Abstract
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
Hyp
) 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
Hyp
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
Hyp
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.
Gobert et al. demonstrate that hypusination, a specific mechanism regulating translation, is induced in macrophages by bacteria. Hypusination is required for the translation of inducible antimicrobial effectors. Mice that specifically lack hypusination in macrophages are highly susceptible to
Helicobacter pylori
and
Citrobacter rodentium
, two pathogens of the gastrointestinal tract.