The HmrABCX pathway regulates the transition between motile and sessile lifestyles in Caulobacter crescentus by a HfiA-independent mechanism

Abstract

Through its cell cycle, the bacterium Caulobacter crescentus switches from a motile, free-living state, to a sessile surface-attached cell. During this coordinated process, cells undergo irreversible morphological changes, such as shedding of their polar flagellum and synthesis of an adhesive holdfast at the same pole. In this work, we used genetic screens to identify genes involved in the regulation of the motile to sessile lifestyle transition. We identified a predicted hybrid histidine kinase that inhibits biofilm formation and activates the motile lifestyle: HmrA (Holdfast and motility regulator A). Genetic screens and genomic localization led to the identification of additional genes that regulate the proportion of cells harboring an active flagellum or a holdfast and that form a putative phosphorelay pathway with HmrA. Further genetic analysis indicates that the Hmr pathway is independent of the holdfast synthesis regulator HfiA and may impact c-di-GMP synthesis through the diguanylate cyclase DgcB pathway. Finally, we provide evidence that the Hmr pathway is involved in the regulation of sessile-to-motile lifestyle as a function of environmental stresses, namely excess copper and non-optimal temperatures. IMPORTANCEComplex communities attached to a surface, or biofilms, represent the major lifestyle of bacteria in the environment. Such a sessile state enables its inhabitants to be more resistant to adverse environmental conditions. Thus, having a deeper understanding of the underlying mechanisms that regulate the transition between the motile and the sessile states could help design strategies to improve biofilms when they are beneficial or impede them when they are detrimental. For C. crescentus motile cells, the transition to the sessile lifestyle is irreversible, and this decision is regulated at several levels. In this work, we describe a putative phosphorelay that promotes the motile lifestyle and inhibits biofilm formation, providing new insights into the control of adhesin production that leads to the formation of biofilms.