PMID- 29981934 OWN - NLM STAT- MEDLINE DCOM- 20190411 LR - 20190411 IS - 1769-714X (Electronic) IS - 1286-4579 (Linking) VI - 21 IP - 1 DP - 2019 Jan-Feb TI - Mycobacterium tuberculosis acyl carrier protein inhibits macrophage apoptotic death by modulating the reactive oxygen species/c-Jun N-terminal kinase pathway. PG - 40-49 LID - S1286-4579(18)30144-8 [pii] LID - 10.1016/j.micinf.2018.06.005 [doi] AB - Mycobacterial acyl carrier protein (AcpM; Rv2244) is a meromycolate extension acyl carrier protein of Mycobacterium tuberculosis (Mtb), which participates in multistep mycolic acid biosynthesis. However, the function of AcpM in host-mycobacterium interactions during infection remains largely uncharacterized. Here we show that AcpM inhibits host cell apoptosis during mycobacterial infection. To examine the function of AcpM during infection, we generated a recombinant Mycobacterium smegmatis (M. smegmatis) strain overexpressing AcpM (Ms_AcpM) and a strain transformed with an empty vector (Ms_Vec). Ms_AcpM promoted intracellular survival of M. smegmatis and led to a significant decrease in the death rate of primary bone marrow-derived macrophages (BMDMs). Importantly, Ms_AcpM showed significantly decreased reactive oxygen species (ROS) generation and activation of c-Jun N-terminal kinase (JNK) signaling compared with Ms_Vec. In addition, treatment of BMDMs with recombinant AcpM significantly inhibited the apoptosis and ROS/JNK signaling induced by M. smegmatis. Moreover, recombinant AcpM enhanced intracellular survival of Mtb H37Rv. Taken together, these results indicate that AcpM plays a role as a virulence factor by modulating host cell apoptosis during mycobacterial infection. CI - Copyright (c) 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. FAU - Paik, Seungwha AU - Paik S AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, South Korea. FAU - Choi, Seunga AU - Choi S AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea. FAU - Lee, Kang-In AU - Lee KI AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea. FAU - Back, Yong Woo AU - Back YW AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, South Korea. FAU - Son, Yeo-Jin AU - Son YJ AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea. FAU - Jo, Eun-Kyeong AU - Jo EK AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, South Korea. Electronic address: hayoungj@cnu.ac.kr. FAU - Kim, Hwa-Jung AU - Kim HJ AD - Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea; Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, South Korea. Electronic address: hjukim@cnu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180705 PL - France TA - Microbes Infect JT - Microbes and infection JID - 100883508 RN - 0 (AcpM protein, Mycobacterium tuberculosis) RN - 0 (Bacterial Proteins) RN - 0 (Carrier Proteins) RN - 0 (Reactive Oxygen Species) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Apoptosis/drug effects/*genetics MH - Bacterial Proteins/genetics/*metabolism/pharmacology MH - Carrier Proteins/genetics/*metabolism/pharmacology MH - Cells, Cultured MH - Female MH - Gene Expression MH - JNK Mitogen-Activated Protein Kinases/genetics/*metabolism MH - Macrophages/metabolism/microbiology/*pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Microbial Viability/drug effects MH - Mycobacterium Infections/immunology/metabolism/microbiology MH - Mycobacterium smegmatis/genetics/physiology MH - Mycobacterium tuberculosis/*chemistry/genetics/physiology MH - RAW 264.7 Cells MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/drug effects OTO - NOTNLM OT - Acyl carrier protein OT - Apoptosis OT - Mycobacterium smegmatis OT - Mycobacterium tuberculosis OT - Reactive oxygen species OT - c-Jun N-terminal kinase EDAT- 2018/07/10 06:00 MHDA- 2019/04/12 06:00 CRDT- 2018/07/09 06:00 PHST- 2017/12/04 00:00 [received] PHST- 2018/03/25 00:00 [revised] PHST- 2018/06/25 00:00 [accepted] PHST- 2018/07/10 06:00 [pubmed] PHST- 2019/04/12 06:00 [medline] PHST- 2018/07/09 06:00 [entrez] AID - S1286-4579(18)30144-8 [pii] AID - 10.1016/j.micinf.2018.06.005 [doi] PST - ppublish SO - Microbes Infect. 2019 Jan-Feb;21(1):40-49. doi: 10.1016/j.micinf.2018.06.005. Epub 2018 Jul 5.