RNA association patterns of Salmonella cold shock proteins direct discovery of essential virulence function of CspC and CspE. Salmonella enterica subsp. enterica serovar Typhimurium str. SL1344

The functions of many bacterial RNA-binding proteins remain obscure due to a lack of knowledge of their cellular ligands. While well-studied cold-shock protein A (CspA) family members are induced and function at low temperature, other are highly expressed in infection-relevant conditions. Here, RNA ligand profiling of all CspA-family members linked CspC and CspE with Salmonella virulence pathways. Phenotypic assays in vitro demonstrated a crucial role for these proteins in membrane stress, motility, and biofilm formation. Moreover, deletion of cspC and cspE fully attenuates Salmonella in systemic mouse infection. Our results highlight RNA-binding proteins as regulators of pathogenicity and potential targets of antimicrobial therapy. Overall design: RIP-seq of bacterial cold-shock proteins; in vitro RNA-seq; RNA-seq in cell culture