Urinary tract infections (UTI) are among the most common human infections, and may have serious health sequelae. Most UTI are caused by members of the bacterial family Enterobacteriaceae. Both epidemiological data and studies with animal models have implicated the important role of specific bacterial adhesins (pili or fimbriae) in the colonization of the UT by bacteria normally found in the human large bowel. The object of this research proposal is to characterize and compare, using modern genetic techniques, the DNA sequences encoding these bacterial adhesins with the ultimate goal of developing methods to prevent bacterial adherence to UT epithelial cells. More specifically, the methods of recombinant DNA technology will be used to (1) isolate and identify the genes coding for mannose-resistant adhesins non-homologous to the P-pili of Escherichia coli (which allow E. coli to bind avidly to uroepithelium); and (2) isolate and identify the gene(s) conferring adherence to uroepithelium from Proteus mirabilis, a common cause of hospital acquired UTI. Extensive DNA hybridization experiments will be carried out to compare the gene for P pilin of a well studied uropathogenic E. coli to other UTI isolates. It is hoped that these experiments may identify common genetic sequences that might be explored as targets for the development of vaccines or for specific chemical inhibitors to prevent the expression or function of bacterial adhesins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018462-06
Application #
3127961
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1982-01-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Hull, S I; Hull, R A (1995) Molecular cloning of adhesion genes. Methods Enzymol 253:258-69
Cook, S W; Mody, N; Valle, J et al. (1995) Molecular cloning of Proteus mirabilis uroepithelial cell adherence (uca) genes. Infect Immun 63:2082-6
Hull, R A; Nowicki, B; Kaul, A et al. (1994) Effect of pap copy number and receptor specificity on virulence of fimbriated Escherichia coli in a murine urinary tract colonization model. Microb Pathog 17:79-86
Klann, A G; Hull, R A; Palzkill, T et al. (1994) Alanine-scanning mutagenesis reveals residues involved in binding of pap-3-encoded pili. J Bacteriol 176:2312-7
Bahrani, F K; Cook, S; Hull, R A et al. (1993) Proteus mirabilis fimbriae: N-terminal amino acid sequence of a major fimbrial subunit and nucleotide sequences of the genes from two strains. Infect Immun 61:884-91
Batchelor, R A; Alifano, P; Biffali, E et al. (1992) Nucleotide sequences of the genes regulating O-polysaccharide antigen chain length (rol) from Escherichia coli and Salmonella typhimurium: protein homology and functional complementation. J Bacteriol 174:5228-36
Klann, A G; Hull, R A; Hull, S I (1992) Sequences of the genes encoding the minor tip components of Pap-3 pili of Escherichia coli. Gene 119:95-100
Andersson, P; Engberg, I; Lidin-Janson, G et al. (1991) Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence. Infect Immun 59:2915-21
Ding, M J; Svanborg, C; Haraguchi, G E et al. (1991) Molecular cloning and expression of the 01 rfb region from a pyelonephritic Escherichia coli 01:H1:K7. Microb Pathog 11:379-85
Swanson, T N; Bilge, S S; Nowicki, B et al. (1991) Molecular structure of the Dr adhesin: nucleotide sequence and mapping of receptor-binding domain by use of fusion constructs. Infect Immun 59:261-8

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