Controlled activation of the Cpx system is essential for growth of Yersinia enterocolitica.

The Cpx two-component signal transduction system regulates the expression of genes in response to stimuli associated with the maintenance of the bacterial cell envelope. Additionally, the Cpx system is important for virulence in several bacterial pathogens. In this study, we analyzed the Cpx system of the human enteropathogen Yersinia enterocolitica. We provide evidence that transcription of cpxR is autoregulated and that the response regulator CpxR negatively affects transcription of rpoE, coding for the extracytoplasmic function sigma factor sigma(E), thereby linking at the transcriptional level two systems involved in envelope maintenance. A mutated form of CpxR that cannot be phosphorylated, CpxRD51A, affects transcription of cpxR and rpoE similar to the wild-type CpxR. In contrast, CpxR and CpxRD51A differentially regulate transcription of htrA, indicating phosphorylation-dependent and -independent mechanisms of transcriptional regulation. Moreover, overproduction of CpxR, CpxRD51A and CpxA result in a growth defect. Interestingly, a cpxA mutant strain could not be obtained. We conclude that the phosphorylation status of CpxR needs to be tightly controlled by CpxA, and that the Cpx system has a central role in regulating basic cellular functions. In addition, we show that cpxR and cpxP mutant strains have no defect in Y. enterocolitica invasion of host cells.