The causative agent of Tuberculosis (TB) Mycobacterium tuberculosis (Mtb) encounters unfavourable environmental conditions in the lungs, including nutrient limitation, low oxygen tensions and/or low/high pH values. These harsh conditions in the host triggers Mtb to enter a dormant state in which the pathogen does not replicate and uses host-derived fatty acids instead of carbohydrates as an energy source. Independent to the energy source, the bacterium’s energy currency ATP is generated by oxidative phosphorylation, in which the F₁F_O-ATP synthase uses the proton motive force generated by the electron transport chain. This catalyst is essential in Mtb and inhibition by the diarylquinoline class of drugs like Bedaquilline, TBAJ-587, TBAJ-876 or squaramides demonstrated that this engine is an attractive target in TB drug discovery. A special feature of the mycobacterial F-ATP synthase is its inability to establish a significant proton gradient during ATP hydrolysis, and its latent ATPase activity, to prevent energy waste and to control the membrane potential. Recently, unique epitopes of mycobacterial F₁F_O-ATP synthase subunits absent in their prokaryotic or mitochondrial counterparts have been identified to contribute to the regulation of the low ATPase activity. Most recent structural insights into individual subunits, the F₁ domain or the entire mycobacterial enzyme added to the understanding of mechanisms, regulation and differences of the mycobacterial F₁F_O-ATP synthase compared to other bacterial and eukaryotic engines. These novel insights provide the basis for the design of new compounds targeting this engine and even novel regimens for multidrug resistant TB.

结核（TB）结核分枝杆菌（Mtb）的病原体在肺部遇到不利的环境条件，包括营养限制，低氧张力和/或低/高pH值。宿主中的这些恶劣条件触发Mtb进入休眠状态，在这种状态下，病原体无法复制，并使用宿主衍生的脂肪酸而不是碳水化合物作为能源。细菌的能量货币ATP独立于能量源，是通过氧化磷酸化产生的，其中F ₁ F _O -ATP合酶利用电子传输链产生的质子原动力。这种催化剂在山楂中必不可少对二芳基喹啉类药物（如Bedaquilline，TBAJ-587，TBAJ-876或方酸酰胺）的抑制作用表明，该引擎是结核病药物发现中有吸引力的靶标。分枝杆菌F-ATP合酶的一个特殊功能是在ATP水解过程中无法建立明显的质子梯度，并且其潜在的ATPase活性无法防止能量浪费并控制膜电位。最近，已经鉴定出在原核或线粒体对应物中不存在的分枝杆菌F ₁ F _O -ATP合酶亚基的独特表位有助于调节低ATPase活性。对单个亚基F _1的最新结构见解与其他细菌和真核引擎相比，分枝结构域或整个分枝杆菌酶增加了对分枝杆菌F ₁ F _O -ATP合酶的机制，调控和差异的理解。这些新颖的见解为针对该发动机的新化合物的设计提供了基础，甚至为耐多药结核病的新颖疗法提供了基础。