Psidium guajava (Myrtaceae) re-sensitizes multidrug-resistant Pseudomonas aeruginosa over-expressing MexAB-OprM efflux pumps to commonly prescribed antibiotics

Abstract
Background: Pseudomonas aeruginosa is a critical-class priority pathogen showing high resistance to almost all classes of conventional antibiotics. As a result, discovering new drugs capable of combating Pseudomonas infections becomes critical. The current study looked at the antibacterial and antibiotic-resistance reversal properties of the leaf (PGL) and bark (PGB) methanol extracts of Psidium guajava (Myrtaceae), a popular food plant, towards multidrug-resistant (MDR) P. aeruginosa over-expressing active efflux.
Methods: The activities were assessed using a 96-well plate microdilution technique, with iodonitrotetrazolium chloride (INT) to detect living bacteria. The action of herbals was further carried out on Pseudomonas kinetic growth, cell membrane, and H+-ATPase mediated proton pumps, using standards.
Results: PGL and PGB produced inhibitory effects on all the fourteen MDR strains and clinical isolates of P. aeruginosa, with the minimum inhibitory concentrations (MIC) recorded ranging from 64 to 2048 μg/mL. PGB was shown to be more effective, having MICs ≤ 512 μg/mL on 100% of the MDR pathogens tested. It also exhibited the lowest MICs (best activity) of 64 μg/mL against three MDR clinical isolates P124, P57, and P29, with activity higher than that of the reference medication (chloramphenicol). PGL and PGB were shown to have significant antibiotic-resistance reversal action when combined with conventional antibiotics, with PGB enhancing the efficacy of all standard drugs employed. PGB was shown to lengthen the latent phase of kinetic growth, also, it significantly inhibited the H+-ATPase-mediated proton pump and altered cell membrane integrity, at MIC and 2×MIC.
Conclusion: The current investigation provides justification for considering P. guajava extracts, alone or in combination with antibiotics, as potential treatments for MDR P. aeruginosa infections.

Keywords: Antibiotics; efflux pumps; food plants; multidrug-resistant bacteria; Pseudomonas aeruginosa; Psidium guajava.