Figure 1.

An overview of the effect of tuberculosis antimicrobials on host mitochondrial function, bioenergetics and immune cell function. Tuberculosis (TB) antimicrobials, that are routinely used to fight TB infection, could affect a range of cellular processes, particularly mitochondrial function and various bioenergetic processes. These antimicrobials could alter MMP (isoniazid and ciprofloxacin), mitochondrial membrane permeability (rifampicin, ciprofloxacin and levofloxacin), mitochondrial mass (linezolid), or result in mitochondrial uncoupling (ciprofloxacin and levofloxacin). They could also inhibit electron transport chain complex activity (ciprofloxacin, levofloxacin, linezolid, bedaquiline, ethambutol, and rifampicin), ROS production (rifampicin and isoniazid), NO production (ciprofloxacin and levofloxacin), or ATP production (rifampicin, isoniazid and ciprofloxacin). Moreover, these antimicrobials have been shown to alter metabolic flux through OXPHOS (rifampicin, linezolid, bedaquiline, and clofazimine), glycolysis (bedaquiline, rifampicin, linezolid, moxifloxacin, ciprofloxacin, and clofazimine), while also affecting the production of TCA cycle intermediates (clofazimine). Such changes in mitochondrial function and host bioenergetics could also be linked with alterations in apoptosis (levofloxacin, ciprofloxacin, and linezolid), the autophagic process (isoniazid and bedaquiline) and a variety of inflammatory phenotypes (rifampicin, ciprofloxacin, levofloxacin, linezolid, bedaquiline, moxifloxacin, and clofazimine). Image produced with the aid of Servier Medical Art software (see copyright license at https://smart.servier.com).