BB0323 Function Is Essential for Borrelia burgdorferi Virulence and Persistence through Tick-Rodent Transmission Cycle

Borrelia burgdorferi bb0323 encodes an immunogenic protein in mammalian hosts, including humans. An analysis of bb0323 expression in vivo showed variable transcription throughout the spirochete infection cycle, with elevated expression during tick-mouse transmission. Deletion of bb0323 in infectious B. burgdorferi did not affect microbial survival in vitro, despite considerable alterations in growth kinetics and cell morphology. The bb0323 mutants were unable to infect either mice or ticks and were quickly eliminated from immunocompetent and immunodeficient hosts and the vector within the first few days after inoculation. Chromosomal complementation of the mutant with native bb0323 and phenotypic analysis in vivo indicated the substantial restoration of spirochete virulence and persistence throughout the mouse-tick infection cycle. The BB0323 protein may serve an indispensable physiological function that is more pronounced during microbial persistence and transitions between the host and the vector in vivo. Strategies to interfere with BB0323 function may interrupt the infectious cycle of spirochetes.