Drugs with multiple targets Drugs inhibiting cell wall synthesis Pyrazinamide leads to intracellular acidification and disrupts plasma membrane Clofazimine targets the outer membrane ,respiratory chain and ion transport Ethambutol inhibits arabinosyltransferases embA, embB, embC Isoniazid and thionamid drugs (ethionamide and prothionamide) inhibit inhA Delamanid and pretomanid inhibit some mycolic acids synthesis Terizidone and cycloserine inhibitL-alanine racemase and D-alanine ligase Carbapenems (meropenem and imipenemcilastin) +clavulanic acid inhibit transpeptidase Bedaquiline inhibits ATP synthesis DNA DNA gyrase mRNA Ribosome RNA polymerase ATP synthase Peptide Para-aminosalicyclic acid inhibits folate metabolism Quinolones (levofloxacin and moxifloxacin) inhibit DNA synthesis Rifamycins (rifampicin, rifabutin and rifapentin) inhibit transcription Oxazolidinones (linezolid) and aminoglycosides (aminkacin, kanamycin, capreomycin and streptomycin) inhibit protein synthesis FIGURE 2Mechanisms of action of the currently used anti-TB medicines. ATP: adenosine 5’ mRNA: messenger ribonucleic acid. Created with BioRender.com. Reproduced and modified from [28] with permission. https://doi.org/10.1183/2312508X.10024622 121 TREATMENT OF DS-TB AND DR-TB |C. LANGE ET AL.