Candida albicans, an opportunistic yeast, is the most frequently encountered and most important fungal pathogen in the oral cavity. Because so little is known about C. albicans-host interactions, this proposal has been designed to investigate those natural host defense factors which might be involved in the regulation and control of chronic and acute oral candidiasis. In particular, basic and clinical research studies shall be utilized in this proposal to focus upon a group of histidine-rich polypeptides which are uniquely present in human saliva. Recent in vitro evidence from our laboratory has promoted us to hypothesize an antifungal role for these salivary histidine-rich polypeptides in the oral cavity. However, detailed studies outlined here are essential to develop this hypothesis and to establish the key role of histidine with its constituent imidazole group in the proposed antifungal activity. In order to aid in a determination of whether physiological concentrations of these naturally secreted molecules play a role in C. albicans disease, both in vivo oral isolates obtained from candidiasis patients and commercially available laboratory strains of C. albicans will be tested for their in vitro susceptibility to the salivary histidine-rich polypeptides and to synthetic homologous histidine peptides. Antimicrobial susceptibility testing will include both growth inhibitory turbidimetric measurements and colony forming unit viability assays. In addition, the effect of natural and synthetic histidine peptides on germ tube formation will be assessed. An in vivo clinical model system employing denture stomatitis patients will be developed to acquire information on the susceptibility of C. albicans in its native oral environment to the histidine peptides. The ability of the histidine peptides to inhibit the growth of and kill C. albicans on the denture acrylic surface will be examined and compared to the candidastatic and candidacidal activities against the corresponding C. albicans in vivo isolates of each patient. Studies will also be initiated at the ultrastructural level to gain insight into the molecular mechanism of antifungal action of the natural and synthetic histidine peptides.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE007441-02
Application #
3221075
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1986-03-01
Project End
1989-02-28
Budget Start
1987-03-01
Budget End
1988-02-29
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Xu, L; Lal, K; Santarpia 3rd, R P et al. (1993) Salivary proteolysis of histidine-rich polypeptides and the antifungal activity of peptide degradation products. Arch Oral Biol 38:277-83
Lal, K; Santarpia 3rd, R P; Pollock, J J et al. (1992) Assessment of antimicrobial treatment of denture stomatitis using an in vivo replica model system: therapeutic efficacy of an oral rinse. J Prosthet Dent 67:72-7
Rayhan, R; Xu, L; Santarpia 3rd, R P et al. (1992) Antifungal activities of salivary histidine-rich polypeptides against Candida albicans and other oral yeast isolates. Oral Microbiol Immunol 7:51-2
Santarpia 3rd, R P; Xu, L; Lal, K et al. (1992) Salivary anti-candidal assays. Oral Microbiol Immunol 7:38-43
Lal, K; Santarpia 3rd, R P; Xu, L et al. (1992) One-step purification of histidine-rich polypeptides form human parotid saliva and determination of anti-candidal activity. Oral Microbiol Immunol 7:44-50
Lal, K; Pollock, J J; Santarpia 3rd, R P et al. (1992) Pilot study comparing the salivary cationic protein concentrations in healthy adults and AIDS patients: correlation with antifungal activity. J Acquir Immune Defic Syndr 5:904-14
Pollock, J J; Santarpia 3rd, R P; Heller, H M et al. (1992) Determination of salivary anticandidal activities in healthy adults and patients with AIDS: a pilot study. J Acquir Immune Defic Syndr 5:610-8
Lal, K; Xu, L; Colburn, J et al. (1992) The use of capillary electrophoresis to identify cationic proteins in human parotid saliva. Arch Oral Biol 37:7-13
Santarpia 3rd, R P; Pollock, J J; Renner, R P et al. (1991) In vivo antifungal efficacy of salivary histidine-rich polypeptides: preliminary findings in a denture stomatitis model system. J Prosthet Dent 66:693-9
Spiechowicz, E; Santarpia 3rd, R P; Pollock, J J et al. (1990) In vitro study on the inhibiting effect of different agents on the growth of Candida albicans on acrylic resin surfaces. Quintessence Int 21:35-40

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