Chemical identification of a glycosphingolipid receptor for Escherichia coli attaching to human urinary tract epithelial cells and agglutinating human erythrocytes

Leffler, Hakon

doi:10.1016/0378-1097(80)90015-4

Cited by 178 publications

(277 citation statements)

References 8 publications

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“…A very high proportion of strains with those two abilities were present among acute pyelonephritis isolates from children, in contrast to the proportion among normal faecal E. coli as shown by Hagberg et al (1981). The attachment is mediated by a specific binding to glycolipid receptors of the globoseries (Leffler & Svanborg Eden, 1981), and fimbriae binding in this way have been termed GS fimbriae (Svanborg Eden et al 1983 a). The receptor is part of the P blood group antigen containing a-D-galactose-(,/1-4)-D-galactose residues, and therefore the fimbriae have also been termed P fimbriae (Kiillenius et al 1980(Kiillenius et al , 1981.…”

Section: Haemolysinmentioning

confidence: 99%

“…These MS fimbriae bind to monkey kidney cells (Salit & Gotschlich, 1977) and to rat uroepithelial cells (Korhonen, Leffler & Svanborg Eden, 1981). Binding to human uroepithelial cells has been described (Schaeffer, Amundsen & Schmidt, 1979;van den Bosch et al 1981), but it has also been reported that most strains with MSHA adhere poorly to human uroepithelial cells, and that if they attach they attach only to squamous cells, not to transitional cells, in contrast to those with MRHA activity ofthe gal-gal binding type (Hagberg et al 1981).…”

Section: Ms Fimbriae (Type 1)mentioning

confidence: 99%

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Escherichia coliin extra-intestinal infections

Ørskov

1985

J. Hyg.

220

161

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When Theodor Escherich (1885a, b) first describedEscherichia colihe looked on it as a saprophytic organism. Soon several investigators found that colibacteria could be isolated from intestinal infections and from many infections outside the intestine, like urinary tract infections (UTI), cholecystitis, wound infections, meningitis, septicaemia, pulmonary infections, and many more. Uhlenhuth (1897) showed that coli strains from pathological processes were more pathogenic in animal experiments than strains isolated from the normal intestine. Smith (1927), who examined strains from white scours in calves, showed that spontaneous acapsular mutants could be obtained from certain colibacteria, and that such mutants were less virulent when injected intra-peritoneally into guinea-pigs.

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Section: Haemolysinmentioning

confidence: 99%

Section: Ms Fimbriae (Type 1)mentioning

confidence: 99%

Escherichia coliin extra-intestinal infections

Ørskov

1985

J. Hyg.

220

161

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“…The host cell receptors for P are glycosphingolipids, and the PapG tip adhesin binds to oligosaccharide receptor epitopes, which are abundantly expressed in the human urinary tract mucosa [19,20]. Type 1 fimbriae differ in receptor specificity, as they recognise mannosylated glycoproteins rather than glycosphingolipids, but both P and type 1 fimbriae trigger the innate host response in the murine urinary tract [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

“…P fimbriae are virulence-associated adherence factors which are expressed by up to 100% of the pathogenic compared to <20% of ABU strains [14,19]. The host cell receptors for P are glycosphingolipids, and the PapG tip adhesin binds to oligosaccharide receptor epitopes, which are abundantly expressed in the human urinary tract mucosa [19,20].…”

Section: Introductionmentioning

confidence: 99%

“…Less virulent strains cause asymptomatic bacteriuria (ABU) [18] where the mucosal barrier remains inert, despite bacterial numbers exceeding 10 5 /mL of urine. The difference in disease severity reflects the virulence of the uropathogenic E. coli strains, which utilise a number of distinct virulence factors to break the inertia of the mucosal barrier.P fimbriae are virulence-associated adherence factors which are expressed by up to 100% of the pathogenic compared to <20% of ABU strains [14,19]. The host cell receptors for P are glycosphingolipids, and the PapG tip adhesin binds to oligosaccharide receptor epitopes, which are abundantly expressed in the human urinary tract mucosa [19,20].…”

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confidence: 99%

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Mechanism of pathogen‐specific TLR4 activation in the mucosa: Fimbriae, recognition receptors and adaptor protein selection

et al. 2006

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The mucosal host defence discriminates pathogens from commensals, and prevents infection while allowing the normal flora to persist. Paradoxically, Toll-like receptors (TLR) control the mucosal defence against pathogens, even though the TLR recognise conserved molecules like LPS, which are shared between pathogens and commensals. This study proposes a mechanism of pathogen-specific mucosal TLR4 activation, involving adhesive ligands and their host cell receptors. TLR4 signalling was activated in CD14-negative, LPS-unresponsive epithelial cells by P fimbriated, uropathogenic Escherichia coli but not by a mutant lacking fimbriae. Epithelial TLR4 signalling in vivo involved the glycosphingolipid receptors for P fimbriae and the adaptor proteins Toll/IL-1R (TIR) domain-containing adaptor inducing IFN-b (TRIF)/TRIF-related adaptor molecule (TRAM), but myeloid differentiation protein 88 (MyD88)/TIR domain-containing adaptor protein were not required for the epithelial response. Substituting the P fimbriae with type 1 fimbriae changed TLR4 signalling from the TRIF to the MyD88 adaptor pathway. In addition, the adaptor proteins and the fimbrial type were found to influence bacterial clearance. Trif -/-and Tram -/-mice remained infected with P fimbriated E. coli but cleared thetype 1 fimbriated strain, while Myd88 -/-mice became carriers of both the P and the type 1 fimbriated bacteria. Thus, TLR4 may be engaged specifically by pathogens, when the proper cell surface receptors are engaged by virulence ligands. IntroductionToll-like receptors (TLR) control the innate host defence at mucosal surfaces and yet commensals do not induce an inflammatory response at those sites. The relative inertia to the commensals is paradoxical, as the TLR recognise conserved pathogen-associated molecular patterns (PAMP), which are present on both pathogenic and commensal bacteria. Lipolysaccharide (LPS), flagellin, peptidoglycan or DNA may bind directly to the TLR but in addition, co-receptors are needed to enhance the TLR response to these conserved ligands [1][2][3]. Myeloid cells use CD14 and MD-2 as co-receptors for LPS in TLR4 signalling, and minute amounts of LPS may elicit a strong systemic inflammatory response [4,5]. However, the TLR response to pathogen attack at mucosal surfaces is controlled by different interactions. Epithelial cells must be protected from constant TLR activation by commensals and their PAMP, in order for mucosal integrity to be maintained. The epithelial cells thus lack co-receptors like CD14 [6][7][8][9][10][11], and in addition, commensals have been suggested to actively suppress epithelia responses through NF-jB [12,13]. Yet, mucosal pathogens evoke rapid TLR4-dependent responses at mucosal sites, suggesting that alternative ligands and receptors might be involved in mucosal TLR activation. Pathogens use adhesive surface ligands to break the inertia of the mucosal barrier [14][15][16]. The innate defence is activated as a direct result of these interactions and epithelial cells produce the first wave of me...

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