Antigenic variation in relapsing fever Borrelia

Sammanfattning: The spirochete Borrelia hermsii avoids the immune response of its mammalian host through multiphasic antigenic variation. Serotype specificity is determined by Variable major proteins (Vmp), in the outer membrane. Through a non reciprocal recombination between linear plasmids, a formerly silent vmp gene replaces another vmp gene at a telomeric expression locus downstream from a common expression site. B. hermsii before and after the switch from serotype 7 to serotype 21, was examined in detail.The nucleotide sequence of the vmp7 and vmp21 genes and flanking regions was determined. The vmp7 and vmp21 are 77% identical in their coding sequence, and the deduced translation products are 63% identical. No antigenic cross reactivity is observed between Vmp7 and Vmp21. This suggests a folding of the proteins in which the similar regions are buried, and not exposed when it is presented at the bacterial surface. Vmp7 and Vmp21 have consensus sequences of prokaryotic lipoproteins and are processed as such when expressed in E. coli.The 5' regions of silent and expressed vmp7 and vmp21 were compared. Silent and active vmp7 and vmp21 genes shared a block of homologous sequence at their 5' ends. Sequences upstream of silent vmp7 and vmp21 genes lacked a promoter and differed substantially from each other. In this antigenic switch a vmp gene was activated by a recombination event which placed it downstream of a promoter.The vmp gene promoter is preceded by a poly(dT dA) ran and three imperfectlyrepeated elements of 2 kb. Each of the 2 kb repeats contains inverted repeats of approximately 0.2 kb at their termini. There is no evidence of the presence of similar elements elsewhere in the genome of B. hermsii. One or more of these elements may stimulate vmp gene switch or expression.The African relapsing fever species Borrelia crocidurae and the American species B. hermsii display many similarities. In both species the vmp genes are localised to linear plasmids, and the vmp genes are activated on the transcriptional level. The nucleotide sequence of their expression sites, however, are not related. Still, the possibility that the switch is mechanistically similar in B. crocidurae and B. hermsii, cannot be ruled out.The binding of B. crocidurae causes aggregation of erythrocytes around the spirochete. The aggregation is reminiscent of the erythrocyte rosetting seen in malarial infections. The erythrocytes at the B. crocidurae surface may protect them from clearance by the host. Thus, the rosetting may constitute an additional mechanism in B. crocidurae for the evasion of the immune reaction.