Enzymatic quorum quenching increases antibiotic susceptibility of multidrug resistant Pseudomonas aeruginosa

Background and objectives: there is increasing emergence of multidrug resistant pseudomonas aeruginosa (mdrpa) strains and drug resistance is positively-correlated with biofilm-forming ability. since about 10% of p. aeruginosa genome is controlled by quorum sensing (qs), alteration in its antibiotic susceptibility by targeting qs was the focus of the present study.materials and methods: one day biofilms of pao1 and three urinary tract infection mdrpa isolates (pa2, pa8 and pa18) were formed in 96-well microtiter plate. biofilms were exposed to concentration gradient of ciprofloxacin and gentamicin to obtain minimum biofilm eradication concentration (mbec) by direct enumeration method. susceptibility of 24 h biofilms was evaluated by treatment with ciprofloxacin and gentamicin per se and in combination with lactonase. the effect was also examined on 72 h biofilms by scanning electron microscopy.results: lactonase treatment did not have any effect on growth of the selected strains but 73.42, 69.1, 77.34 and 72.5% reduction of biofilm was observed after lactonase (1 unit) treatment, respectively. antibiotics in combination with lactonase (0.3 units) resulted in an increased susceptibility of the biofilm forms by > 3.3, 4, 5 and 1.5 folds of mbec, for ciprofloxacin and > 6.67, 12.5, 6 and > 2.5 folds, for gentamicin respectively, which could be due to the disruption of biofilm by lactonase treatment as shown by scanning electron microscopy. also there was significant reduction (p < 0.001) in virulence factor production by the strains.conclusion: lactonase treatment increased antibiotic susceptibility of the biofilms of mdrpa isolates underscoring the potential of quorum quenching in antimicrobial therapeutics