Activation of the RcsC/YojN/RcsB phosphorelay system attenuates Salmonella virulence

Bacterial pathogens have the ability to sense their presence in host tissues and to promote expression of their virulence factors in a time- and location-dependent manner. However, little is known about those genes whose expression is detrimental and thus suppressed during infection. Here we report that constitutive activation of the RcsC/YojN/RcsB system resulting from a mutation in the rcsC sensor gene dramatically attenuates Salmonella virulence. Mutation of the cognate response regulator gene rcsB restored full virulence to the rcsC constitutive mutant, indicating that virulence attenuation results from aberrant expression of RcsB-regulated genes. The virulence attenuation phenotype was partially dependent on the regulatory gene rcsA, which is necessary for transcription of certain RcsB-regulated genes, and on the RcsB- and RcsA-dependent colanic acid capsule synthesis cps operon. The rcsC constitutive mutant was phagocytized less efficiently by macrophages and it was defective for invasion of non-phagocytic cells and survival within macrophages; but it could protect mice upon challenge with wild-type Salmonella. Our results suggest that a successful infection demands that pathogens turn off expression of products that might interfere with virulence functions.