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Series GSE267063 Query DataSets for GSE267063
Status Public on May 08, 2024
Title Genome-wide screening of Mycobacterium tuberculosis-infected macrophages identified the GID/CTLH complex as a determinant of intracellular bacterial growth
Organisms Mycobacterium tuberculosis; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The eukaryotic GID/CTLH complex is a highly conserved E3 ubiquitin ligase involved in a broad range of biological processes. However, a role of this complex in host antimicrobial defenses has not been described. We exploited Mycobacterium tuberculosis (Mtb) induced cytotoxicity in macrophages in a FACS based CRISPR genetic screen to identify host determinants of intracellular Mtb growth restriction. Our screen identified 5 (GID8, YPEL5, WDR26, UBE2H, MAEA) of the 10 predicted members of the GID/CTLH complex as determinants of intracellular growth of both Mtb and Salmonella serovar Typhimurium. We show that the antimicrobial properties of the GID/CTLH complex knockdown macrophages are mediated by enhanced GABAergic signaling, activated AMPK, increased autophagic flux and resistance to cell death. Meanwhile, Mtb isolated from GID/CTLH knockdown macrophages are nutritionally starved and oxidatively stressed. Our study identifies the GID/CTLH complex activity as broadly suppressive of host antimicrobial responses against intracellular bacterial infections.
 
Overall design Analysis of the transcriptional profile of both the host and Mtb in Mtb infected GID/CTLH knockdown macrophages (Scramble (SC), GID8, WDR26 and MAEA)
 
Contributor(s) Simwela NV, Johnston L, Bita P, Altier C, Sassetti CM, Russell DG
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Submission date May 08, 2024
Last update date May 08, 2024
Contact name Nelson Victor Simwela
E-mail(s) nvs23@cornell.edu
Phone 6072619389
Organization name Cornell University
Department Microbiology and Immunology
Street address 930 Campus Rd
City Ithaca
State/province NY
ZIP/Postal code 14853
Country USA
 
Platforms (1)
GPL34461 Illumina NovaSeq 6000 (Mus musculus; Mycobacterium tuberculosis)
Samples (12)
GSM8259157 Mtb infected Scramble sgRNA macrophages 4 days post infection_1
GSM8259158 Mtb infected Scramble sgRNA macrophages 4 days post infection_2
GSM8259159 Mtb infected Scramble sgRNA macrophages 4 days post infection_3
Relations
BioProject PRJNA1109426

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE267063_GID_CTLH_norm_counts_Mouse.txt.gz 1.2 Mb (ftp)(http) TXT
GSE267063_GID_CTLH_norm_counts_Mtb.txt.gz 201.0 Kb (ftp)(http) TXT
GSE267063_GID_CTLH_raw_counts_Mouse.txt.gz 527.4 Kb (ftp)(http) TXT
GSE267063_GID_CTLH_raw_counts_Mtb.txt.gz 73.8 Kb (ftp)(http) TXT
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Raw data are available in SRA

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