Modulation of secreted virulence factor genes by subinhibitory concentrations of antibiotics in Pseudomonas aeruginosa

Abstract

Recent studies have shown that subinhibitory antibiotics play important roles in regulating bacterial genes including virulence factor genes. In this study, the expression of 13 secreted virulence related gene clusters of Pseudomonas aeruginosa, an important opportunistic pathogen, was examined in the presence of subinhibitory concentrations of 4 antibiotics: vancomycin, tetracycline, ampicillin and azithromycin. Activation of gene expression was observed with phzAl, rhlAB, phzA2, lasB, exoY, and exoS. Subinhibitory concentrations of vancomycin resulted in more than 10-fold increase of rhlAB and phzA2 transcription. Both rhamnolipid production and pyocyanin production were significantly elevated, correlating phenotypes with the increased transcription. P. aeruginosa swarming and swimming motility also increased. Similar results were observed with subinhibitory tetracycline, azithromycin and ampicillin. These results indicate that the antibiotics at low concentrations can up-regulate virulence factors and therefore influence bacterial pathogenesis.

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

“…Enhanced production of phenazines in response to subinhibitory concentrations of other antibiotics has already been reported (Mitova et al, 2008;Shen et al, 2008). Exposure to subinhibitory concentrations of colistin resulted in upregulation of the phenazine biosynthesis operon (Table 2).…”

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).…”

Modulatory Effects of Dexamethasone upon Virulence Attributes of Pseudomonas Aeruginosa ATCC® 27853™

“…Among all virulence factors here investigated, may be the secretion of pyocyanin, an important molecule involved in P. aeruginosa's infection 9,[22][23][24][25] , was the more affected by dexamethasone. It was shown that even with a lower number of cells, biofilms under dexamethasone influence secrete higher amounts of this phenazine.…”

“…From our knowledge, only few groups are evaluating the interference of xenobiotics on pyocyanin secretion modulation. Shen et al 24 expressed their concern on the fact that sub-inhibitory concentrations of various antibiotics cause up-regulation on the expression of genes that codify the pyocyanin synthesis and it could complicate the antibiotic therapy expectatives. Other compounds such as curcumin 26 and salicylic acid 16 cause down-regulation on the genes with consequent virulence reduction.…”