Dual Regulatory Role Exerted by Cyclic Dimeric GMP To Control FsnR-Mediated Bacterial Swimming

Bacterial motility has great medical and ecological significance because of its essential role in bacterial survival and pathogenesis. Cyclic dimeric GMP (c-di-GMP), a second messenger in bacteria, is the predominant regulator of flagellar synthesis and motility and possesses turnover mechanisms that have been thoroughly investigated. Therefore, much attention has been focused on identifying the upstream stimulatory signals and downstream modules that respond to altered c-di-GMP levels. Here, we systematically analyzed c-di-GMP cyclases and phosphodiesterases in Stenotrophomonas maltophilia to screen for motility regulators. Of these enzymes, we identified and characterized a new phosphodiesterase named SisP, which was found to facilitate bacterial swimming upon stimulation with ferrous iron. SisP-mediated degradation of c-di-GMP leads to FsnR-dependent transcription of flagellar genes. Remarkably, c-di-GMP controls FsnR via two independent mechanisms: by direct binding and indirectly by modulating its phosphorylation state. In this study, we deciphered a novel “one stone, two birds” regulatory strategy of c-di-GMP and uncovered the signal that stimulates c-di-GMP hydrolysis. Facilitation of bacterial swimming motility by ferrous iron might contribute to the higher risk of bacterial infection in acutely ill patients.