title: The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity.
abstract: The Cpx envelope stress response mediates adaptation to stresses that cause envelope protein misfolding. Adaptation is partly conferred through increased expression of protein folding and degradation factors. The Cpx response also plays a conserved role in the regulation of virulence determinant expression and impacts antibiotic resistance. We sought to identify adaptive mechanisms that may be involved in these important functions by characterizing changes in the transcriptome of two different Escherichia coli strains when the Cpx response is induced. We show that, while there is considerable strain- and condition-specific variability in the Cpx response, the regulon is enriched for proteins and functions that are inner membrane associated under all conditions. Genes that were changed by Cpx pathway induction under all conditions were involved in a number of cellular functions and included several intergenic regions, suggesting that posttranscriptional regulation is important during Cpx-mediated adaptation. Some Cpx-regulated genes are centrally involved in energetics and play a role in antibiotic resistance. We show that a number of small, uncharacterized envelope proteins are Cpx regulated and at least two of these affect phenotypes associated with membrane integrity. Altogether, our work suggests new mechanisms of Cpx-mediated envelope stress adaptation and antibiotic resistance.
authors.affiliation: Centennial Centre for Interdisciplinary Science, Department of Biological Sciences, Faculty of Science, University of Alberta, Edmonton, AB, Canada. traivio@ualberta.ca
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Raivio
authors.forename: Shannon K D
authors.initials: SK
authors.lastname: Leblanc
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Price
mesh_terms: D002462:Cell Membrane / Q000502:physiology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D013312:Stress, Physiological; D059467:Transcriptome
chemical_list: D029968:Escherichia coli Proteins
references.citation: Science. 2009 Aug 7;325(5941):753-6
references.pmid: 19661432
references.citation: J Mol Biol. 1976 Jul 5;104(3):541-55
references.pmid: 781293
references.citation: J Bacteriol. 2005 Mar;187(5):1763-72
references.pmid: 15716448
references.citation: Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2287-92
references.pmid: 11830644
references.citation: Mol Microbiol. 2006 Jan;59(1):231-47
references.pmid: 16359331
references.citation: Mol Microbiol. 2008 Oct;70(1):236-57
references.pmid: 18713317
references.citation: Cell. 2007 Sep 7;130(5):797-810
references.pmid: 17803904
references.citation: J Bacteriol. 1991 Jul;173(13):4039-48
references.pmid: 1648075
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19462-7
references.pmid: 19052235
references.citation: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2657-61
references.pmid: 2181444
references.citation: J Biol Chem. 2011 Sep 16;286(37):32464-74
references.pmid: 21778229
references.citation: J Biol Chem. 1976 Jan 25;251(2):414-23
references.pmid: 1391
references.citation: FEMS Microbiol Rev. 2005 Jan;29(1):83-98
references.pmid: 15652977
references.citation: J Bacteriol. 2010 Jan;192(1):46-58
references.pmid: 19734316
references.citation: Proc Natl Acad Sci U S A. 1980 Jan;77(1):513-7
references.pmid: 6102380
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17775-9
references.pmid: 16303867
references.citation: J Bacteriol. 2013 May;195(9):1869-74
references.pmid: 23335416
references.citation: Cell. 1991 Nov 1;67(3):581-9
references.pmid: 1934062
references.citation: Mol Microbiol. 2009 Jun;72(6):1408-22
references.pmid: 19432797
references.citation: Eur J Biochem. 1977 Jan;72(2):341-52
references.pmid: 319999
references.citation: Curr Opin Microbiol. 2008 Dec;11(6):535-40
references.pmid: 18983936
references.citation: Infect Immun. 2008 Apr;76(4):1465-75
references.pmid: 18227171
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: J Bacteriol. 2005 Oct;187(19):6622-30
references.pmid: 16166523
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16696-701
references.pmid: 23010927
references.citation: Mol Cell. 2009 Dec 11;36(5):845-60
references.pmid: 20005847
references.citation: Biosci Biotechnol Biochem. 2006 Jul;70(7):1688-95
references.pmid: 16861804
references.citation: Mol Microbiol. 2002 Sep;45(6):1599-611
references.pmid: 12354228
references.citation: Proc R Soc Med. 1970 Dec;63(12):1297-301
references.pmid: 4923353
references.citation: Mol Syst Biol. 2006;2:2006.0008
references.pmid: 16738554
references.citation: Nat Struct Mol Biol. 2011 Mar;18(3):262-9
references.pmid: 21317898
references.citation: J Bacteriol. 1998 Feb;180(4):831-9
references.pmid: 9473036
references.citation: Genes Dev. 1997 May 1;11(9):1169-82
references.pmid: 9159398
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12147-52
references.pmid: 22778419
references.citation: PLoS Genet. 2009 Sep;5(9):e1000651
references.pmid: 19763168
references.citation: Nucleic Acids Res. 2003 Feb 15;31(4):e15
references.pmid: 12582260
references.citation: Infect Immun. 1997 Jul;65(7):2606-12
references.pmid: 9199427
references.citation: J Biol Chem. 2002 Jul 19;277(29):26652-61
references.pmid: 11953442
references.citation: J Bacteriol. 2003 Apr;185(8):2432-40
references.pmid: 12670966
references.citation: Genes Dev. 1997 May 1;11(9):1183-93
references.pmid: 9159399
references.citation: Cold Spring Harb Symp Quant Biol. 2001;66:509-14
references.pmid: 12762053
references.citation: Science. 2011 Nov 18;334(6058):986-90
references.pmid: 22096201
references.citation: Mol Microbiol. 2012 May;84(3):414-27
references.pmid: 22324810
references.citation: J Bacteriol. 2009 Mar;191(6):1798-815
references.pmid: 19103922
references.citation: J Bacteriol. 2005 Aug;187(16):5723-31
references.pmid: 16077119
references.citation: Infect Immun. 2007 Sep;75(9):4386-99
references.pmid: 17620356
references.citation: Gene. 1987;53(1):85-96
references.pmid: 3596251
references.citation: J Bacteriol. 2008 Jul;190(13):4782-5
references.pmid: 18456808
references.citation: Genes Genet Syst. 1999 Aug;74(4):179-83
references.pmid: 10650844
references.citation: Bacteriol Rev. 1972 Dec;36(4):525-57
references.pmid: 4568763
references.citation: Genome Biol. 2003;4(5):P3
references.pmid: 12734009
references.citation: Adv Exp Med Biol. 2008;631:80-110
references.pmid: 18792683
references.citation: DNA Res. 2005;12(5):291-9
references.pmid: 16769691
references.citation: Genes Cells. 2000 Dec;5(12):965-74
references.pmid: 11168583
references.citation: J Biol Chem. 2011 Mar 18;286(11):9805-14
references.pmid: 21239493
references.citation: Curr Opin Microbiol. 2005 Apr;8(2):122-6
references.pmid: 15802241
references.citation: Biochem Biophys Res Commun. 2004 Jul 23;320(2):354-8
references.pmid: 15219834
references.citation: J Infect Dis. 1985 Sep;152(3):550-9
references.pmid: 2863318
references.citation: J Bacteriol. 2005 Mar;187(6):2038-49
references.pmid: 15743952
references.citation: J Biotechnol. 2008 Jan 20;133(2):196-200
references.pmid: 17884222
references.citation: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12345-9
references.pmid: 10535924
references.citation: J Bacteriol. 1997 Dec;179(24):7724-33
references.pmid: 9401031
references.citation: J Bacteriol. 1980 Oct;144(1):60-7
references.pmid: 6998969
references.citation: PLoS Biol. 2006 Jan;4(1):e2
references.pmid: 16336047
references.citation: J Bacteriol. 2009 Jan;191(2):461-76
references.pmid: 18978044
references.citation: J Bacteriol. 1999 Nov;181(21):6772-8
references.pmid: 10542180
references.citation: Genes Dev. 1995 Feb 15;9(4):387-98
references.pmid: 7883164
references.citation: Science. 2011 Nov 25;334(6059):1081-6
references.pmid: 22116877
references.citation: J Bacteriol. 1999 Sep;181(17):5263-72
references.pmid: 10464196
references.citation: Mol Microbiol. 2010 Jun 1;76(5):1095-110
references.pmid: 20444097
references.citation: Infect Immun. 2004 Aug;72(8):4654-61
references.pmid: 15271926
references.citation: J Mol Biol. 2002 Aug 9;321(2):185-99
references.pmid: 12144778
references.citation: Infect Immun. 2007 Aug;75(8):3913-24
references.pmid: 17517869
references.citation: J Biol Chem. 2007 Mar 23;282(12):8583-93
references.pmid: 17259177
references.citation: Res Microbiol. 2012 Sep-Oct;163(8):518-30
references.pmid: 22842077
references.citation: Mol Microbiol. 2004 Feb;51(3):659-74
references.pmid: 14731270
references.citation: Mol Microbiol. 2008 Feb;67(3):516-27
references.pmid: 18069965
references.citation: Genes Cells. 2004 Apr;9(4):271-8
references.pmid: 15066119
references.citation: Mol Microbiol. 2000 Sep;37(5):1186-97
references.pmid: 10972835
references.citation: Infect Immun. 2012 May;80(5):1766-72
references.pmid: 22331433
references.citation: Mol Microbiol. 1995 Nov;18(3):491-505
references.pmid: 8748033
references.citation: J Bacteriol. 2006 Oct;188(20):7165-75
references.pmid: 17015655
references.citation: Bioinformatics. 2003 Jan 22;19(2):185-93
references.pmid: 12538238
references.citation: Microbiology (Reading). 2005 Jun;151(Pt 6):1779-1788
references.pmid: 15941987
references.citation: Infect Immun. 1999 Apr;67(4):1560-8
references.pmid: 10084987
references.citation: J Bacteriol. 1995 Aug;177(15):4216-23
references.pmid: 7635808
references.citation: Biochem Biophys Res Commun. 1995 Sep 14;214(2):410-7
references.pmid: 7677746
references.citation: Mol Microbiol. 2005 Feb;55(4):1113-26
references.pmid: 15686558
references.citation: Nucleic Acids Res. 1988 Feb 25;16(4):1617
references.pmid: 3279397
references.citation: FEMS Microbiol Lett. 1999 Sep 1;178(1):169-75
references.pmid: 10483736
references.citation: J Bacteriol. 1994 Dec;176(23):7345-51
references.pmid: 7961507
references.citation: Mol Microbiol. 1995 May;16(4):761-8
references.pmid: 7476170