title: Regulatory RNAs and the HptB/RetS signalling pathways fine-tune Pseudomonas aeruginosa pathogenesis.
abstract: Bacterial pathogenesis often depends on regulatory networks, two-component systems and small RNAs (sRNAs). In Pseudomonas aeruginosa, the RetS sensor pathway downregulates expression of two sRNAs, rsmY and rsmZ. Consequently, biofilm and the Type Six Secretion System (T6SS) are repressed, whereas the Type III Secretion System (T3SS) is activated. We show that the HptB signalling pathway controls biofilm and T3SS, and fine-tunes P. aeruginosa pathogenesis. We demonstrate that RetS and HptB intersect at the GacA response regulator, which directly controls sRNAs production. Importantly, RetS controls both sRNAs, whereas HptB exclusively regulates rsmY expression. We reveal that HptB signalling is a complex regulatory cascade. This cascade involves a response regulator, with an output domain belonging to the phosphatase 2C family, and likely an anti-anti-sigma factor. This reveals that the initial input in the Gac system comes from several signalling pathways, and the final output is adjusted by a differential control on rsmY and rsmZ. This is exemplified by the RetS-dependent but HptB-independent control on T6SS. We also demonstrate a redundant action of the two sRNAs on T3SS gene expression, while the impact on pel gene expression is additive. These features underpin a novel mechanism in the fine-tuned regulation of gene expression.
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bordi
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Lamy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ventre
authors.forename: Elise
authors.initials: E
authors.lastname: Termine
authors.forename: Abderrahman
authors.initials: A
authors.lastname: Hachani
authors.forename: Sandy
authors.initials: S
authors.lastname: Fillet
authors.forename: Béatrice
authors.initials: B
authors.lastname: Roche
authors.forename: Sophie
authors.initials: S
authors.lastname: Bleves
authors.forename: Vincent
authors.initials: V
authors.lastname: Méjean
authors.forename: Andrée
authors.initials: A
authors.lastname: Lazdunski
authors.forename: Alain
authors.initials: A
authors.lastname: Filloux
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D001692:Biological Transport; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D012329:RNA, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C091100:GacA protein, Bacteria; D012329:RNA, Bacterial; D034741:RNA, Small Interfering; C507835:RetS protein, Pseudomonas aeruginosa; D001616:beta-Galactosidase
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