2001 Fiscal Year Final Research Report Summary
New type of functional heterogeneity with urinary p* E. coli fimbriae adhesin
| Project/Area Number |
10671500
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Fujita Health University |
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Principal Investigator |
TANAKA Toshiyuki Fujita Health University, School of Medicine, Assistant, 医学部, 助手 (40322763)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Kiyohito Fujita Health University, School of Medicine, Lecturer, 医学部, 講師 (80312114)
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| Project Period (FY) |
1998 – 2001
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| Keywords | Urinary tract infection / E. coli / Type 1 fimbriae / P-fimbriae |
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| Research Abstract |
Objective: To study the expression of receptors allowing adhesin mediated binding of Escherichia coli to urogenital tissues from kidney to vagina in cynomolgus monkeys, using an in situ assay.
M&M. Receptors specific for four relevant adhesins were investigated - PapG and PrsG of P-fimbriae binding to gal-α(1-4)gal glycosphingolipids (preferentially globoside and the Forssman antigen respectively) and two variants of FimH of type 1 fimbriae one binding to monomannose/trimannose and the other to trimannose only. To asccertain the specificity of the observed bindings we used adhesion inhibition by receptor analogues as well as E. coli adhesin knock out mutants.
Results. The distribution of PapG and FimH receptors in monkey tissues showed great similarities to available data in humans. While monomanose receptors were expressed on surface epithelium both in the monkey bladder and ureter timannose receptors were not. The different distribution of FimH isoreceptors and the heterogeneity of FimH adhesin variants among E. coli may explain contradictory earlier findings in type 1 fimbrae mediated adhesion to the human bladder and to renal tissues. We also found evidence of a hetherto unknown type of host-aggressor interaction on vaginal and urethral mucosae, not uncovered until type 1 fimbriae had been eliminated.
Conclusions. A precise molecular fit between hot receptors and bacterial lectins is important in infectious pathogenesis. We conclude that UTI in the cynomolgous monkey is a relevant model of the human disease because of the similarity in expression of receptors for E. coli adhesins on epithelial surfaces in the two species.
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