Through a series of studies, the researchers identified the target-binding protein on Candida albicans by creating mutant strains of the fungus without the target and exposing the mutants to histatin. Results showed that histatin was significantly less active when the suspect target was missing.
Further research indicated that histatin binding to the target protein killed the fungal cells by preventing it from regulating its ions, the positive and negative charged molecules that move into, and out of, cells. Ions regulate electrostatic pressure between the cells' internal and external environments, which, in turn, regulates their volume and water content. Cells that lose their water content without being able to regulate its re-uptake die rapidly, Edgerton said.
"Now that the target for histatin has been identified, we can design a better protein that will be even more effective in binding and holding the channel open, causing even better and more rapid killing of the fungus," said Edgerton.
"In addition, many other pathogenic fungi that cause disease in elderly individuals or AIDS patients also should be able to be killed by histatins or drugs designed to target their potassium channels."