Antigen polymorphism in Borrelia hermsii , a clonal pathogenic bacterium

Abstract

The relapsing fever spirochete, Borrelia hermsii, escapes immune selection by alternating expression of surface lipoprotein alleles. The switch results from a duplicative transposition of one of several surface lipoprotein-encoding nucleotide sequences into the singular expression site. These nucleotide sequences constitute a large gene family whose diversity originated, in some cases, before the major divergences of Borrelia species. We have examined the B. hermsii vsp subfamily of alleles, which are carried on linear plasmids within each cell and maintained in several diverse copies as an antigenic archive. Each encodes a distinct serotype-specific protein. We sequenced more than 90% of the alleles within a single strain-B. hermsii strain HS1. A preponderance of allelic mosaicism suggests that intragenic recombination, coupled with selection imposed by host immune response, has driven diversification of the archived ensemble of vsp alleles. The recombinational diversification of vsp alleles generates change in the associated serotypes of the magnitude (30 -40% amino acid differentiation) necessary for overcoming cross-reactivity of neutralizing antibodies. We conclude that evolution of vsp has occurred by punctuated occurrence of allelic differentiation, rather than by gradual selection of incremental point mutations that do not meet the threshold for antigenic diversity.homologous recombination ͉ antigenic variation ͉ evolution

Superinfection as a driver of genomic diversification in antigenically variant pathogens

“…However, the presence of identical alleles at two different chromosomal loci within a strain (observed for both the St. Maries and Florida strains) (12) suggests that gene duplication may provide the template for additional interallelic recombination (22), alone or combined with mutation, to generate diverse alleles with consequent selection at the level of successful superinfection. The ability of a strain with a single diverse allele to superinfect long-term persistently infected hosts, represented by the experiments using the St. Maries and 6DE strains, support that duplication followed by divergence would confer a significant selective advantage.…”

Contingent, non-neutral evolution in a multicellular parasite: natural selection and gene conversion in the Echinococcus granulosus antigen B gene family

“…In the clonal pathogenic bacterium Borrelia hermsii, serotype switching occurs when one serotype-specific variant replaces another by duplicative transposition into the ES (review in Rich et al, 2001). In the African protozoan Trypanosoma brucei, switching of the VSG genes to the ES occurs by gene conversion (review in Borst, 2002).…”

Expansion of Variant Diversity Associated with a High Prevalence of Pathogen Strain Superinfection under Conditions of Natural Transmission

“…Msp2 variants are generated by a process of gene conversion in which donor alleles or oligonucleotide segments of the alleles are recombined into an expression site (4,(7)(8)(9). This mechanism is common among numerous bacterial and protozoal pathogens, including those causing relapsing fever, sleeping sickness, and syphilis (5,11,19,31,33,42). The resulting new Msp2 variants evade recognition by the existing immune response (14).…”