Identified virulence factors of UPEC: Adherence

Dr adhesins  

Related genes: draA; draB; draC; draD; draE; draP;
Keywords: Adherence;
The Dr family of adhesins of E. coli is associated with urinary tract infections (UTI), in particular cystitis and pregnancy-associated pyelonephritis, and diarrhoeal disease.
The Dr family includes fimbrial adhesins, such as the Dr haemagglutinin (O75X adhesin) and F1845, and afimbrial adhesins, such as AFA-I, AFA-II, AFA-III, AFA-IV, Nfa-I and Dr-II.
Facilitates colonization.
The Dr adhesins bind to the Dr blood group antigen (Dra) present on decay accelerating factor (DAF) of erythrocytes and other cell types. DAF is a membrane protein that prevents cell lysis by complement.
Inducing a cytopathic effect characterized by the development of long cellular extensions that wrap around the adherent bacteria. (All members of the Dr family including UPEC elicit this effect).
Binding of Dr adhesins is accompanied by the activation of several signal transduction cascades, including activation of PI-3 kinase.
Nowicki B, et al., 1993. Short consensus repeat-3 domain of recombinant decay-accelerating factor is recognized by Escherichia coli recombinant Dr adhesin in a model of a cell-cell interaction. J. Exp. Med. 178(6):2115-2121.
Goluszko P, et al., 1997. Dr fimbriae operon of uropathogenic Escherichia coli mediate microtubule-dependent invasion to the HeLa epithelial cell line. J. Infect. Dis. 176(1):158-167.
Selvarangan R, et al., 2000. Role of decay-accelerating factor domains and anchorage in internalization of Dr-fimbriated Escherichia coli. Infect. Immun. 68(3):1391-1399.
Hart A, et al., 2001. Ampicillin-resistant Escherichia coli in gestational pyelonephritis: increased occurrence and association with the colonization factor Dr adhesin. J. Infect. Dis. 183(10):1526-1529.
Van Loy CP, et al., 2002. Identification of amino acids in the Dr adhesin required for binding to decay-accelerating factor. Mol. Microbiol. 45(2):439-452.
Fang L, et al., 2004. Epithelial invasion by Escherichia coli bearing Dr fimbriae is controlled by nitric oxide-regulated expression of CD55. Infect. Immun. 72(5):2907-2914.

F1C fimbriae  

Related genes: focA; focC; focD; focF; focG; focH; focI;
Keywords: Adherence;
A nonhemagglutinating adherence factor and is expressed by approximately 14% of the E. coli known to cause urinary tract infections and 7% of E. coli fecal isolates.
Genetically homologous to S fimbriae, but differ in their receptor specificity.
Structure features:
The F1C fimbrial complex is composed of the major subunit protein FocA (16 kDa) and the minor subunits FocF (17 kDa), FocG (15 kDa), and FocH (30 kDa). These fimbriae share high sequence homology to the major and minor subunits of the S fimbriae.
Binds of to the GalNAcβ1-4Galβ sequence of glycolipids, i.e., asialo-GM1 and asialo-GM2 with high affinity.
An additional binding to carbohydrate structures GlcNAcβ1-3Galβ, Galβ1-4Glc, Gal, and Glc of glycolipids may indicate functional low-affinity receptor sites.
Bahrani-Mougeot F, et al., 2002. Uropathogenic Escherichia coli In Donnenberg MS (ed.), Escherichia coli: virulence mechanisms of a versatile pathogen. Academic Press. San Diego, Calif. pp. 239-268.
Riegman N, et al., 1990. F1C fimbriae of a uropathogenic Escherichia coli strain: genetic and functional organization of the foc gene cluster and identification of minor subunits. J. Bacteriol. 172(2):1114-1120.
Khan AS, et al., 2000. Receptor structure for F1C fimbriae of uropathogenic Escherichia coli. Infect. Immun. 68(6):3541-3547.
Backhed F, et al., 2002. Identification of target tissue glycosphingolipid receptors for uropathogenic, F1C-fimbriated Escherichia coli and its role in mucosal inflammation. J. Biol. Chem. 277(20):18198-18205.
Mulvey MA, 2002. Adhesion and entry of uropathogenic Escherichia coli. Cell Microbiol. 4(5):257-271.

P fimbriae  

Related genes: papA; papA; papB; papB; papC; papC; papD; papD; papE; papE; papF; papF; papG; papG; papH; papH; papI; papI; papJ; papJ; papK; papK;
Keywords: Adherence;
Mannose-resistant (MRHA).
Pap pili expression is tightly regulated in response to several environmental and nutritional factors, also controlled by a methylation-dependent phase variation mechanims.
The pap operon is a useful example of pilus assembly since it contains many conserved features:
PapD, a conserved chaperone molecule with an Ig-like domain, is necessary to transport several pilus subunits from the cytoplasmic membrane to the outer membrane
PapD-subunit complexes are targeted to the PapC outer membrane usher, which forms a pore through which the the pili are translocated across the OM
The major subunit is PapA, which is assembled into a 6.8-nm thick helical rod that is anchored in the OM by PapH
At the distal end of the pilus rod is a 2-nm linear tip fibrillum composed of a PapE, which is adapted to the PapA rod by PapK. PapG is joined to the PapE tip fibrillum by the adapter protein PapF.
Structure features:
PapG adhesin receptor binding domain-unbound form: 1J8S.
Binary complex of the PapG receptor-binding domain bound To Gbo4 receptor.
P fimbriae operon

Model for P fimbriae biogenesis (From: Thanassi DG, et al., 2012. Surface organelles assembled by secretion systems of Gram-negative bacteria: diversity in structure and function. FEMS Microbiol Rev 36(6):1046-82.).

PapG mediates binding to the α-D-galactopyranosyl-(1-4)-β-D-galactopyranoside (Galα(1,4)Gal) moiety present in a globoseries of glycolipids found on host cells lining the upper urinary tract and erythrocytes.
Three adhesin variants of PapG-G-I, G-II, G-III recognize three different but related Galα(1,4)Gal receptors.
PapG-mediated interactions with its Galα(1,4)Gal-containing glycolipid receptor can activate specific responses in the bacteria and in the epithelial cell that promote virulence: activating the UPEC iron-acquisition system and triggering the intracellular release from receptor glycolipids of ceramide, an important second messenger that can activate cytokine production, through the activation of serine/threonine protein kinases and phosphatase.
Bann JG, et al., 2002. Adhesive pili of the chaperone-usher family. In Donnenberg MS (ed.), Escherichia coli: virulence mechanisms of a versatile pathogen. Academic Press. San Diego, Calif. pp. 289-306.
Stromberg N, et al., 1990. Host-specificity of uropathogenic Escherichia coli depends on differences in binding specificity to Gal alpha 1-4Gal-containing isoreceptors. EMBO J. 9(6):2001-2010.
Tewari R, et al., 1994. The PapG tip adhesin of P fimbriae protects Escherichia coli from neutrophil bactericidal activity. Infect. Immun. 62(12):5296-5304.
Roberts JA, et al., 1994. The Gal(alpha 1-4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract. Proc. Natl. Acad. Sci. USA. 91(25):11889-11893.
Goetz GS, et al., 1999. Binding of pili from uropathogenic Escherichia coli to membranes secreted by human colonocytes and enterocytes. Infect. Immun. 67(11):6161-6163.
Jantunen ME, et al., 2000. Predominance of class II papG allele of Escherichia coli in pyelonephritis in infants with normal urinary tract anatomy. J. Infect. Dis. 181(5):1822-1824.
Wullt B, et al., 2000. P fimbriae enhance the early establishment of Escherichia coli in the human urinary tract. Mol. Microbiol. 38(3):456-464.
Mahmood A, et al., 2000. Role of intestinal surfactant-like particles as a potential reservoir of uropathogenic Escherichia coli. Biochim. Biophys. Acta. 1523(1):49-55.
Wullt B, et al., 2001. P-fimbriae trigger mucosal responses to Escherichia coli in the human urinary tract. Cell Microbiol. 3(4):255-264.
Wullt B, 2003. The role of P fimbriae for Escherichia coli establishment and mucosal inflammation in the human urinary tract. Int. J. Antimicrob. Agents. 21(6):605-621.

S fimbriae  

Related genes: sfaA; sfaB; sfaC; sfaD; sfaE; sfaF; sfaG; sfaH; sfaS; sfaX; sfaY;
Keywords: Adherence;
Encoded by sfa operon composed of nine genes.
Structure features:
Composed of a major subunit SfaA and three minor subunits SfaG, SfaH and SfaS. The SfaS subunit has been localized to S pilus tips and can mediate bacterial interactions with sialic acid residues on receptors.
S fimbriae operon

S fimbriae binds to receptors containing sialic acid sugar moieties, the sialic acid residues are presented on UP3, one of four integral membrane uroplakin proteins.
Bahrani-Mougeot F, et al., 2002. Uropathogenic Escherichia coli In Donnenberg MS (ed.), Escherichia coli: virulence mechanisms of a versatile pathogen. Academic Press. San Diego, Calif. pp. 239-268.
Kreft B, et al., 1995. S fimbriae of uropathogenic Escherichia coli bind to primary human renal proximal tubular epithelial cells but do not induce expression of intercellular adhesion molecule 1. Infect. Immun. 63(8):3235-3238.
Hanisch FG, et al., 1993. Specificity of S fimbriae on recombinant Escherichia coli: preferential binding to gangliosides expressing NeuGc alpha (2-3)Gal and NeuAc alpha (2-8)NeuAc. Infect. Immun. 61(5):2108-2115.
Prasadarao NV, et al., 1993. Adhesion of S-fimbriated Escherichia coli to brain glycolipids mediated by sfaA gene-encoded protein of S-fimbriae. J. Biol. Chem. 268(14):10356-10363.
Malagolini N, et al., 2000. Terminal glycosylation of bovine uroplakin III, one of the major integral-membrane glycoproteins of mammalian bladder. Biochim. Biophys. Acta. 1475(3):231-237.
Mulvey MA, 2002. Adhesion and entry of uropathogenic Escherichia coli. Cell Microbiol. 4(5):257-271.

Type 1 fimbriae  

Related genes: fimA; fimB; fimC; fimD; fimE; fimF; fimG; fimH; fimI;
Keywords: Adherence; Invasion;
Mannose-sensitive (MSHA) fimbriae, the ability to hemagglutinate erythrocytes was blocked by the presence of mannose.
The genes responsible for type I fimbriae are found in almost all subgroups of E.coli, not just in UPEC strains, but the fimbriae function as a virulence factor in the pathogenesis of E.coli UTI.
Expression of type I fimbriae undergoes phase variation controlled at the transcriptional level by invertible element. The σ70 promoter for FimA is located within this 314bp invertible DNA element flanked on both ends by inverted DNA repeats of 9bp in length. Leucine-responsive protein (LRP), integration host factor (IHF), and the histone-like protein (H-NS) affect the switching of the invertible element by binding to DNA sequences around and within the invertible element region, thus assisting or blocking the switching actions of the FimB and FimE recombinases.
Structure features:
FimC-FimH chaperone adhesin complex: 1QUN.
Type 1 fimbriae operon

Makes an important contribution to colonization of the bladder.
FimH is the adhesin protein binding to mannose-containing glycoprotein receptors, known as uroplakins, which are located on the luminal surface of the bladder epithelial cells. This binding is followed by invasion of uroepithelia cells.
Bahrani-Mougeot F, et al., 2002. Uropathogenic Escherichia coli In Donnenberg MS (ed.), Escherichia coli: virulence mechanisms of a versatile pathogen. Academic Press. San Diego, Calif. pp. 239-268.
Sokurenko EV, et al., 1998. Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin. Proc. Natl. Acad. Sci. USA. 95(15):8922-8926.
Mulvey MA, et al., 1998. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282(5393):1494-1497.
Pouttu R, et al., 1999. Amino acid residue Ala-62 in the FimH fimbrial adhesin is critical for the adhesiveness of meningitis-associated Escherichia coli to collagens. Mol. Microbiol. 31(6):1747-1757.
Pak J, et al., 2001. Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors. J. Biol. Chem. 276(13):9924-9930.
Schembri MA, Klemm P, 2001. Biofilm formation in a hydrodynamic environment by novel fimh variants and ramifications for virulence. Infect. Immun. 69(3):1322-1328.
Harris SL, et al., 2001. Characterization of Escherichia coli type 1 pilus mutants with altered binding specificities. J. Bacteriol. 183(13):4099-4102.
Schembri MA, et al., 2001. FimH-mediated autoaggregation of Escherichia coli. Mol. Microbiol. 41(6):1419-1430.
Zhou G, et al., 2001. Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. J. Cell Sci. 114:4095-4103.
Mulvey MA, 2002. Adhesion and entry of uropathogenic Escherichia coli. Cell Microbiol. 4(5):257-271.

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