title: Hfq-dependent, co-ordinate control of cyclic diguanylate synthesis and catabolism in the plague pathogen Yersinia pestis.
abstract: 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.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Bellows
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Koestler
authors.forename: Sara M
authors.initials: SM
authors.lastname: Karaba
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Waters
authors.forename: Wyndham W
authors.initials: WW
authors.lastname: Lathem
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000096:biosynthesis; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D035001:Host Factor 1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism; D010930:Plague / Q000382:microbiology*; D015010:Yersinia pestis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D035001:Host Factor 1 Protein; C062025:bis(3',5')-cyclic diguanylic acid; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP