Keith Wilson
Faculty Member
Last active: 3/17/2021

Hypusination Orchestrates the Antimicrobial Response of Macrophages.

Gobert AP, Finley JL, Latour YL, Asim M, Smith TM, Verriere TG, Barry DP, Allaman MM, Delagado AG, Rose KL, Calcutt MW, Schey KL, Sierra JC, Piazuelo MB, Mirmira RG, Wilson KT
Cell Rep. 2020 33 (11): 108510

PMID: 33326776 · PMCID: PMC7812972 · DOI:10.1016/j.celrep.2020.108510

Innate responses of myeloid cells defend against pathogenic bacteria via inducible effectors. Deoxyhypusine synthase (DHPS) catalyzes the transfer of the N-moiety of spermidine to the lysine-50 residue of eukaryotic translation initiation factor 5A (EIF5A) to form the amino acid hypusine. Hypusinated EIF5A (EIF5A) transports specific mRNAs to ribosomes for translation. We show that DHPS is induced in macrophages by two gastrointestinal pathogens, Helicobacter pylori and Citrobacter rodentium, resulting in enhanced hypusination of EIF5A. EIF5A was also increased in gastric macrophages from patients with H. pylori gastritis. Furthermore, we identify the bacteria-induced immune effectors regulated by hypusination. This set of proteins includes essential constituents of antimicrobial response and autophagy. Mice with myeloid cell-specific deletion of Dhps exhibit reduced EIF5A in macrophages and increased bacterial burden and inflammation. Thus, regulation of translation through hypusination is a critical hallmark of the defense of eukaryotic hosts against pathogenic bacteria.

Published by Elsevier Inc.

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