Host salivary antimicrobial peptides and oral candidiasis.

The oral cavity is a primary target for opportunistic infections, particularly oropharyngeal candidiasis. The etiologic agent Candida albicans is the most pathogenic human fungal species that can either colonize asymptomatically or cause superficial or even life-threatening infections, particularly in HIV+ and other immunocompromised individuals. However, the reasons behind this transition from commensal to pathogen and the enhanced susceptibility of HIV+ individuals to oral candidiasis, are not clear. In the oral cavity, salivary antimicrobial peptides are considered to be an important part of the host innate defense system in the prevention of microbial colonization. Histatin-5 has specifically exhibited potent activity against C. albicans. Our previous studies have shown histatin-5 levels to be significantly reduced in the saliva of HIV+ individuals, indicating an important role for this peptide in keeping C. albicans in its commensal stage. However, the versatility in the pathogenic potential of C. albicans is the result of its ability to adapt through the regulation of virulence determinants, most notably of which are secreted proteolytic enzymes involved in tissue degradation and invasion. In this report, we present novel findings demonstrating that C. albicans secreted proteolytic enzymes efficiently and rapidly degrade and deactivate a host peptide involved in the protection of the oral mucosa against C. albicans, thereby providing new insights into the factors directing the transition of C. albicans from commensal to pathogen. The dissemination of such crucial information has important clinical implications for alternative therapy for the prevention of oral candidiaisis, particularly in susceptible hosts.