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Siregar TAP, Prombutara P, Kanjanasirirat P, et al. The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction. Pathog Dis. 2022;doi: 10.1093/femspd/ftac004.
Siregar, T. A. P., Prombutara, P., Kanjanasirirat, P., Kunkaew, N., Tubsuwan, A., Boonmee, A., Palaga, T., Khumpanied, T., Borwornpinyo, S., Chaiprasert, A., Utaisincharoen, P., & Ponpuak, M. (2022). The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction. Pathogens and disease, . https://doi.org/10.1093/femspd/ftac004
Siregar, Tegar Adriansyah Putra, et al. "The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction." Pathogens and disease vol. (2022). doi: https://doi.org/10.1093/femspd/ftac004
Siregar TAP, Prombutara P, Kanjanasirirat P, Kunkaew N, Tubsuwan A, Boonmee A, Palaga T, Khumpanied T, Borwornpinyo S, Chaiprasert A, Utaisincharoen P, Ponpuak M. The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction. Pathog Dis. 2022 Jan 17; doi: 10.1093/femspd/ftac004. Epub 2022 Jan 17. PMID: 35038342.
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Pathog Dis. 2022 Jan 17; doi: 10.1093/femspd/ftac004. Epub 2022 Jan 17.

The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction.

Pathogens and disease

Tegar Adriansyah Putra Siregar, Pinidphon Prombutara, Phongthon Kanjanasirirat, Nawapol Kunkaew, Alisa Tubsuwan, Atsadang Boonmee, Tanapat Palaga, Tanawadee Khumpanied, Suparerk Borwornpinyo, Angkana Chaiprasert, Pongsak Utaisincharoen, Marisa Ponpuak

Affiliations

  1. Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  2. Department of Microbiology, Faculty of Medicine, University of Muhammadiyah Sumatera Utara, Medan, Indonesia.
  3. Omics Sciences and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
  4. Microbiome Research Unit for Probiotics in Food and Cosmetics, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
  5. Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, Thailand.
  6. Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  7. Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
  8. Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
  9. Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  10. Office of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  11. Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

PMID: 35038342 DOI: 10.1093/femspd/ftac004

Abstract

Mycobacterium tuberculosis utilizes several mechanisms to block phagosome-lysosome fusion to evade host cell restriction. However, induction of host cell autophagy by starvation was shown to overcome this block, resulting in enhanced lysosomal delivery to mycobacterial phagosomes and the killing of the M. tuberculosis reference strain H37Rv. Nevertheless, our previous studies found that strains belonging to the M. tuberculosis Beijing genotype can resist starvation-induced autophagic elimination, though the mycobacterial factors involved remain unclear. In this study, we showed that KatG expression is upregulated in the autophagy-resistant M. tuberculosis Beijing strain (BJN) during autophagy induction by the starvation of host macrophages, while such increase was not observed in the H37Rv. KatG depletion using the CRISPR-dCas9 interference system in the BJN resulted in increased lysosomal delivery to its phagosome and decreased its survival upon autophagy induction by starvation. As KatG functions by catabolizing ROS, we determined the source of ROS contributing to the starvation-induced autophagic elimination of mycobacteria. Using siRNA-mediated knockdown, we found that Superoxide dismutase 2, which generates mitochondrial ROS but not NADPH oxidase 2, is important for the starvation-induced lysosomal delivery to mycobacterial phagosomes. Taken together, these findings showed that KatG is vital for the BJN to evade starvation-induced autophagic restriction.

© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.

Keywords: Mycobacterium tuberculosis ; Autophagy; CRISPR; KatG; ROS; Tuberculosis

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