Streptococcus pneumoniae triggers hierarchical autophagy through reprogramming of LAPosome-like vesicles via NDP52-delocalization.,Communications Biology

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Streptococcus pneumoniae triggers hierarchical autophagy through reprogramming of LAPosome-like vesicles via NDP52-delocalization.
Communications Biology ( IF 5.2 ) Pub Date : 2020-01-13 , DOI: 10.1038/s42003-020-0753-3
Michinaga Ogawa ₁ , Naoki Takada _{1,

2} , Sayaka Shizukuishi _{1,

3} , Mikado Tomokiyo _{1,

4} , Bin Chang ₁ , Mitsutaka Yoshida ₅ , Soichiro Kakuta _{5,

6} , Isei Tanida ₆ , Akihide Ryo ₃ , Jun-Lin Guan ₇ , Haruko Takeyama _{2,

8,

9,

10} , Makoto Ohnishi ₁

Affiliation

Department of Bacteriology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan.
Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Department of Microbiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa, 236-0004, Japan.
School of Veterinary Medicine, Azabu University, Fuchinobe, Sagamihara-shi, Kanagawa, 229-8501, Japan.
Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Department of Cellular and Molecular Neuropathology, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Department of Cancer Biology, University of Cincinnati College of Medicine, CARE/Crawley Building, Suite E-870 3230 Eden Avenue, Cincinnati, OH, 45267, USA.
Computational Bio Big-Data Open Innovation Laboratory, AIST-Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-0072, Japan.
Research Organization for Nano & Life Innovation, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo, 162-0041, Japan.
Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.

In innate immunity, multiple autophagic processes eliminate intracellular pathogens, but it remains unclear whether noncanonical autophagy and xenophagy are coordinated, and whether they occur concomitantly or sequentially. Here, we show that Streptococcus pneumoniae, a causative of invasive pneumococcal disease, can trigger FIP200-, PI3P-, and ROS-independent pneumococcus-containing LC3-associated phagosome (LAPosome)-like vacuoles (PcLVs) in an early stage of infection, and that PcLVs are indispensable for subsequent formation of bactericidal pneumococcus-containing autophagic vacuoles (PcAVs). Specifically, we identified LC3- and NDP52-delocalized PcLV, which are intermediates between PcLV and PcAV. Atg14L, Beclin1, and FIP200 were responsible for delocalizing LC3 and NDP52 from PcLVs. Thus, multiple noncanonical and canonical autophagic processes are deployed sequentially against intracellular S. pneumoniae. The Atg16L1 WD domain, p62, NDP52, and poly-Ub contributed to PcLV formation. These findings reveal a previously unidentified hierarchical autophagy mechanism during bactericidal xenophagy against intracellular bacterial pathogens, and should improve our ability to control life-threating pneumococcal diseases.

中文翻译：

肺炎链球菌通过NDP52-去定位，通过对LAPosome样小泡进行重编程来触发分级自噬。

在先天免疫中，多种自噬过程消除了细胞内病原体，但尚不清楚非规范自噬和异种吞噬是否协调，以及它们是同时发生还是相继发生。在这里，我们显示了肺炎链球菌（一种侵袭性肺炎球菌病的病因）在感染的早期阶段可以触发FIP200，PI3P和ROS独立的含肺炎球菌LC3相关吞噬体（LAPosome）样液泡（PcLV），并且PcLV对于随后形成的含有杀菌肺炎球菌的自噬泡（PcAVs）必不可少。具体来说，我们确定了LC3和NDP52离域的PcLV，它们是PcLV和PcAV之间的中间产物。Atg14L，Beclin1和FIP200负责将LC3和NDP52从PcLV中脱域。从而，针对细胞内肺炎链球菌依次部署了多个非典型和典型的自噬过程。Atg16L1 WD域，p62，NDP52和poly-Ub有助于PcLV的形成。这些发现揭示了在针对细胞内细菌病原体的杀菌异种过程中以前未知的分层自噬机制，并应提高我们控制威胁生命的肺炎球菌疾病的能力。

更新日期：2020-01-13

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