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

Abstract

Background

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 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 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 . 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 strains. This research opened up the possibility of using this plant compound α-Bisabolol and resistance drug Meropenem combination in the development of medicines for human consumption, possibly for the treatment of Hospital-Acquired Pneumonia, and multidrug-resisting infection caused by including wound and urinary infections which have been reported important HAI carbapenem class multidrug infections caused by the bacteria.

Method

The present study investigates the interactions of plant secondary metabolites Tables on Mex B efflux protein. It identifies lead molecules for developing adjuvants against efflux-mediated multidrug resistance in infections, enhances antibiotic activity against MDR pathogens, and evaluates the MIC value of the test plant compound (Bisabolol) and the resistant antibiotic (Meropenem).

Result

Among plant compounds, α-Bisabolol, myricetin, capsaicin, equenin, aloe-emodin, terpinene, fisetin, taxifolin, catechin, and galangin showed G-Scorehigher than -7 kcal/mol, and interact with active amino acids Mex B efflux protein which may affect the efflux transport of drug and enhance the antibiotic activity against MDR infection. According to docking experiments, α-bisabolol has a higher affinity energy to the MexB protein than Meropenem. Furthermore, α-bisabolol binds to the MexB binding site hydrophobic trap region of MexB, which may cause a conformational change in the transporter's pumping process, thereby affecting antibiotic efflux inhibition. The MICs against Meropenem were 12.5 µg/ml for antibiotic Meropenem and 6.24 μg/ml for the combination.

Conclusion

The study concluded that these plant secondary metabolite compounds could be used to develop adjuvant along with antibiotics to increase their activity against MexAB-OprM efflux-mediated multidrug-resisting infections. It was determined that α-bisabolol may have the potential to boost antibacterial activity when combined with antibiotics, as well as being a strong candidate for an efflux pump inhibitor. This is the first inclusion of the properties of a natural plant phytochemical, Bisabolol, utilized in combination with commercial resistant antibiotic Meropenem to enhance its activity against MDR pneumonia infection caused by .

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2025-04-21
2025-08-13

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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
Bentham Science Publishers ; https://doi.org/10.2174/0127724344343717250404114236
/content/journals/raaidd/10.2174/0127724344343717250404114236
/content/journals/raaidd/10.2174/0127724344343717250404114236
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  • Article Type:     Research Article
Keywords: Pseudomonas aeruginosa ; MexAB-OprM ; in-silico screening of plant compounds ; novel mex B efflux pump inhibitors ; multidrug resistance. antibiotic efflux pumps

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