1.C.79 The Channel-forming Histatin Antimicrobial Peptide (Histatin) Family
Salivary histatins (Hst) are potent in vitro antifungal histidine-rich proteins that have promise as therapeutic agents. Three inhibitors of mitochondrial metabolism: carbonyl cyanide p-chlorophenylhydrazone, dinitrophenol, and azide inhibited Hst 5 killing of Candida albicans, while not inhibiting cellular ATP production (Koshlukova et al., 1999). In contrast, Hst 5 caused a drastic reduction of C. albicans intracellular ATP content, which was a result of efflux of ATP. Carbonyl cyanide p-chlorophenylhydrazone, dinitrophenol, and azide inhibited Hst 5-induced ATP efflux, thus establishing a correlation between ATP release and cell killing. Furthermore, C. albicans cells were respiring and had polarized membranes at least 80 min after ATP release, thus implying a non-lytic exit of cellular ATP in response to Hst 5. Transmembrane ATP efflux can occur in the absence of cytolysis through a channel-like pathway. Energy depletion may protect C. albicans against antimicrobial peptides by rigidifying its membrane (Veeman et al., 2007).
The transport reaction shown to be mediated by histatin 5 is:
ATP(in) → ATP(out)