Chemotaxis Coupling Protein CheW Is Not Required for the Chemotaxis but Contributes to the Full Pathogenicity of Borreliella burgdorferi.

The bacterial chemotaxis regulatory circuit mainly consists of coupling protein CheW, sensor histidine kinase CheA, and response regulator CheY. Most bacteria, such as Escherichia coli, have a single gene encoding each of these proteins. Interestingly, the Lyme disease pathogen, Borreliella burgdorferi, has multiple chemotaxis proteins, e.g., two CheA, three CheW, and three CheY proteins. The genes encoding these proteins mainly reside in two operons: () and (). Previous studies demonstrate that all the genes in are essential for the chemotaxis of B. burgdorferi; however, the role of those genes in remains unknown. This study aimed to fill this gap using the CheW gene, the first gene in , as a surrogate. We first mapped the transcription start site of upstream of and identified a σ-like promoter () and two binding sites (BS1 and BS2) of BosR, an unorthodox Fur/Per homolog. We then demonstrated that BosR binds to via BS1 and BS2 and that deletion of significantly represses the expression of and other genes in , implying that BosR is a positive regulator of . Deletion of has no impact on the chemotaxis of B. burgdorferi but abrogates its ability to evade host adaptive immunity, because the mutant can establish systemic infection only in SCID mice and not in immunocompetent BALB/c mice. This report substantiates the previous proposition that is not implicated in chemotaxis; rather, it may function as a signaling transduction pathway to regulate B. burgdorferi virulence gene expression.