The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction
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...
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th-mahidol.850582023-06-19T00:25:09Z The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction Siregar T.A.P. Mahidol University Immunology and Microbiology 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. 2023-06-18T17:25:09Z 2023-06-18T17:25:09Z 2022-01-01 Article Pathogens and Disease Vol.80 No.1 (2022) 10.1093/femspd/ftac004 2049632X 35038342 2-s2.0-85124440989 https://repository.li.mahidol.ac.th/handle/123456789/85058 SCOPUS |
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Immunology and Microbiology Siregar T.A.P. The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction |
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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. |
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Mahidol University |
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Mahidol University Siregar T.A.P. |
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Siregar T.A.P. |
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Siregar T.A.P. |
title |
The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction |
title_short |
The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction |
title_full |
The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction |
title_fullStr |
The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction |
title_full_unstemmed |
The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction |
title_sort |
autophagy-resistant mycobacterium tuberculosis beijing strain upregulates katg to evade starvation-induced autophagic restriction |
publishDate |
2023 |
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https://repository.li.mahidol.ac.th/handle/123456789/85058 |
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1781414885017518080 |