The QseC adrenergic signaling cascade in Enterohemorrhagic E. coli (EHEC).
The ability to respond to stress is at the core of an organism's survival. The hormones epinephrine and norepinephrine play a central role in stress responses in mammals, which require the synchronized interaction of the whole neuroendocrine system. Mammalian adrenergic receptors are G-coupled protein receptors (GPCRs); bacteria, however, sense these hormones through histidine sensor kinases (HKs). HKs autophosphorylate in response to signals and transfer this phosphate to response regulators (RRs). Two bacterial adrenergic receptors have been identified in EHEC, QseC and QseE, with QseE being downstream of QseC in this signaling cascade. Here we mapped the QseC signaling cascade in the deadly pathogen enterohemorrhagic E. coli (EHEC), which exploits this signaling system to promote disease. Through QseC, EHEC activates expression of metabolic, virulence and stress response genes, synchronizing the cell response to these stress hormones. Coordination of these responses is achieved by QseC phosphorylating three of the thirty-two EHEC RRs. The QseB RR, which is QseC's cognate RR, activates the flagella regulon which controls bacteria motility and chemotaxis. The QseF RR, which is also phosphorylated by the QseE adrenergic sensor, coordinates expression of virulence genes involved in formation of lesions in the intestinal epithelia by EHEC, and the bacterial SOS stress response. The third RR, KdpE, controls potassium uptake, osmolarity, and also the formation of lesions in the intestine. Adrenergic regulation of bacterial gene expression shares several parallels with mammalian adrenergic signaling having profound effects in the whole organism. Understanding adrenergic regulation of a bacterial cell is a powerful approach for studying the underlying mechanisms of stress and cellular survival.
Hughes
David T
DT
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Clarke
Marcie B
MB
Yamamoto
Kaneyoshi
K
Rasko
David A
DA
Sperandio
Vanessa
V
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054324:Enterohemorrhagic Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D054884:Host-Pathogen Interactions; D006801:Humans; D009154:Mutation; D009638:Norepinephrine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C455504:QseC protein, E coli; C540352:QseF protein, E coli; D015534:Trans-Activators; D037521:Virulence Factors; C075615:kdpE protein, E coli; D009638:Norepinephrine; D004837:Epinephrine
Infect Immun. 2004 Apr;72(4):2288-302
15039354
J Bacteriol. 2008 Oct;190(20):6881-93
18676672
Genes Cells. 1998 Dec;3(12):777-88
10096019
Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5889-94
19289831
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
10829079
Mol Microbiol. 2005 Oct;58(2):441-55
16194231
Annu Rev Genet. 2007;41:121-45
18076326
Infect Immun. 2005 May;73(5):2573-85
15845459
J Lab Clin Med. 1996 Oct;128(4):392-8
8833888
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8951-6
12847292
Science. 2008 Aug 22;321(5892):1078-80
18719281
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2736-41
14981238
Microbiology (Reading). 2004 Apr;150(Pt 4):877-883
15073297
Physiol Behav. 1999 Sep;67(3):359-64
10497953
Mol Microbiol. 1998 Jun;28(6):1255-67
9680214
Lancet. 1983 Dec 3;2(8362):1299-1300
6139632
J Bacteriol. 1994 Jan;176(2):269-75
8288518
Microb Pathog. 2008 Apr;44(4):271-8
17997077
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6037-42
17389372
Mol Microbiol. 1999 Jul;33(2):296-306
10411746
Life Sci. 1992;50(3):203-12
1731173
Nat Rev Microbiol. 2004 Feb;2(2):123-40
15040260
Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10420-10425
16803956
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1664-8
7878036
Am J Physiol Endocrinol Metab. 2000 Oct;279(4):E815-22
11001763
J Bacteriol. 2006 Aug;188(16):5668-81
16885435
Cell. 2008 Jun 13;133(6):1043-54
18555780
Infect Immun. 2006 Oct;74(10):5445-55
16988219
Mol Microbiol. 2002 Feb;43(3):809-21
11929534
Mol Microbiol. 1992 Jul;6(13):1777-84
1630317
J Auton Nerv Syst. 2000 Jul 3;81(1-3):87-96
10869706
Cell Microbiol. 2004 Dec;6(12):1167-83
15527496
Am J Physiol. 1998 Dec;275(6):G1367-76
9843774
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3597-602
14988506
Biochem Biophys Res Commun. 1997 Mar 27;232(3):682-6
9126336
Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7996-8000
7644527
Mol Microbiol. 2005 Sep;57(6):1734-49
16135237
Infect Immun. 2007 Oct;75(10):4875-84
17635870
J Biol Chem. 1995 Nov 10;270(45):26849-56
7592927
J Biol Chem. 2005 Jan 14;280(2):1448-56
15522865
Annu Rev Biochem. 2000;69:183-215
10966457
Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14941-6
16990433
J Bacteriol. 2007 Mar;189(6):2468-76
17220220
Dev Cell. 2004 Aug;7(2):217-28
15296718
Nat Rev Microbiol. 2008 Feb;6(2):111-20
18197168
Mol Microbiol. 2004 Mar;51(5):1233-49
14982621