Subinhibitory concentrations of the cationic antimicrobial peptide colistin induce the pseudomonas quinolone signal in Pseudomonas aeruginosa

Abstract

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.

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

“…Although cells exposed to carbenicillin exhibit a dramatic morphology change, we found that exposure to tobramycin, but not carbenicillin, resulted in profile shifts of both PQS and AQNO families during swarming. This is in contrast to reports that have suggested a general PQS response to antimicrobials (22,26,27). Our findings are consistent with the hypothesis that AQ modulations following tobramycin exposure during pre-biofilm swarming should contribute to antibiotic tolerance (22,25,38), however, other factors must control P. aeruginosa tolerance to carbenicillin.…”

“…Because previous reports have shown various roles for PQS, namely as a stress response, for planktonic P. aeruginosa cells exposed to antimicrobials (22,26,(38)(39)(40), we were interested to explore how AQs mediate P. aeruginosa behavior in motile, prebiofilm swarm communities. Additionally, the CRM chemical profile of P. aeruginosa swarms provided evidence that tobramycin exposure cues aspects of PQS production or regulation that carbenicillin does not (Fig.…”

“…Of the molecules that belong to these subclasses, the roles of HHQ, PQS, and HQNO are particularly well-documented. The AQs belonging to the PQS pathway participate in processes as diverse as intercellular quorum sensing signaling, virulence regulation, biofilm development, iron chelation, antimicrobial activity, stress response, and control of cell death (15,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). In the Pseudomonas literature, AQs are generally presented to contain 7-Carbon (C7) side chains (HHQ, PQS, and HQNO), yet 9-Carbon (C9; NHQ, C9-PQS, and NQNO) and 11-Carbon (C11; UHQ, C11-PQS, and UQNO) side chain variants of these molecules are also common (16,17).…”

Role of the phenazine-inducing protein Pip in stress resistance of Pseudomonas chlororaphis

“…In particular, at subinhibitory concentrations, many antibiotics appear to influence the expression of virulence factor genes, such as those for phenazine biosynthesis and regulation in pseudomonads (Cummins et al, 2009;Liang et al, 2008;Linares et al, 2006;Mitova et al, 2008;Shen et al, 2008;Skindersoe et al, 2008). The observations indicate that the effects of antibiotics may vary depending on the target bacterial species and the kind of antibiotic (Fajardo & Martinez, 2008).…”

“…So far, an interpretation was only suggested for the effect of subinhibitory antibiotic concentrations on the triggering of virulence factor expression. Sensing such foreign toxic molecules would allow pseudomonas species to obtain increased fitness in a competitive environment (Cummins et al, 2009;Shen et al, 2008).…”