Binding, internalisation and degradation of histatin 3 in histatin-resistant derivatives of Candida albicans

The antifungal mechanism of salivary histatin has been studied in Candida albicans and involves binding to a specific receptor, translocation across the membrane and targeting intracellularly. Cell death correlates with non-lytic release of ATP that may function as a cytotoxic mediator extracellularly. By sequential exposure to increasing concentrations of histatin 3, we generated histatin-resistant derivatives of C. albicans strain CA132A that show five-fold less killing at physiological concentrations of histatin 3. Protection against histatin killing in histatin-resistant derivatives is not-due to alterations in binding, internalisation or degradation of histatin or efflux of ATP. These results indicate that protective mechanisms activated by exposure to histatin 3 may involve unidentified pathways downstream of binding and internalisation events. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.