Juxtaposition of expressed variable antigen genes with a conserved telomere in the bacterium Borrelia hermsii.

Abstract

Borrelia hermsii, an agent of relapsing fever, survives in mammals through antigenic variation. Change in serotype-specific variable outer membrane proteins (Vmps) occurs when a Vmp gene at an expression site is replaced with a previously silent gene for another Vmp. Silent and active genes are on separate linear plasmids. The upstream site for a nonreciprocal recombination between two linear plasmids is near the 5' ends of the expressed and silent genes. In the present study we sought the downstream recombination sites in two serotypes, 7 and 21. Restriction fragments containing plasmid telomeres were identified by susceptibility to digestion with BAL-31 and rapid reannealment following denaturation.Whereas both silent genes and a minority population of both expression-linked genes were several kilobases from the telomeres, the predominant population of both expressed genes had 3' ends near plasmid telomeres. Sequence analysis of the predominant expression plasmids revealed that the telomeric sequences were the same in serotypes 7 and 21. Identical sequence was also downstream of silent Vmp genes. Switching of Vmp genes appears to occur by recombination that involves both upstream and downstream sites. The expression plasmid's telomere is preserved in the recombination event.

Telomeres of the linear chromosomes of Lyme disease spirochaetes: nucleotide sequence and possible exchange with linear plasmid telomeres

“…Gonzalez et al, 1986;Rohozinski et al, 1989), the linear E. coli bacteriophage N15 prophage plasmid (Svarchevsky and Rybchin, 1984;Malinin et al, 1992), and several linear plasmids present in B. burgdorferi and B. hermsii (Hinnebusch et al, 1990;Kitten and Barbour, 1990). In addition, several eukaryotes are known to carry mitochondrial DNAs with one or two hairpin ends (e.g.…”

Pathogen escape from host immunity by a genome program for antigenic variation

“…The frequency of new variants in expanding B. hermsii populations either in animals or in culture medium is 10 Ϫ4 to 10 Ϫ3 (19). The molecular event underlying the majority of switches in surface proteins is a nonreciprocal recombination involving all or nearly all of a variant gene at a single expression site by one of several variant genes at silent loci on linear plasmids (20)(21)(22). We identified most of the silent variants that comprise the antigenic repertoire of B. hermsii, located 59 silent loci on several linear plasmids in the bacterium, and described the 5Ј and 3Ј flanking sequences (23).…”

“…Most variant genes are arrayed on the same strand in a given plasmid, but some are oppositely oriented. The upstream homology sequence (UHS) element at the expression site comprises 61 nt around the start codon of the variant gene (20,26). Silent genes vary in the extent to which their UHS regions are identical to the expression site UHS.…”

Antigen polymorphism in Borrelia hermsii , a clonal pathogenic bacterium

“…However, B. hermsii antigenic variation is unique when compared with antigenic variation of most closely studied bacteria (5), because the set of B. hermsii's sequentially expressed alleles constitute an archive located among the linear plasmids of the genome (6)(7)(8)(9). Serotype switching results when one of these serotype-specific variants replaces another by duplicative transposition into the single expression site (10,11). This situation contrasts with antigenic variation of N. gonorrhoeae, wherein only portions of the pilin genes are exchanged between alleles to generate novel proteins (12).…”