Bacterial oxidative phosphorylation system (OXPHOS) (OXPHOS)

The bacterial bioenergetic machinery is a sophisticated system of membrane-bound protein complexes and enzymes that drive energy production through oxidative phosphorylation (Cook et al., 2017). This machinery primarily includes the electron transport chain (ETC)—comprising NADH dehydrogenases, succinate dehydrogenases, and terminal oxidases like the cytochrome bc1 and cytochrome bd complexes—and the F1Fo-ATP synthase (Hards et al., 2018). These components work in concert to generate a transmembrane electrochemical gradient, known as the proton motive force, which is then utilized by ATP synthase to produce ATP from ADP and inorganic phosphate (NIH, 2013). This system is vital for bacterial growth and survival, particularly for persistent or dormant cells that rely on efficient energy management to withstand environmental stress and antibiotic pressure (Cook et al., 2017). In drug development, the bacterial bioenergetic machinery has emerged as a high-value target space, especially for treating Mycobacterium tuberculosis (Pethe et al., 2013). Inhibitors such as bedaquiline target the ATP synthase, while others like telacebec (Q203) target the cytochrome bc1 complex, leading to energy depletion and bacterial cell death (Cook et al., 2017). Targeting bioenergetics is particularly valuable because it can kill both actively replicating and metabolically dormant bacilli that are often resistant to conventional antibiotics (NIH, 2017).

Other names

Bacterial bioenergetic machineryBacterial respiratory chainBacterial electron transport chainBacterial energy generating machinery

Inhibition of F1Fo-ATP synthase, inhibition of the cytochrome bc1 complex (QcrB), inhibition of cytochrome bd oxidase, uncoupling of the transmembrane electrochemical gradient (proton motive force), and inhibition of NADH dehydrogenase.