Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for several infections in humans. The infections caused by this bacterial strain are difficult to treat due to the resistance of MRSA to clinically used antibiotics. Several medicinal plants extracts and their phytoconstituents have been reported to possess modulation and efflux pump inhibitory (EPI) activity against MRSA strains. Alpinia calcarata rhizomes have been reported to be used in Ayurveda for several ailments including fungal infections. Based on this information and in continuation with our efforts to discover EPIs from Indian medicinal plants, we describe EPI activity of flavonoids isolated from A. calcarata. Galangin and kaempferol showed ≥ 32-fold modulation in minimum inhibitory concentration (MIC) of ethidium bromide (EtBr) as well as norfloxacin in NorA-overexpressed S. aureus (SA-1199B) strain. Pinocembrin showed 32-fold modulation of EtBr MIC in SA-1199 strain, but not in SA-1199B and K1758 strains. A significant difference was not observed in the modulation of norfloxacin MIC by galangin in SA-1199 and SA-1199B strains, which may be due to non-specific nature of galangin as modulator or EPI. However, kaempferol modulated the MIC of EtBr as well as norfloxacin 64-fold and 32-fold, respectively. Also, the best modulatory effect of kaempferol was observed only in SA-1199B strain compared to two other strains. The EPI activity of kaempferol and galangin were found to be competitive with respect to verapamil. In dose-response assay, kaempferol at 31.25 µg/mL concentration was found to be better EPI by inhibiting NorA pump in SA-1199B strain and also demonstrated further confocal microscopy.

This review article describes the current TB drugs, their merits and demerits as well as the new promising anti-TB agents such as diarylquinolines, oxazolidinones and nitroimdiazoles. It also includes the future development of new antitubercular agents according to the potential drug targets of Mycobacterium tuberculosis and structure-activity relationship studies on important anti-TB drugs.

MsrA, an efflux pump belonging to ATP‐binding cassette (ABC) transporter family that conferred resistance to macrolides, was detected in Staphylococcus aureus strains. Herein, we report the isolation of phytoconstituents from Piper cubeba fruit methanol extract and investigated their efflux pump inhibitory potential against S. aureus MsrA pump. Four isolated compounds, viz. pellitorine, sesamin, piperic acid and tetrahydropiperine studied in combination with erythromycin in S. aureus RN4220, exhibited 2–8‐fold reduction in minimum inhibitory concentration (MIC) of erythromycin. Pellitorine and sesamin decreased MIC of erythromycin by 8‐fold. The real‐time fluorometry‐based efflux and accumulation studies of ethidium bromide (EtBr) on S. aureus RN4220 in the presence of these compounds showed reduced efflux and enhanced uptake, thus indicating inhibition of the efflux pump. Pellitorine showed significant post‐antibiotic effect of erythromycin. The results revealed that the primary mechanism of action of these compounds involves steady ATP production impairment.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for several infections in humans. The infections caused by this bacterial strain are difficult to treat due to resistance of MRSA to clinically used antibiotics. Over past two decades medicinal plant extracts and their phytoconstituents have been reported to possess modulation and efflux pump inhibitory (EPI) activity against MRSA strains. Sida cordifolia aerial parts, roots and Sida rhombifolia aerial parts have been reported to be used in Ayurveda for several ailments including bacterial/fungal infections. Based on this information and in continuation of our efforts to discover EPIs from Indian medicinal plants, we describe modulation activity of methanol extracts of aerial parts and roots of S. cordifolia and S. rhombifolia and alkaloid-rich fraction prepared from methanol extracts. Methanol extract of S. cordifolia and S. rhombifolia aerial parts showed 4-fold reduction each in MIC of norfloxacin at 125 µg/mL concentration whereas alkaloid-rich fraction of both the plants did not show any reduction in MIC of norfloxacin. Fractionation of bioactive MeOH extract of S. cordifolia aerial resulted in isolation and characterization of 8 compounds including 2 alkaloids, 5 flavonoids and 1 coumarin compound whereas LC-MS analysis of alkaloid-rich fraction of S. rhombifolia aerial parts revealed presence of alkaloids including cryptolepine and 11-methoxyquindoline. Although the methanol extracts of aerial parts of S. cordifolia and S. rhombifolia showed weak modulatory activity in NorA over expressed S. aureus 1199B strain, the present study helped to assess EPI activity potential of these plants.

This chapter discusses the potential use of natural products as efflux pump inhibitors (EPIs) in several drug-resistant microbial pathogens, i.e., Mycobacterium, Staphylococcus aureus, Candida albicans. These natural products include various plant flavonoids, curcumin, polyphenols, diterpenes, oligosaccharides and alkaloids. In vitro assays used to screen EPI-related activities of these natural compounds are also outlined.