Mycobacterial membrane and membrane-associated redox enzymes

Mycobacterial membrane and membrane-associated redox enzymes comprise the essential components of the respiratory electron transport chain in Mycobacterium tuberculosis (Mtb). This group includes key enzymes such as NADH dehydrogenase 2 (NDH-2), the cytochrome bc1-aa3 oxidase complex, and cytochrome bd oxidase, which collectively maintain the bacterial proton motive force [1][2]. These enzymes are critical for energy production and redox balance, allowing the pathogen to survive in various physiological states, including the dormant phase characteristic of latent tuberculosis [3]. Unlike human mitochondria, which primarily use NADH dehydrogenase 1, mycobacteria rely heavily on NDH-2, making these enzymes attractive targets for selective antimicrobial therapy [4]. Drugs targeting these redox enzymes, such as Telacebec (Q203) and Clofazimine, work by interrupting electron flow or inducing the production of reactive oxygen species, ultimately leading to bacterial cell death [5]. This target class is particularly significant for the development of new regimens against multi-drug-resistant tuberculosis strains [6].

Other names

Mycobacterial respiratory chainMycobacterial electron transport chainMtb redox enzymesMycobacterial oxidative phosphorylation system

Inhibition of electron transfer within the respiratory chain (e.g., at the QcrB subunit or NDH-2), leading to the collapse of the electrochemical gradient, depletion of cellular ATP, and induction of oxidative stress.