Oral candidiasis
Oral candidiasis is an increasing health issue. Oral candidiasis is a superficial mucosal infection in which Candida albicans is the predominant species isolated from infected areas. Incidence of oropharyngeal candidiasis has increased dramatically in the past 20 years due to increased antibiotic and pharmaceutic drug use and longer survival of people with compromised immune systems and cancer patients. Oropharyngeal candidiasis is so frequently associated with AIDS that is a criterion for staging progression of disease. Increased use of azole and polyene drugs to treat candidiasis in AIDS and cancer patients has resulted in emergence of Candidal species with antifungal drug resistance, especially to azole-based drugs. Mortality from systemic C. albicans infections in immunocompromised patients is nearly 30%, even with aggressive treatment with antifungal drugs. These data point to a pressing need for improved drug therapies or means of enhancing innate immune mechanisms in immunocompromised and cancer patients.
Innate Immunity
Endogenous antimicrobial proteins are evolutionarily ancient contributors to innate host defense mechanisms, which are found throughout plant and animal species. Most of these bioactive proteins are basic and of small size (3-5 kDa) and have wide spectra of activity directed against bacteria, fungi and enveloped viruses. Antimicrobial defense mechanisms in the oral cavity are provided by four major non-immune proteins of salivary gland origin: lactoperoxidase, lysozyme, lactoferrin, and histatins (Hsts). These salivary proteins have unique structures, although they display overlapping antimicrobial activities and serve to rapidly limit infections. Histatins (Hsts) are structurally related histidine-rich basic proteins of acinar cell origin which possess in vitro candidacidal and candidastatic activities. Understanding mechanisms by which salivary antimicrobial proteins exert candidacidal activity and use of these bioactive peptides as theraeutic agents has been the objective of our research program.
