ANTIGENIC VARIATION IN LYME-DISEASE BORRELIAE BY PROMISCUOUS RECOMBINATION OF VMP-LIKE SEQUENCE CASSETTES

We have identified and characterized an elaborate genetic system in th e Lyme disease spirochete Borrelia burgdorferi that promotes extensive antigenic variation of a surface-exposed lipoprotein, VlsE. A 28 kb l inear plasmid of B. burgdorferi B31 (Ip28-1) was found to contain a vm p-like sequence (vls) locus that closely resembles the variable major protein (vmp) system for antigenic variation of relapsing fever organi sms. Portions of several of the 15 nonexpressed (silent) vls cassette sequences located upstream of vlsE recombined into the central vlsE ca ssette region during infection of C3H/HeN mice, resulting in antigenic variation of the expressed lipoprotein. This combinatorial variation could potentially produce millions of antigenic variants in the mammal ian host.