Inflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection.
Uropathogenic E. coli (UPEC) is the dominant cause of urinary tract infections, clinically described as cystitis. UPEC express CUP pili, which are extracellular fibers tipped with adhesins that bind mucosal surfaces of the urinary tract. Here we identify the role of the F9/Yde/Fml pilus for UPEC persistence in the inflamed urothelium. The Fml adhesin FmlH binds galactose β1-3 N-acetylgalactosamine found in core-1 and -2 O-glycans. Deletion of fmlH had no effect on UPEC virulence in an acute mouse model of cystitis. However, FmlH provided a fitness advantage during chronic cystitis, which is manifested as persistent bacteriuria, high bladder bacterial burdens, and chronic inflammation. In situ binding confirmed that FmlH bound avidly to the inflamed, but not the naive bladder. In accordance with its pathogenic profile, vaccination with FmlH significantly protected mice from chronic cystitis. Thus, UPEC employ separate CUP pili to adapt to the rapidly changing niche during bladder infection.
Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Matt S
MS
Conover
Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
Ségolène
S
Ruer
Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
Joemar
J
Taganna
Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Vasilios
V
Kalas
Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
Henri
H
De Greve
Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jerome S
JS
Pinkner
Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Karen W
KW
Dodson
Structural and Molecular Microbiology, Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. Electronic address: han.remaut@vib-vub.be.
Han
H
Remaut
Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: hultgren@wusm.wustl.edu.
Scott J
SJ
Hultgren
D018830:Adhesins, Escherichia coli / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D003556:Cystitis / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000382:microbiology* / Q000517:prevention & control; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000276:immunology; D017353:Gene Deletion; D005936:Glucans / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D056689:Uropathogenic Escherichia coli / Q000254:growth & development / Q000502:physiology*; D014774:Virulence
D018830:Adhesins, Escherichia coli; D022361:Escherichia coli Vaccines; D005936:Glucans; D011956:Receptors, Cell Surface
Nucleic Acids Res. 2015 Jul 27;43(13):e83
25800749
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9630-5
8790381
Kidney Int. 2004 Mar;65(3):791-7
14871399
Urol Int. 1996;56(2):90-5
8659017
Microbiol Mol Biol Rev. 2007 Dec;71(4):551-75
18063717
Science. 2003 Jul 4;301(5629):105-7
12843396
Sci Transl Med. 2011 Nov 16;3(109):109ra115
22089451
Infect Immun. 2007 Jan;75(1):52-60
17074856
J Urol. 2011 Dec;186(6):2359-64
22019034
Biochim Biophys Acta. 2014 Sep;1840(9):2783-93
24797039
Ann Epidemiol. 2000 Nov;10(8):509-15
11118930
PLoS One. 2013;8(1):e52835
23382825
EBioMedicine. 2014 Oct 24;1(1):46-57
26125048
J Infect Dis. 2009 Aug 15;200(4):528-36
19586416
Arch Dermatol Res. 1996 Feb;288(2):63-7
8932582
J Infect Dis. 2000 Feb;181(2):774-8
10669375
Infect Immun. 1998 Jun;66(6):2798-802
9596750
PLoS One. 2014 Mar 26;9(3):e93177
24671091
Int J Antimicrob Agents. 2002 Jun;19(6):539-45
12135845
PLoS Pathog. 2007 Jul;3(7):e100
17630833
J Infect Dis. 2001 Mar 1;183 Suppl 1:S84-6
11171023
FEMS Microbiol Rev. 2012 May;36(3):616-48
22404313
J Natl Cancer Inst. 1977 Jul;59(1):221-6
327080
J Urol. 1990 Feb;143(2):330-2
2405189
Carbohydr Res. 1986 Aug 15;151:391-402
3768900
Pathog Dis. 2013 Aug;68(3):78-81
23733378
Cell. 2015 Jun 4;161(6):1306-19
26027738
Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19884-9
17172451
Rev Infect Dis. 1991 Jan-Feb;13(1):77-84
2017637
Infect Immun. 1985 Nov;50(2):370-7
2865209
Infect Immun. 1987 Feb;55(2):472-6
3542836
Microbiol Spectr. 2015 Oct;3(5):
26542042
Eur J Clin Microbiol Infect Dis. 2012 Aug;31(8):1699-704
22052606
PLoS One. 2008 Apr 30;3(4):e2040
18446213
Angew Chem Int Ed Engl. 2011 Feb 18;50(8):1770-91
21259410
Am J Med. 2002 Jul 8;113 Suppl 1A:1S-4S
12113865
Science. 1998 Nov 20;282(5393):1494-7
9822381
PLoS Pathog. 2010 Aug 12;6(8):e1001042
20811584
Pathog Dis. 2015 Jul;73(5):
25986378
Infect Immun. 2001 Jul;69(7):4572-9
11402001
Clin Infect Dis. 2009 Jan 1;48(1):1-12
19035777
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18327-32
25489107
Infect Immun. 2011 Oct;79(10):4250-9
21807904
PLoS Med. 2007 Dec;4(12):e329
18092884
Science. 1999 Aug 13;285(5430):1061-6
10446051
PLoS Pathog. 2015 Jan 08;11(1):e1004599
25569799
Curr Opin Infect Dis. 2015 Feb;28(1):97-105
25517222
Infect Immun. 1988 Apr;56(4):892-7
2894363
J Biol Chem. 2001 Mar 30;276(13):9924-30
11134021
Glycoconj J. 1994 Dec;11(6):507-17
7696853
J Med Chem. 2012 Apr 26;55(8):3945-59
22449031
Int J Cancer. 1973 May;11(3):765-73
4133950
Proc Soc Exp Biol Med. 1950 May;74(1):106-8
15430405
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17020-4
12471157
Infect Immun. 1996 Apr;64(4):1369-72
8606102
J Biol Chem. 2006 Jul 21;281(29):20171-80
16704980