|ROGOVSKYY, ARTEM - Washington State University
|CASSELLI, TIMOTHY - Washington State University
|TOURAND, YVONNE - Washington State University
|JONES, CAMI - Washington State University
|OWEN, JEB - Washington State University
|BANKHEAD, TROY - Washington State University
Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2015
Publication Date: 4/20/2015
Citation: Rogovskyy, A.S., Casselli, T., Tourand, Y., Jones, C.R., Owen, J.P., Mason, K.L., Scoles, G.A., Bankhead, T. 2015. Evaluation of the importance of VlsE antigenic variation for the enzootic cycle of borrelia burgdorferi . PLoS One. doi: 10.1371/journal.pone.0124268.
Interpretive Summary: Borrelia burgdorferi is the causative bacterial agent of Lyme disease, which can clinically present as arthritis, carditis, and/or neurological disorders. In nature, B. burgdorferi is maintained in an enzootic life cycle that involves an arthropod vector and small vertebrate host. In North America, B. burgdorferi is transmitted mainly by the tick vectors, Ixodes scapularis and Ixodes pacificus. Peromyscus leucopus mice are considered the primary vertebrate reservoir, and Peromyscus maniculatis has also been shown to be a competent host in nature. Ixodes larvae acquire spirochetes when feeding on an infected host, and B. burgdorferi is subsequently transmitted when infected nymphs feed on young uninfected animals. Transmission from infected nymphs of one cohort to larvae of another through reservoir hosts is believed to be largely responsible for maintenance of B. burgdorferi in nature. Efficient B. burgdorferi acquisition and transmission by the tick vector, and the ability to persistently infect both vector and host, are important elements for the life cycle of the Lyme pathogen. Previous studies involving laboratory strains of mice have provided strong evidence implicating the significance of a particular region of the genome, vls locus, for B. burgdorferi persistence. In the present work, Ixodes scapularis and Peromyscus maniculatus were utilized as a model to study the significance of the variation in the gene VlsE for the B. burgdorferi enzootic cycle. Specifically, this work examines the importance of VlsE antigenic variation for B. burgdorferi to establish infection in both natural murine and arthropod hosts by taking advantage of previously generated B. burgdorferi vls mutants. Overall, the study provides the first direct evidence of the importance of the vls locus during the enzootic cycle of Lyme spirochetes, and highlights the relevance of VlsE antigenic variation for maintaining B. burgdorferi in nature.
Technical Abstract: 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.