SagS and its unorthodox contributions to Pseudomonas aeruginosa biofilm development

The Pseudomonas aeruginosa orphan sensor SagS (PA2824) was initially reported as one of three orphan sensor kinases capable of activating HptB, a component of the HptB signaling pathway that intersects with the Gac/Rsm signaling pathway and fine-tunes P. aeruginosa motility and pathogenesis. Since then, this orphan sensor has been reported to be involved in other, unorthodox signaling pathways serving additional functions. The present review is aimed at summarizing the various functions of SagS, with an emphasis on its toggle or dual switch functions, and highlighting the role of SagS as a hub at which the various signaling pathways intersect, to regulate the transition from the planktonic to the sessile mode of growth, as well as the transition of surface-associated cells to a drug tolerant state.