Bacterial terminal oxidase

Bacterial terminal oxidases are the primary enzymes responsible for the final step of the aerobic respiratory chain, where they catalyze the reduction of molecular oxygen to water (Borisov et al., 2021, Frontiers in Microbiology). These enzymes are categorized into two distinct superfamilies: the heme-copper oxidases (HCOs), such as cytochrome aa3, and the cytochrome bd-type quinol oxidases (Theunissen et al., 2022, Nature Communications). By coupling the exergonic reduction of oxygen to the translocation of protons across the cytoplasmic membrane, they establish the proton motive force (PMF) essential for ATP production via ATP synthase (Cook et al., 2021, Biological Chemistry). In many human pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, these oxidases are critical for survival under low-oxygen conditions and during host-induced stress (Saini et al., 2021, mBio). Because cytochrome bd-type oxidases are unique to bacteria and absent in the human mitochondrial respiratory chain, they are considered highly attractive targets for the development of selective, narrow-spectrum antibiotics (Ho et al., 2021, Nature Communications). Inhibition of these enzymes leads to a rapid collapse of the PMF, depletion of cellular ATP, and eventual bacterial cell death, particularly when used in combination with other respiratory inhibitors (Beites et al., 2019, Cell Chemical Biology).

Other names

Cytochrome bd oxidaseCytochrome c oxidaseQuinol oxidaseHeme-copper oxidaseTerminal respiratory oxidase

Inhibition of the terminal step of the respiratory electron transport chain, preventing the reduction of oxygen to water and halting the generation of the proton motive force required for ATP synthesis.