Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. © 2012 Elsevier Inc.

Jwa Jin Kim, Hye Mi Lee, Dong Min Shin, Wonho Kim, Jae Min Yuk, Hyo Sun Jin, Sang Hee Lee, Guang Ho Cha, Jin Man Kim, Zee Won Lee, Sung Jae Shin, Heekyung Yoo, Young Kil Park, Jin Bong Park, Jongkyeong Chung, Tamotsu Yoshimori, Eun Kyeong Jo

Research output: Contribution to journalArticle

124 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)457-468
Number of pages12
JournalCell Host and Microbe
Volume11
Issue number5
DOIs
Publication statusPublished - 2012 May 17

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Autophagy
Anti-Bacterial Agents
Pyrazinamide
Isoniazid
Mycobacterium tuberculosis
Pharmaceutical Preparations
Mycobacterium marinum
Macrophages
Drug Therapy
Therapeutics
Mycobacterium
Hydroxyl Radical
Drosophila
Reactive Oxygen Species
Tuberculosis

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Cite this

Kim, Jwa Jin ; Lee, Hye Mi ; Shin, Dong Min ; Kim, Wonho ; Yuk, Jae Min ; Jin, Hyo Sun ; Lee, Sang Hee ; Cha, Guang Ho ; Kim, Jin Man ; Lee, Zee Won ; Shin, Sung Jae ; Yoo, Heekyung ; Park, Young Kil ; Park, Jin Bong ; Chung, Jongkyeong ; Yoshimori, Tamotsu ; Jo, Eun Kyeong. / Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. © 2012 Elsevier Inc. In: Cell Host and Microbe. 2012 ; Vol. 11, No. 5. pp. 457-468.
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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.",
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Kim, JJ, Lee, HM, Shin, DM, Kim, W, Yuk, JM, Jin, HS, Lee, SH, Cha, GH, Kim, JM, Lee, ZW, Shin, SJ, Yoo, H, Park, YK, Park, JB, Chung, J, Yoshimori, T & Jo, EK 2012, 'Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. © 2012 Elsevier Inc.', Cell Host and Microbe, vol. 11, no. 5, pp. 457-468. https://doi.org/10.1016/j.chom.2012.03.008

Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. © 2012 Elsevier Inc. / Kim, Jwa Jin; Lee, Hye Mi; Shin, Dong Min; Kim, Wonho; Yuk, Jae Min; Jin, Hyo Sun; Lee, Sang Hee; Cha, Guang Ho; Kim, Jin Man; Lee, Zee Won; Shin, Sung Jae; Yoo, Heekyung; Park, Young Kil; Park, Jin Bong; Chung, Jongkyeong; Yoshimori, Tamotsu; Jo, Eun Kyeong.

In: Cell Host and Microbe, Vol. 11, No. 5, 17.05.2012, p. 457-468.

Research output: Contribution to journalArticle

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AU - Jin, Hyo Sun

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AU - Cha, Guang Ho

AU - Kim, Jin Man

AU - Lee, Zee Won

AU - Shin, Sung Jae

AU - Yoo, Heekyung

AU - Park, Young Kil

AU - Park, Jin Bong

AU - Chung, Jongkyeong

AU - Yoshimori, Tamotsu

AU - Jo, Eun Kyeong

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