title: Loss of elongation factor P disrupts bacterial outer membrane integrity.
abstract: Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits increased uptake of the hydrophobic dye 1-N-phenylnaphthylamine (NPN). Analysis of the membrane proteomes of wild-type and efp mutant Salmonella strains reveals few changes, including the prominent overexpression of a single porin, KdgM, in the efp mutant outer membrane. Removal of KdgM in the efp mutant background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious overexpression of an outer membrane porin.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: S Betty
authors.initials: SB
authors.lastname: Zou
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hersch
authors.forename: Hervé
authors.initials: H
authors.lastname: Roy
authors.forename: J Brad
authors.initials: JB
authors.lastname: Wiggers
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Leung
authors.forename: Stephen
authors.initials: S
authors.lastname: Buranyi
authors.forename: Jinglin Lucy
authors.initials: JL
authors.lastname: Xie
authors.forename: Kiley
authors.initials: K
authors.lastname: Dare
authors.forename: Michael
authors.initials: M
authors.lastname: Ibba
authors.forename: William Wiley
authors.initials: WW
authors.lastname: Navarre
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology*; D003902:Detergents; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D009154:Mutation; D009994:Osmolar Concentration; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D010957:Plasmids; D012486:Salmonella typhimurium / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003902:Detergents; D010445:Peptide Elongation Factors; C020746:factor EF-P
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6554-9
references.pmid: 18451031
references.citation: Mol Syst Biol. 2006;2:2006.0008
references.pmid: 16738554
references.citation: Mol Cell. 2010 Jul 30;39(2):209-21
references.pmid: 20670890
references.citation: Microbiol Mol Biol Rev. 2002 Sep;66(3):460-85, table of contents
references.pmid: 12209000
references.citation: J Bacteriol. 2003 Oct;185(19):5673-84
references.pmid: 13129938
references.citation: Microbiol Rev. 1993 Sep;57(3):655-82
references.pmid: 7504166
references.citation: Foodborne Pathog Dis. 2011 Jun;8(6):725-32
references.pmid: 21348575
references.citation: Proc Natl Acad Sci U S A. 1973 Mar;70(3):782-6
references.pmid: 4577135
references.citation: FEBS J. 2006 Mar;273(6):1102-14
references.pmid: 16519677
references.citation: Biochemistry. 2006 Oct 24;45(42):12639-46
references.pmid: 17042480
references.citation: Microbiology (Reading). 2009 Jan;155(Pt 1):229-237
references.pmid: 19118363
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):425-30
references.pmid: 16407165
references.citation: Biol Direct. 2010 Jan 13;5:3
references.pmid: 20070887
references.citation: Nature. 2009 May 7;459(7243):118-21
references.pmid: 19424157
references.citation: Mol Genet Genomics. 2006 Mar;275(3):264-76
references.pmid: 16408210
references.citation: Microbiol Mol Biol Rev. 2004 Sep;68(3):518-37, table of contents
references.pmid: 15353568
references.citation: Eur J Biochem. 2003 Nov;270(21):4254-63
references.pmid: 14622290
references.citation: J Biol Chem. 1988 Oct 15;263(29):14684-9
references.pmid: 3049584
references.citation: Biochem Biophys Res Commun. 2009 Mar 20;380(4):785-90
references.pmid: 19338753
references.citation: J Biochem. 2006 Feb;139(2):161-9
references.pmid: 16452303
references.citation: Virulence. 2011 Mar-Apr;2(2):147-51
references.pmid: 21317554
references.citation: Eur J Biochem. 1979 Jun;97(1):23-8
references.pmid: 383483
references.citation: Annu Rev Microbiol. 1984;38:237-64
references.pmid: 6093683
references.citation: J Biomol Screen. 2006 Oct;11(7):736-42
references.pmid: 16928980
references.citation: Science. 2009 Aug 21;325(5943):966-70
references.pmid: 19696344
references.citation: Antimicrob Agents Chemother. 1992 Apr;36(4):826-9
references.pmid: 1503445
references.citation: Mol Syst Biol. 2009;5:335
references.pmid: 20029369
references.citation: J Bacteriol. 2007 Oct;189(20):7213-22
references.pmid: 17693506
references.citation: FEBS Lett. 2010 Jul 16;584(14):3055-60
references.pmid: 20580719
references.citation: Genetics. 2002 Feb;160(2):393-405
references.pmid: 11861547
references.citation: Nat Struct Mol Biol. 2010 Sep;17(9):1136-43
references.pmid: 20729861
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
references.pmid: 10829079
references.citation: J Bacteriol. 1987 Oct;169(10):4540-6
references.pmid: 2820932
references.citation: Biol Chem. 2000 Jul;381(7):553-9
references.pmid: 10987361
references.citation: Microbiol Mol Biol Rev. 2003 Dec;67(4):593-656
references.pmid: 14665678
references.citation: Biochem J. 2004 Dec 15;384(Pt 3):585-90
references.pmid: 15303967
references.citation: Gene. 1995 May 26;158(1):9-14
references.pmid: 7789817
references.citation: Amino Acids. 2010 Feb;38(2):491-500
references.pmid: 19997760
references.citation: Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6399-403
references.pmid: 7604003
references.citation: Nat Chem Biol. 2011 Aug 14;7(10):667-9
references.pmid: 21841797
references.citation: J Bacteriol. 2006 Dec;188(23):8259-71
references.pmid: 17012394
references.citation: J Biol Chem. 1997 Dec 19;272(51):32254-9
references.pmid: 9405429
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10268-73
references.pmid: 8816789
references.citation: Science. 2006 Jul 14;313(5784):236-8
references.pmid: 16763111
references.citation: Appl Microbiol Biotechnol. 2007 Nov;77(2):489-96
references.pmid: 17896105
references.citation: J Mol Biol. 2009 Dec 11;394(4):718-31
references.pmid: 19796645
references.citation: J Bacteriol. 1992 Apr;174(8):2460-5
references.pmid: 1556066
references.citation: Infect Immun. 1998 Dec;66(12):5599-606
references.pmid: 9826331
references.citation: Antimicrob Agents Chemother. 1984 Oct;26(4):546-51
references.pmid: 6440475
references.citation: Biochim Biophys Acta. 1990 May 9;1024(1):152-8
references.pmid: 2159802
references.citation: Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6415-9
references.pmid: 21451136
references.citation: J Bacteriol. 2001 Jan;183(1):36-45
references.pmid: 11114898
references.citation: Mol Gen Genet. 1971;110(4):378-81
references.pmid: 4932889
references.citation: Proc Natl Acad Sci U S A. 1975 Nov;72(11):4257-60
references.pmid: 1105576
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9595-600
references.pmid: 15210970
references.citation: Nat Methods. 2009 May;6(5):343-5
references.pmid: 19363495
references.citation: Biochimie. 1997;79(1):7-11
references.pmid: 9195040
references.citation: Gene. 2000 Jan 4;241(1):185-91
references.pmid: 10607913
references.citation: Gene. 1991 Dec 1;108(1):163-4
references.pmid: 1761227
references.citation: J Bacteriol. 1995 Jul;177(14):4121-30
references.pmid: 7608087
references.citation: J Biol Chem. 1972 Jun 25;247(12):3962-72
references.pmid: 4555955