Csr (Rsm) System and Its Overlap and Interplay with Cyclic Di-GMP Regulatory Systems

Abstract

Free-living bacteria must respond rapidly to changing environmental and physiological conditions to survive stresses, maintain homeostasis and growth, and compete with other species. This chapter describes recent evidence of shared regulatory targets and interconnections between two global regulatory systems that antagonistically influence bacterial lifestyle choices by governing surface properties, biofilm development, motility, and in many species, virulence factors. The CsrD protein, which triggers the turnover of CsrB and CsrC RNAs by RNaseE, contains degenerate GGDEF and EAL domains but does not synthesize or degrade cyclic di-GMP (c-di-GMP). The chapter illustrates the interactions of Csr and its interplay with c-di-GMP global regulatory systems. Various features of the Csr (Rsm) system have been the subjects of previous reviews. BarA-UvrY homologs, which are present in many gram-negative bacteria, are variously known as Gac, Var, Exp, and Let two-component signal transduction system (TCS), and also work in conjunction with Csr systems. Importantly, the BarA-UvrY system also activates rpoS transcription in E. coli, possibly through DNA binding by the response regulator UvrY. Synthesis of c-di-GMP from two GTPs is catalyzed by diguanylate cyclases (DGC) that contain the GGDEF (DUF-1) domain. A recently discovered c-di-GMP binding element is not a protein but a riboswitch. This c-di-GMP binding RNA domain or aptamer was originally identified as a conserved GEMM sequence motif (genes for the environment, membranes, and motility) in the 5'-untranslated segment of numerous mRNAs involved in c-di-GMP metabolism, virulence, motility, and pilus formation.