title: The two-component system CprRS senses cationic peptides and triggers adaptive resistance in Pseudomonas aeruginosa independently of ParRS.
abstract: Cationic antimicrobial peptides pass across the outer membrane by interacting with negatively charged lipopolysaccharide (LPS), leading to outer membrane permeabilization in a process termed self-promoted uptake. Resistance can be mediated by the addition of positively charged arabinosamine through the action of the arnBCADTEF operon. We recently described a series of two-component regulators that lead to the activation of the arn operon after recognizing environmental signals, including low-Mg(2+) (PhoPQ, PmrAB) or cationic (ParRS) peptides. However, some peptides did not activate the arn operon through ParRS. Here, we report the identification of a new two-component system, CprRS, which, upon exposure to a wide range of antimicrobial peptides, triggered the expression of the LPS modification operon. Thus, mutations in the cprRS operon blocked the induction of the arn operon in response to several antimicrobial peptides independently of ParRS but did not affect the response to low Mg(2+). Distinct patterns of arn induction were identified. Thus, the responses to polymyxins were abrogated by either parR or cprR mutations, while responses to other peptides, including indolicidin, showed differential dependency on the CprRS and ParRS systems in a concentration-dependent manner. It was further demonstrated that, following exposure to inducing antimicrobial peptides, cprRS mutants did not become adaptively resistant to polymyxins as was observed for wild-type cells. Our microarray studies demonstrated that the CprRS system controlled a quite modest regulon, indicating that it was quite specific to adaptive peptide resistance. These findings provide greater insight into the complex regulation of LPS modification in Pseudomonas aeruginosa, which involves the participation of at least 4 two-component systems.
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández
authors.forename: Håvard
authors.initials: H
authors.lastname: Jenssen
authors.forename: Manjeet
authors.initials: M
authors.lastname: Bains
authors.forename: Irith
authors.initials: I
authors.lastname: Wiegand
authors.forename: W James
authors.initials: WJ
authors.lastname: Gooderham
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology*; D002412:Cations / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D004251:DNA Transposable Elements / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics / Q000502:physiology*; D005816:Genetic Complementation Test; D046228:Microarray Analysis; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009876:Operon / Q000235:genetics; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D011112:Polymyxin B / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000254:growth & development / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002412:Cations; D004251:DNA Transposable Elements; D010455:Peptides; D011494:Protein Kinases; D011112:Polymyxin B