(lifted from Abstract): Histatins (Hst) are one of the major salivary proteins that appear to have fungicidal activity in the mouth. Oropharyngeal candidiasis (OPC) in HIV-infected individuals may be the result of an alteration in the interactions between Hst and Candida albicans. These researchers have identified a surface protein on Candida, HstBP, that may be the receptor or binding protein for Hst. They suggest that HstBP may be related to efflux pumps such as the ABC transporters or the Major Facilitator superfamily. They hypothesize that OPC may be the result of Candida strains with altered expression of HstBP. They propose to characterize HstBP expression as an underlying mechanism in the development of candidiasis in HIV patients by the following specific aims: 1. Purify HstBP by standard biochemical methods, clone and sequence the HstBP gene. 2. Define the biologic role of HstBP by identifying common structural features, and by assessing the effects of certain physiological mediators on HstBP. 3. Compare HstBP expression in yeasts that are sensitive or resistant to Hst from patients with OPC by determining HstBP molecules/cell using standard binding assays and by levels of mRNA expression using Northern blot analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE012159-02
Application #
2634147
Study Section
Special Emphasis Panel (ZDE1-YS (31))
Project Start
1997-01-01
Project End
1999-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Dentistry
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Edgerton, M; Koshlukova, S E (2000) Salivary histatin 5 and its similarities to the other antimicrobial proteins in human saliva. Adv Dent Res 14:16-21
Edgerton, M; Koshlukova, S E; Araujo, M W et al. (2000) Salivary histatin 5 and human neutrophil defensin 1 kill Candida albicans via shared pathways. Antimicrob Agents Chemother 44:3310-6
Koshlukova, S E; Araujo, M W; Baev, D et al. (2000) Released ATP is an extracellular cytotoxic mediator in salivary histatin 5-induced killing of Candida albicans. Infect Immun 68:6848-56
Koshlukova, S E; Lloyd, T L; Araujo, M W et al. (1999) Salivary histatin 5 induces non-lytic release of ATP from Candida albicans leading to cell death. J Biol Chem 274:18872-9
Edgerton, M; Koshlukova, S E; Lo, T E et al. (1998) Candidacidal activity of salivary histatins. Identification of a histatin 5-binding protein on Candida albicans. J Biol Chem 273:20438-47