Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 13 1 2021 02 10 37 49 Amel Elsheredy Department of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt Ingy El-Soudany Department of Microbiology and Immunology, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt Eglal Elsherbini Department of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt Dalia Metwally Department of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt Abeer Ghazal Department of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt 2020 07 24 2020 11 30 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. https://ijm.tums.ac.ir/index.php/ijm/article/view/2713 https://ijm.tums.ac.ir/index.php/ijm/article/download/2713/1314