Regulation of chemotaxis, motility, and virulence in the lyme disease spirochete Borrelia burgdorferi
Sze, Ching Wooen
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The Lyme disease spirochete, Borrelia burgdorferi, is endowed with several important virulence factors to institute an infection, such as the expression of various surface lipoproteins and motility. In depth regulatory mechanisms of these factors are just beginning to be understood. Herein, we identified a mutual regulatory protein for motility and virulence-associated genes, the carbon storage regulator A (CsrA Bb ), as well as demonstrated for the first time that chemotaxis is a virulence factor of this spirochete. We showed that CsrA Bb affects the infectivity of B. burgdorferi by regulating the level of acetyl-phosphate from the acetate metabolism via binding to the leader region of the bb0589 (phosphate acetyltransferase) transcript. Modulation of the intracellular acetyl-phosphate level allows CsrA Bb to regulate the activation of the Rrp2-RpoN-RpoS pathway, a central regulon of B. burgdorferi , and subsequent expression of several RpoS-dependent surface lipoproteins. We have also identified CsrA Bb as the first regulatory element for flagellar synthesis in B. burgdorferi . CsrA Bb acts as a negative regulator of the flagellin protein, FlaB, by interacting with two binding sites present within the leader transcript of flaB and affects its expression post-transcriptionally. The presence of intact flagella is required for the motility and invasiveness of the spirochete. Finally, by dissecting the role of the chemotaxis gene, cheA 2 , we demonstrated that chemotaxis is essential for B. burgdorferi to accomplish its enzootic life cycle in both tick vector and mammalian host.