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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)

References associated with 1.C.79 family:

Koshlukova, S.E., T.L. Lloyd, M.W. Araujo, and M. Edgerton. (1999). Salivary histatin 5 induces non-lytic release of ATP from Candida albicans leading to cell death. J. Biol. Chem. 274: 18872-18879. 10383383
Veerman, E.C., M. Valentijn-Benz, K. Nazmi, A.L. Ruissen, E. Walgreen-Weterings, J. van Marle, A.B. Doust, W. van't Hof, J.G. Bolscher, and A.V. Amerongen. (2007). Energy depletion protects Candida albicans against antimicrobial peptides by ritcidifying its cell membrane. J. Biol. Chem. 282: 18831-18841. 17485465