Rejuvenating the Potential of Antimicrobials Via Targeted Therapy of Efflux Pumps: The Advent of Phytotherapeutics

Antimicrobial resistance (AMR) and the emergence of multidrug-resistant organisms are one of the most eminent impediments of recent times. The intrinsic resistance mechanisms of the pathogenic organisms, especially the efflux pumps, play a significant part in the development of AMR and have to date resulted in the failure of a wide range of antimicrobial drugs. The efflux mechanisms exude the drugs from the cells and prevent their accumulation, thereby rendering the drug futile against the pathogenic microbe. Therefore, in order to combat with these evolving MDR microorganisms, their intrinsic resistance processes like the efflux pumps need to be targeted. In this regard, the advent of phytotherapeutic molecules isolated from specific medicinal plants has shown promising potential as efflux pump inhibitors (EPIs) with their capability of modifying the resistance mechanisms of pathogens. These botanicals show structural similarity or mimic certain peptide structure that increases their binding affinity to the efflux pump proteins. As a result, either the EPI binds to the drug binding pocket or the configuration of the efflux pumps is altered as a result of the binding, thus preventing the drug efflux. This review primarily focuses on the mode of action of the microbial efflux pumps, their contribution to enhancing microbial resistance, the emerging role of phytotherapeutics, and their potential to act as efflux pump inhibitors (EPIs).