Antibacterial and antibiofilm activity of Peganum harmala seed extract against multidrug-resistant Pseudomonas aeruginosa pathogenic isolates and molecular mechanism of action.

Biofilm formation of the opportunistic pathogen Pseudomonas (P). aeruginosa is one of the major global challenges to control nosocomial infections due to their high resistance to antimicrobials and host defense mechanisms. The present study aimed to assess the antibacterial and the antibiofilm activities of Peganum (P). harmala seed extract against multidrug-resistant P. aeruginosa isolates. Chemical identification of the active compound and determination of its molecular mechanism of action were also investigated. Results showed that P. harmala n-butanol "n-BuOH" extract exhibited antibacterial activity against multidrug-resistant P. aeruginosa isolates. This extract was even more active than conventional antibiotics cefazolin and vaamox when tested against three P. aeruginosa multidrug-resistant isolates. In addition, P. harmala n-BuOH extract exhibited potent bactericidal activity against PAO1 strain at MIC value corresponding to 500 µg/mL and attained 100% killing effect at 24 h of incubation. Furthermore, P. harmala n-BuOH extract showed an antibiofilm activity against P. aeruginosa PAO1 and exhibited 80.43% inhibition at sub-inhibitory concentration. The extract also eradicated 83.99% of the biofilm-forming bacteria. The active compound was identified by gas chromatography-mass spectrometry as an indole alkaloid harmaline. Transcriptomic analysis showed complete inhibition of the biofilm-related gene pilA when PAO1 cells were treated with harmaline. Our results revealed that P. harmala seed extract and its active compound harmaline could be considered as a candidate for a new treatment of multidrug-resistant P. aeruginosa pathogens-associated biofilm infections.