PMID- 38282619
OWN - NLM
STAT- MEDLINE
DCOM- 20240130
LR  - 20240301
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 13
DP  - 2023
TI  - Lysosomal trafficking regulator restricts intracellular growth of Coxiella 
      burnetii by inhibiting the expansion of Coxiella-containing vacuole and 
      upregulating nos2 expression.
PG  - 1336600
LID - 10.3389/fcimb.2023.1336600 [doi]
LID - 1336600
AB  - Coxiella burnetii is an obligate intracellular bacterium that causes Q fever, a 
      zoonotic disease typically manifests as a severe flu-illness. After invading into 
      the host cells, C. burnetii delivers effectors to regulate the vesicle 
      trafficking and fusion events to form a large and mature Coxiella-containing 
      vacuole (CCV), providing sufficient space and nutrition for its intracellular 
      growth and proliferation. Lysosomal trafficking regulator (LYST) is a member of 
      the Beige and Chediak-Higashi syndrome (BEACH) family, which regulates the 
      transport of vesicles to lysosomes and regulates TLR signaling pathway, but the 
      effect of LYST on C. burnetii infection is unclear. In this study, a series of 
      experiments has been conducted to investigate the influence of LYST on 
      intracellular growth of C. burnetii. Our results showed that lyst transcription 
      was up-regulated in the host cells after C. burnetii infection, but there is no 
      significant change in lyst expression level after infection with the Dot/Icm type 
      IV secretion system (T4SS) mutant strain, while CCVs expansion and significantly 
      increasing load of C. burnetii appeared in the host cells with a silenced lyst 
      gene, suggesting LYST inhibits the intracellular proliferation of C. burnetii by 
      reducing CCVs size. Then, the size of CCVs and the load of C. burnetii in the 
      HeLa cells pretreated with E-64d were significantly decreased. In addition, the 
      level of iNOS was decreased significantly in LYST knockout THP-1 cells, which was 
      conducive to the intracellular replication of C. burnetii. This data is 
      consistent with the phenotype of L-NMMA-treated THP-1 cells infected with C. 
      burnetii. Our results revealed that the upregulation of lyst transcription after 
      infection is due to effector secretion of C. burnetii and LYST inhibit the 
      intracellular replication of C. burnetii by reducing the size of CCVs and 
      inducing nos2 expression.
CI  - Copyright (c) 2024 Wan, Zhang, Zhao, OuYang, Yu, Xiong, Zhao and Jiao.
FAU - Wan, Weiqiang
AU  - Wan W
AD  - College of Life Sciences, Southwest Forestry University, Kunming, China.
AD  - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of 
      Microbiology and Epidemiology, Beijing, China.
FAU - Zhang, Shan
AU  - Zhang S
AD  - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of 
      Microbiology and Epidemiology, Beijing, China.
FAU - Zhao, Mingliang
AU  - Zhao M
AD  - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of 
      Microbiology and Epidemiology, Beijing, China.
FAU - OuYang, Xuan
AU  - OuYang X
AD  - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of 
      Microbiology and Epidemiology, Beijing, China.
FAU - Yu, Yonghui
AU  - Yu Y
AD  - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of 
      Microbiology and Epidemiology, Beijing, China.
FAU - Xiong, Xiaolu
AU  - Xiong X
AD  - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of 
      Microbiology and Epidemiology, Beijing, China.
FAU - Zhao, Ning
AU  - Zhao N
AD  - College of Life Sciences, Southwest Forestry University, Kunming, China.
FAU - Jiao, Jun
AU  - Jiao J
AD  - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of 
      Microbiology and Epidemiology, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240111
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (LYST protein, human)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - 0 (Vesicular Transport Proteins)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Humans
MH  - *Coxiella burnetii/pathogenicity
MH  - HeLa Cells
MH  - Host-Pathogen Interactions/genetics
MH  - Lysosomes/metabolism
MH  - *Q Fever/microbiology
MH  - Vacuoles/microbiology
MH  - THP-1 Cells
MH  - *Vesicular Transport Proteins/genetics
MH  - Nitric Oxide Synthase Type II/metabolism
PMC - PMC10812120
OTO - NOTNLM
OT  - Coxiella burnetii
OT  - Coxiella-containing vacuole
OT  - Dot/Icm type IV secretion system
OT  - inducible nitric oxide synthase
OT  - lysosomal trafficking regulator
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/01/29 06:44
MHDA- 2024/01/30 12:43
PMCR- 2023/01/01
CRDT- 2024/01/29 04:04
PHST- 2023/11/11 00:00 [received]
PHST- 2023/12/26 00:00 [accepted]
PHST- 2024/01/30 12:43 [medline]
PHST- 2024/01/29 06:44 [pubmed]
PHST- 2024/01/29 04:04 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2023.1336600 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2024 Jan 11;13:1336600. doi: 
      10.3389/fcimb.2023.1336600. eCollection 2023.