Exploring Mangifera indica (Anacardiaceae) leaf and bark methanol extracts as potential adjuvant therapy in the management of multidrug-resistant Staphylococcus aureus

Abstract

Background: After several decades of antibiotic use, pathogenic bacteria have reached alarming levels of resistance. Staphylococcus aureus is the most common cause of nosocomial infections, and treatment is difficult owing to the advent of multidrug-resistant (MDR) strains. This motivates the search for more potent drugs. Foremost, adjuvant compounds that increase the effectiveness of conventional antibiotics are also being researched extensively. The current study examined the anti-staphylococcal and antibiotic-resistance reversal effects of the methanol extracts of Mangifera indica (leaves and bark). Methods: Botanicals were tested alone, in the presence of reserpine (efflux pump inhibitor), and in association with commonly prescribed antibiotics, using a 96-well broth microdilution method against a panel of seventeen MDR strains and clinical isolates of S. aureus, including methicillin-resistant strains (MRSA). The ability of the leaf extract to inhibit H+-ATPase-mediated proton pumping was determined by controlling the acidification of the bacterial solution, whereas the influence on bacterial kinetic growth was determined by measuring absorbance (OD600 nm) after exposure to various concentrations of the test extract. Results: M. indica leaf and bark extracts exhibited exceptional anti-staphylococcal capabilities, inhibiting 100% of the S. aureus strains tested. The minimal inhibitory concentrations (MICs) recorded varied from 256 to 2048 µg/mL; the effects were bactericidal (MBC/MIC ≤ 4) in most cases. The bark extract demonstrated an outstanding potential to improve the efficacy of conventional antibiotics. The activity of chloramphenicol, doxycycline, tetracycline, levofloxacin, and ampicillin was enhanced against 100% of studied MDR S. aureus in association with the bark extract at sub-inhibitory concentrations of MIC/2 and MIC/4. The leaf extract of M. indica induced a concentration-dependent inhibition of S. aureus MRSA4 growth over 20 hours of exposure at 0.5×MIC, MIC, and 2×MIC. The latent phase has been extended up to 6 hours after treatment with the extract. Similarly, M. indica leaf extract significantly reduced the acidity of the bacterial solution in a concentration-dependent manner, indicating a possible target of its antibacterial effect. Conclusion: The present study revealed the remarkable activity of M. indica leaf and bark extracts against MDR strains and clinical isolates of S. aureus, including MRSA. The bark extract might be used as an adjuvant to antibiotic therapy, as indicated by its notable potentiation activity when combined with conventional antibiotics. Keywords: Antibacterial activity; Mangifera indica; multidrug resistance; potentiation; Staphylococcus aureus.