Mycobacterium tuberculosis efflux pump (None (individual pumps have their own abbreviations: e.g., EfpA, MmpL5, Tap))

Efflux pumps in *Mycobacterium tuberculosis* are a diverse group of energy-dependent membrane transport proteins belonging predominantly to the MFS, RND, and ABC transporter families. They are responsible for exporting a wide variety of compounds, including antibiotics and endogenous metabolites, from the cytoplasm to the extracellular environment or cell wall. These transporters play critical roles in intrinsic and acquired resistance to first- and second-line anti-tuberculosis drugs, notably isoniazid and bedaquiline, often through upregulation triggered by mutations in regulatory genes such as Rv0678. Some, such as EfpA, function as lipid flippases, participating in membrane lipid transport and affecting cell wall biosynthesis and bacterial physiology. Inhibitors like BRD-8000.3 have shown promise in blocking efflux function and restoring antibiotic susceptibility. Despite their druggable potential, efflux pumps present several therapeutic challenges: functional redundancy, structural and mechanistic diversity among subtypes, and the risk of resistance emergence through genetic alterations. Additionally, their essential cellular roles complicate the development of highly selective and non-toxic inhibitors.

Other names

Efflux pumps of Mycobacterium tuberculosisDrug efflux transporter (generic)Specific member names: EfpA, Tap (Rv1258c), MmpL5/S5, Rv1273c/72c

Active transport of drugs and endogenous substrates out of the bacterial cell, reducing intracellular drug concentration and conferring tolerance/resistance. Inhibition via small molecules (e.g., BRD-8000.3) that block substrate binding or the transport pathway. Upregulation of efflux pumps due to regulatory mutations (e.g., Rv0678 in MmpS5/MmpL5), leading to drug resistance.