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Title: NLRX1 Negatively Regulates Group A Streptococcus Invasion and Autophagy Induction by Interacting With the Beclin 1–UVRAG Complex
Authors: Aikawa, Chihiro
Nakajima, Shintaro
Karimine, Miho
Nozawa, Takashi
Minowa-Nozawa, Atsuko
Toh, Hirotaka
Yamada, Shunsuke
Nakagawa, Ichiro
Author's alias: 相川, 知宏
中島, 慎太郎
狩峰, 美保
野澤, 孝志
野澤, 敦子
藤, 博貴
山田, 俊介
中川, 一路
Keywords: NLRX1
Beclin 1
UVRAG
bacterial invasion
autophagy
Group A Streptococcus
Issue Date: 14-Nov-2018
Publisher: Frontiers Media SA
Journal title: Frontiers in Cellular and Infection Microbiology
Volume: 8
Thesis number: 403
Abstract: Group A Streptococcus (GAS) can invade epithelial cells; however, these bacteria are targeted and eventually destroyed by autophagy. Members of the Nod-like receptor (NLR) family are thought to be critical for the autophagic response to invasive bacteria. However, the intracellular sensors within host cells that are responsible for bacterial invasion and the induction of autophagy are largely unknown. Thus, our aim was to examine the role of one such NLR, namely NLRX1, in invasion and autophagy during GAS infection. We found that GAS invasion was markedly increased in NLRX1 knockout cells. This led to the potentiation of autophagic processes such as autophagosome and autolysosome formation. NLRX1 was found to interact with Beclin 1 and UVRAG, members of Beclin1 complex, and knockout of these proteins inhibited invasion and autophagy upon GAS infection. Especially, NLRX1 interacted with Beclin 1 via its NACHT domain and this interaction was responsible for the NLRX1-mediated inhibition of invasion and autophagic processes including autophagosome and autolysosome formation during GAS infection. These findings demonstrate that NLRX1 functions as a negative regulator to inactivate the Beclin 1–UVRAG complex, which regulates invasion and autophagy during GAS infection. Thus, our study expands our knowledge of the role of NLRX1 during bacterial invasion and autophagy and could lead to further investigations to understand pathogen–host cell interactions, facilitating novel targeted therapeutics.
Rights: © 2018 Aikawa, Nakajima, Karimine, Nozawa, Minowa-Nozawa, Toh, Yamada and Nakagawa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
URI: http://hdl.handle.net/2433/242862
DOI(Published Version): 10.3389/fcimb.2018.00403
PubMed ID: 30488027
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