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.
Fitzgerald
Deirdre H
DH
Department of Restorative Dentistry, School of Dental Science and Dublin Dental Hospital, University of Dublin, Trinity College, Dublin 2, Ireland. deirdre.fitzgerald@dental.tcd.ie
Coleman
David C
DC
O'Connell
Brian C
BC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000935:Antifungal Agents / Q000378:metabolism*; D001673:Biodegradation, Environmental; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D025141:Drug Resistance, Fungal; D054808:Histatins; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*
D000935:Antifungal Agents; C068075:HTN3 protein, human; D054808:Histatins; D011506:Proteins; D000255:Adenosine Triphosphate; D010100:Oxygen