The transcriptional regulator CzcR modulates antibiotic resistance and quorum sensing in Pseudomonas aeruginosa.
The opportunistic pathogen Pseudomonas aeruginosa responds to zinc, cadmium and cobalt by way of the CzcRS two-component system. In presence of these metals the regulatory protein CzcR induces the expression of the CzcCBA efflux pump, expelling and thereby inducing resistance to Zn, Cd and Co. Importantly, CzcR co-regulates carbapenem antibiotic resistance by repressing the expression of the OprD porin, the route of entry for these antibiotics. This unexpected co-regulation led us to address the role of CzcR in other cellular processes unrelated to the metal response. We found that CzcR affected the expression of numerous genes directly involved in the virulence of P. aeruginosa even in the absence of the inducible metals. Notably the full expression of quorum sensing 3-oxo-C12-HSL and C4-HSL autoinducer molecules is impaired in the absence of CzcR. In agreement with this, the virulence of the czcRS deletion mutant is affected in a C. elegans animal killing assay. Additionally, chromosome immunoprecipitation experiments allowed us to localize CzcR on the promoter of several regulated genes, suggesting a direct control of target genes such as oprD, phzA1 and lasI. All together our data identify CzcR as a novel regulator involved in the control of several key genes for P. aeruginosa virulence processes.
Microbiology Unit, Department of Botany and Plant Biology, Sciences III, University of Geneva, Switzerland.
Guennaëlle
G
Dieppois
Véréna
V
Ducret
Olivier
O
Caille
Karl
K
Perron
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000472:pathogenicity; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D019216:Metals, Heavy / Q000494:pharmacology; D010641:Phenotype; D018272:Porins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011710:Pyocyanine / Q000096:biosynthesis; D053038:Quorum Sensing; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D019216:Metals, Heavy; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; D011710:Pyocyanine