Mycobacterium tuberculosis respiratory chain (Mtb respiratory chain) (Mtb respiratory chain)

The Mycobacterium tuberculosis (Mtb) respiratory chain is a critical metabolic system located within the bacterial plasma membrane that is essential for the generation of adenosine triphosphate (ATP) through oxidative phosphorylation (Cook et al., 2014; Lu et al., 2018). This system consists of several membrane-bound protein complexes, including NADH dehydrogenases (NDH-1 and NDH-2), succinate dehydrogenases, the cytochrome bc1-aa3 oxidase complex, and the F1F0-ATP synthase (Cook et al., 2014). These components work in concert to transfer electrons from donors to oxygen, simultaneously pumping protons across the membrane to create a proton motive force (PMF) (Lu et al., 2018). This PMF is then utilized by ATP synthase to catalyze the synthesis of ATP, providing the energy necessary for Mtb to survive in both actively growing and dormant (latent) states (Andries et al., 2005). Because Mtb relies heavily on this pathway for bioenergetics, the respiratory chain has become a primary focus for the development of new anti-tuberculosis drugs (Pethe et al., 2013). For example, bedaquiline inhibits the ATP synthase, while telacebec (Q203) targets the QcrB subunit of the cytochrome bc1 complex, both leading to a lethal depletion of cellular energy (Andries et al., 2005; Pethe et al., 2013). The unique composition of the Mtb respiratory chain, such as the reliance on NDH-2 rather than NDH-1 for primary electron entry, provides opportunities for selective toxicity over human mitochondrial systems (Lu et al., 2018). Targeting this pathway is particularly effective against multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains of tuberculosis (Pethe et al., 2013).

Other names

Mtb electron transport chainMtb oxidative phosphorylation systemMtb bioenergetics pathwayMycobacterium tuberculosis respiratory chain

Inhibition of ATP synthase, inhibition of cytochrome bc1 complex (QcrB), inhibition of NADH dehydrogenase-2 (NDH-2), and disruption of the proton motive force.