Combinations of Respiratory Chain Inhibitors Have Enhanced Bactericidal Activity against Mycobacterium tuberculosis.

摘要: As an obligate aerobe, Mycobacterium tuberculosis uses its electron transport chain (ETC) to produce energy via oxidative phosphorylation. This pathway has recently garnered a lot of attention and is target for several new antimycobacterials. We tested the respiratory adaptation M. phenoxyalkylbenzimidazoles (PABs), compounds proposed QcrB, component cytochrome bc1 complex. show that able reroute ETC provide temporary resistance PABs. However, combination treatment PAB with agents targeting other components overcomes this flexibility. in clofazimine resulted synergistic killing under both replicating nonreplicating conditions. PABs bedaquiline demonstrated antagonism at early time points, particularly antagonistic effect disappeared within 3 weeks, when PAB-BDQ combinations became highly bactericidal; some cases, they were better than either drug alone. study highlights potential supports development as part novel regimen against tuberculosis.