<i>Borrelia burgdorferi ospC</i>
            Heterogeneity among Human and Murine Isolates from a Defined Region of Northern Maryland and Southern Pennsylvania: Lack of Correlation with Invasive and Noninvasive Genotypes

Alghaferi, Muneera Y.; Anderson, Jennifer M.; Park, Jinho; Auwaerter, Paul G.; Aucott, John N.; Norris, Douglas E.; Dumler, J. Stephen

doi:10.1128/jcm.43.4.1879-1884.2005

Cited by 55 publications

(62 citation statements)

References 33 publications

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“…Third, the severe human virulence of B. burgdorferi s.s. is itself evidence for it being a generalist parasite of mammalian hosts, since despite the fact that humans are not its natural reservoir hosts, B. burgdorferi s.s. is capable of invading and infecting the human tissues. Although B. burgdorferi s.s. strains appear to vary in human virulence (Dykhuizen et al 2008;Wormser et al 2008), it has been argued that associations between human pathogenecity and genomic groups are weak and all groups have the potential to cause invasive infections in humans (Alghaferi et al 2005;Jones et al 2006).…”

Section: Maintenance Of Genome Clusters By Frequency-dependent Selectionmentioning

confidence: 99%

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Vargas²,

et al. 2011

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How genomic diversity within bacterial populations originates and is maintained in the presence of frequent recombination is a central problem in understanding bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, consist of diverse genomic groups co-infecting single individual vertebrate hosts and tick vectors. To understand mechanisms of sympatric genome differentiation in B. burgdorferi, we sequenced and compared 23 genomes representing major genomic groups in North America and Europe. Linkage analysis of .13,500 single-nucleotide polymorphisms revealed pervasive horizontal DNA exchanges. Although three times more frequent than point mutation, recombination is localized and weakly affects genome-wide linkage disequilibrium. We show by computer simulations that, while enhancing population fitness, recombination constrains neutral and adaptive divergence among sympatric genomes through periodic selective sweeps. In contrast, simulations of frequency-dependent selection with recombination produced the observed pattern of a large number of sympatric genomic groups associated with major sequence variations at the selected locus. We conclude that negative frequency-dependent selection targeting a small number of surface-antigen loci (ospC in particular) sufficiently explains the maintenance of sympatric genome diversity in B. burgdorferi without adaptive divergence. We suggest that pervasive recombination makes it less likely for local B. burgdorferi genomic groups to achieve host specialization. B. burgdorferi genomic groups in the northeastern United States are thus best viewed as constituting a single bacterial species, whose generalist nature is a key to its rapid spread and human virulence. G ENETIC discontinuity, the basis of biodiversity, is ubiquitous in prokaryotes as well as in eukaryotes. Most bacterial populations display a highly clonal genetic structure, in which the observable number of multilocus genotypes is far fewer than the number expected under the assumption of free recombination (Maynard Smith et al. 1993). Bacterial clonality was originally thought of as a result of a lack or rarity of recombination among asexually reproducing and independently evolving clones (Ochman and Selander 1984). Since then, molecular surveys of natural bacterial populations using protein electrophoresis, multilocus sequencing typing (MLST), and whole-genome PRJNA3, PRJNA28633, PRJNA19839, PRJNA29359, PRJNA28629, PRJNA29357, PRJNA21003, PRJNA19835, PRJNA28627, PRJNA21001, PRJNA29361, PRJNA28621, PRJNA19837, PRJNA20999, PRJNA28631, PRJNA29363, PRJNA17057, PRJNA19841, PRJNA12554, PRJNA28625, PRJNA29573, PRJNA19843, and PRJNA28635. 1 Present address: Odum School of Ecology, University of Georgia, Athens, GA 30602. sequencing revealed that horizontal genetic exchange is in fact often more frequent than point mutations in bacteria, including species known as strongly clonal (Maynard Smith et al. 1993;Feil and Spratt 2001;Didelot and Maiden 2010;Retc...

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Section: Maintenance Of Genome Clusters By Frequency-dependent Selectionmentioning

confidence: 99%

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Vargas²,

et al. 2011

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“…Of 118 EM skin biopsy samples in patients from Long Island, NY, 51 (43%) were type A, B, or I, 32 (27%) were type K, and 35 (30%) were other types, but hematogenous dissemination was associated only with types A, B, I, and K (27). In a later study of six B. burgdorferi blood isolates and one skin isolate from patients in Maryland and Pennsylvania, dissemination occurred with these and two other OspC types (H and N) (1). Recently, OspC was shown to bind a tick salivary gland protein, Salp15 (25,26), which is important in establishing early infection in mice (10).…”

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confidence: 99%

Borrelia burgdorferi Genetic Markers and Disseminated Disease in Patients with Early Lyme Disease

et al. 2006

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Three genetic markers of Borrelia burgdorferi have been associated with disseminated disease: the OspC type, the 16S-23S rRNA intergenic spacer type (RST), and vlsE. Here, we modified previous methods so as to identify the three markers by PCR and restriction fragment length polymorphism in parallel, analyzed B. burgdorferi isolates from erythema migrans (EM) skin lesions in 91 patients, and correlated the results with evidence of dissemination. OspC type A was found approximately twice as frequently in patients with disseminated disease, whereas type K was identified approximately twice as often in those without evidence of dissemination, but these trends were not statistically significant. The remaining seven types identified were found nearly equally in patients with or without evidence of dissemination. RST 1 strains were significantly associated with dissemination (P ‫؍‬ 0.03), whereas RST 2 and RST 3 strains tended to have an inverse association with this outcome. The vlsE gene was identified in all 91 cases, using primer sets specific for an N-terminal sequence of B. burgdorferi strain B31 (vlsE B31 ) or strain 297 (vlsE 297 ), but neither marker was associated with dissemination. Specific combinations of the three genetic markers usually occurred together. OspC type A was always found with RST 1 and vlsE B31 , type K was always identified with RST 2 and more often with vlsE 297 , and types E and I were almost always found with RST 3 and equally often with vlsE B31 and vlsE 297 . We conclude that B. burgdorferi strains vary in their capacity to disseminate, but almost all strains isolated from EM lesions sometimes caused disseminated disease.

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“…The OspC types of human clinical isolates have also been correlated with invasive and non-invasive phenotypes (38,39). However, similar studies demonstrated greater diversity among invasive types than previously recognised, calling into question any causative effect of OspC sequence on invasion (40,41). Carefully controlling for variables other than OspC has not been possible in such studies, since additional genome components of these isolates also differ.…”

Section: Discussionmentioning

confidence: 90%

Enhanced Adhesion and OspC Protein Synthesis of the Lyme Disease Spirochete Borrelia Burgdorferi Cultivated in a Host-Derived Tissue Co-Culture System

Şen

Sigal

2013

Balkan Med J

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Background: The adhesion process of Borrelia burgdorferi to susceptible host cell has not yet been completely understood regarding the function of OspA, OspB and OspC proteins and a conflict exists in the infection process.Aims: The adhesion rates of pathogenic (low BSK medium passaged or susceptible rat joint tissue co-cultivated ) or non-pathogenic Borrelia burgdorferi (high BSK medium passaged) isolate (FNJ) to human umbilical vein endothelial cells (HUVEC) cultured on coverslips and the synthesis of OspA and OspC proteins were investigated to analyze the infection process of this bacterium.Study Design: In-vitro study.Methods: Spirochetes were cultured in BSK medium or in a LEW/N rat tibiotarsal joint tissue feeder layer supported co-culture system using ESG coculture medium and labelled with 3H-adenine for 48 hours. SDS-PAGE, Western Blotting, Immunogold A labeling as well as radiolabeling experiments were used to compare pathogenic or non pathogenic spirochetes during the adhesion process.Results: Tissue co-cultured B. burgdorferi adhered about ten times faster than BSK-grown spirochetes. Trypsin inhibited attachment to HUVEC and coculture of trypsinized spirochetes with tissues reversed the inhibition. Also, the synthesis of OspC protein by spirochetes was increased in abundance after tissue co-cultures, as determined by SDS-PAGE and by electron microscopy analysis of protein A-immunogold staining by anti-OspC antibodies. OspA protein was synthesized in similar quantities in all Borrelia cultures analyzed by the same techniques.Conclusion: Low BSK passaged or tissue co-cultured pathogenic Lyme disease spirochetes adhere to HUVEC faster than non-pathogenic high BSK passaged forms of this bacterium. Spirochetes synthesized OspC protein during host tissue-associated growth. However, we did not observe a reduction of OspA synthesis during host tissue co-cultivation in vitro.

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Borrelia burgdorferi ospC Heterogeneity among Human and Murine Isolates from a Defined Region of Northern Maryland and Southern Pennsylvania: Lack of Correlation with Invasive and Noninvasive Genotypes

Cited by 55 publications

References 33 publications

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Borrelia burgdorferi Genetic Markers and Disseminated Disease in Patients with Early Lyme Disease

Enhanced Adhesion and OspC Protein Synthesis of the Lyme Disease Spirochete Borrelia Burgdorferi Cultivated in a Host-Derived Tissue Co-Culture System

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