Genome-wide screen of Mycobacterium tuberculosis-infected macrophages revealed GID/CTLH complex-mediated modulation of bacterial growth

Nelson V. Simwela, Luana Johnston, Paulina Pavinski Bitar, Eleni Jaecklein, Craig Altier, Christopher M. Sassetti and David G. Russell ()
Additional contact information
Nelson V. Simwela: Cornell University
Luana Johnston: Cornell University
Paulina Pavinski Bitar: Cornell University
Eleni Jaecklein: UMass Chan Medical School
Craig Altier: Cornell University
Christopher M. Sassetti: UMass Chan Medical School
David G. Russell: Cornell University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract The eukaryotic Glucose Induced Degradation/C-Terminal to LisH (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 anti-microbial 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 12 predicted members of the GID/CTLH complex as determinants of intracellular growth of both Mtb and Salmonella serovar Typhimurium. We show that the anti-microbial properties of the GID/CTLH complex knockout macrophages are mediated by enhanced GABAergic signaling, activated AMPK, increased autophagic flux and resistance to Mtb induced necrotic cell death. Meanwhile, Mtb isolated from GID/CTLH knockout macrophages are nutritionally starved and oxidatively stressed. Our study identifies the GID/CTLH complex activity as broadly suppressive of host anti-microbial responses against intracellular bacterial infections.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53637-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53637-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53637-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().