Mycobacterium tuberculosis oxidative phosphorylation system (Mtb OXPHOS)

The Mycobacterium tuberculosis oxidative phosphorylation system, often referred to as membrane energetics, is a critical metabolic pathway responsible for generating adenosine triphosphate (ATP) required for bacterial survival, growth, and persistence. Unlike many other bacteria, M. tuberculosis is an obligate aerobe that relies heavily on its respiratory chain to maintain a proton motive force across the plasma membrane, even during periods of dormancy or low metabolic activity. This system comprises several key components, including NADH dehydrogenases, the menaquinone pool, the cytochrome bc1-aa3 oxidase complex, and the F1F0-ATP synthase. Targeting membrane energetics has emerged as a highly effective strategy for treating both drug-sensitive and multi-drug-resistant tuberculosis (MDR-TB). Drugs like bedaquiline specifically bind to the c-subunit of ATP synthase, effectively 'starving' the bacteria of energy, while newer candidates like telacebec target the QcrB subunit of the cytochrome complex. Because these bioenergetic processes are distinct from those in human mitochondria or are sufficiently divergent in structure, they offer a high degree of selectivity. This pathway is particularly vital for killing non-replicating persistent mycobacteria, which are often responsible for treatment relapse and require long-duration therapy.

Other names

Mycobacterium tuberculosis membrane energeticsMycobacterium tuberculosis respiratory chainMtb electron transport chainMtb bioenergetics pathway

Inhibition of ATP synthase (subunit c), inhibition of the cytochrome bc1-aa3 complex (QcrB), or disruption of the proton motive force across the mycobacterial inner membrane.