Appl Biochem Biotechnol. 2021 Apr 7. doi: 10.1007/s12010-021-03557-1. Online ahead of print.
Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is one of the principal causes of death in the world despite the existence of a significant number of antibiotics aimed against it. This is mainly due to the drug resistance mechanisms present in the bacterium, which leads to multidrug-resistant tuberculosis (MDR-TB). Additionally, the development of new antibiotics has become limited over the years. Although there are various drug resistance mechanisms present, efflux pumps are of utmost importance because they extrude out several dissimilar antitubercular drugs out of the cell. There are many efflux pump proteins present in Mycobacterium tuberculosis. Therefore, blocking these efflux pumps by inhibitors can raise the efficacy of the existing antibiotics and may also pave the path for the discovery and synthesis of new drugs. Plant compounds can act as a resource for the development of efflux pump inhibitors (EPIs), which may eventually replace or augment the current therapeutic options. This is mainly because plants have been traditionally used for ages for food or treatment and are considered safe with little or no side effects. Various computational tools are available which are used for the virtual screening of a large number of phytocompounds within a short span of time. This review aims to highlight the mechanism and appearance of drug resistance in Mycobacterium tuberculosis with emphasis on efflux pumps along with the significance of phytochemicals as inhibitors of these pumps and their screening strategy by computational approaches.