Evolution and Distribution of the ospC Gene, a Transferable Serotype Determinant of Borrelia burgdorferi

Abstract

Borrelia burgdorferi, an emerging bacterial pathogen, is maintained in nature by transmission from one vertebrate host to another by ticks. One of the few antigens against which mammals develop protective immunity is the highly polymorphic OspC protein, encoded by the ospC gene on the cp26 plasmid. Intragenic recombination among ospC genes is known, but the extent to which recombination extended beyond the ospC locus itself is undefined. We accessed and supplemented collections of DNA sequences of ospC and other loci from ticks in three U.S. regions (the Northeast, the Midwest, and northern California); a total of 839 ospC sequences were analyzed. Three overlapping but distinct populations of B. burgdorferi corresponded to the geographic regions. In addition, we sequenced 99 ospC flanking sequences from different lineages and compared the complete cp26 sequences of 11 strains as well as the cp26 bbb02 loci of 56 samples. Besides recombinations with traces limited to the ospC gene itself, there was evidence of lateral gene transfers that involved (i) part of the ospC gene and one of the two flanks or (ii) the entire ospC gene and different lengths of both flanks. Lateral gene transfers resulted in different linkages between the ospC gene and loci of the chromosome or other plasmids. By acquisition of the complete part or a large part of a novel ospC gene, an otherwise adapted strain would assume a new serotypic identity, thereby being comparatively fitter in an area with a high prevalence of immunity to existing OspC types.

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

“…Nucleotide polymorphisms are retained at surface-antigen loci like ospC by positive natural selection (Wang et al 1999a;Barbour and Travinsky 2010). More directly, we found at least three independent gene-conversion events at the guaA-ospC-bbb22 loci in a single B. burgdorferi s.s. genome ( Figure S4).…”

“…This tree improves upon previously published phylogenies of the B. burgdorferi s.s. genomic groups by gaining significant statistical support for most of the branches (Bunikis et al 2004;Margos et al 2008;Qiu et al 2008;Barbour and Travinsky 2010). This and other intraspecific phylogenies of B. burgdorferi s.l.…”

“…This and other intraspecific phylogenies of B. burgdorferi s.l. isolates share the characteristics of nearly one-to-one association between the genomic lineages and the major ospC alleles, with rare exceptions of the same ospC allele appearing polyphyletically due to recombination (Qiu et al 2008;Barbour and Travinsky 2010). Using a bootstrap cutoff value of 75%, we identified three pairs of strongly supported sister-group genomes, consisting of two North American pairs (118a-72a and 156a-297) and one European pair (Bol26-ZS7).…”

“…Considering that ospC is a serotype determinant of B. burgdorferi s.l., negative FDS operating at ospC is highly plausible. Presumably, cells with rare amino acid types in OspC would encounter weaker adaptive immune responses from the host population than cells with common OspC alleles (Wang et al 1999b;Barbour and Travinsky 2010).…”

Outer Surface Protein C Peptide Derived from Borrelia burgdorferi Sensu Stricto as a Target for Serodiagnosis of Early Lyme Disease

“…Current CDC guidelines for the serodiagnosis of Lyme disease mandate a two-tier analysis for improved accuracy, as current IgM and IgG serological assays lack sufficient specificity and/or are insensitive for the detection of antibody present at the time that many patients with early Lyme disease seek initial medical care (13)(14)(15)(16)(17)(18)(19). The first-tier assay is an enzyme-linked immunosorbent assay (ELISA), typically utilizing lysates of whole Borrelia as the target, which if positive or equivocal is followed by a Western blot assay containing several whole Borrelia proteins (9,10,20,21).…”