Comparative Investigation of the Genomic Regions Involved in Antigenic Variation of the TprK Antigen among Treponemal Species, Subspecies, and Strains

Abstract

Although the threeTreponema pallidumsubspecies (T. pallidumsubsp.pallidum,T. pallidumsubsp.pertenue, andT. pallidumsubsp.endemicum),Treponema paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme cause clinically distinct diseases, these pathogens are genetically and antigenically highly related and are able to cause persistent infection. Recent evidence suggests that the putative surface-exposed variable antigen TprK plays an important role in both treponemal immune evasion and persistence.tprKheterogeneity is generated by nonreciprocal gene conversion between thetprKexpression site and donor sites. Although each of the above-mentioned species and subspecies has a functionaltprKantigenic variation system, it is still unclear why the level of expression and the rate at whichtprKdiversifies during infection can differ significantly among isolates. To identify genomic differences that might affect the generation and expression of TprK variants among these pathogens, we performed comparative sequence analysis of the donor sites, as well as thetprKexpression sites, among eightT. pallidumsubsp.pallidumisolates (Nichols Gen, Nichols Sea, Chicago, Sea81-4, Dal-1, Street14, UW104, and UW126), threeT. pallidumsubsp.pertenueisolates (Gauthier, CDC2, and Samoa D), oneT. pallidumsubsp.endemicumisolate (Iraq B), the unclassified Fribourg-Blanc isolate, and the Cuniculi A strain ofT. paraluiscuniculi. Synteny and sequence conservation, as well as deletions and insertions, were found in the regions harboring the donor sites. These data suggest that thetprKrecombination system is harbored within dynamic genomic regions and that genomic differences might be an important key to explain discrepancies in generation and expression oftprKvariants among theseTreponemaisolates.