Microbial bioenergetic pathways

Microbial bioenergetic pathways comprise the essential biochemical networks, such as the electron transport chain (ETC) and oxidative phosphorylation, that microorganisms utilize to generate ATP and maintain the proton motive force (PMF) (Cook et al., 2014) [1]. These pathways are critical for bacterial growth and survival, particularly for pathogens like Mycobacterium tuberculosis that can persist in low-oxygen or nutrient-limited environments by shifting their metabolic state (Hasenoehrl et al., 2021) [2, 5]. Therapeutic targeting of these pathways has gained significant traction, exemplified by the FDA approval of bedaquiline, which inhibits the mycobacterial F1Fo-ATP synthase (Inhibitors of energy metabolism, 2019) [4, 6]. Other key targets within these pathways include NADH dehydrogenase type II (NDH-2) and the cytochrome bc1:aa3 complex, which are often structurally distinct from human mitochondrial counterparts, allowing for selective toxicity (Cook et al., 2014) [1, 4]. These pathways also play a role in antibiotic tolerance and biofilm formation, where metabolic suppression helps bacteria survive traditional antibiotic treatments (Targeting bioenergetics, 2020) [12]. However, safety concerns such as potential cross-reactivity with host bioenergetics and drug-induced cardiotoxicity (e.g., QT prolongation) remain important considerations in the development of bioenergetic inhibitors (Targeting bioenergetics, 2020) [12, 17]. Overall, microbial bioenergetics represents a fertile area for the discovery of next-generation antimicrobials capable of tackling drug-resistant infections.

Other names

Bacterial bioenergeticsMicrobial energy metabolismBacterial respiratory chainOxidative phosphorylation in bacteriaMicrobial cellular energetics

Inhibition of ATP synthase, inhibition of the cytochrome bc1:aa3 complex, inhibition of NADH dehydrogenase type II (NDH-2), and disruption of the proton motive force (PMF).