Effect of azithromycin and phenylalanine-arginine beta-naphthylamide on quorum sensing and virulence factors in clinical isolates of Pseudomonas aeruginosa

Abstract

Background and Objectives:Pseudomonas aeruginosa is a problematic opportunistic pathogen causing several types of nosocomial infections with a high resistance rate to antibiotics. Production of many virulence factors in P. aeruginosa is regulated by quorum sensing (QS), a cell-to-cell communication mechanism. In this study, we aimed to assess and compare the inhibitory effect of azithromycin (AZM) and EPI-PAβN (efflux pump inhibitor-Phenylalanine-Arginine Beta-Naphthylamide) on QS system and QS-dependent virulence factors in P. aeruginosa clinical isolates.Materials and Methods:A total of 50 P. aeruginosa isolates were obtained from different types of clinical specimens. Isolates were investigated for detection of QS system molecules by AHL cross-feeding bioassay and QS-dependent virulence factors; this was also confirmed by detection of QS genes (lasR, lasI, rhlR, and rhlI) using PCR assay. The inhibitory effect of sub-MIC AZM and EPI PAβN on these virulence factors was assessed.Results:All the P. aeruginosa, producing QS signals C4HSL, failed to produce C4HSL in the presence of sub-MIC AZM, In the presence of EPI PAβN (20 μg/ml) only 14 isolates were affected, there was a significant reduction in QS-dependent virulence factors production (protease, biofilm, rhamnolipid and pyocyanin) in the presence of either 20 μg/ml EPI or sub-MIC of AZM with the inhibitory effect of AZM was more observed than PAβN.Conclusion:Anti-QS agents like AZM and EPI (PAβN) are useful therapeutic options for P. aeruginosa due to its inhibitory effect on QS-dependent virulence factors production without selective pressure on bacteria growth, so resistance to these agents is less likely to develop.