The adherence of bacteria to mucosal surfaces is the first step in the infectious process. It is now generally accepted that type 1 fimbriae mediate the adhesion of some pathogenic as well as non-pathogenic Escherichia coli and are characterized by their ability to bind specifically to D-mannose residues on mucosal cells. Very little fimbriae is known of the binding region of type 1 fimbriae. Recently, we observed that dissociated by guanidine hydrochloride retained binding activities suggesting that mannose binding adhesins resided either on the fimbrial subunit or on a minor component of the fimbriae. We have also observed that a deletion mutation remote from the structural gene encoding the 17 kDa subunit of type 1 fimbriae of E. coli results in loss of mannose binding activity of the fimbriae.
The aim of this project is to identify and characterize the mannose binding moiety(s) of type 1 fimbriae. Specifically, we plan to identify and isolate the adhesin(s) by affinity chromatography using a glycoprotein receptor recently isolated from guinea pig erythrocyte membranes. We plan to raise monoclonal antibodies against the purified adhesin that block the adhesion of the fimbriae. Finally, we plan to determine the minimum structure required for mannose binding; the adhesin will be cleaved by various proteolytic enzymes and the resulting fragments examined for mannose binding and ractivity with antiadhesive monoclonal antibodies. The proposed studies should provide valuable information on the biochemistry and immunology of the mannose binding adhesin. It may also prove useful in the development of a fimbrial vaccine to prevent against bacterial colonization of susceptible mucosal surfaces.
|Ponniah, S; Abraham, S N; Endres, R O (1992) T-cell-independent stimulation of immunoglobulin secretion in resting human B lymphocytes by the mannose-specific adhesin of Escherichia coli type 1 fimbriae. Infect Immun 60:5197-203|
|Babu, J P; Dabbous, M K; Abraham, S N (1991) Isolation and characterization of a 180-kiloDalton salivary glycoprotein which mediates the attachment of Actinomyces naeslundii to human buccal epithelial cells. J Periodontal Res 26:97-106|
|Ponniah, S; Endres, R O; Hasty, D L et al. (1991) Fragmentation of Escherichia coli type 1 fimbriae exposes cryptic D-mannose-binding sites. J Bacteriol 173:4195-202|
|Christensen, G D; Baddour, L M; Madison, B M et al. (1990) Colonial morphology of staphylococci on Memphis agar: phase variation of slime production, resistance to beta-lactam antibiotics, and virulence. J Infect Dis 161:1153-69|
|Ponniah, S; Abraham, S N; Dockter, M E et al. (1989) Mitogenic stimulation of human B lymphocytes by the mannose-specific adhesin on Escherichia coli type 1 fimbriae. J Immunol 142:992-8|
|Beachey, E H; Giampapa, C S; Abraham, S N (1988) Bacterial adherence. Adhesin receptor-mediated attachment of pathogenic bacteria to mucosal surfaces. Am Rev Respir Dis 138:S45-8|
|Abraham, S N; Goguen, J D; Beachey, E H (1988) Hyperadhesive mutant of type 1-fimbriated Escherichia coli associated with formation of FimH organelles (fimbriosomes). Infect Immun 56:1023-9|
|Abraham, S N; Beachey, E H (1988) Binding of bacteria to mucosal surfaces. Monogr Allergy 24:38-43|
|Sun, D; Abraham, S N; Beachey, E H (1988) Influence of berberine sulfate on synthesis and expression of Pap fimbrial adhesin in uropathogenic Escherichia coli. Antimicrob Agents Chemother 32:1274-7|
|Giampapa, C S; Abraham, S N; Chiang, T M et al. (1988) Isolation and characterization of a receptor for type 1 fimbriae of Escherichia coli from guinea pig erythrocytes. J Biol Chem 263:5362-7|
Showing the most recent 10 out of 13 publications