Anti-Bacterial Agents/*administration & dosage
Colistin/*administration & dosage
DNA, Bacterial/genetics/metabolism
Dose-Response Relationship, Drug
Gene Expression Profiling
Gene Expression Regulation, Bacterial/drug effects
Genes, Bacterial
Humans
Hydroxyquinolines/metabolism
Oligonucleotide Array Sequence Analysis
Pseudomonas Infections/drug therapy/metabolism
Pseudomonas aeruginosa/*drug effects/genetics/*metabolism
Pyocyanine/biosynthesis
Quinolones/*metabolism
Quorum Sensing
*Transcriptional Activation
Colistin is an important cationic antimicrobial peptide (CAMP) in the fight against Pseudomonas aeruginosa infection in cystic fibrosis (CF) lungs. The effects of subinhibitory concentrations of colistin on gene expression in P. aeruginosa were investigated by transcriptome and functional genomic approaches. Analysis revealed altered expression of 30 genes representing a variety of pathways associated with virulence and bacterial colonization in chronic infection. These included response to osmotic stress, motility, and biofilm formation, as well as genes associated with LPS modification and quorum sensing (QS). Most striking was the upregulation of Pseudomonas quinolone signal (PQS) biosynthesis genes, including pqsH, pqsB and pqsE, and the phenazine biosynthesis operon. Induction of this central component of the QS network following exposure to subinhibitory concentrations of colistin may represent a switch to a more robust population, with increased fitness in the competitive environment of the CF lung.