A new class of protein sensor links spirochete pleomorphism, persistence, and chemotaxis

Abstract

Pathogenic spirochetes can alter their morphologies and behaviors to infect and survive within their hosts. Previous reports demonstrate that the formation of the so-called “round bodies” and biofilms, and chemotaxis are involved in spirochete pathogenesis. Here, we report a direct link between these cellular states that involve a new class of protein sensor with hitherto unclear function. Using cryo-electron microscopy, genetics, behavioral assays, and molecular modeling, we demonstrate that spirochetes regulate these behaviors in response to the small molecule S-adenosylmethionine (SAM) via a SAM sensor that is anchored to chemotaxis arrays. Furthermore, we establish an improved model for round body formation that now includes characterizations during log phase growth. IMPORTANCE A new class of bacterial protein sensors monitors intracellular levels of S-adenosylmethionine to modulate cell morphology, chemotaxis, and biofilm formation. Simultaneous regulation of these behaviors enables bacterial pathogens to survive within their niche. This sensor, exemplified by Treponema denticola CheWS, is anchored to the chemotaxis array and its sensor domain is located below the chemotaxis rings. This position may allow the sensor to directly interact with the chemotaxis histidine kinase CheA. Collectively, these data establish a critical role of CheWS in pathogenesis and further illustrate the impact of studying non-canonical chemotaxis proteins.