Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy

Tianliang Li; Ligang Kong; Xinghui Li; Sijin Wu; Kuldeep S. Attri; Yan Li; Weipeng Gong; Bao Zhao; Lupeng Li; Laura E. Herring; John M. Asara; Lei Xu; Xiaobo Luo; Yu L. Lei; Qin Ma; Stephanie Seveau; John S. Gunn; Xiaolin Cheng; Pankaj K. Singh; Douglas R. Green; Haibo Wang; Haitao Wen

doi:10.1038/s41564-020-00843-2

Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy

Tianliang Li, Ligang Kong, Xinghui Li, Sijin Wu, Kuldeep S. Attri, Yan Li, Weipeng Gong, Bao Zhao, Lupeng Li, Laura E. Herring, John M. Asara, Lei Xu, Xiaobo Luo, Yu L. Lei, Qin Ma, Stephanie Seveau, John S. Gunn, Xiaolin Cheng, Pankaj K. Singh, Douglas R. GreenHaibo Wang^*, Haitao Wen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

40 Citations (Scopus)

Abstract

Mitochondria are believed to have originated ~2.5 billion years ago. As well as energy generation in cells, mitochondria have a role in defence against bacterial pathogens. Despite profound changes in mitochondrial morphology and functions following bacterial challenge, whether intracellular bacteria can hijack mitochondria to promote their survival remains elusive. We report that Listeria monocytogenes—an intracellular bacterial pathogen—suppresses LC3-associated phagocytosis (LAP) by modulation of mitochondrial Ca²⁺ (mtCa²⁺) signalling in order to survive inside cells. Invasion of macrophages by L. monocytogenes induced mtCa²⁺ uptake through the mtCa²⁺ uniporter (MCU), which in turn increased acetyl-coenzyme A (acetyl-CoA) production by pyruvate dehydrogenase. Acetylation of the LAP effector Rubicon with acetyl-CoA decreased LAP formation. Genetic ablation of MCU attenuated intracellular bacterial growth due to increased LAP formation. Our data show that modulation of mtCa²⁺ signalling can increase bacterial survival inside cells, and highlight the importance of mitochondrial metabolism in host–microbial interactions.

Original language	English
Pages (from-to)	366-379
Number of pages	14
Journal	Nature Microbiology
Volume	6
Issue number	3
DOIs	https://doi.org/10.1038/s41564-020-00843-2
Publication status	Published - Mar 2021
Externally published	Yes

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Li, T., Kong, L., Li, X., Wu, S., Attri, K. S., Li, Y., Gong, W., Zhao, B., Li, L., Herring, L. E., Asara, J. M., Xu, L., Luo, X., Lei, Y. L., Ma, Q., Seveau, S., Gunn, J. S., Cheng, X., Singh, P. K., ... Wen, H. (2021). Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy. Nature Microbiology, 6(3), 366-379. https://doi.org/10.1038/s41564-020-00843-2

@article{ecd6cd20ddda472e99076cd835469dd7,

title = "Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy",

abstract = "Mitochondria are believed to have originated ~2.5 billion years ago. As well as energy generation in cells, mitochondria have a role in defence against bacterial pathogens. Despite profound changes in mitochondrial morphology and functions following bacterial challenge, whether intracellular bacteria can hijack mitochondria to promote their survival remains elusive. We report that Listeria monocytogenes—an intracellular bacterial pathogen—suppresses LC3-associated phagocytosis (LAP) by modulation of mitochondrial Ca2+ (mtCa2+) signalling in order to survive inside cells. Invasion of macrophages by L. monocytogenes induced mtCa2+ uptake through the mtCa2+ uniporter (MCU), which in turn increased acetyl-coenzyme A (acetyl-CoA) production by pyruvate dehydrogenase. Acetylation of the LAP effector Rubicon with acetyl-CoA decreased LAP formation. Genetic ablation of MCU attenuated intracellular bacterial growth due to increased LAP formation. Our data show that modulation of mtCa2+ signalling can increase bacterial survival inside cells, and highlight the importance of mitochondrial metabolism in host–microbial interactions.",

author = "Tianliang Li and Ligang Kong and Xinghui Li and Sijin Wu and Attri, {Kuldeep S.} and Yan Li and Weipeng Gong and Bao Zhao and Lupeng Li and Herring, {Laura E.} and Asara, {John M.} and Lei Xu and Xiaobo Luo and Lei, {Yu L.} and Qin Ma and Stephanie Seveau and Gunn, {John S.} and Xiaolin Cheng and Singh, {Pankaj K.} and Green, {Douglas R.} and Haibo Wang and Haitao Wen",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = mar,

doi = "10.1038/s41564-020-00843-2",

language = "English",

volume = "6",

pages = "366--379",

journal = "Nature Microbiology",

issn = "2058-5276",

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Li, T, Kong, L, Li, X, Wu, S, Attri, KS, Li, Y, Gong, W, Zhao, B, Li, L, Herring, LE, Asara, JM, Xu, L, Luo, X, Lei, YL, Ma, Q, Seveau, S, Gunn, JS, Cheng, X, Singh, PK, Green, DR, Wang, H & Wen, H 2021, 'Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy', Nature Microbiology, vol. 6, no. 3, pp. 366-379. https://doi.org/10.1038/s41564-020-00843-2

TY - JOUR

T1 - Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy

AU - Li, Tianliang

AU - Kong, Ligang

AU - Li, Xinghui

AU - Wu, Sijin

AU - Attri, Kuldeep S.

AU - Li, Yan

AU - Gong, Weipeng

AU - Zhao, Bao

AU - Li, Lupeng

AU - Herring, Laura E.

AU - Asara, John M.

AU - Xu, Lei

AU - Luo, Xiaobo

AU - Lei, Yu L.

AU - Ma, Qin

AU - Seveau, Stephanie

AU - Gunn, John S.

AU - Cheng, Xiaolin

AU - Singh, Pankaj K.

AU - Green, Douglas R.

AU - Wang, Haibo

AU - Wen, Haitao

PY - 2021/3

Y1 - 2021/3

N2 - Mitochondria are believed to have originated ~2.5 billion years ago. As well as energy generation in cells, mitochondria have a role in defence against bacterial pathogens. Despite profound changes in mitochondrial morphology and functions following bacterial challenge, whether intracellular bacteria can hijack mitochondria to promote their survival remains elusive. We report that Listeria monocytogenes—an intracellular bacterial pathogen—suppresses LC3-associated phagocytosis (LAP) by modulation of mitochondrial Ca2+ (mtCa2+) signalling in order to survive inside cells. Invasion of macrophages by L. monocytogenes induced mtCa2+ uptake through the mtCa2+ uniporter (MCU), which in turn increased acetyl-coenzyme A (acetyl-CoA) production by pyruvate dehydrogenase. Acetylation of the LAP effector Rubicon with acetyl-CoA decreased LAP formation. Genetic ablation of MCU attenuated intracellular bacterial growth due to increased LAP formation. Our data show that modulation of mtCa2+ signalling can increase bacterial survival inside cells, and highlight the importance of mitochondrial metabolism in host–microbial interactions.

AB - Mitochondria are believed to have originated ~2.5 billion years ago. As well as energy generation in cells, mitochondria have a role in defence against bacterial pathogens. Despite profound changes in mitochondrial morphology and functions following bacterial challenge, whether intracellular bacteria can hijack mitochondria to promote their survival remains elusive. We report that Listeria monocytogenes—an intracellular bacterial pathogen—suppresses LC3-associated phagocytosis (LAP) by modulation of mitochondrial Ca2+ (mtCa2+) signalling in order to survive inside cells. Invasion of macrophages by L. monocytogenes induced mtCa2+ uptake through the mtCa2+ uniporter (MCU), which in turn increased acetyl-coenzyme A (acetyl-CoA) production by pyruvate dehydrogenase. Acetylation of the LAP effector Rubicon with acetyl-CoA decreased LAP formation. Genetic ablation of MCU attenuated intracellular bacterial growth due to increased LAP formation. Our data show that modulation of mtCa2+ signalling can increase bacterial survival inside cells, and highlight the importance of mitochondrial metabolism in host–microbial interactions.

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U2 - 10.1038/s41564-020-00843-2

DO - 10.1038/s41564-020-00843-2

M3 - Article

C2 - 33462436

AN - SCOPUS:85099343822

SN - 2058-5276

VL - 6

SP - 366

EP - 379

JO - Nature Microbiology

JF - Nature Microbiology

IS - 3

ER -

Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy

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