Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain
Abstract Induction of host cell autophagy by starvation was shown to enhance lysosomal delivery to mycobacterial phagosomes, resulting in the restriction of Mycobacterium tuberculosis reference strain H37Rv. Our previous study showed that strains belonging to M. tuberculosis Beijing genotype resiste...
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2021
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oai:doaj.org-article:9f7ba98315674f0d80cc83b7dfaa29142021-12-02T16:23:21ZLysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain10.1038/s41598-021-83835-42045-2322https://doaj.org/article/9f7ba98315674f0d80cc83b7dfaa29142021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83835-4https://doaj.org/toc/2045-2322Abstract Induction of host cell autophagy by starvation was shown to enhance lysosomal delivery to mycobacterial phagosomes, resulting in the restriction of Mycobacterium tuberculosis reference strain H37Rv. Our previous study showed that strains belonging to M. tuberculosis Beijing genotype resisted starvation-induced autophagic elimination but the factors involved remained unclear. Here, we conducted RNA-Seq of macrophages infected with the autophagy-resistant Beijing strain (BJN) compared to macrophages infected with H37Rv upon autophagy induction by starvation. Results identified several genes uniquely upregulated in BJN-infected macrophages but not in H37Rv-infected cells, including those encoding Kxd1 and Plekhm2, which function in lysosome positioning towards the cell periphery. Unlike H37Rv, BJN suppressed enhanced lysosome positioning towards the perinuclear region and lysosomal delivery to its phagosome upon autophagy induction by starvation, while depletion of Kxd1 and Plekhm2 reverted such effects, resulting in restriction of BJN intracellular survival upon autophagy induction by starvation. Taken together, these data indicated that Kxd1 and Plekhm2 are important for the BJN strain to suppress lysosome positioning towards the perinuclear region and lysosomal delivery into its phagosome during autophagy induction by starvation to evade starvation-induced autophagic restriction.Thanida LaopanupongPinidphon PrombutaraPhongthon KanjanasiriratSalisa BenjaskulluechaAtsadang BoonmeeTanapat PalagaStephane MéresseJiraporn PahaTegar Adriansyah Putra SiregarTanawadee KhumpaniedSuparerk BorwornpinyoAngkana ChaiprasertPongsak UtaisincharoenMarisa PonpuakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
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Medicine R Science Q Thanida Laopanupong Pinidphon Prombutara Phongthon Kanjanasirirat Salisa Benjaskulluecha Atsadang Boonmee Tanapat Palaga Stephane Méresse Jiraporn Paha Tegar Adriansyah Putra Siregar Tanawadee Khumpanied Suparerk Borwornpinyo Angkana Chaiprasert Pongsak Utaisincharoen Marisa Ponpuak Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain |
| description |
Abstract Induction of host cell autophagy by starvation was shown to enhance lysosomal delivery to mycobacterial phagosomes, resulting in the restriction of Mycobacterium tuberculosis reference strain H37Rv. Our previous study showed that strains belonging to M. tuberculosis Beijing genotype resisted starvation-induced autophagic elimination but the factors involved remained unclear. Here, we conducted RNA-Seq of macrophages infected with the autophagy-resistant Beijing strain (BJN) compared to macrophages infected with H37Rv upon autophagy induction by starvation. Results identified several genes uniquely upregulated in BJN-infected macrophages but not in H37Rv-infected cells, including those encoding Kxd1 and Plekhm2, which function in lysosome positioning towards the cell periphery. Unlike H37Rv, BJN suppressed enhanced lysosome positioning towards the perinuclear region and lysosomal delivery to its phagosome upon autophagy induction by starvation, while depletion of Kxd1 and Plekhm2 reverted such effects, resulting in restriction of BJN intracellular survival upon autophagy induction by starvation. Taken together, these data indicated that Kxd1 and Plekhm2 are important for the BJN strain to suppress lysosome positioning towards the perinuclear region and lysosomal delivery into its phagosome during autophagy induction by starvation to evade starvation-induced autophagic restriction. |
| format |
article |
| author |
Thanida Laopanupong Pinidphon Prombutara Phongthon Kanjanasirirat Salisa Benjaskulluecha Atsadang Boonmee Tanapat Palaga Stephane Méresse Jiraporn Paha Tegar Adriansyah Putra Siregar Tanawadee Khumpanied Suparerk Borwornpinyo Angkana Chaiprasert Pongsak Utaisincharoen Marisa Ponpuak |
| author_facet |
Thanida Laopanupong Pinidphon Prombutara Phongthon Kanjanasirirat Salisa Benjaskulluecha Atsadang Boonmee Tanapat Palaga Stephane Méresse Jiraporn Paha Tegar Adriansyah Putra Siregar Tanawadee Khumpanied Suparerk Borwornpinyo Angkana Chaiprasert Pongsak Utaisincharoen Marisa Ponpuak |
| author_sort |
Thanida Laopanupong |
| title |
Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain |
| title_short |
Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain |
| title_full |
Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain |
| title_fullStr |
Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain |
| title_full_unstemmed |
Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain |
| title_sort |
lysosome repositioning as an autophagy escape mechanism by mycobacterium tuberculosis beijing strain |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/9f7ba98315674f0d80cc83b7dfaa2914 |
| work_keys_str_mv |
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| _version_ |
1718384126401183744 |