Mycobacterium tuberculosis energy metabolism and membrane energetics

Energy metabolism and membrane energetics in Mycobacterium tuberculosis (Mtb) refer to the integrated system of enzymes and transporters that generate ATP and maintain the electrochemical gradient across the bacterial inner membrane [1]. This system is primarily driven by oxidative phosphorylation, involving an electron transport chain (ETC) that terminates in oxygen-dependent reductases and an F1F0-ATP synthase [4]. Mtb is an obligate aerobe, making this pathway essential for survival during both active replication and latent persistence [1]. Therapeutic targeting of this system has been validated by the success of Bedaquiline, which binds to the c-ring of ATP synthase to halt energy production [2]. Other clinical candidates, such as Telacebec (Q203), target the QcrB subunit of the cytochrome bc1:aa3 complex, further demonstrating the vulnerability of mycobacterial respiration [3]. Disrupting these energetics leads to rapid bactericidal effects and is a cornerstone of modern multi-drug resistant tuberculosis (MDR-TB) treatment regimens [4].

Other names

Mtb oxidative phosphorylationMycobacterial respiratory chainMtb bioenergeticsMtb electron transport chain

Inhibition of the F1F0-ATP synthase (e.g., Bedaquiline) or the cytochrome bc1:aa3 oxidase complex (e.g., Telacebec) to deplete cellular ATP levels and collapse the membrane potential [1][2][3].