BUSCADOR RECOLECTA

Digital.CSIC. Repositorio Institucional del CSIC

oai:digital.csic.es:10261/227978

Bacterial genomes encode several families of protein paralogs. Discrimination between functional divergence and redundancy among paralogs is challenging due to their sequence conservation. Here, we investigated whether the amino acid differences present in the cold shock protein (CSP) paralogs of Staphylococcus aureus were responsible for functional specificity. Since deletion of cspA reduces the synthesis of staphyloxanthin (STX), we used it as an in vivo reporter of CSP functionality. Complementation of a ΔcspA strain with the different S. aureus CSP variants showed that only CspA could specifically restore STX production by controlling the activity of the stress-associated sigma B factor (σ). To determine the amino acid residues responsible for CspA specificity, we created several chimeric CSPs that interchanged the amino acid differences between CspA and CspC, which shared the highest identity. We demonstrated that CspA Pro58 was responsible for the specific control of σ activity and its associated phenotypes. Interestingly, CspC gained the biological function of CspA when the E58P substitution was introduced. This study highlights how just one evolutionarily selected amino acid change may be sufficient to modify the specific functionality of CSP paralogs., his work was supported by the European Research Council (ERC), under the European Union Horizon 2020 research and innovation program (Grant Agreement No. 646869), and the Spanish Ministry of Economy and Competitiveness (BFU2014‐56698‐P). C.J.C. was supported by a predoctoral contract from the Public University of Navarre, Spain. J.L.‐S. is a recipient of a Ramón y Cajal Contract (RYC‐2017‐21683).