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diagnosis and management of borrelia turicatae infection in febrile soldier, texas, usa.in august 2015, a soldier returned from field exercises in texas, usa, with nonspecific febrile illness. culture and sequencing of spirochetes from peripheral blood diagnosed borrelia turicatae infection. the patient recovered after receiving doxycycline. no illness occurred in asymptomatic soldiers potentially exposed to the vector tick and prophylactically given treatment.201728418310
an in vitro blood-feeding method revealed differential borrelia turicatae (spirochaetales: spirochaetaceae) gene expression after spirochete acquisition and colonization in the soft tick ornithodoros turicata (acari: argasidae).in the midwestern, southwestern, and southern part of the united states, the soft tick ornithodoros turicata transmits the spirochete borrelia turicatae, the causative agent of relapsing fever in humans. in this study, we report a simplified and an efficient method of in vitro feeding to evaluate o. turicata-b. turicatae interactions. both nymphal and adult female ticks successfully acquired spirochetes upon in vitro feeding on the b. turicatae-infected blood. we also noted transstadial transmis ...201728399292
synanthropic mammals as potential hosts of tick-borne pathogens in panama.synanthropic wild mammals can be important hosts for many vector-borne zoonotic pathogens. the aim of this study was determine the exposure of synanthropic mammals to two types of tick-borne pathogens in panama, spotted fever group rickettsia (sfgr) and borrelia relapsing fever (rf) spirochetes. one hundred and thirty-one wild mammals were evaluated, including two gray foxes, two crab-eating foxes (from zoos), four coyotes, 62 opossum and 63 spiny rats captured close to rural towns. to evaluate ...201728060928
imaging of borrelia turicatae producing the green fluorescent protein reveals persistent colonization of the ornithodoros turicata midgut and salivary glands from nymphal acquisition through transmission.relapsing fever (rf) spirochetes colonize and are transmitted to mammals primarily by ornithodoros ticks, and little is known regarding the pathogen's life cycle in the vector. to further understand vector colonization and transmission of rf spirochetes, borrelia turicatae expressing a green fluorescent protein (gfp) marker (b. turicatae-gfp) was generated. the transformants were evaluated during the tick-mammal infectious cycle, from the third nymphal instar to adult stage. b. turicatae-gfp rem ...201727986725
host associations and genomic diversity of borrelia hermsii in an endemic focus of tick-borne relapsing fever in western north america.an unrecognized focus of tick-borne relapsing fever caused by borrelia hermsii was identified in 2002 when five people became infected on wild horse island in flathead lake, montana. the terrestrial small mammal community on the island is composed primarily of pine squirrels (tamiasciurus hudsonicus) and deer mice (peromyscus maniculatus), neither of which was known as a natural host for the spirochete. thus a 3-year study was performed to identify small mammals as hosts for b. hermsii.201627832805
chromosome and linear plasmid sequences of a 2015 human isolate of the tick-borne relapsing fever spirochete, borrelia turicatae.the sequences of the complete linear chromosome and 7 linear plasmids of the relapsing fever spirochete borrelia turicatae are presented in this report. the 925,547 bp of chromosome and 380,211 bp of plasmid sequence were predicted to contain a total of 1,131 open reading frames, with an average g+c content of 29.7%.201627417836
consensus computational network analysis for identifying candidate outer membrane proteins from borrelia spirochetes.similar to gram-negative organisms, borrelia spirochetes are dual-membrane organisms with both an inner and outer membrane. although the outer membrane contains integral membrane proteins, few of the borrelial outer membrane proteins (omps) have been identified and characterized to date. therefore, we utilized a consensus computational network analysis to identify novel borrelial omps.201627400788
tick-borne relapsing fever in dogs.in the united states, tick-borne relapsing fever (tbrf) in dogs is caused by the spirochete bacteria borrelia turicatae and borrelia hermsii, transmitted by ornithodoros spp. ticks. the hallmark diagnostic feature of this infection is the visualization of numerous spirochetes during standard blood smear examination. although the course of spirochetemia has not been fully characterized in dogs, in humans infected with tbrf the episodes of spirochetemia and fever are intermittent.201627353196
novel borrelia species detected in echidna ticks, bothriocroton concolor, in australia.to date, little has been documented about microorganisms harboured within australian native ticks or their pathogenic potential. recently, a borrelia sp. related to the relapsing fever (rf) group was identified in a single tick removed from a wild echidna (tachyglossus aculeatus). the present study investigated the presence of borrelia in 97 bothriocroton concolor ticks parasitizing echidnas in queensland, new south wales, and victoria, australia, using nested pcr with borrelia-specific primers ...201627301754
transcriptional profiling the 150 kb linear megaplasmid of borrelia turicatae suggests a role in vector colonization and initiating mammalian infection.adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. while plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. we utilized recent advances in genome sequencing to generate the most complete vers ...201626845332
assessment of the geographic distribution of ornithodoros turicata (argasidae): climate variation and host diversity.ornithodoros turicata is a veterinary and medically important argasid tick that is recognized as a vector of the relapsing fever spirochete borrelia turicatae and african swine fever virus. historic collections of o. turicata have been recorded from latin america to the southern united states. however, the geographic distribution of this vector is poorly understood in relation to environmental variables, their hosts, and consequently the pathogens they transmit.201626829327
functional basis of microorganism classification.correctly identifying nearest "neighbors" of a given microorganism is important in industrial and clinical applications where close relationships imply similar treatment. microbial classification based on similarity of physiological and genetic organism traits (polyphasic similarity) is experimentally difficult and, arguably, subjective. evolutionary relatedness, inferred from phylogenetic markers, facilitates classification but does not guarantee functional identity between members of the same ...201526317871
mini-review: strategies for variation and evolution of bacterial antigens.across the eubacteria, antigenic variation has emerged as a strategy to evade host immunity. however, phenotypic variation in some of these antigens also allows the bacteria to exploit variable host niches as well. the specific mechanisms are not shared-derived characters although there is considerable convergent evolution and numerous commonalities reflecting considerations of natural selection and biochemical restraints. unlike in viruses, mechanisms of antigenic variation in most bacteria inv ...201526288700
a novel quality measure and correction procedure for the annotation of microbial translation initiation sites.the identification of translation initiation sites (tiss) constitutes an important aspect of sequence-based genome analysis. an erroneous tis annotation can impair the identification of regulatory elements and n-terminal signal peptides, and also may flaw the determination of descent, for any particular gene. we have formulated a reference-free method to score the tis annotation quality. the method is based on a comparison of the observed and expected distribution of all tiss in a particular gen ...201526204119
lengths of orthologous prokaryotic proteins are affected by evolutionary factors.proteins of the same functional family (for example, kinases) may have significantly different lengths. it is an open question whether such variation in length is random or it appears as a response to some unknown evolutionary driving factors. the main purpose of this paper is to demonstrate existence of factors affecting prokaryotic gene lengths. we believe that the ranking of genomes according to lengths of their genes, followed by the calculation of coefficients of association between genome ...201526114113
case report: a retrospective serological analysis indicating human exposure to tick-borne relapsing fever spirochetes in texas. 201525856342
current and past strategies for bacterial culture in clinical microbiology.a pure bacterial culture remains essential for the study of its virulence, its antibiotic susceptibility, and its genome sequence in order to facilitate the understanding and treatment of caused diseases. the first culture conditions empirically varied incubation time, nutrients, atmosphere, and temperature; culture was then gradually abandoned in favor of molecular methods. the rebirth of culture in clinical microbiology was prompted by microbiologists specializing in intracellular bacteria. th ...201525567228
pathogens in ticks collected from dogs in berlin/brandenburg, germany.tick-borne diseases are a major health risk for humans and dogs. in addition to collection and analysis of questing ticks, analysis of host-associated ticks for the presence of pathogens is a valuable method to gain insight into transmission patterns of tick-borne diseases.201425441762
high seroprevalence of borrelia miyamotoi antibodies in forestry workers and individuals suspected of human granulocytic anaplasmosis in the netherlands.substantial exposure to borrelia miyamotoi occurs through bites from ixodes ricinus ticks in the netherlands, which also transmit borrelia burgdorferi sensu lato and anaplasma phagocytophilum. direct evidence for b. miyamotoi infection in european populations is scarce. a flu-like illness with high fever, resembling human granulocytic anaplasmosis, has been attributed to b. miyamotoi infections in relatively small groups. borrelia miyamotoi infections associated with chronic meningoencephalitis ...201425356364
lymphocytes modulate innate immune responses and neuronal damage in experimental meningitis.in bacterial meningitis, excessive immune responses carry significant potential for damage to brain tissue even after successful antibiotic therapy. bacterial meningitis is regarded primarily as the domain of innate immunity, and the role of lymphocytes remains unclear. we studied the contribution of lymphocytes to acute inflammation and neurodegeneration in experimental toll-like receptor 2-driven meningitis, comparing wild-type mice with rag-1-deficient mice that have no mature t and b lymphoc ...201425348636
lymphocytes modulate innate immune responses and neuronal damage in experimental meningitis.in bacterial meningitis, excessive immune responses carry significant potential for damage to brain tissue even after successful antibiotic therapy. bacterial meningitis is regarded primarily as the domain of innate immunity, and the role of lymphocytes remains unclear. we studied the contribution of lymphocytes to acute inflammation and neurodegeneration in experimental toll-like receptor 2-driven meningitis, comparing wild-type mice with rag-1-deficient mice that have no mature t and b lymphoc ...201425348636
african relapsing fever borreliae genomospecies revealed by comparative genomics.relapsing fever borreliae are vector-borne bacteria responsible for febrile infection in humans in north america, africa, asia, and in the iberian peninsula in europe. relapsing fever borreliae are phylogenetically closely related, yet they differ in pathogenicity and vectors. their long-term taxonomy, based on geography and vector grouping, needs to be re-apprised in a genomic context. we therefore embarked into genomic analyses of relapsing fever borreliae, focusing on species found in africa.201425229054
tick surveillance for relapsing fever spirochete borrelia miyamotoi in hokkaido, japan.during 2012-2013, a total of 4325 host-seeking adult ticks belonging to the genus ixodes were collected from various localities of hokkaido, the northernmost island of japan. tick lysates were subjected to real-time pcr assay to detect borrelial infection. the assay was designed for specific detection of the relapsing fever spirochete borrelia miyamotoi and for unspecific detection of lyme disease-related spirochetes. overall prevalence of b. miyamotoi was 2% (71/3532) in ixodes persulcatus, 4.3 ...201425111141
veillonella, firmicutes: microbes disguised as gram negatives.the firmicutes represent a major component of the intestinal microflora. the intestinal firmicutes are a large, diverse group of organisms, many of which are poorly characterized due to their anaerobic growth requirements. although most firmicutes are gram positive, members of the class negativicutes, including the genus veillonella, stain gram negative. veillonella are among the most abundant organisms of the oral and intestinal microflora of animals and humans, in spite of being strict anaerob ...201324976898
genetic characterization of the human relapsing fever spirochete borrelia miyamotoi in vectors and animal reservoirs of lyme disease spirochetes in france.in france as elsewhere in europe the most prevalent tbd in humans is lyme borreliosis, caused by different bacterial species belonging to borrelia burgdorferi sensu lato complex and transmitted by the most important tick species in france, ixodes ricinus. however, the diagnosis of lyme disease is not always confirmed and unexplained syndromes occurring after tick bites have become an important issue. recently, b. miyamotoi belonging to the relapsing fever group and transmitted by the same ixodes ...201424886071
real-time monitoring of disease progression in rhesus macaques infected with borrelia turicatae by tick bite.the hallmark of disease caused by tick- and louse-borne relapsing fever due to borrelia infection is cyclic febrile episodes, which in humans results in severe malaise and may lead to death. to evaluate the pathogenesis of relapsing fever due to spirochetes in an animal model closely related to humans, disease caused by borrelia turicatae after tick bite was compared in 2 rhesus macaques in which radiotelemetry devices that recorded body temperatures in 24-hour increments were implanted. the rad ...201424879799
the borrelia hermsii factor h binding protein fhba is not required for infectivity in mice or for resistance to human complement in vitro.the primary causative agent of tick-borne relapsing fever in north america is borrelia hermsii. it has been hypothesized that b. hermsii evades complement-mediated destruction by binding factor h (fh), a host-derived negative regulator of complement. in vitro, b. hermsii produces a single fh binding protein designated fhba (fh binding protein a). the properties and ligand binding activity of fhba suggest that it plays multiple roles in pathogenesis. it binds plasminogen and has been identified a ...201424866803
annotation of protein domains reveals remarkable conservation in the functional make up of proteomes across superkingdoms.the functional repertoire of a cell is largely embodied in its proteome, the collection of proteins encoded in the genome of an organism. the molecular functions of proteins are the direct consequence of their structure and structure can be inferred from sequence using hidden markov models of structural recognition. here we analyze the functional annotation of protein domain structures in almost a thousand sequenced genomes, exploring the functional and structural diversity of proteomes. we find ...201124710297
transmission dynamics of borrelia turicatae from the arthropod vector.with the global distribution, morbidity, and mortality associated with tick and louse-borne relapsing fever spirochetes, it is important to understand the dynamics of vector colonization by the bacteria and transmission to the host. tick-borne relapsing fever spirochetes are blood-borne pathogens transmitted through the saliva of soft ticks, yet little is known about the transmission capability of these pathogens during the relatively short bloodmeal. this study was therefore initiated to unders ...201424699275
genome sequence of borrelia parkeri, an agent of enzootic relapsing fever in western north america.borrelia parkeri is a relapsing fever agent that rarely causes human infection, unlike other north american species. b. parkeri strain hr1 was isolated from ornithodoros parkeri ticks. the sequences of its linear chromosome and large plasmid were determined by next-generation sequencing. these confirmed its closer relatedness to borrelia turicatae than to borrelia hermsii.201424526628
first isolation of the relapsing fever spirochete, borrelia hermsii, from a domestic dog.in north america, tick-borne relapsing fever of humans is most frequently caused by infection with the spirochete borrelia hermsii. prior to our investigation, this spirochete was not known to infect dogs although another species, borrelia turicatae, has been isolated from domestic canids in florida and texas. a clinically ill dog in washington, usa, was spirochetemic upon examination. spirochetes were isolated from the dog's serum and examined by pcr and multi-locus sequence typing. dna sequenc ...201324252262
first isolation of the relapsing fever spirochete, borrelia hermsii, from a domestic dog.in north america, tick-borne relapsing fever of humans is most frequently caused by infection with the spirochete borrelia hermsii. prior to our investigation, this spirochete was not known to infect dogs although another species, borrelia turicatae, has been isolated from domestic canids in florida and texas. a clinically ill dog in washington, usa, was spirochetemic upon examination. spirochetes were isolated from the dog's serum and examined by pcr and multi-locus sequence typing. dna sequenc ...201324252262
development of genetic system to inactivate a borrelia turicatae surface protein selectively produced within the salivary glands of the arthropod vector.borrelia turicatae, an agent of tick-borne relapsing fever, is an example of a pathogen that can adapt to disparate conditions found when colonizing the mammalian host and arthropod vector. however, little is known about the genetic factors necessary during the tick-mammalian infectious cycle, therefore we developed a genetic system to transform this species of spirochete. we also identified a plasmid gene that was up-regulated in vitro when b. turicatae was grown in conditions mimicking the tic ...201324205425
sequence analysis and serological responses against borrelia turicatae bipa, a putative species-specific antigen.relapsing fever spirochetes are global yet neglected pathogens causing recurrent febrile episodes, chills, nausea, vomiting, and pregnancy complications. given these nonspecific clinical manifestations, improving diagnostic assays for relapsing fever spirochetes will allow for identification of endemic foci and expedite proper treatment. previously, an antigen designated the borrelia immunogenic protein a (bipa) was identified in the north american species borrelia hermsii. thus far, bipa appear ...201324069498
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
relapsing fever borreliae in africa.the study of relapsing fever borreliae in africa has long suffered from the use of non-specific laboratory tools for the direct detection of these spirochetes in clinical and vector specimens. accordingly, borrelia hispanica, borrelia crocidurae, borrelia duttonii, and borrelia recurrentis have traditionally been distinguished on the basis of geography and vector and the unproven hypothesis that each species was exclusive to one vector. the recent sequencing of three relapsing fever borrelia gen ...201323926141
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
the first case of imported relapsing fever in japan.tick-borne relapsing fever (tbrf) is endemic in discrete areas throughout the world; however, a domestic or imported case of relapsing fever has not been reported in japan. here, we report the first imported case. a previously healthy 20-year-old woman presented to our hospital on october 8, 2010, because of recurrent fever and lower leg pain. before consultation, she had experienced four febrile episodes at 10-12-day intervals after returning from her stay in uzbekistan from 1 to 8 september. g ...201323857020
what is the risk for exposure to vector-borne pathogens in united states national parks?united states national parks attract > 275 million visitors annually and collectively present risk of exposure for staff and visitors to a wide range of arthropod vector species (most notably fleas, mosquitoes, and ticks) and their associated bacterial, protozoan, or viral pathogens. we assessed the current state of knowledge for risk of exposure to vector-borne pathogens in national parks through a review of relevant literature, including internal national park service documents and organismal ...201323540107
methods of combinatorial optimization to reveal factors affecting gene length.in this paper we present a novel method for genome ranking according to gene lengths. the main outcomes described in this paper are the following: the formulation of the genome ranking problem, presentation of relevant approaches to solve it, and the demonstration of preliminary results from prokaryotic genomes ordering. using a subset of prokaryotic genomes, we attempted to uncover factors affecting gene length. we have demonstrated that hyperthermophilic species have shorter genes as compared ...201223300345
endemic foci of the tick-borne relapsing fever spirochete borrelia crocidurae in mali, west africa, and the potential for human infection.tick-borne relapsing fever spirochetes are maintained in endemic foci that involve a diversity of small mammals and argasid ticks in the genus ornithodoros. most epidemiological studies of tick-borne relapsing fever in west africa caused by borrelia crocidurae have been conducted in senegal. the risk for humans to acquire relapsing fever in mali is uncertain, as only a few human cases have been identified. given the high incidence of malaria in mali, and the potential to confuse the clinical dia ...201223209863
comparison of pcr/electron spray ionization-time-of-flight-mass spectrometry versus traditional clinical microbiology for active surveillance of organisms contaminating high-use surfaces in a burn intensive care unit, an orthopedic ward and healthcare workers.understanding nosocomial pathogen transmission is restricted by culture limitations. novel platforms, such as pcr-based electron spray ionization-time-of-flight-mass spectrometry (esi-tof-ms), may be useful as investigational tools.201223050585
different patterns of expression and of il-10 modulation of inflammatory mediators from macrophages of lyme disease-resistant and -susceptible mice.c57bl/6j (c57) mice develop mild arthritis (lyme disease-resistant) whereas c3h/hen (c3h) mice develop severe arthritis (lyme disease-susceptible) after infection with the spirochete borrelia burgdorferi. we hypothesized that susceptibility and resistance to lyme disease, as modeled in mice, is associated with early induction and regulation of inflammatory mediators by innate immune cells after their exposure to live b. burgdorferi spirochetes. here, we employed multiplex elisa and qrt-pcr to in ...201223024745
molecular characterization of podoviral bacteriophages virulent for clostridium perfringens and their comparison with members of the picovirinae.clostridium perfringens is a gram-positive, spore-forming anaerobic bacterium responsible for human food-borne disease as well as non-food-borne human, animal and poultry diseases. because bacteriophages or their gene products could be applied to control bacterial diseases in a species-specific manner, they are potential important alternatives to antibiotics. consequently, poultry intestinal material, soil, sewage and poultry processing drainage water were screened for virulent bacteriophages th ...201222666499
alp, an arthropod-associated outer membrane protein of borrelia species that cause relapsing fever.borrelia hermsii and other relapsing fever (rf) species are noted for their highly polymorphic surface antigens, the variable major proteins (vmp). less is known about other surface proteins of these pathogens in either their vertebrate reservoirs or arthropod vectors. to further characterize these proteins, we elicited antibodies against vmp-less cells, noted antibody reactions against whole cells and cell components, and then subjected selected antigens to mass spectroscopy for amino acid sequ ...201222354035
localized production of il-10 suppresses early inflammatory cell infiltration and subsequent development of ifn-γ-mediated lyme arthritis.il-10 is a nonredundant inflammatory modulator that suppresses arthritis development in borrelia burgdorferi-infected mice. infected c57bl/6 (b6) il-10(-/-) mice were previously found to have a prolonged ifn-inducible response in joint tissue. infection of b6 il-10 reporter mice identified macrophages and cd4(+) t cells as the primary sources of il-10 in the infected joint tissue, suggesting that early local production of il-10 dampened the proarthritic ifn response. treatment of b6 il-10(-/-) m ...201122180617
localized production of il-10 suppresses early inflammatory cell infiltration and subsequent development of ifn-γ-mediated lyme arthritis.il-10 is a nonredundant inflammatory modulator that suppresses arthritis development in borrelia burgdorferi-infected mice. infected c57bl/6 (b6) il-10(-/-) mice were previously found to have a prolonged ifn-inducible response in joint tissue. infection of b6 il-10 reporter mice identified macrophages and cd4(+) t cells as the primary sources of il-10 in the infected joint tissue, suggesting that early local production of il-10 dampened the proarthritic ifn response. treatment of b6 il-10(-/-) m ...201122180617
Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever.Rodents are natural reservoirs for a variety of species of Borrelia that cause relapsing fever (RF) in humans. The murine model of this disease recapitulates many of the clinical manifestations of the human disease and has revealed that T cell-independent antibody responses are required to resolve the bacteremic episodes. However, it is not clear whether such protective humoral responses are mounted in humans. We examined Borrelia hermsii infection in human hematopoietic stem cell-engrafted nono ...201122143787
probing the borrelia burgdorferi surface lipoprotein secretion pathway using a conditionally folding protein domain.surface lipoproteins of borrelia spirochetes are important virulence determinants in the transmission and pathogenesis of lyme disease and relapsing fever. to further define the conformational secretion requirements and to identify potential lipoprotein translocation intermediates associated with the bacterial outer membrane (om), we generated constructs in which borrelia burgdorferi outer surface lipoprotein a (ospa) was fused to calmodulin (cam), a conserved eukaryotic protein undergoing calci ...201121965569
relapsing fever borrelia in ornithodoros ticks from bolivia. 201121929883
determination of borrelia surface lipoprotein anchor topology by surface proteolysis.we used a surface trypsinolysis assay to probe accessibility of the membrane-proximal n-terminal tether peptides of borrelia surface lipoproteins ospa and vsp1. our findings with both wild-type and mutant proteins are only compatible with the anchoring of these surface lipoproteins in the outer leaflet of the outer spirochetal membrane.201121908659
comparative analyses imply that the enigmatic sigma factor 54 is a central controller of the bacterial exterior.sigma-54 is a central regulator in many pathogenic bacteria and has been linked to a multitude of cellular processes like nitrogen assimilation and important functional traits such as motility, virulence, and biofilm formation. until now it has remained obscure whether these phenomena and the control by sigma-54 share an underlying theme.201121806785
il-10 prevents apoptosis of brain endothelium during bacteremia.il-10-deficient mice infected with the relapsing fever bacterium borrelia turicatae rapidly succumb to a brain hemorrhage if they are unable to clear peak bacteremia. in this study, we investigated the protective role of il-10 during relapsing-remitting bacteremia and explored the molecular events involved in the protection of brain endothelium by il-10. brain endothelial injury was measured with cytotoxicity and diverse apoptotic assays, whereas the signaling pathway analysis was done by quanti ...201121602495
genetic transformation of the relapsing fever spirochete borrelia hermsii: stable integration and expression of green fluorescent protein from linear plasmid 200 (lp200).tick-borne relapsing fever (tbrf) is a spirochetal disease caused by at least 15 different borrelia species. it is a serious human health concern in endemic regions of the world. transmission to humans occurs through the bites of infected ornithordoros ticks. in north america, the primary borrelia species associated with human disease are b. hermsii and b. turicatae. direct demonstration of the role of putative tbrf spirochete virulence factors in the disease process has been hindered by the lac ...201121551306
surface localization determinants of borrelia ospc/vsp family lipoproteins.the dimeric ospc/vsp family surface lipoproteins of borrelia spirochetes are crucial to the transmission and persistence of lyme borreliosis and tick-borne relapsing fever. however, the requirements for their proper surface display remained undefined. in previous studies, we showed that localization of borrelia burgdorferi monomeric surface lipoprotein ospa was dependent on residues in the n-terminal "tether" peptide. here, site-directed mutagenesis of the b. burgdorferi ospc tether revealed two ...201121441503
interaction of variable bacterial outer membrane lipoproteins with brain endothelium.previously we reported that the variable outer membrane lipoprotein vsp1 from the relapsing fever spirochete borrelia turicatae disseminates from blood to brain better than the closely related vsp2 [1]. here we studied the interaction between vsp1 and vsp2 with brain endothelium in more detail.201021063459
cholesterol lipids of borrelia burgdorferi form lipid rafts and are required for the bactericidal activity of a complement-independent antibody.borrelia burgdorferi, the agent of lyme disease, is unusual as it contains free cholesterol and cholesterol glycolipids. it is also susceptible to complement-independent bactericidal antibodies, such as cb2, a monoclonal igg1 against outer surface protein b (ospb). we find that the bactericidal action of cb2 requires the presence of cholesterol glycolipids and cholesterol. ultrastructural, biochemical, and biophysical analysis revealed that the bacterial cholesterol glycolipids exist as lipid ra ...201020951967
characterizing the native codon usages of a genome: an axis projection approach.codon usage can provide insights into the nature of the genes in a genome. genes that are "native" to a genome (have not been recently acquired by horizontal transfer) range in codon usage from a low-bias "typical" usage to a more biased "high-expression" usage characteristic of genes encoding abundant proteins. genes that differ from these native codon usages are candidates for foreign genes that have been recently acquired by horizontal gene transfer. in this study, we present a method for cha ...201120679093
characterizing the native codon usages of a genome: an axis projection approach.codon usage can provide insights into the nature of the genes in a genome. genes that are "native" to a genome (have not been recently acquired by horizontal transfer) range in codon usage from a low-bias "typical" usage to a more biased "high-expression" usage characteristic of genes encoding abundant proteins. genes that differ from these native codon usages are candidates for foreign genes that have been recently acquired by horizontal gene transfer. in this study, we present a method for cha ...201120679093
bacterial lipoproteins can disseminate from the periphery to inflame the brain.the current view is that bacteria need to enter the brain to cause inflammation. however, in mice infected with the spirochete borrelia turicatae, we observed widespread cerebral inflammation despite a paucity of spirochetes in the brain parenchyma at times of high bacteremia. here we studied the possibility that bacterial lipoproteins may be capable of disseminating from the periphery across the blood-brain barrier to inflame the brain. for this we injected normal and infected mice intraperiton ...201020431027
diversity of 16s rrna genes within individual prokaryotic genomes.analysis of intragenomic variation of 16s rrna genes is a unique approach to examining the concept of ribosomal constraints on rrna genes; the degree of variation is an important parameter to consider for estimation of the diversity of a complex microbiome in the recently initiated human microbiome project (http://nihroadmap.nih.gov/hmp). the current genbank database has a collection of 883 prokaryotic genomes representing 568 unique species, of which 425 species contained 2 to 15 copies of 16s ...201020418441
translocation of borrelia burgdorferi surface lipoprotein ospa through the outer membrane requires an unfolded conformation and can initiate at the c-terminus.borrelia burgdorferi surface lipoproteins are essential to the pathogenesis of lyme borreliosis, but the mechanisms responsible for their localization are only beginning to emerge. we have previously demonstrated the critical nature of the amino-terminal 'tether' domain of the mature lipoprotein for sorting a fluorescent reporter to the borrelia cell surface. here, we show that individual deletion of four contiguous residues within the tether of major surface lipoprotein ospa results in its inef ...201020398211
molecular characterization of the interaction of borrelia parkeri and borrelia turicatae with human complement regulators.in north america, tick-borne relapsing fever is caused by the species borrelia hermsii, b. parkeri, and b. turicatae, which are transmitted to humans through the bite of the respective infected tick vectors. here we describe the identification and functional characterization of a surface lipoprotein of b. parkeri, designated bpca, that binds the human complement regulators factor h and factor h-related protein 1 and, simultaneously, the host protease plasminogen. in contrast, the homologous b. t ...201020231403
a novel surface antigen of relapsing fever spirochetes can discriminate between relapsing fever and lyme borreliosis.in a previous immunoproteome analysis of borrelia hermsii, candidate antigens that bound igm antibodies from mice and patients infected with relapsing fever spirochetes were identified. one candidate that was identified is a hypothetical protein with a molecular mass of 57 kda that we have designated borrelia immunogenic protein a (bipa). this protein was further investigated as a potential diagnostic antigen for b. hermsii given that it is absent from the borrelia burgdorferi genome. the bipa l ...201020147497
identification and molecular characterization of a cyclic-di-gmp effector protein, plza (bb0733): additional evidence for the existence of a functional cyclic-di-gmp regulatory network in the lyme disease spirochete, borrelia burgdorferi.the borrelia burgdorferi rrp1 protein is a diguanylate cyclase that controls a regulon consisting of approximately 10% of the total genome. because rrp1 lacks a dna-binding domain, its regulatory capability is most likely mediated through the production of bis-(3'-5')-cyclic dimeric gmp (c-di-gmp). c-di-gmp binds to and activates the regulatory activity of proteins that harbor a pilz domain. the occurrence of a pilz domain within a protein is not in and of itself sufficient to convey c-di-gmp bi ...201020030712
identification and molecular characterization of a cyclic-di-gmp effector protein, plza (bb0733): additional evidence for the existence of a functional cyclic-di-gmp regulatory network in the lyme disease spirochete, borrelia burgdorferi.the borrelia burgdorferi rrp1 protein is a diguanylate cyclase that controls a regulon consisting of approximately 10% of the total genome. because rrp1 lacks a dna-binding domain, its regulatory capability is most likely mediated through the production of bis-(3'-5')-cyclic dimeric gmp (c-di-gmp). c-di-gmp binds to and activates the regulatory activity of proteins that harbor a pilz domain. the occurrence of a pilz domain within a protein is not in and of itself sufficient to convey c-di-gmp bi ...201020030712
niche partitioning of borrelia burgdorferi and borrelia miyamotoi in the same tick vector and mammalian reservoir species.the lyme borreliosis agent borrelia burgdorferi and the relapsing fever group species borrelia miyamotoi co-occur in the united states. we used species-specific, quantitative polymerase chain reaction to study both species in the blood and skin of peromyscus leucopus mice and host-seeking ixodes scapularis nymphs at a connecticut site. bacteremias with b. burgdorferi or b. miyamotoi were most prevalent during periods of greatest activity for nymphs or larvae, respectively. whereas b. burgdorferi ...200919996447
structure-function investigation of vsp serotypes of the spirochete borrelia hermsii.relapsing fever (rf) spirochetes are notable for multiphasic antigenic variation of polymorphic outer membrane lipoproteins, a phenomenon responsible for immune evasion. an additional role in tissue localization is suggested by the finding that isogenic serotypes 1 (bt1) and 2 (bt2) of the rf spirochete borrelia turicatae, which differ only in the vsp they express, exhibit marked differences in clinical disease severity and tissue localization during infection.200919888463
fatal borreliosis in bat caused by relapsing fever spirochete, united kingdom. 200919751613
analysis of borrelia burgdorferi genotypes in patients with lyme arthritis: high frequency of ribosomal rna intergenic spacer type 1 strains in antibiotic-refractory arthritis.most of the borrelia burgdorferi genotypes have been isolated from erythema migrans (em) skin lesions in patients with lyme disease. ospc type k strains, which are 16s-23s ribosomal rna intergenic spacer type 2 (rst2) strains, are most commonly recovered, but a higher percentage of ospc type a strains (rst1), the next most commonly recovered type, is detectable in blood. the goal of this study was to determine the b burgdorferi genotypes in the joints of patients with lyme arthritis.200919565522
identification of the determinant conferring permissive substrate usage in the telomere resolvase, rest.linear genome stability requires specialized telomere replication and protection mechanisms. a common solution to this problem in non-eukaryotes is the formation of hairpin telomeres by telomere resolvases (also known as protelomerases). these enzymes perform a two-step transesterification on replication intermediates to generate hairpin telomeres using an active site similar to that of tyrosine recombinases and type ib topoisomerases. unlike phage telomere resolvases, the telomere resolvase fro ...200919561077
understanding tropism and immunopathological mechanisms of relapsing fever spirochaetes.mice infected with relapsing fever (rf) spirochaetes survive recurrent waves of high-level bacteraemia with little, if any, clinical complications or tissue injury. in the absence of b-cells, peak bacteraemia does not resolve, resulting in multi-organ complications. during peak bacteraemia, large amounts of interleukin-10 (il-10) are produced in blood and tissues. in mice unable to clear peak bacteraemia, exogenous il-10 greatly reduced the clinical manifestations, serum levels of cxcl13, cerebr ...200919489924
borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity.borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. here we identify for the first time a multifunctional surface lipoprotein of b. recurrentis, termed hcpa, and demonstrate that it binds human complement regulators, factor h, cfhr-1, and simultaneously, the host protease plasminogen. cell surface bound factor h was found to re ...200919308255
characterization of a novel relapsing fever spirochete in the midgut, coxal fluid, and salivary glands of the bat tick carios kelleyi.bat ticks, carios kelleyi, from iowa were examined for the presence of relapsing fever group borreliae. a novel spirochete was characterized by dna sequence analysis of polymerase chain reaction amplicons for the 16s rrna, flab, and glpq genes in either triturated tick pools or single ticks. all loci and the concatenated dna sequence of 3,289 bases identified the carios bacterium as a relapsing fever spirochete most closely related to, but distinct from, borrelia turicatae. spirochetes reactive ...200919281412
detailed analysis of sequence changes occurring during vlse antigenic variation in the mouse model of borrelia burgdorferi infection.lyme disease borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. the vls antigenic variation system, which expresses the surface-exposed lipoprotein vlse, plays a major role in b. burgdorferi immune evasion. gene conversion between vls silent cassettes and the vlse expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the vlse product. in this study, we examined vlse sequence variati ...200919214205
rrp1, a cyclic-di-gmp-producing response regulator, is an important regulator of borrelia burgdorferi core cellular functions.two-component systems (tcs) are universal among bacteria and play critical roles in gene regulation. our understanding of the contributions of tcs in the biology of the borrelia is just now beginning to develop. borrelia burgdorferi, a causative agent of lyme disease, harbours a tcs comprised of open reading frames (orfs) bb0419 and bb0420. bb0419 encodes a response regulator designated rrp1, and bb0420 encodes a hybrid histidine kinase-response regulator designated hpk1. rrp1, which contains a ...200919210621
adenoviral delivery of interleukin-10 fails to attenuate experimental lyme disease.production of interleukin-10 (il-10) by c57bl/6 mice following infection with borrelia burgdorferi has been proposed as a mechanism whereby resistance to the development of experimental lyme arthritis is maintained. in the current study, we sought to determine the role of il-10 during infection of arthritis- and carditis-susceptible c3h mice. infection of c3h il-10(-/-) mice led to increased joint swelling and arthritis severity scores over those of wild-type c3h mice. measurement of b. burgdorf ...200818824530
interleukin 10 protects the brain microcirculation from spirochetal injury.spirochetal infections are an important cause of neurological disease. in previous studies of the pathogenesis of spirochetal brain infection, mice inoculated with borrelia turicatae, an agent of tick-borne relapsing fever in north america, developed mild meningitis and parenchymal activation/infiltration by interleukin 10 (il-10)-producing microglia/macrophages. here, we investigated the neuroprotective effects of il-10 during spirochetal infection by comparing the outcomes of b. turicatae infe ...200818800010
relapsing fever borreliosis in interleukin-10-deficient mice.relapsing fever (rf) is a spirochetal infection characterized by periods of sickness with fever at time of high bacteremia that alternate with afebrile periods of relative well being during low bacteremia. patients with epidemic rf who are doing relatively well have extraordinarily high levels of interleukin-10 (il-10) in the circulation. we investigated the possibility that il-10 plays an important protective role in this infection using wild-type and il-10-deficient mice inoculated with virule ...200818794280
the genome of borrelia recurrentis, the agent of deadly louse-borne relapsing fever, is a degraded subset of tick-borne borrelia duttonii.in an effort to understand how a tick-borne pathogen adapts to the body louse, we sequenced and compared the genomes of the recurrent fever agents borrelia recurrentis and b. duttonii. the 1,242,163-1,574,910-bp fragmented genomes of b. recurrentis and b. duttonii contain a unique 23-kb linear plasmid. this linear plasmid exhibits a large polyt track within the promoter region of an intact variable large protein gene and a telomere resolvase that is unique to borrelia. the genome content is char ...200818787695
tick-borne relapsing fever.each year, many residents of and visitors to endemic regions of the western united states are exposed to the tick vectors of tick-borne relapsing fever (tbrf), ornithodoros hermsi, ornithodoros turicata, or ornithodoros parkeri. this disease is remarkable because the human host is unaware of the tick bite, usually becomes very ill, may experience an exacerbation of symptoms rather than improvement shortly after beginning appropriate treatment, and, despite often high numbers of the etiologic org ...200818755384
new feel for new phyla. 200818665943
il-10 helps control pathogen load during high-level bacteremia.during relapsing fever borreliosis, a high pathogen load in the blood occurs at times of peak bacteremia. specific igm abs are responsible for spirochetal clearance so in absence of b cells there is persistent high-level bacteremia. previously, we showed that b cell-deficient mice persistently infected with borrelia turicatae produce high levels of il-10 and that exogenous il-10 reduces bacteremia. this suggested that il-10 helps reduce bacteremia at times of high pathogen load by a b cell-indep ...200818641346
relapsing fever spirochetes retain infectivity after prolonged in vitro cultivation.borrelia hermsii and borrelia burgdorferi, two closely related spirochetes, are the etiological agents of tick-borne relapsing fever and lyme disease, respectively. previous studies have shown the loss of infectivity of b. burgdorferi is associated with in vitro cultivation. this diminished infectivity of b. burgdorferi has occurred as early as three in vitro passages, and the loss of plasmids have been observed with these less virulent to noninfective cultures. the effects of long-term in vitro ...200818637723
mechanisms of microbial traversal of the blood-brain barrier.central nervous system (cns) infections continue to be an important cause of morbidity and mortality. microbial invasion and traversal of the blood-brain barrier is a prerequisite for cns infections. pathogens can cross the blood-brain barrier transcellularly, paracellularly and/or in infected phagocytes (the so-called trojan-horse mechanism). consequently, pathogens can cause blood-brain barrier dysfunction, including increased permeability, pleocytosis and encephalopathy. a more complete under ...200818604221
human interleukin-10 gene transfer is protective in a rat model of parkinson's disease.in parkinson's disease (pd) chronic inflammation occurs in the substantia nigra (snc) concurrently with dopaminergic neurodegeneration. in models of pd, microglial activation precedes neurodegeneration in the snc, suggesting that the underlying pathogenesis involves a complex response in the nigrostriatal pathway, and that the innate immune system plays a significant role. we have investigated the neuroprotective effect of an adeno-associated viral type-2 (aav2) vector containing the complementa ...200818545225
novel relapsing fever spirochete in bat tick. 200818325285
identification of an antiparallel coiled-coil/loop domain required for ligand binding by the borrelia hermsii fhba protein: additional evidence for the role of fhba in the host-pathogen interaction.borrelia hermsii, an etiological agent of tick-borne relapsing fever in north america, binds host-derived serum proteins including factor h (fh), plasminogen, and an unidentified 60-kda protein via its fhba protein. two distinct phylogenetic types of fhba have been delineated (fhba1 and fhba2). these orthologs share a conserved c-terminal domain that contains two alpha helices with a high predictive probability of coiled-coil formation that are separated by a 14-amino-acid loop domain. through s ...200818299341
spirochetemia caused by borrelia turicatae infection in 3 dogs in texas.spirochetemia was diagnosed in 2 siberian huskies and a rottweiler from the northwestern region of texas between june 1999 and october 2001. clinical findings were nonspecific; tick exposure was documented in 2 of the dogs. hematologic abnormalities included anemia (n=2), neutrophilia (n=2, including 1 with a left shift), lymphopenia (n=3), eosinopenia (n=3), and thrombocytopenia (n=2). one anemic dog had a positive coombs' test. in 1 dog, western blot analysis of serum yielded multiple positive ...200717523100
purine salvage pathways among borrelia species.genome sequencing projects on two relapsing fever spirochetes, borrelia hermsii and borrelia turicatae, revealed differences in genes involved in purine metabolism and salvage compared to those in the lyme disease spirochete borrelia burgdorferi. the relapsing fever spirochetes contained six open reading frames that are absent from the b. burgdorferi genome. these genes included those for hypoxanthine-guanine phosphoribosyltransferase (hpt), adenylosuccinate synthase (pura), adenylosuccinate lya ...200717502392
coinfection with borrelia turicatae serotype 2 prevents the severe vestibular dysfunction and earlier mortality caused by serotype 1.relapsing fever (rf) is a multisystemic spirochetal infection caused by different borrelia species. studies in our laboratory have shown that disease severity varies depending on the infecting serotype. however, the relative contribution of each serotype to pathogenesis during mixed infections is not known. to investigate this, we compared the outcome of infection with isogenic serotypes 1 (bt1) or 2 (bt2) of the rf agent b. turicatae alone or in combination.200717471439
high production of cxcl13 in blood and brain during persistent infection with the relapsing fever spirochete borrelia turicatae.relapsing fever (rf) is a multisystemic borrelial infection with frequent neurologic involvement referred to as neuroborreliosis. the absence of an effective antibody response results in persistent infection. to study the consequences to the brain of persistent infection with the rf spirochete borrelia turicatae, we studied b cell (igh6-/-) and b and t (rag1-/-) cell-deficient mice inoculated with isogenic serotypes 1 (bt1) or 2 (bt2). we found that bt1 was more tissue tropic than bt2, not only ...200717356382
role of interleukin 10 during persistent infection with the relapsing fever spirochete borrelia turicatae.relapsing fever is an infection characterized by peaks of spirochetemia attributable to antibody selection against variable serotypes. in the absence of b cells, serotypes cannot be cleared, resulting in persistent infection. we previously identified differences in spirochetemia and disease severity during persistent infection of severe combined immunodeficiency mice with isogenic serotypes 1 (bt1) or 2 (bt2) of borrelia turicatae. to investigate this further, we studied pathogen load, clinical ...200717200198
the mammalian host response to borrelia infection.tick-borne relapsing fever (rf) and lyme disease (ld) are spirochetal infections of humans caused by different borrelia species in endemic areas throughout the world. our laboratory is studying the response of mammalian hosts to borrelia infection in rf and ld. for this, we use mice and non-human primates infected with b. burgdorferi sensu stricto strain n40 (n40) and the oz1 strain of borrelia turicatae (bt), agents of ld and rf in north america, respectively. our results have revealed that out ...200617160603
identification of pathogenic leptospira species by conventional or real-time pcr and sequencing of the dna gyrase subunit b encoding gene.leptospira is the causative genus of the disease, leptospirosis. species identification of pathogenic leptospira in the past was generally performed by either dna-dna hybridisation or 16s rrna gene sequencing. both methods have inherent disadvantages such as the need for radio-labelled isotopes or significant homology between species. a conventional and real-time pcr amplification and sequencing method was developed for an alternate gene target: dna gyrase subunit b (gyrb). phylogenetic comparis ...200617067399
interaction of a neurotropic strain of borrelia turicatae with the cerebral microcirculation system.relapsing fever (rf) is a spirochetal infection characterized by relapses of a febrile illness and spirochetemia due to the sequential appearance and disappearance of isogenic serotypes in the blood. the only difference between isogenic serotypes is the variable major outer membrane lipoprotein. in the absence of specific antibody, established serotypes cause persistent infection. studies in our laboratory indicate that another consequence of serotype switching in rf is a change in neuroinvasive ...200616940140
immunological and molecular analyses of the borrelia hermsii factor h and factor h-like protein 1 binding protein, fhba: demonstration of its utility as a diagnostic marker and epidemiological tool for tick-borne relapsing fever.it has been demonstrated that borrelia hermsii, a causative agent of relapsing fever, produces a factor h (fh) and fh-like protein 1 (fhl-1) binding protein. the binding protein has been designated fhba. to determine if fh/fhl-1 binding is widespread among b. hermsii isolates, a diverse panel of strains was tested for the fh/fhl-1 binding phenotype and fhba production. most isolates (23/24) produced fhba and bound fh/fhl-1. potential variation in fhba among isolates was analyzed by dna sequence ...200616861638
crystal structure of neurotropism-associated variable surface protein 1 (vsp1) of borrelia turicatae.vsp surface lipoproteins are serotype-defining antigens of relapsing fever spirochetes that undergo multiphasic antigenic variation to allow bacterial persistence in spite of an immune response. two isogenic serotypes of borrelia turicatae strain oz1 differ in their vsp sequences and in disease manifestations in infected mice: vsp1 is associated with the selection of a neurological niche, while vsp2 is associated with blood and skin infection. we report here crystal structures of the vsp1 dimer ...200616740958
relapsing fever spirochaetes produce a serine protease that provides resistance to oxidative stress and killing by neutrophils.the spirochaetes that cause tick-borne relapsing fever and lyme disease are closely related human pathogens, yet they differ significantly in their ecology and pathogenicity. genome sequencing of two species of relapsing fever spirochaetes, borrelia hermsii and borrelia turicatae, identified a chromosomal open reading frame, designated bhpa, not present in the lyme disease spirochaete borrelia burgdorferi. the predicted amino acid sequence of bhpa was homologous with the htra serine proteases, w ...200616629672
residual brain infection in relapsing-fever borreliosis.neurological involvement is common in the spirochetal infection relapsing fever (rf) in both humans and experimental animals. rf is best known for antigenic variation caused by the sequential expression of variable outer membrane lipoproteins of 2 sizes, variable small (vsp) and variable large (vlp) proteins. less understood is the persistence of rf borreliae in the brain after they are cleared from the blood, referred to as residual brain infection (rbi). our goal was to investigate the phenome ...200616619194
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