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, 11 (5), 457-68

Host Cell Autophagy Activated by Antibiotics Is Required for Their Effective Antimycobacterial Drug Action

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Host Cell Autophagy Activated by Antibiotics Is Required for Their Effective Antimycobacterial Drug Action

Jwa-Jin Kim et al. Cell Host Microbe.

Abstract

The current standard of treatment against tuberculosis consists of a cocktail of first-line drugs, including isoniazid and pyrazinamide. Although these drugs are known to be bactericidal, contribution of host cell responses in the context of antimycobacterial chemotherapy, if any, remains unknown. We demonstrate that isoniazid and pyrazinamide promote autophagy activation and phagosomal maturation in Mycobacterium tuberculosis (Mtb)-infected host cells. Treatment of Mtb-infected macrophages with isoniazid or pyrazinamide caused significant activation of cellular and mitochondrial reactive oxygen species and autophagy, which was triggered by bacterial hydroxyl radical generation. Mycobacterium marinum-infected autophagy-defective, atg7 mutant Drosophila exhibited decreased survival rates, which could not be rescued by antimycobacterial treatment, indicating that autophagy is required for effective antimycobacterial drug action in vivo. Moreover, activation of autophagy by antibiotic treatment dampened Mtb-induced proinflammatory responses in macrophages. Together, these findings underscore the importance of host autophagy in orchestrating successful antimicrobial responses to mycobacteria during chemotherapy.

Comment in

  • Old Antibiotics Target TB With a New Trick
    AJ Zullo et al. Cell Host Microbe 11 (5), 419-20. PMID 22607793.
    Autophagy is now recognized as a cellular defense mechanism that can restrict the growth of Mycobacterium tuberculosis (Mtb). In this issue of Cell Host & Microbe, Ki …

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