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Efficient acquisition and transmission of  Borrelia burgdorferi  by the tick vector, and the ability to persistently infect both vector and host, are important elements for the life cycle of the Lyme disease pathogen. Previous work has provided strong evidence implicating the significance of the  vls  locus for  B .  burgdorferi  persistence. However, studies involving  vls  mutant clones have thus far only utilized  in vitro -grown or host-adapted spirochetes and laboratory strains of mice. Additionally, the effects of  vls  mutation on tick acquisition and transmission has not yet been tested. Thus, the importance of VlsE antigenic variation for persistent infection of the natural reservoir host, and for the  B .  burgdorferi  enzootic life cycle in general, has not been examined to date. In the current work,  Ixodes scapularis  and  Peromyscus maniculatus  were infected with different  vls  mutant clones to study the importance of the  vls  locus for the enzootic cycle of the Lyme disease pathogen. The findings highlight the significance of the  vls  system for long-term infection of the natural reservoir host, and show that VlsE antigenic variability is advantageous for efficient tick acquisition of  B .  burgdorferi  from the mammalian reservoir. The data also indicate that the adaptation state of infecting spirochetes influences  B .  burgdorferi  avoidance from host antibodies, which may be in part due to its respective VlsE expression levels. Overall, the current findings provide the most direct evidence on the importance of VlsE for the enzootic cycle of Lyme disease spirochetes, and underscore the significance of VlsE antigenic variation for maintaining  B .  burgdorferi  in nature.

Evaluation of the Importance of VlsE Antigenic Variation for the Enzootic Cycle of Borrelia burgdorferi