title: The Pseudomonas aeruginosa sensor RetS switches type III and type VI secretion via c-di-GMP signalling.
abstract: Acute bacterial infections are associated with motility and cytotoxicity via the type III secretion system (T3SS), while chronic infections are linked to biofilm formation and reduced virulence. In Pseudomonas aeruginosa, the transition between motility and sessility involves regulatory networks including the RetS/GacS sensors, as well as the second messenger c-di-GMP. The RetS/GacS signalling cascade converges on small RNAs, RsmY and RsmZ, which control a range of functions via RsmA. A retS mutation induces biofilm formation, and high levels of c-di-GMP produce a similar response. In this study, we connect RetS and c-di-GMP pathways by showing that the retS mutant displays high levels of c-di-GMP. Furthermore, a retS mutation leads to repression of the T3SS, but also upregulates the type VI secretion system (T6SS), which is associated with chronic infections. Strikingly, production of the T3SS and T6SS can be switched by artificially modulating c-di-GMP levels. We show that the diguanylate cyclase WspR is specifically involved in the T3SS/T6SS switch and that RsmY and RsmZ are required for the c-di-GMP-dependent response. These results provide a firm link between the RetS/GacS and the c-di-GMP pathways, which coordinate bacterial lifestyles, as well as secretion systems that determine the infection strategy of P. aeruginosa.
authors.affiliation: Imperial College London, Division of Cell and Molecular Biology, Centre for Molecular Microbiology and Infection, South Kensington Campus, Flowers Building, London SW7 2AZ, UK.
authors.forename: Joana A
authors.initials: JA
authors.lastname: Moscoso
authors.forename: Helga
authors.initials: H
authors.lastname: Mikkelsen
authors.forename: Stephan
authors.initials: S
authors.lastname: Heeb
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.forename: Alain
authors.initials: A
authors.lastname: Filloux
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D018441:Biofilms; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D019761:Phosphorus-Oxygen Lyases / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D029968:Escherichia coli Proteins; C507835:RetS protein, Pseudomonas aeruginosa; D037521:Virulence Factors; C062025:bis(3',5')-cyclic diguanylic acid; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP