Evaluating the effect of antibiotics sub-inhibitory dose on Pseudomonas aeruginosa quorum sensing dependent virulence and its phenotypes

Abstract

The opportunistic Pseudomonas aeruginosa virulence controlled by quorum sensing (QS) also identified as, cell-cell communication. QS system is organized by the LasI-LasR and the RhlI-RhlR components. Provided that QS tends to perform a key role in virulence gene expression and host defence function, QS inhibitors have been proposed as potential antipseudomonal therapies. Sub-inhibitory concentrations (sub-MIC) of antibiotics, although having biostatic effect on bacteria, but can interfere with bacterial QS system and virulence. This research aimed to examine the impact of sub-MIC of azithromycin, imipenem, cefepime and piperacillin/tazobactam on the QS-dependent virulence including pyocyanin and biofilm production, haemolysin, protease and DNase in P. aeruginosa wildtype and mutant strains; transcriptional-regulator (ΔLasR), autoinducer synthesis protein (ΔLasI), transcriptional-regulator (ΔRhlR), protease precursor (ΔLasA) and double regulators mutants (ΔLasR/RhlR). The growth of all strains showed similar pattern, however, in presence of antibiotics significant growth variation was observed among mutant strains when compared to wild type strain. Antimicrobial activity tested by agar diffusion method of all antibiotics on all strains were used to compare the zones of therapeutic and sub-MIC doses showing a significant difference in the inhibition zone. QS-dependant virulence as biofilm, pyocyanin, protease, haemolysin and DNase production showed significant variation on all strains compared to wild type in response to antibiotics used at sub-MIC doses. In conclusion well known antibiotics can be used in sub-MIC doses to decrease the virulence of P. aeruginosa in addition to overcoming the major side effect of the high doses and the occurrence of resistance.