title: RavA/RavR two-component system regulates Xanthomonas campestris pathogenesis and c-di-GMP turnover.
abstract: The two-component system (TCS), consisting of a response regulator (RR) and a cognate histidine kinase (HK), responds to extra-/intercellular cues and triggers adaptive changes. The RR, RavR, has been reported to act as a positive virulence regulator and a c-di-GMP hydrolase in Xanthomonas campestris pv. campestris (Xcc). Here, we identified the cognate HK, RavA, that regulate RavR phosphorylation levels and bacterial pathogenesis. Deletion of ravA, a putative HK gene flanking ravR, dramatically attenuated Xcc virulence. Phenotypes of the double mutant ΔravR/ΔravA were similar to those of ΔravR, suggesting that RavR is a downstream component of RavA signaling. RavA interacts with RavR and positively influences the phosphorylated RavR levels. In vitro analysis suggests that RavR is a bifunctional enzyme involved in c-di-GMP synthesis and degradation. Importantly, mutation and enzyme activity assays indicate that the phosphorylation level affects RavR c-di-GMP turnover activity. These results show that RavA acts as the RavR cognate HK, which fine-tunes RavR functions and enables bacteria to adapt quickly to intracellular changes.
authors.affiliation: State Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.forename: Chunxia
authors.initials: C
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Luo
authors.forename: Chaozu
authors.initials: C
authors.lastname: He
mesh_terms: D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D017353:Gene Deletion; D000071677:Histidine Kinase; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D016959:Xanthomonas campestris / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; C062025:bis(3',5')-cyclic diguanylic acid; D011494:Protein Kinases; D000071677:Histidine Kinase; D006152:Cyclic GMP
keywords: C-di-GMP turnover; RavA; RavR; phosphorylation; two-component system