PMID- 37961430
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
DP  - 2023 Oct 31
TI  - Legionella pneumophila exploits the endo-lysosomal network for phagosome 
      biogenesis by co-opting SUMOylated Rab7.
LID - 2023.10.31.564884 [pii]
LID - 10.1101/2023.10.31.564884 [doi]
AB  - L. pneumophila strains harboring wild-type rpsL such as Lp02rpsL(WT) cannot 
      replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of 
      extensive lysosome damage and apoptosis. The mechanism of this unique 
      infection-induced cell death remains unknown. Using a genome-wide CRISPR/Cas9 
      screening, we identified Hmg20a and Nol9 as host factors important for 
      restricting strain Lp02rpsL(WT) in BMDMs. Depletion of Hmg20a protects 
      macrophages from infection-induced lysosomal damage and apoptosis, allowing 
      productive bacterial replication. The restriction imposed by Hmg20a was mediated 
      by repressing the expression of several endo-lysosomal proteins, including the 
      small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial 
      phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif 
      (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain 
      Lp02rpsL(WT) in BMDMs. Our results establish that L. pneumophila exploits the 
      lysosomal network for the biogenesis of its phagosome in BMDMs.
FAU - Li, Chuang
AU  - Li C
AD  - Purdue Institute of Inflammation, Immunology and Infectious Disease, Department 
      of Biological Sciences, Purdue University, West Lafayette, IN 47906, USA.
FAU - Fu, Jiaqi
AU  - Fu J
AD  - Purdue Institute of Inflammation, Immunology and Infectious Disease, Department 
      of Biological Sciences, Purdue University, West Lafayette, IN 47906, USA.
FAU - Shao, Shuai
AU  - Shao S
AD  - College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
AD  - Department of Biomedical Informatics, College of Medicine, The Ohio State 
      University, Columbus, OH 43210, USA.
FAU - Luo, Zhao-Qing
AU  - Luo ZQ
AUID- ORCID: 0000-0001-8890-6621
AD  - Purdue Institute of Inflammation, Immunology and Infectious Disease, Department 
      of Biological Sciences, Purdue University, West Lafayette, IN 47906, USA.
AD  - Lead Contact.
LA  - eng
GR  - R01 AI127465/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20231031
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10634985
OTO - NOTNLM
OT  - CRISPR/Cas9
OT  - Caspases
OT  - Hmg20a
OT  - Lysosomes
OT  - Rab GTPase
OT  - SUMOylation
OT  - effectors
OT  - macrophages
COIS- DECLARATION OF INTERESTS The authors declare no competing interests.
EDAT- 2023/11/14 06:43
MHDA- 2023/11/14 06:44
PMCR- 2023/11/09
CRDT- 2023/11/14 03:57
PHST- 2023/11/14 06:43 [pubmed]
PHST- 2023/11/14 06:44 [medline]
PHST- 2023/11/14 03:57 [entrez]
PHST- 2023/11/09 00:00 [pmc-release]
AID - 2023.10.31.564884 [pii]
AID - 10.1101/2023.10.31.564884 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Oct 31:2023.10.31.564884. doi: 
      10.1101/2023.10.31.564884.