Bacterial oxidative phosphorylation (OxPhos) (OxPhos)

Bacterial oxidative phosphorylation is a vital metabolic pathway used by aerobic bacteria, such as Mycobacterium tuberculosis, to generate adenosine triphosphate (ATP) through a series of redox reactions [2, 8]. This process occurs in the bacterial plasma membrane and involves the electron transport chain (ETC), where electrons are transferred from donors like NADH to terminal acceptors like oxygen via protein complexes including NADH dehydrogenase and the cytochrome bcc complex [1, 2, 14]. The energy released during these reactions is used to pump protons across the membrane, establishing a proton motive force (PMF) that drives the F1F0-ATP synthase to produce ATP [3, 4, 6]. Because this pathway is essential for the survival of both actively replicating and dormant, non-replicating bacteria, it has become a major focus for antimicrobial drug development [2, 14]. Clinically validated drugs such as bedaquiline and telacebec target specific components of this pathway, namely ATP synthase and the cytochrome bcc complex, respectively [1, 11, 12]. Targeting oxidative phosphorylation is particularly effective against multi-drug resistant pathogens, although challenges remain regarding metabolic redundancy and ensuring selectivity over human mitochondrial processes [4, 9, 12].

Other names

Bacterial respirationElectron transport chain (ETC)Energy metabolismRespiration-driven ATP synthesisTerminal oxidation

Inhibition of F1F0-ATP synthase, inhibition of the cytochrome bcc complex, inhibition of type II NADH dehydrogenase (NDH-2), dissipation of the transmembrane proton motive force, uncoupling of respiration-driven ATP synthesis, and nitric oxide release [1, 2, 3, 6, 10].