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Sci Rep. 2021 Feb 22;11(1):4342. doi: 10.1038/s41598-021-83835-4.

Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain.

Scientific reports

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

Affiliations

  1. Department of Microbiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand.
  2. Omics Sciences and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
  3. Microbiome Research Unit for Probiotics in Food and Cosmetics, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
  4. Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, Thailand.
  5. Inter-Disciplinary Graduate Program in Medical Microbiology, Graduate School, Chulalongkorn University, Bangkok, Thailand.
  6. Department of Microbiology, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
  7. Aix Marseille University, CNRS, INSERM, CIML, Marseille, France.
  8. Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  9. Drug-Resistance Tuberculosis Research Fund, Siriraj Foundation, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  10. Office of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  11. Department of Microbiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand. [email protected].
  12. Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand. [email protected].

PMID: 33619301 PMCID: PMC7900199 DOI: 10.1038/s41598-021-83835-4

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.

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