CosR Is a Global Regulator of the Osmotic Stress Response with Widespread Distribution among Bacteria

• Published in: Applied and environmental microbiology 2020-05, Vol.86 (10)
• Main Authors: Gregory, Gwendolyn J, Morreale, Daniel P, Boyd, E Fidelma
• Format: Article
• Language: English
• Subjects: Bacteria; Bioinformatics; Biosynthesis; Carnitine; Choline; Compatibility; Deletion mutant; Deoxyribonucleic acid; DNA; E coli; Ectoine; Fluorescence; Gammaproteobacteria; Gene deletion; Genetics and Molecular Biology; Glycine; Glycine betaine; Green fluorescent protein; Homology; Mutants; Organic compounds; Osmosis; Osmotic stress; Phylogenetics; Phylogeny; Salinity; Salinity effects; Solutes; Spotlight; Stress concentration; Transcription; Turgor; Vibrio; Vibrio parahaemolyticus; Vibrionaceae; Waterborne diseases
• ISSN: 0099-2240; 1098-5336
• DOI: 10.1128/AEM.00120-20

Bacteria accumulate small, organic compounds called compatible solutes via uptake from the environment or biosynthesis from available precursors to maintain the turgor pressure of the cell in response to osmotic stress. The halophile has biosynthesis pathways for the compatible solutes ectoine (encoded by ) and glycine betaine (encoded by ), four betaine-carnitine-choline transporters (encoded by to ), and a second ProU transporter (encoded by ). All of these systems are osmotically inducible with the exception of Previously, it was shown that CosR, a MarR-type regulator, was a direct repressor of in species. In this study, we investigated whether CosR has a broader role in the osmotic stress response. Expression analyses demonstrated that , , , , and are repressed in low salinity. Examination of an in-frame deletion mutant showed that expression of these systems is derepressed in the mutant at low salinity compared with the wild type. DNA binding assays demonstrated that purified CosR binds directly to the regulatory region of both biosynthesis systems and four transporters. In green fluorescent protein (GFP) reporter assays, we demonstrated that CosR directly represses transcription of , , and Similar to , we showed was directly activated by the quorum-sensing LuxR homolog OpaR, suggesting a conserved mechanism of regulation among species. Phylogenetic analysis demonstrated that CosR is ancestral to the family, and bioinformatics analysis showed widespread distribution among in general. Incidentally, in , , , and , an unrelated MarR-type regulator gene named was clustered with , which suggests the presence of another novel ectoine biosynthesis regulator. Overall, these data show that CosR is a global regulator of osmotic stress response that is widespread among bacteria. can accumulate compatible solutes via biosynthesis and transport, which allow the cell to survive in high salinity conditions. There is little need for compatible solutes under low salinity conditions, and biosynthesis and transporter systems need to be repressed. However, the mechanism(s) of this repression is not known. In this study, we showed that CosR played a major role in the regulation of multiple compatible solute systems. Phylogenetic analysis showed that CosR is present in all members of the family as well as numerous Collectively, these data establish CosR as a global regulator of the osmotic stress response that is widespread in bacteria, controlling many more systems than p