Direct interaction between the transcription factors CadC and OmpR involved in the acid stress response of Salmonella enterica

In Salmonella enterica serovar Typhimurium, the acid-sensing regulator CadC activates transcription of the cadBA operon which contributes to the acid tolerance response. The DNA-binding response regulator OmpR in two-component regulatory system with EnvZ binds to its own promoter for autoinduction. We previously reported that CadC exerts a negative influence on ompR transcription during acid adaptation. However, its underlying mechanisms remain to be elucidated. Here we show that the level of OmpR protein is gradually reduced by a gradual increase in the CadC level using an arabinose-inducible expression system, indicating there exists a negative correlation between the expression levels of two transcription factors. To explore the molecular basis for OmpR repression by CadC, we performed in vitro binding assays and determined that CadC directly interacts with OmpR. We further show that inactivation of cadC inhibits transcription of the fliC gene, which encodes the major flagellar subunit, resulting in impaired flagellar motility under acid-adaptation conditions. Together, our findings suggest that CadC may repress autoinduction of the OmpR response regulator through their direct interaction.