Inhibition of Virulence of Pseudomonas aeruginosa: A Novel Role of Metronidazole Against Aerobic Bacteria

Antibiotic resistance is one of the most dangerous challenges in modern medicine. Pseudomonas aeruginosa is a common nosocomial bacterium that shows high resistance to antibiotics. Anti-virulence agents are alternatives to antibiotics to combat the emergence of resistance. Quorum sensing controls the production of virulence factors. Metronidazole is an analogue of acylhomoserine lactones, the signaling molecules of quorum sensing in Gramnegative bacteria. This study aimed to investigate the inhibitory activity of metronidazole against virulence factors of Pseudomonas aeruginosa. The effect of sub-inhibitory concentration of metronidazole on twitching and swimming motilities in addition to bio film formation, pyocyanin, pyoverdin, protease, hemolysin was investigated. As compared to the control, metronidazole showed significant inhibition of virulence factors. It reduced twitching motility by 47.57% and swimming motility by 64.81%. Pyocyanin and pyoverdin production was reduced by 43.79% and 82.82%, respectively. Metronidazole also showed high inhibiting activity against protease, hemolysin and biofilm formation. Metronidazole inhibited protease by 60.22% and biofilm formation by 86.49%. Moreover, hemolytic activities in the presence of metronidazole was 7.16% as compared to the control (100% hemolytic activity). In conclusion, metronidazole is suggested as a potential anti-virulence agent for the treatment of Pseudomonas aeruginosa infection.