Gram-negative bacterial inner membrane NADH-quinone oxidoreductases (NDH/NQR)

Gram-negative bacterial inner membrane NADH-quinone oxidoreductases are essential components of the bacterial respiratory chain, responsible for transferring electrons from NADH to the quinone pool (ubiquinone or menaquinone) [1, 10]. This group of enzymes includes the proton-pumping NADH dehydrogenase 1 (NDH-1), the non-proton-pumping NADH dehydrogenase 2 (NDH-2), and the sodium-translocating NADH:quinone oxidoreductase (Na+-NQR) [3, 17]. These enzymes are vital for maintaining the bacterial energy budget by generating the transmembrane electrochemical gradient (proton or sodium motive force) required for ATP synthesis, flagellar rotation, and active transport [1, 6]. Because Na+-NQR and NDH-2 are absent in human mitochondria, they represent highly selective targets for the development of new antibiotics against multi-drug resistant Gram-negative pathogens such as Vibrio cholerae, Pseudomonas aeruginosa, and Acinetobacter baumannii [1, 11, 15]. Drugs like polymyxins have been shown to inhibit NDH-2 as a secondary mechanism, while experimental inhibitors like clofazimine and korormicin target the Na+-NQR complex [2, 5, 9]. Inhibition of these enzymes leads to metabolic collapse, depletion of ATP, and the production of lethal reactive oxygen species [2, 4].

Other names

NADH:ubiquinone oxidoreductaseNADH dehydrogenaseComplex INDH-1NDH-2Na+-NQRSodium-translocating NADH:quinone oxidoreductaseNADH:quinone reductase

Inhibition of electron transfer from NADH to the quinone pool in the bacterial respiratory chain, which disrupts the generation of the transmembrane electrochemical gradient (proton or sodium motive force), leads to ATP depletion, and induces the formation of lethal reactive oxygen species (ROS) [1, 2, 5, 11].