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Dramatic alteration of surface lipoprotein profiles is a key strategy that Borrelia burgdorferi, the
Lyme disease pathogen, has evolved for adapting to the diverse environments of arthropod and mammalian hosts. Several of these differentially expressed lipoproteins have been shown to play important roles in the enzootic cycle of B. burgdorferi. The BBA05 protein is a previously identified putative lipoprotein (P55 or S1 antigen) that elicits antibody responses in mammals. Recent microarray analyses indicate that the BBA05 gene is differentially expressed by many environmental factors, including temperature. However, the role of the BBA05 protein in the life cycle of B. burgdorferi has not been elucidated. Here we show that expression of the BBA05 gene was exclusively induced in feeding nymphal ticks during the spirochetal transmission from ticks to mammals. Upon generating a BBA05 mutant in an infectious strain of B. burgdorferi, we showed that the BBA05 mutant remained capable of establishing infection in mice, being acquired by ticks, persisting through tick molting, and reinfecting new mammalian hosts. These results indicate that, despite being a highly conserved and regulated antigen, the BBA05 protein has a nonessential role in the transmission cycle of B. burgdorferi, at least in the animal model.