Sinorhizobium meliloti CtrA Stability Is Regulated in a CbrA-Dependent Manner That Is Influenced by CpdR1

• Published in: Journal of bacteriology Vol. 197; no. 13; pp. 2139 - 2149
• Main Authors: Schallies, Karla B, Sadowski, Craig, Meng, Julia, Chien, Peter, Gibson, Katherine E
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.07.2015
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Caulobacter crescentus; Cell Cycle; Gene Expression Regulation, Bacterial - physiology; Gram-negative bacteria; Kinases; Mutation; Phosphorylation; Phylogeny; Protein Stability; Signal transduction; Sinorhizobium meliloti; Sinorhizobium meliloti - genetics; Sinorhizobium meliloti - metabolism; Symbiosis
• ISSN: 0021-9193; 1098-5530
• DOI: 10.1128/JB.02593-14

CbrA is a DivJ/PleC-like histidine kinase of DivK that is required for cell cycle progression and symbiosis in the alphaproteobacterium Sinorhizobium meliloti. Loss of cbrA results in increased levels of CtrA as well as its phosphorylation. While many of the known Caulobacter crescentus regulators of CtrA phosphorylation and proteolysis are phylogenetically conserved within S. meliloti, the latter lacks the PopA regulator that is required for CtrA degradation in C. crescentus. In order to investigate whether CtrA proteolysis occurs in S. meliloti, CtrA stability was assessed. During exponential growth, CtrA is unstable and therefore likely to be degraded in a cell cycle-regulated manner. Loss of cbrA significantly increases CtrA stability, but this phenotype is restored to that of the wild type by constitutive ectopic expression of a CpdR1 variant that cannot be phosphorylated (CpdR1(D53A)). Addition of CpdR1(D53A) fully suppresses cbrA mutant cell cycle defects, consistent with regulation of CtrA stability playing a key role in mediating proper cell cycle progression in S. meliloti. Importantly, the cbrA mutant symbiosis defect is also suppressed in the presence of CpdR1(D53A). Thus, regulation of CtrA stability by CbrA and CpdR1 is associated with free-living cell cycle outcomes and symbiosis. The cell cycle is a fundamental process required for bacterial growth, reproduction, and developmental differentiation. Our objective is to understand how a two-component signal transduction network directs cell cycle events during free-living growth and host colonization. The Sinorhizobium meliloti nitrogen-fixing symbiosis with plants is associated with novel cell cycle events. This study identifies a link between the regulated stability of an essential response regulator, free-living cell cycle progression, and symbiosis.