Research ArticleTuberculosis

Targeting redox heterogeneity to counteract drug tolerance in replicating Mycobacterium tuberculosis

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Science Translational Medicine  13 Nov 2019:
Vol. 11, Issue 518, eaaw6635
DOI: 10.1126/scitranslmed.aaw6635

Antibiotic redox-based redux

Phagosomal pH and redox heterogeneity in Mycobacterium tuberculosis (Mtb) can promote tolerance of the bacterium to antibiotics. Mishra et al. found that the approved antimalarial drug chloroquine inhibited this acidification and resulted in altered redox metabolism and improved susceptibility of Mtb to first-line antituberculosis drugs, particularly isoniazid, in infected macrophages in vitro. Coadministration of chloroquine improved isoniazid treatment outcomes in both mouse and guinea pig models of Mtb infection. This work suggests the repurposing of chloroquine to potentiate and possibly shorten antibiotic treatment of tuberculosis.

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