Regulatory RNAs and the HptB/RetS signalling pathways fine-tune Pseudomonas aeruginosa pathogenesis.
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.
Bordi
Christophe
C
Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
Lamy
Marie-Cécile
MC
Ventre
Isabelle
I
Termine
Elise
E
Hachani
Abderrahman
A
Fillet
Sandy
S
Roche
Béatrice
B
Bleves
Sophie
S
Méjean
Vincent
V
Lazdunski
Andrée
A
Filloux
Alain
A
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
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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