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PMID:22666466

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Citation

Dieppois, G, Ducret, V, Caille, O and Perron, K (2012) The transcriptional regulator CzcR modulates antibiotic resistance and quorum sensing in Pseudomonas aeruginosa. PLoS ONE 7:e38148

Abstract

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.

Links

PubMed PMC3362554 Online version:10.1371/journal.pone.0038148

Keywords

Animals; Anti-Bacterial Agents/pharmacology; Bacterial Proteins/metabolism; Caenorhabditis elegans/metabolism; Caenorhabditis elegans/pathogenicity; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial/drug effects; Metals, Heavy/pharmacology; Phenotype; Porins/genetics; Promoter Regions, Genetic/genetics; Pseudomonas aeruginosa/cytology; Pseudomonas aeruginosa/drug effects; Pseudomonas aeruginosa/genetics; Pseudomonas aeruginosa/metabolism; Pyocyanine/biosynthesis; Quorum Sensing; Signal Transduction/drug effects; Stress, Physiological/drug effects; Stress, Physiological/genetics; Transcription, Genetic/drug effects

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

PSEAE:G3XD16

involved_in

GO:1900377: negative regulation of secondary metabolite biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

PSEAE:G3XD16

involved_in

GO:1900233: positive regulation of single-species biofilm formation on inanimate substrate

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

PSEAE:G3XD16

involved_in

GO:0043902: positive regulation of multi-organism process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

PSEAE:G3XD16

involved_in

GO:0045862: positive regulation of proteolysis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

PSEAI:Q9RLJ1

involved_in

GO:0043902: positive regulation of multi-organism process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

PSEAI:Q9RLJ1

involved_in

GO:0045862: positive regulation of proteolysis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

PSEAI:Q9RLJ1

involved_in

GO:1900233: positive regulation of single-species biofilm formation on inanimate substrate

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

PSEAI:Q9RLJ1

involved_in

GO:1900377: negative regulation of secondary metabolite biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

PSEAI:Q9RLJ1

GO:0009405: pathogenesis

ECO:0000316:

UniProtKB:M4NAR4


P

Pseudomonas aeruginosa (PA01 Strain) czcR "Figure 4 CzcR is required for the full virulence of P. aeruginosa."

" In our assay, an infection with the wild type strain killed 50% of the population within circa 3 days of contact with bacteria and all worms were dead after 4 days (Fig. 4). In contrast, the virulence of the ΔczcRS mutant was significantly reduced since 50% of the worms were still alive after 5 days of contact. The virulence of the ΔczcRS mutant strain complemented with czcR on the pRWT plasmid was partially restored since 50% of the worms were dead after 4 days and less than 20% of the worm population was alive after 5 days, while no complementation was observed with the czcS gene (Fig. 4).

complete
CACAO 12487

Notes

See also

References

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