Targeting mycobacterial efflux system to enhance tuberculosis therapy

Abstract

The worldwide health epidemic of tuberculosis (TB) persists. It still claims millions of lives each year despite medical breakthroughs. Long-term therapies, drug-resistant TB strains, and co-infections with conditions like HIV necessitate novel approaches. The use of Mycobacterium tuberculosis (Mtb) efflux pumps, which actively expel drugs and decrease their effectiveness, is one such approach. EPIs (Efflux Pump Inhibitors) have the potential to treat tuberculosis. This review offers insights into Mtb's immune evasion mechanisms, including its strong cell wall, granuloma formation, immunological modulation, and dormancy, as well as TB epidemiology, worldwide eradication efforts, and those processes. Dissecting Efflux Pumps highlights their significance in drug resistance, particularly against first-line TB medications. Efflux pumps are notorious for causing antibiotic resistance. EPIs may have benefits such as increased drug efficacy, resistance reversal, shortened treatment durations, less toxicity, improved adherence, and targeting of latent TB. The effectiveness of various EPI classes, including phenylalkylamines, protonophores, phenothiazines, and plant-derived derivatives, against Mtb growth and efflux pumps is evaluated. The creation of effective EPIs, a clearer understanding of efflux pump control, and essential clinical trials for validation remain obstacles.