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In silico Screening of Plant Compounds to Inhibit MexB Efflux Protein for the Enhancement of Meropenem Resistance against Pseudomonas aeruginosa MDR Infections

Praveena Nanjan, B. Bose

Recent Advances in Anti-Infective Drug Discovery, 2025

1 citation

Abstract

BACKGROUND

Pseudomonas aeruginosa is a common cause of healthcare-associated infections such as Pneumonia, Bloodstream, Urinary tract, and Surgical site infections this bacterium is also reported to cause infections in cancerous cells. It is one of the most considered opportunistic human pathogens, especially in immunocompromised patients, and one of the top five pathogens of nosocomial diseases worldwide. Some P. aeruginosa are becoming more resistant to even antibiotics of last resort, including beta-lactams, fluoroquinolones, tetracycline, chloramphenicol, macrolides, and aminoglycosides, and are described as multidrug-resistant. Multiple lines of evidence suggest that the chief mechanism for P. aeruginosa is resistance to antibiotics regulated by the efflux pumps. Antibiotic efflux pumps are membrane proteins that actively remove antibiotics from the bacterial cell, lowering on-target antibiotic concentrations to sub-toxic levels. The MexAB-OprM system is one of the largest multi-drug resistant clinically relevant efflux pumps with high expression levels in P. aeruginosa. Inhibition of these MDR efflux pumps can restore the activity of antimicrobial agents that are substrates for this protein. We performed molecular modelling studies in this study to discover novel Mex B efflux pump inhibitors. We evaluated the MIC of α-Bisabolol and Meropenem combination against Meropenem-resistant Pseudomonas Aeruginosa strains. This research opened up the possibility of using this…

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