Candida albicans is a double agent: In most of us, it lives peacefully, but for people whose immune systems are compromised by HIV or other severe illnesses, it is frequently deadly. Now a new study from Harvard Medical School and Johns Hopkins shows how targeting a specific fungal component might turn the fungus from a lion back into a kitten.

“Treatment options for systemic Candida infections are limited, and a major difficulty in finding new drug targets is that fungi are closely related to us, so we risk hurting the patient as much as the pathogen,” says Rajini Rao – Ph.D, a professor of Physiology in the Institute For Basic Biomedical Sciences at the Johns Hopkins University, School of Medicine.

“What we’ve identified is a function that is critical for virulence. If we could block this through medication, it would leave both the fungus and the host healthy while taking away Candida’s ability to harm.” Candida lives in the guts of most people as one of many so-called “commensal microbes” that is, harmlessly. It can sometimes cause local infections of the mouth or genitals, known as thrush, that are treatable with over-the-counter anti-fungals. But given the opportunity to breach our defenses, Candida can cross into the bloodstream and switch from peaceful coexistence to attack mode, producing long filaments that dig into tissues and destroy them. Unfortunately, Rao says, “there are only a few antifungal drugs, so it’s particularly dangerous when drug resistance develops in Candida.” For that reason, she says, “we’re always looking for new chinks in its armor.” Rao says that this study reveals a vulnerability that could be exploited using drugs known to alter the pH of the vacuole, rendering Candida harmless, while potentially posing little risk to infected patients.

For example, previous studies from her lab showed that a drug already in use to treat a heart condition, known as arrhythmia, had the unexpected effect of blocking acidification of the fungal vacuole. The next step, she says, would be to screen drugs already approved by the U. S. Food and Drug Administration to increase the repertoire of antifungal agents to combat deadly fungal infections

November 10, 2013

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