RNA association patterns of Salmonella cold shock proteins direct discovery of essential virulence function of CspC and CspE

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. RIP-seq of bacterial cold-shock proteins; in vitro RNA-seq; RNA-seq in cell culture