Induction by cationic antimicrobial peptides and involvement in intrinsic polymyxin and antimicrobial peptide resistance, biofilm formation, and swarming motility of PsrA in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is an important opportunistic pathogen that causes infections that can be extremely difficult to treat due to its high intrinsic antibiotic resistance and broad repertoire of virulence factors, both of which are highly regulated. It is demonstrated here that the psrA gene, encoding a transcriptional regulator, was upregulated in response to subinhibitory concentrations of cationic antimicrobial peptides. Compared to the wild type and the complemented mutant, a P. aeruginosa PAO1 psrA::Tn5 mutant displayed intrinsic supersusceptibility to polymyxin B, a last-resort antimicrobial used against multidrug-resistant infections, and the bovine neutrophil antimicrobial peptide indolicidin; this supersusceptibility phenotype correlated with increased outer membrane permeabilization by these agents. The psrA mutant was also defective in simple biofilm formation, rapid attachment, and swarming motility, all of which could be complemented by the cloned psrA gene. The role of PsrA in global gene regulation was studied by comparing the psrA mutant to the wild type by microarray analysis, demonstrating that 178 genes were up- or downregulated >or=2-fold (P <or= 0.05). Dysregulated genes included those encoding certain known PsrA targets, those encoding the type III secretion apparatus and effectors, adhesion and motility genes, and a variety of metabolic, energy metabolism, and outer membrane permeability genes. This suggests that PsrA might be a key regulator of antimicrobial peptide resistance and virulence.
Center for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, 232-2259 Lower Mall Research Station, Vancouver, BC, Canada.
W James
WJ
Gooderham
Manjeet
M
Bains
Joseph B
JB
McPhee
Irith
I
Wiegand
Robert E W
RE
Hancock
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000096:biosynthesis*; D018441:Biofilms / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005816:Genetic Complementation Test; D008124:Locomotion / Q000187:drug effects*; D050296:Microbial Viability; D016254:Mutagenesis, Insertional; D020411:Oligonucleotide Array Sequence Analysis; D010539:Permeability; D011113:Polymyxins / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D011113:Polymyxins; C430183:PsrA protein, Pseudomonas; D014157:Transcription Factors