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Modification of Borrelia burgdorferi to overproduce OspA or VlsE alters its infectious behaviour

Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA

Correspondence
Fang Ting Liang
fliang{at}vetmed.lsu.edu

The surface lipoproteins of the Lyme disease spirochaete Borrelia burgdorferi directly interact with tissue microenvironments during mammalian infection, and thus potentially affect various aspects of infection. To investigate the influence of surface antigen synthesis on infectious behaviour, B. burgdorferi was modified to constitutively produce the well-characterized surface lipoproteins OspA and invariant VlsE. Although increasing OspA or VlsE production did not significantly affect synthesis of other surface lipoproteins or spirochaetal growth in vitro, overexpressing vlsE resulted in increased ospA but decreased ospC expression, and overexpressing ospA led to decreased ospC and vlsE expression in severe combined immunodeficient (SCID) mice. Increasing the expression of either ospA or vlsE did not alter the ID₅₀, but affected spirochaetal dissemination and significantly reduced tissue spirochaete loads in SCID mice. In immunocompetent mice, increased vlsE expression resulted in quick clearance of infection, while constitutive ospA expression led to a substantial ID₅₀ increase and severely impaired dissemination. Furthermore, B. burgdorferi with constitutive ospA expression persisted in the skin tissue but was cleared from both heart and joints of chronically infected immunocompetent mice. Taken together, the study indicates that increasing production of OspA or invariant VlsE influences lipoprotein gene expression in the murine host and alters the infectious behaviour of B. burgdorferi.

Supplementary material describing the determination of ID₅₀ values, and two supplementary tables showing the influence of increasing OspA and VlsE expression on dissemination and ID₅₀ of B. burgdorferi in SCID mice, and that constitutive ospA expression severely impairs dissemination and significantly increases ID₅₀ in immunocompetent mice, are available with the online version of this paper.