title: PoxA, yjeK, and elongation factor P coordinately modulate virulence and drug resistance in Salmonella enterica.
abstract: We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-beta-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, including attenuated virulence in mice, an increased ability to respire under nutrient-limiting conditions, hypersusceptibility to a variety of diverse growth inhibitors, and altered expression of multiple proteins, including several encoded on the SPI-1 pathogenicity island. PoxA mediates posttranslational modification of bacterial elongation factor P (EF-P), analogous to the modification of the eukaryotic EF-P homolog, eIF5A, with hypusine. The modification of EF-P is a mechanism of regulation whereby PoxA acts as an aminoacyl-tRNA synthetase that attaches an amino acid to a protein resembling tRNA rather than to a tRNA.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. william.navarre@utoronto.ca
authors.forename: William Wiley
authors.initials: WW
authors.lastname: Navarre
authors.forename: S Betty
authors.initials: SB
authors.lastname: Zou
authors.forename: Hervé
authors.initials: H
authors.lastname: Roy
authors.forename: Jinglin Lucy
authors.initials: JL
authors.lastname: Xie
authors.forename: Alexei
authors.initials: A
authors.lastname: Savchenko
authors.forename: Alexander
authors.initials: A
authors.lastname: Singer
authors.forename: Elena
authors.initials: E
authors.lastname: Edvokimova
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Prost
authors.forename: Runjun
authors.initials: R
authors.lastname: Kumar
authors.forename: Michael
authors.initials: M
authors.lastname: Ibba
authors.forename: Ferric C
authors.initials: FC
authors.lastname: Fang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D044404:Genomic Islands / Q000235:genetics; D008239:Lysine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D008250:Lysine-tRNA Ligase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D019779:Salmonella enterica / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010445:Peptide Elongation Factors; D037521:Virulence Factors; C020746:factor EF-P; C100028:hypusine; D008250:Lysine-tRNA Ligase; D008239:Lysine