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Journal of Bacteriology, August 2008, p. 5624-5634, Vol. 190, No. 16
0021-9193/08/$08.00+0 doi:10.1128/JB.00594-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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Center for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
Received 29 April 2008/ Accepted 5 June 2008
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
2-fold (P
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.
Published ahead of print on 13 June 2008.
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