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Tom G. Schwan - One of the best experts on this subject based on the ideXlab platform.
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vector specificity of the relapsing fever spirochete Borrelia hermsii spirochaetales Borreliaceae for the tick ornithodoros hermsi acari argasidae involves persistent infection of the salivary glands
Journal of Medical Entomology, 2021Co-Authors: Tom G. SchwanAbstract:The relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae are each maintained and transmitted in nature by their specific tick vectors, Ornithodoros hermsi Wheeler (Acari: Argasidae) and Ornithodoros turicata (Duges), respectively. The basis for this spirochete and vector specificity is not known, but persistent colonization of spirochetes in the tick's salivary glands is presumed to be essential for transmission by these long-lived ticks that feed in only minutes on their warm-blooded hosts. To examine this hypothesis further, cohorts of O. hermsi and O. turicata were infected with B. hermsii and examined 7-260 d later for infection in their midgut, salivary glands, and synganglion. While the midgut from all ticks of both species at all time points examined were infected with spirochetes, the salivary glands of only O. hermsi remained persistently infected. The salivary glands of O. turicata were susceptible to an early transient infection. However, no spirochetes were observed in these tissues beyond the first 32 d after acquisition. Ticks of both species were fed on mice 112 d after they acquired spirochetes and only those mice fed upon by O. hermsi became infected. Thus, the vector competency for B. hermsii displayed by O. hermsi but not O. turicata lies, in part, in the persistent infection of the salivary glands of the former but not the latter species of tick. The genetic and biochemical mechanisms supporting this spirochete and vector specificity remain to be identified.
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Conspecific hyperparasitism: An alternative route for Borrelia hermsii transmission by the tick Ornithodoros hermsi.
Ticks and tick-borne diseases, 2017Co-Authors: Brandi N Williamson, Tom G. SchwanAbstract:Abstract Ixodid and argasid ticks may hyperparasitize other individuals of their own species to acquire a blood meal, however most accounts are based on single observations and the behavior has rarely been studied. While maintaining laboratory colonies of Ornithodoros species, we noticed that unfed ticks occasionally fed on other ticks that were feeding on mice, and unfed ticks parasitized engorged ticks when confined together in tubes. Therefore, we investigated hyperparasitism by Ornithodoros hermsi and the ability of these ticks to acquire and transmit the relapsing fever spirochete Borrelia hermsii when feeding on other ticks. Various combinations of unfed and recently engorged male, female and nymphal ticks were confined for 1–2 h as individual pairs or in groups, then examined to determine the number of ticks that acquired blood by feeding on others. Unfed O. hermsi males were far more likely to hyperparasitize other ticks than were females and nymphs, as 78.6% of males (114 of 145 ticks) fed when confined with recently engorged ticks. Unfed females and nymphs also hyperparasitized other ticks but far less frequently (only 6.7% combined; 17 of 254 ticks). Infection experiments demonstrated that unfed males acquired B. hermsii when parasitizing nymphs that had recently engorged on a spirochetemic mouse, and unfed infected males transmitted spirochetes to recently engorged nymphs. Some ticks infected via hyperparasitism subsequently transmitted B. hermsii to mice. Hyperparasitism by O. hermsi occurred more frequently than expected, although possibly influenced by our experimental design. The significance of this behavior as it may influence the horizontal transfer of B. hermsii in nature is not known but worthy of future consideration.
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colony formation in solid medium by the relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae
Ticks and Tick-borne Diseases, 2017Co-Authors: Brandi N Williamson, Tom G. Schwan, Frank C GherardiniAbstract:Abstract Relapsing fever (RF) in North America is caused primarily by the spirochete Borrelia hermsii and is associated with the bite of its tick vector Ornithodoros hermsi. Although this spirochete was known long before the discovery of the Lyme disease (LD) spirochete, Borrelia burgdorferi, basic methods to facilitate the study of B. hermsii have lagged behind. One important technique to expedite the study of the molecular biology and pathogenesis of B. hermsii would be a reliable method to grow and clone these bacteria in solid medium, which we now describe. We have defined the solidifying agent, plating temperature, oxygen concentration, and pH for the efficient plating of two species of RF spirochetes, B. hermsii and Borrelia turicatae. Importantly, this technique allowed us to successfully isolate virulent, clonal cell lines of spirochetes, and to enumerate and isolate viable B. hermsii from infected mouse blood and tick tissues. Our results also demonstrate the value of testing a range of several environmental variables to increase the efficiency of bacterial isolation, which may be helpful for researchers working on other prokaryotes that are intractable for in vitro growth.
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Estimates of the relative contribution of elevation and six uncorrelated environmental variables used to model the distribution of Ornithodoros hermsi and Borrelia hermsii in western North America.
2017Co-Authors: Kylie M. Sage, Tammi L. Johnson, Mike B. Teglas, Nathan C Nieto, Tom G. SchwanAbstract:Estimates of the relative contribution of elevation and six uncorrelated environmental variables used to model the distribution of Ornithodoros hermsi and Borrelia hermsii in western North America.
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Host associations and genomic diversity of Borrelia hermsii in an endemic focus of tick-borne relapsing fever in western North America
Parasites & Vectors, 2016Co-Authors: Tammi L. Johnson, Tom G. SchwanAbstract:Background 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. Methods Small mammals were captured alive on two island and three mainland sites, blood samples were collected and examined for spirochetes, and serological tests performed to detect anti- B. hermsii antibodies. Ornithodoros hermsi ticks were collected and fed on laboratory mice to assess infection. Genomic DNA samples from spirochetes isolated from infected mammals and ticks were analyzed by multilocus sequence typing. Results Eighteen pine squirrels and one deer mouse had detectable spirochetemias when captured, from which 12 isolates of B. hermsii were established. Most pine squirrels were seropositive, and the five species of sciurids combined had a significantly higher prevalence of seropositive animals than did the other six small mammal species captured. The greater diversity of small mammals on the mainland in contrast to the islands demonstrated that other species in addition to pine squirrels were also involved in the maintenance of B. hermsii at Flathead Lake. Ornithodoros hermsi ticks produced an additional 12 isolates of B. hermsii and multilocus sequence typing identified both genomic groups of B. hermsii described previously, and identified a new genomic subdivision. Experimental infections of deer mice with two strains of B. hermsii demonstrated that these animals were susceptible to infection with spirochetes belonging to Genomic Group II but not Genomic Group I. Conclusions Pine squirrels are the primary hosts for the maintenance of B. hermsii on the islands in Flathead Lake, however serological evidence showed that numerous additional species are also involved on the mainland. Future studies testing the susceptibility of several small mammal species to infection with different genetic types of B. hermsii will help define their role as hosts in this and other endemic foci.
Alan G. Barbour - One of the best experts on this subject based on the ideXlab platform.
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pathogen and host response dynamics in a mouse model of Borrelia hermsii relapsing fever
Veterinary Sciences, 2016Co-Authors: Christopher D Crowder, Eric R G Lewis, Renee A Marcsisin, Arash Ghalyanchi Langeroudi, Azadeh Shojaee Estabragh, Alan G. BarbourAbstract:Most Borrelia species that cause tick-borne relapsing fever utilize rodents as their natural reservoirs, and for decades laboratory-bred rodents have served as informative experimental models for the disease. However, while there has much progress in understanding the pathogenetic mechanisms, including antigenic variation, of the pathogen, the host side of the equation has been neglected. Using different approaches, we studied, in immunocompetent inbred mice, the dynamics of infection with and host responses to North American relapsing fever agent B. hermsii. The spirochete's generation time in blood of infected mice was between 4-5 h and, after a delay, was matched in rate by the increase of specific agglutinating antibodies in response to the infection. After initiating serotype cells were cleared by antibodies, the surviving spirochetes were a different serotype and, as a population, grew more slowly. The retardation was attributable to the host response and not an inherently slower growth rate. The innate responses at infection peak and immediate aftermath were characterized by elevations of both pro-inflammatory and anti-inflammatory cytokines and chemokines. Immunodeficient mice had higher spirochete burdens and severe anemia, which was accounted for by aggregation of erythrocytes by spirochetes and their partially reversible sequestration in greatly enlarged spleens and elsewhere.
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Chromosome and Plasmids of the Tick-Borne Relapsing Fever Agent Borrelia hermsii.
Genome announcements, 2016Co-Authors: Alan G. BarbourAbstract:The zoonotic pathogen Borrelia hermsii bears its multiple paralogous genes for variable antigens on several linear plasmids. Application of combined long-read and short-read next-generation sequencing provided complete sequences for antigen-encoding plasmids as well as other linear and circular plasmids and the linear chromosome of the genome.
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Expression of the Tick-Associated Vtp Protein of Borrelia hermsii in a Murine Model of Relapsing Fever.
PloS one, 2016Co-Authors: Renee A Marcsisin, Eric R G Lewis, Alan G. BarbourAbstract:Borrelia hermsii, a spirochete and cause of relapsing fever, is notable for its immune evasion by multiphasic antigenic variation within its vertebrate host. This is based on a diverse repertoire of surface antigen genes, only one of which is expressed at a time. Another major surface protein, the Variable Tick Protein (Vtp), is expressed in the tick vector and is invariable at its genetic locus. Given the limited immune systems of ticks, the finding of considerable diversity among the Vtp proteins of different strains of B. hermsii was unexpected. We investigated one explanation for this diversity of Vtp proteins, namely expression of the protein in mammals and a consequent elicitation of a specific immune response. Mice were infected with B. hermsii of either the HS1 or CC1 strain, which have antigenically distinctive Vtp proteins but otherwise have similar repertoires of the variable surface antigens. Subsequently collected sera were examined for antibody reactivities against Vtp and other antigens using Western blot analysis, dot blot, and protein microarray. Week-6 sera of infected mice contained antibodies that were largely specific for the Vtp of the infecting strain and were not attributable to antibody cross-reactivities. The antibody responses of the mice infected with different strains were otherwise similar. Further evidence of in vivo expression of the vtp gene was from enumeration of cDNA sequence reads that mapped to a set of selected B. hermsii genes. This measure of transcription of the infecting strain's vtp gene was ~10% of that for the abundantly-expressed, serotype-defining variable antigen gene but similar to that of genes known for in vivo expression. The findings of Vtp expression in a vertebrate host and elicitation of a specific anti-Vtp antibody response support the view that balancing selection by host adaptive immunity accounts in part for the observed diversity of Vtp proteins.
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fibronectin binding protein of Borrelia hermsii expressed in the blood of mice with relapsing fever
Infection and Immunity, 2014Co-Authors: Eric R G Lewis, Renee A Marcsisin, Shelley Campeau Miller, April Phillips, David P Aucoin, Alan G. BarbourAbstract:To identify and characterize surface proteins expressed by the relapsing fever (RF) agent Borrelia hermsii in the blood of infected mice, we used a cell-free filtrate of their blood to immunize congenic naive mice. The resultant antiserum was used for Western blotting of cell lysates, and gel slices corresponding to reactive bands were subjected to liquid chromatography-tandem mass spectrometry, followed by a search of the proteome database with the peptides. One of the immunogens was identified as the BHA007 protein, which is encoded by a 174-kb linear plasmid. BHA007 had sequence features of lipoproteins, was surface exposed by the criteria of in situ protease susceptibility and agglutination of Vtp− cells by anti-BHA007 antibodies, and was not essential for in vitro growth. BHA007 elicited antibodies during experimental infection of mice, but immunization with recombinant protein did not confer protection against needle-delivered infection. Open reading frames (ORFs) orthologous to BHA007 were found on large plasmids of other RF species, including the coding sequences for the CihC proteins of Borrelia duttonii and B. recurrentis, but not in Lyme disease Borrelia species. Recombinant BHA007 bound both human and bovine fibronectin with Kd (dissociation constant) values of 22 and 33 nM, respectively, and bound to C4-binding protein with less affinity. The distant homology of BHA007 and its orthologs to BBK32 proteins of Lyme disease species, as well as to previously described BBK32-like proteins in relapsing fever species, indicates that BHA007 is a member of a large family of multifunctional proteins in Borrelia species that bind to fibronectin as well as other host proteins.
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Genome Sequence of Borrelia parkeri, an Agent of Enzootic Relapsing Fever in Western North America.
Genome announcements, 2014Co-Authors: Alan G. Barbour, Shelley Campeau MillerAbstract: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.
Richard T. Marconi - One of the best experts on this subject based on the ideXlab platform.
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The Borrelia hermsii Factor H Binding Protein FhbA Is Not Required for Infectivity in Mice or for Resistance to Human Complement In Vitro
Infection and immunity, 2014Co-Authors: Lindy M. Fine, Daniel P. Miller, Katherine L. Mallory, Brittney K. Tegels, Christopher G. Earnhart, Richard T. MarconiAbstract:ABSTRACT 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 as a significant target of a B1b B cell-mediated IgM response in mice. FhbA has also been explored as a potential diagnostic antigen for B. hermsii infection in humans. The ability to test the hypothesis that FhbA is a critical virulence factor in vivo has been hampered by the lack of well-developed systems for the genetic manipulation of the relapsing fever spirochetes. In this report, we have successfully generated a B. hermsii fhbA deletion mutant (the B. hermsii YORΔ fhbA strain) through allelic exchange mutagenesis. Deletion of fhbA abolished FH binding by the YORΔ fhbA strain and eliminated cleavage of C3b on the cell surface. However, the YORΔ fhbA strain remained infectious in mice and retained resistance to killing in vitro by human complement. Collectively, these results indicate that B. hermsii employs an FhbA/FH-independent mechanism of complement evasion that allows for resistance to killing by human complement and persistence in mice.
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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
Infection and Immunity, 2008Co-Authors: Kelley M. Hovis, John C. Freedman, Hongming Zhang, Jonathan L. Forbes, Richard T. MarconiAbstract: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 site-directed mutagenesis, we have identified residues within these domains that influence the binding of both mouse and human FH, plasminogen, and/or the 60-kDa protein. To further investigate the involvement of FhbA in the host-pathogen interaction, strains that are either FhbA+ (isolate YOR) or FhbA− (isolate REN) were tested for serum sensitivity. Significant differences were observed, with YOR and REN being serum resistant and serum sensitive (intermediate), respectively. To test the abilities of these strains to infect and persist in mice, mice were needle inoculated, and infectivity and persistence were then assessed. While both strains REN and YOR infected mice, only the FhbA+ YOR strain persisted beyond day 4. Survival of the YOR isolate in blood correlated with the upregulation of the fhbA gene, as demonstrated by real-time reverse transcriptase PCR. These data advance our understanding of the unique interactions of FhbA with individual serum proteins and provide support for the hypothesis that FhbA is an important contributor to the pathogenesis of the relapsing fever spirochete B. hermsii.
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Molecular Analyses of the Interaction of Borrelia hermsii FhbA with the Complement Regulatory Proteins Factor H and Factor H-Like Protein 1
Infection and immunity, 2006Co-Authors: Kelley M. Hovis, Janice P. Jones, Tania Sadlon, Gauri Raval, David L. Gordon, Richard T. MarconiAbstract:Borrelia hermsii, the primary etiological agent of tick-borne relapsing fever in North America, binds the complement regulatory protein factor H (FH) as a means of evading opsonophagocytosis and the alternative complement pathway. The ability of FH-binding protein A (FhbA) to bind FH-like protein 1 (FHL-1) has not been assessed previously. In this study, using a whole-cell absorption assay, we demonstrated that B. hermsii absorbs both FH and FHL-1 from human serum. Consistent with this, affinity ligand binding immunoblot analyses revealed that FH constructs spanning short consensus repeats 1 to 7 and 16 to 20 bind to FhbA. To investigate the molecular basis of the interaction of FhbA with FH/FHL-1, recombinant FhbA truncated proteins were generated and tested for FH/FHL-1 binding. Binding required determinants located in both the N- and C-terminal domains of FhbA, suggesting that long-range intramolecular interactions are involved in the formation and presentation of the FH/FHL-1-binding pocket. To identify specific FhbA residues involved in binding, random mutagenesis was performed. These analyses identified a loop region of FhbA that may serve as a contact point for FH/FHL-1. The data presented here expand our understanding of the pathogenic mechanisms of the relapsing fever spirochetes and of the molecular nature of the interaction between FH/FHL-1 and FhbA.
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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.
Infection and immunity, 2006Co-Authors: Kelley M. Hovis, Martin E. Schriefer, Sonia Bahlani, Richard T. MarconiAbstract: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 analyses. Two genetically distinct FhbA types, designated fhbA1 and fhbA2, were delineated, and type-specific PCR primers were generated to allow for rapid differentiation. Pulsed-field gel electrophoresis and hybridization analyses demonstrated that all isolates that possess the gene carry it on a 200-kb linear plasmid (lp200), whereas isolates that lack the gene lack lp200 and instead carry an lp170. To determine if FhbA is antigenic during infection and to assess the specificity of the response, recombinant FhbA1 (rFhbA1) and rFhbA2 were screened with serum from infected mice and humans. FhbA was found to be expressed and antigenic and to elicit a potentially type-specific FhbA response. To localize the epitopes of FhbA1 and FhbA2, truncations were generated and screened with infection serum. The epitopes were determined to be conformationally defined. Collectively, these analyses indicate that FH/FHL-1 binding is a widespread virulence mechanism for B. hermsii and provide insight into the genetic and antigenic structure of FhbA. The data also have potential implications for understanding the epidemiology of relapsing fever in North America and can be applied to the future development of species-specific diagnostic tools.
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Identification and Characterization of a Linear-Plasmid-Encoded Factor H-Binding Protein (FhbA) of the Relapsing Fever Spirochete Borrelia hermsii
Journal of bacteriology, 2004Co-Authors: Kelley M. Hovis, John V. Mcdowell, Latoya Griffin, Richard T. MarconiAbstract:In North America, tick-borne relapsing fever (TBRF) is caused by the spirochete species Borrelia hermsii, Borrelia parkeri, and Borrelia turicatae. We previously demonstrated that some isolates of B. hermsii and B. parkeri are capable of binding factor H and that cell-bound factor H can participate in the factor I-mediated cleavage of C3b. Isolates that bound factor H expressed a factor H-binding protein (FHBP) that we estimated to be approximately 19 to 20 kDa in size and thus, pending further characterization, temporarily designated FHBP19. Until this report, none of the FHBPs of the TBRF spirochetes had been characterized. Here we have recovered the gene encoding the FHBP of B. hermsii YOR from a lambda ZAP II library and determined its sequence. The gene encodes a full-length protein of 22.7 kDa, which after processing is predicted to be 20.5 kDa. This protein, which we redesignate factor H-binding protein A (FhbA), is unique to B. hermsii. Two-dimensional pulsed-field gel electrophoresis and hybridization analyses revealed that the B. hermsii gene encoding FhbA is a single genetic locus that maps to a linear plasmid of approximately 220 kb. The general properties of FhbA were also assessed. The protein was found to be surface exposed and lipidated. Analysis of the antibody response to FhbA in infected mice revealed that it is antigenic during infection, indicating expression during infection. The identification and characterization of FhbA provides further insight into the molecular mechanisms of pathogenesis of the relapsing fever spirochetes.
Sandra J Raffel - One of the best experts on this subject based on the ideXlab platform.
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vaccination with the variable tick protein of the relapsing fever spirochete Borrelia hermsii protects mice from infection by tick bite
Parasites & Vectors, 2015Co-Authors: Benjamin J. Krajacich, Sandra J Raffel, Job E Lopez, Tom G. SchwanAbstract:Tick-borne relapsing fevers of humans are caused by spirochetes that must adapt to both warm-blooded vertebrates and cold-blooded ticks. In western North America, most human cases of relapsing fever are caused by Borrelia hermsii, which cycles in nature between its tick vector Ornithodoros hermsi and small mammals such as tree squirrels and chipmunks. These spirochetes alter their outer surface by switching off one of the bloodstream-associated variable major proteins (Vmps) they produce in mammals, and replacing it with the variable tick protein (Vtp) following their acquisition by ticks. Based on this reversion to Vtp in ticks, we produced experimental vaccines comprised on this protein and tested them in mice challenged by infected ticks. The vtp gene from two isolates of B. hermsii that encoded antigenically distinct types of proteins were cloned, expressed, and the recombinant Vtp proteins were purified and used to vaccinate mice. Ornithodoros hermsi ticks that were infected with one of the two strains of B. hermsii from which the vtp gene originated were used to challenge mice that received one of the two Vtp vaccines or only adjuvant. Mice were then followed for infection and seroconversion. The Vtp vaccines produced protective immune responses in mice challenged with O. hermsi ticks infected with B. hermsii. However, polymorphism in Vtp resulted in mice being protected only from the spirochete strain that produced the same Vtp used in the vaccine; mice challenged with spirochetes producing the antigenically different Vtp than the vaccine succumbed to infection. We demonstrate that by having knowledge of the phenotypic changes made by B. hermsii as the spirochetes are acquired by ticks from infected mammals, an effective vaccine was developed that protected mice when challenged with infected ticks. However, the Vtp vaccines only protected mice from infection when challenged with that strain producing the identical Vtp. A vaccine containing multiple Vtp types may have promise as an oral vaccine for wild mammals if applied to geographic settings such as small islands where the mammal diversity is low and the Vtp types in the B. hermsii population are defined.
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Tickborne Relapsing Fever, Bitterroot Valley, Montana, USA
Emerging infectious diseases, 2015Co-Authors: Joshua Christensen, Sandra J Raffel, Robert J. Fischer, Brandi N. Mccoy, Tom G. SchwanAbstract:In July 2013, a resident of the Bitterroot Valley in western Montana, USA, contracted tickborne relapsing fever caused by an infection with the spirochete Borrelia hermsii. The patient’s travel history and activities before onset of illness indicated a possible exposure on his residential property on the eastern side of the valley. An onsite investigation of the potential exposure site found the vector, Ornithodoros hermsi ticks, and 1 chipmunk infected with spirochetes, which on the basis of multilocus sequence typing were identical to the spirochete isolated from the patient. Field studies in other locations found additional serologic evidence and an infected tick that demonstrated a wider distribution of spirochetes circulating among the small mammal populations. Our study demonstrates that this area of Montana represents a previously unrecognized focus of relapsing fever and poses a risk for persons of acquiring this tickborne disease.
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first isolation of the relapsing fever spirochete Borrelia hermsii from a domestic dog
Ticks and Tick-borne Diseases, 2014Co-Authors: Ashley L Kelly, Sandra J Raffel, Robert J. Fischer, Michael Bellinghausen, Connie Stevenson, Tom G. SchwanAbstract: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 sequences for 7 loci all typed the spirochete as B. hermsii and a member of genomic group II of this species. Therefore, companion dogs that reside in rustic cabins in higher elevation forests are at risk of infection with B. hermsii.
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a novel surface antigen of relapsing fever spirochetes can discriminate between relapsing fever and lyme borreliosis
Clinical and Vaccine Immunology, 2010Co-Authors: Job E Lopez, Sandra J Raffel, Brandi N. Mccoy, Merry E Schrumpf, Vijayaraj Nagarajan, Tom G. SchwanAbstract: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 locus was amplified and sequenced from 39 isolates of B. hermsii that had been acquired from western North America. bipA was also expressed as a recombinant fusion protein. Serum samples from mice and patients infected with B. hermsii or B. burgdorferi were used to confirm the immunogenicity of the recombinant protein in patients infected with relapsing fever spirochetes. Lastly, in silico and experimental analysis indicated that BipA is a surface-exposed lipoprotein in B. hermsii. These findings enhance the capabilities of diagnosing infection with relapsing fever spirochetes.
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identification of conserved antigens for early serodiagnosis of relapsing fever Borrelia
Microbiology, 2009Co-Authors: Job E Lopez, Sandra J Raffel, Merry E Schrumpf, Stephen F. Porcella, Carl H Hammer, Ming Zhao, Mary Ann Robinson, Tom G. SchwanAbstract:Borrelia hermsii is a blood-borne pathogen transmitted by the argasid tick Ornithodoros hermsi. Since spirochaete clearance in mice is associated with an IgM-mediated response, an immunoproteomic analysis was used to identify proteins reactive with IgM. We report that IgM from both mice and human patients infected with B. hermsii not only reacted with the previously identified variable membrane proteins but also identified candidate antigens including heat-shock proteins, an adhesin protein, ABC transporter proteins, flagellar proteins, housekeeping proteins, an immune evasion protein, and proteins with unknown function. Furthermore, IgM reactivity to recombinant glycerophosphodiester phosphodiesterase was detected during early spirochaete infection and prior to a detectable IgG response. Lastly, a conserved hypothetical protein was produced in Escherichia coli and tested with immune serum against B. hermsii and Borrelia recurrentis. These results identify a much larger set of immunoreactive proteins, and could help in the early serodiagnosis of this tick-borne infection.
Stephen F. Porcella - One of the best experts on this subject based on the ideXlab platform.
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identification of conserved antigens for early serodiagnosis of relapsing fever Borrelia
Microbiology, 2009Co-Authors: Job E Lopez, Sandra J Raffel, Merry E Schrumpf, Stephen F. Porcella, Carl H Hammer, Ming Zhao, Mary Ann Robinson, Tom G. SchwanAbstract:Borrelia hermsii is a blood-borne pathogen transmitted by the argasid tick Ornithodoros hermsi. Since spirochaete clearance in mice is associated with an IgM-mediated response, an immunoproteomic analysis was used to identify proteins reactive with IgM. We report that IgM from both mice and human patients infected with B. hermsii not only reacted with the previously identified variable membrane proteins but also identified candidate antigens including heat-shock proteins, an adhesin protein, ABC transporter proteins, flagellar proteins, housekeeping proteins, an immune evasion protein, and proteins with unknown function. Furthermore, IgM reactivity to recombinant glycerophosphodiester phosphodiesterase was detected during early spirochaete infection and prior to a detectable IgG response. Lastly, a conserved hypothetical protein was produced in Escherichia coli and tested with immune serum against B. hermsii and Borrelia recurrentis. These results identify a much larger set of immunoreactive proteins, and could help in the early serodiagnosis of this tick-borne infection.
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Diversity and distribution of Borrelia hermsii.
Emerging infectious diseases, 2007Co-Authors: Tom G. Schwan, Stephen F. PorcellaAbstract:Tickborne relapsing fever in humans in North America is most often caused by the spirochete Borrelia hermsii, which is transmitted by its argasid tick vector, Ornithodoros hermsi (1). The spirochete is endemic to the western United States and southern British Columbia in Canada (Figure 1) but restricted to higher elevations with coniferous forests where both the ticks and appropriate vertebrate hosts coexist (1). The most common exposure for humans occurs while they are sleeping in tick-infested cabins, where the nocturnal ticks seek their hosts and feed quickly within 15 to 90 minutes and then return to their refuge in the walls, floor, or attic. Figure 1 Western United States showing the approximate endemic range of tickborne relapsing fever associated with Ornithodoros hermsi and the localities of origin for the 37 Borrelia hermsii isolates included in this study. Genome group I (GGI) isolates are shown ... The specific association of this spirochete with O. hermsi led to the bacterium’s being named B. hermsii, to distinguish it from other species of relapsing fever spirochetes transmitted by other species of ticks in the western United States (2). The ability to propagate B. hermsii in pure culture (3) and the development of molecular techniques and databases to identify, type, and compare spirochetes were critical advances for the study of these bacteria. We are now able to characterize and better define these species and to elucidate the geographic distribution and role that O. hermsi and various vertebrate hosts play in maintaining B. hermsii in nature. These advances are countered, however, by the difficulty in finding infected O. hermsi ticks or rodents in the wild and the infrequent access to infected blood samples from patients when they are acutely ill and spirochetemic. Additionally, although B. hermsii is cultivatable, establishing these spirochetes in vitro from infected samples is not always successful. Recently, we identified 2 genomic groups in B. hermsii by multilocus sequence typing of 31 isolates (4). Four loci were examined (16S rRNA, flaB, gyrB, and glpQ), which cumulatively totaled 5,197–5,203 bp per isolate. The 2 genomic groups of B. hermsii were also distinct from isolates of B. turicatae and B. parkeri, for which we undertook a similar analysis (5). Bunikis and co-workers recently typed relapsing fever spirochetes based on the intergenic spacer (IGS) region of noncoding DNA located between the 16S rRNA and ileT tRNA genes (6). In their report, 4 IGS types were identified among 9 isolates or DNA extracted from tissues infected with B. hermsii. Given that less effort is needed to type B. hermsii with only the IGS sequence than to several larger loci, we undertook an analysis of the IGS region in our isolates to determine its utility to define the 2 genomic groups in these spirochetes. Here we compare results obtained with the IGS locus to results obtained by multilocus sequence typing, which included recently acquired spirochetes from an outbreak of relapsing fever that were not examined previously. We use these data to discuss the geographic distribution of B. hermsii and explain how birds may help maintain and disperse these spirochetes in nature.
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antigenic variation by Borrelia hermsii occurs through recombination between extragenic repetitive elements on linear plasmids
Molecular Microbiology, 2006Co-Authors: Qiyuan Dai, Alan G. Barbour, Tom G. Schwan, Blanca I. Restrepo, Stephen F. PorcellaAbstract:The relapsing fever agent Borrelia hermsii undergoes multiphasic antigenic variation through gene conversion of a unique expression site on a linear plasmid by an archived variable antigen gene. To further characterize this mechanism we assessed the repertoire and organization of archived variable antigen genes by sequencing approximately 85% of plasmids bearing these genes. Most archived genes shared with the expressed gene a
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variable tick protein in two genomic groups of the relapsing fever spirochete Borrelia hermsii in western north america
Infection and Immunity, 2005Co-Authors: Stephen F. Porcella, Donald E Anderson, Stacey D Gilk, James L Bono, Tom G. SchwanAbstract:Borrelia hermsii is the primary cause of tick-borne relapsing fever in North America. When its tick vector, Ornithodoros hermsi, acquires these spirochetes from the blood of an infected mammal, the bacteria switch their outer surface from one of many bloodstream variable major proteins (Vmps) to a unique protein, Vtp (Vsp33). Vtp may be critical for successful tick transmission of B. hermsii; however, the gene encoding this protein has been described previously in only one isolate. Here we identified and sequenced the vtp gene in 31 isolates of B. hermsii collected over 40 years from localities throughout much of its known geographic distribution. Seven major Vtp types were found. Little or no sequence variation existed within types, but between them significant variation was observed, similar to the pattern of diversity described for the outer surface protein C (OspC) gene in Lyme disease spirochetes. The pattern of sequence relatedness among the Vtp types was incongruent in two branches compared to two genomic groups identified among the isolates by multilocus sequence typing of the 16S rRNA, flaB, gyrB, and glpQ genes. Therefore, both horizontal transfer and recombination within and between the two genomic groups were responsible for some of the variation observed in the vtp gene. O. hermsi ticks were capable of transmitting spirochetes in the newly identified genomic group. Therefore, given the longevity of the tick vector and persistent infection of spirochetes in ticks, these arthropods rather than mammals may be the likely host where the exchange of spirochetal DNA occurs.
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phylogenetic analysis of the spirochetes Borrelia parkeri and Borrelia turicatae and the potential for tick borne relapsing fever in florida
Journal of Clinical Microbiology, 2005Co-Authors: Tom G. Schwan, Sandra J Raffel, Paul F. Policastro, Merry E Schrumpf, Robert S Lane, Julie A Rawlings, Edward B Breitschwerdt, Stephen F. PorcellaAbstract:Isolates of Borrelia turicatae, Borrelia parkeri, and the Florida canine Borrelia (FCB) were examined to further phylogenetically characterize the identities of these spirochetes in the United States. DNA sequences of four chromosomal loci (the 16S rRNA gene, flaB, gyrB, and glpQ) were determined for eight isolates of B. turicatae and six isolates of B. parkeri, which grouped the spirochetes into two distinct but closely related taxa (>98% sequence identity) separate from Borrelia hermsii. The FCB was clearly separated with the group identified as B. turicatae, confirming this bacterium as a relapsing fever spirochete. Therefore, the potential for tick-borne relapsing fever in humans and other animals exists in Florida and future efforts are needed to determine the enzootic hosts and distribution of this spirochete in the southeastern United States. Analysis of plasmids demonstrated both linear and circular forms in B. turicatae but only linear plasmids in B. parkeri, which should be of interest to investigators concerned with plasmid diversity and evolution within this group of spirochetes.