621
standardisation and application of polymerase chain reaction for detection of lru a and lru b gene of leptospira interrogans in aqueous humors of uveitic patients.		2011	21834695
assessment of clinical pathology and pathogen exposure in sea otters (enhydra lutris) bordering the threatened population in alaska.	northern sea otter (enhydra lutris kenyoni) abundance has decreased dramatically over portions of southwest alaska, usa, since the mid-1980s, and this stock is currently listed as threatened under the endangered species act. in contrast, adjacent populations in south central alaska, usa, and russia have been stable to increasing during the same period. sea otters bordering the area classified in the recent decline were live-captured during 2004-2006 at bering island, russia, and the kodiak archi ...	2011	21719822
leptospirosis is associated with markedly increased triglycerides and small dense low-density lipoprotein and decreased high-density lipoprotein.	the objective of the present study was to evaluate the effects of acute infection with leptospira interrogans on lipids, lipoproteins and associated enzymes. fasting serum levels of total cholesterol (tc), low-density lipoprotein cholesterol (ldl-c), high-density lipoprotein cholesterol (hdl-c), triglycerides (tg), apolipoproteins (apo) a-+ö, b, e, c-ii, c-iii and lipoprotein (a) [lp(a)] were determined in patients with leptospirosis on diagnosis and 4-ámonths after recovery as well as in age- a ...	2011	21688175
characteristic features of intracellular pathogenic leptospira in infected murine macrophages.	leptospira interrogans is a spirochaete responsible for a zoonotic disease known as leptospirosis. leptospires are able to penetrate the abraded skin and mucous membranes and rapidly disseminate to target organs such as the liver, lungs and kidneys. how this pathogen escape from innate immune cells and spread to target organs remains poorly understood. in this paper, the intracellular trafficking undertaken by non-pathogenic leptospira biflexa and pathogenic l.ôçâinterrogans in mouse bone marrow ...	2011	21819516
leptospirosis and tularaemia in raccoons (procyon lotor) of larimer country, colorado.	raccoons (procyon lotor) are commonly implicated as carriers of many zoonotic pathogens. the purpose of this cross-sectional study was to look for leptospira interrogans and francisella tularensis in opportunistically sampled, free-ranging raccoons of larimer country, colorado, usa. sixty-five animals were included in the study and testing consisted of gross post-mortem examination, histopathology, and both immunohistochemistry and pcr for l. interrogans and f. tularensis. no significant gross l ...	2011	21824365
community structures of fecal bacteria in cattle from different animal feeding operations.	the fecal microbiome of cattle plays a critical role not only in animal health and productivity but also in food safety, pathogen shedding, and the performance of fecal pollution detection methods. unfortunately, most published molecular surveys fail to provide adequate detail about variability in the community structures of fecal bacteria within and across cattle populations. using massively parallel pyrosequencing of a hypervariable region of the rrna coding region, we profiled the fecal micro ...	2011	21378055
the minimal proteome in the reduced mitochondrion of the parasitic protist giardia intestinalis.	the mitosomes of giardia intestinalis are thought to be mitochondria highly-reduced in response to the oxygen-poor niche. we performed a quantitative proteomic assessment of giardia mitosomes to increase understanding of the function and evolutionary origin of these enigmatic organelles. mitosome-enriched fractions were obtained from cell homogenate using optiprep gradient centrifugation. to distinguish mitosomal proteins from contamination, we used a quantitative shot-gun strategy based on isob ...	2011	21390322
maximizing the chances of detecting pathogenic leptospires in mammals: the evaluation of field samples and a multi-sample-per-mammal, multi-test approach.	identification of wild animals that harbour the causative leptospires, and the identification of the most important of these 'wild reservoirs' (in terms of threat to human health), are key factors in the epidemiology of human leptospirosis. in an epidemiological investigation in the australian state of queensland, in 2007-2008, samples were collected from fruit bats (pteropus conspicillatus) and rodents (to investigate the potential role of fruit bats in the maintenance and transmission of lepto ...	2011	21396251
recombinant lipl32 and liga from leptospira are unable to stimulate protective immunity against leptospirosis in the hamster model.	the major antigenic component of pathogenic leptospira spp. is lipopolysaccharide (lps). however, due to the specificity of the immune response generated towards lps and the diversity in leptospiral lps carbohydrate structure, current commercial vaccines stimulate protection only against homologous or closely related serovars. vaccines that confer heterologous protection would enhance protection in vaccinated animals and reduce transmission to humans. several studies have investigated the potent ...	2011	21396409
evaluation of envelope domain iii-based single chimeric tetravalent antigen and monovalent antigen mixtures for the detection of anti-dengue antibodies in human sera.	flavivirus cross-reactive antibodies in human sera interfere with the definitive identification of dengue virus (denv) infections especially in areas with multiple co-circulating flaviviruses. use of denv envelope domain-iii (ediii) can partially resolve the problem. this study has examined the effect of (i) incorporating the ediiis of four denv serotypes into a single chimeric antigen, and (ii) immobilizing the antigen through specific interaction on the sensitivity and specificity of anti-denv ...	2011	21401963
comparative proteogenomic analysis of the leptospira interrogans virulence-attenuated strain ipav against the pathogenic strain 56601.	the virulence-attenuated leptospira interrogans serovar lai strain ipav was derived by prolonged laboratory passage from a highly virulent ancestral strain isolated in china. we studied the genetic variations of ipav that render it avirulent via comparative analysis against the pathogenic l. interrogans serovar lai strain 56601. the complete genome sequence of the ipav strain was determined and used to compare with, and then rectify and reannotate the genome sequence of strain 56601. aside from ...	2011	21423275
electrocardiographic changes in hospitalized patients with leptospirosis over a 10-year period.	the aim of this study was to investigate the incidence and type of ecg changes in patients with leptospirosis regardless of clinical evidence of cardiac involvement.	2011	21709630
inactivation of clpb in the pathogen leptospira interrogans reduces virulence and resistance to stress conditions.	leptospira interrogans is the causative agent of leptospirosis, which is an emerging zoonotic disease. resistance to stress conditions is largely uncharacterized for this bacterium. we therefore decided to analyze a clpb mutant that we obtained by random transposon mutagenesis. the mutant did not produce any of the two isoforms of clpb. the clpb mutant exhibited growth defects at 30-¦ and 37-¦c and in poor nutrient medium and showed increased susceptibility to oxidative stress, whereas the genet ...	2011	21730091
improvement of trivalent leptospira vaccine by removal of anaphylactic agents.	the anaphylactic reactions in cattle following leptospira vaccination mostly booster dose in different parts of iran have been reported. the serum proteins as allergic substances are components of liquid phase of the vaccine. therefore, the vaccine was modified by washing the whole cultures by centrifugations. the modified vaccine was safe in laboratory animals and cattle as well as under field conditions. microagglutination test revealed a similar pattern of antibody response to the three lepto ...	2011	21698521
complete genome sequence of brachyspira intermedia reveals unique genomic features in brachyspira species and phage-mediated horizontal gene transfer.	abstract:	2011	21816042
the novel leptospiral surface adhesin, lsa20, binds laminin, human plasminogen and is probably expressed during infection.	leptospirosis is an emerging infectious disease caused by pathogenic species of leptospira. in this work, we report the cloning, expression, purification and characterization of two predicted leptospiral outer membrane proteins, lic11469, and lic11030. the lic11469 protein is well conserved among leptospiral strains while lic11030 was identified only in l. interrogans. we confirmed by surface proteolysis of intact leptospires with proteinase k that these proteins are most likely new surface lept ...	2011	21844229
Gene expression profiles of immune mediators and histopathological findings in animal models of leptospirosis: comparison between susceptible hamsters and resistant mice.	Leptospirosis is a widespread zoonosis characterised by multiple organ failures and the variability of host susceptibility towards pathogenic Leptospira strains. In this study, we put the role of inflammatory mediators in parallel with bacterial burdens and organ lesions by comparing a susceptible animal model, the hamster, and a resistant one, the OF1 mouse, both infected with virulent L. interrogans serovar Icterohaemorrhagiae strain Verdun. Histological observations evidenced oedema, congesti ...	2011	21844232
[Southern taiga combined natural foci of spirochetoses].	Study of possibility of existence of combined natural foci of spirochetoses (ixodes tick borrelioses and leptospiroses) in typical taiga forests, and their etiologic and reservoir-host structure.	2011	22145345
deciphering morphological determinants of the helix-shaped leptospira.	leptospira spp. are thin, highly motile, slow-growing spirochetes that can be distinguished from other bacteria on the basis of their unique helical shape. defining the mechanisms by which these bacteria generate and maintain this atypical morphology should greatly enhance our understanding of the fundamental physiology of these pathogens. in this study, we showed that peptidoglycan sacculi from leptospira spp. retain the helical shape of intact cells. interestingly, the distribution of muropept ...	2011	21926230
Borrelia burgdorferi enolase is a surface-exposed plasminogen binding protein.	Borrelia burgdorferi is the causative agent of Lyme disease, the most commonly reported arthropod-borne disease in the United States. B. burgdorferi is a highly invasive bacterium, yet lacks extracellular protease activity. In order to aid in its dissemination, B. burgdorferi binds plasminogen, a component of the hosts' fibrinolytic system. Plasminogen bound to the surface of B. burgdorferi can then be activated to the protease plasmin, facilitating the bacterium's penetration of endothelial cel ...	2011	22087329
leptospirosis outbreak in sri lanka in 2008: lessons for assessing the global burden of disease.	global leptospirosis disease burden estimates are hampered by the lack of scientifically sound data from countries with probable high endemicity and limited diagnostic capacities. we describe the seroepidemiologic and clinical characteristics of the leptospirosis outbreak in 2008 in sri lanka. definitive/presumptive case definitions proposed by the world health organization leptospirosis epidemiology reference group were used for case confirmation. of the 404 possible cases, 155 were confirmed t ...	2011	21896807
interaction of human complement factor h variants tyr⁴⁰² and his⁴⁰² with leptospira spp.	leptospirosis is a zoonosis caused by pathogenic bacteria from the genus leptospira. the disease represents a serious public health problem in underdeveloped tropical countries. leptospires infect hosts through small abrasions in the skin or mucous membranes and they rapidly disseminate to target organs. the capacity of some pathogenic leptospiral strains to acquire the negative complement regulators factor h (fh) and c4b binding protein correlates with their ability to survive in human serum. i ...	2011	22566834