Hfq-dependent, co-ordinate control of cyclic diguanylate synthesis and catabolism in the plague pathogen Yersinia pestis

Summary Yersinia pestis, the cause of the disease plague, forms biofilms to enhance flea‐to‐mammal transmission. Biofilm formation is dependent on exopolysaccharide synthesis and is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (c‐di‐GMP), but the mechanisms by which Y. pestis regulates c‐di‐GMP synthesis and turnover are not fully understood. Here we show that the small RNA chaperone Hfq contributes to the regulation of c‐di‐GMP levels and biofilm formation by modulating the abundance of both the c‐di‐GMP phosphodiesterase HmsP and the diguanylate cyclase HmsT. To do so, Hfq co‐ordinately promotes hmsP mRNA accumulation while simultaneously decreasing the stability of the hmsT transcript. Hfq‐dependent regulation of HmsP occurs at the transcriptional level while the regulation of HmsT is post‐transcriptional and is localized to the 5′ untranslated region/proximal coding sequence of the hmsT transcript. Decoupling HmsP from Hfq‐based regulation is sufficient to overcome the effects of Δhfq on c‐di‐GMP and biofilm formation. We propose that Y. pestis utilizes Hfq to link c‐di‐GMP levels to environmental conditions and that the disregulation of c‐di‐GMP turnover in the absence of Hfq may contribute to the severe attenuation of Y. pestis lacking this RNA chaperone in animal models of plague.