Selected purified plant compounds as possible inhibitors of rv1819c a drug efflux pump (abc protein) from mycobacterium tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) is among the most worrisome aspects of the pandemic of antibiotic resistance because TB patients that fail treatment have a high risk of death. The active multidrug efflux pump (EP) has been described as one of the mechanisms involved in the natural drug resistance of bacteria, such as mycobacteria. Rv1819c a putative efflux pump ATP binding cassette (ABC) protein gene from Mycobacterium tuberculosis, was cloned and transformed into Corynebacterium glutamicum. Susceptibility to standard anti-TB drugs and purified plant compounds, in the presence or absence of standard efflux pump inhibitors (EPIs), (carbonyl cyanide m-chlorophenylhydrazone (CCCP), reserpine and verapamil) was determined. A fluorometric method was used to assess the ability of the purified plant compounds to inhibit efflux pumps in comparison with three standard EPIs: reserpine, verapamil, and CCCP. Three of the plant compounds coded Ma8, IXLE1B and IXLE2FA were found to have potent antibacterial activity with the extract from Mammea africana (Ma8) being the most potent with an MIC of 4 mg/L. The three purified plant extracts were also shown to reduce the efflux of ciprofloxacin from the mycobacteria cells. The plant extracts have the potential to augment conventional drugs in the treatment of drug resistant M. tuberculosis upon further studies.,International Programme in the Chemical Sciences (IPICS, Uppsala University, Sweden