The <i>Yersinia pseudotuberculosis</i> Cpx envelope stress system contributes to transcriptional activation of <i>rovM</i>

<p>The Gram-negative enteropathogen <i>Yersinia pseudotuberculosis</i> possesses a number of regulatory systems that detect cell envelope damage caused by noxious extracytoplasmic stresses. The CpxA sensor kinase and CpxR response regulator two-component regulatory system is one such pathway. Active Cpx signalling upregulates various factors designed to repair and restore cell envelope integrity. Concomitantly, this pathway also down-regulates key determinants of virulence. In <i>Yersinia, cpxA</i> deletion accumulates high levels of phosphorylated CpxR (CpxR~P). Accumulated CpxR~P directly repressed <i>rovA</i> expression and this limited expression of virulence-associated processes. A second transcriptional regulator, RovM, also negatively regulates <i>rovA</i> expression in response to nutrient stress. Hence, this study aimed to determine if CpxR~P can influence <i>rovA</i> expression through control of RovM levels. We determined that the active CpxR~P isoform bound to the promoter of <i>rovM</i> and directly induced its expression, which naturally associated with a concurrent reduction in <i>rovA</i> expression. Site-directed mutagenesis of the CpxR~P binding sequence in the <i>rovM</i> promoter region desensitised <i>rovM</i> expression to CpxR~P. These data suggest that accumulated CpxR~P inversely manipulates the levels of two global transcriptional regulators, RovA and RovM, and this would be expected to have considerable influence on <i>Yersinia</i> pathophysiology and metabolism.</p>