Antibacterial potential and modes of action of the methanol extracts of Elephantopus mollis Kunth (Asteraceae) against multidrug-resistant Gram-negative bacteria overexpressing efflux pumps

Background: Bacterial drug resistance still constitutes a major clinical issue. In the present study, the in vitro antibacterial potential, and modes of action of Elephantopus mollis were investigated. Methods: The antibacterial activity of methanol extracts of the various parts of E. mollis, their association with an efflux pump inhibitor, phenylalanine-arginine β-naphthylamide (PAβN) and the potentiating effect of several standard antibiotics were determined using the broth microdilution method. The effects of E. mollis leaf extract on H+ proton pump/ATPase function and bacterial growth kinetics were determined using standard methods. Phytochemical screening of the extracts was carried out using standard qualitative methods. Results: The crude extract (botanicals) from E. mollis leaf and flower had antibacterial activity with a 100% inhibition spectrum against bacterial strains and isolates with MICs ranging from 16 to 256 µg/mL and 64 to 1024 µg/mL respectively. Botanicals from the leaf extract showed excellent activity with a MIC of 16 µg/mL against K. pneumoniae KP55, a MIC of 32 µg/mL against K. pneumoniae (K2), and P. stuartti (NEA16). Botanicals from the leaf extract inhibited the exponential growth phase and H+-proton pump/ATPases of K. pneumoniae ATCC11296. In the presence of PAβN, the activity of E. mollis extracts was improved on 90% (leaves and flowers) and 63% (roots) of multidrug-resistant (MDR) bacterial strains and isolates. The various extracts of E. mollis potentiated the activities of the antibiotics: doxycycline, levofloxacin, vancomycin, imipenem, ceftriaxone, and ciprofloxacin against at least 70% of bacterial strains and isolates, with factors of increase in activity ranging from 2 to 128. Extracts from all parts of E. mollis contained alkaloids, flavonoids, tannins, and phenols. Conclusion: The results show that E. mollis is a source of antibacterial phytomedicine that can be used to treat bacterial infections caused by Gram-negative bacteria expressing MDR phenotypes. Keywords: Antibiotics; Asteraceae; bacteria; efflux pumps; Elephantopus mollis; multidrug resistance.