Turning Fungus into a Less Harmful Infection

Scientists may have discovered a way to turn fungus, a potentially deadly bacteria for those with compromised immune systems by HIV or other severe illnesses, into a more peaceful fungal component.

"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," Rajini Rao, Ph.D., a professor of physiology in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine said, via a press release. "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."

Background information from the study notes that Candida lives in most people's intestines as one of the many so-called "commensal microbes" and is relatively harmless. Yet sometimes this can cause local infections of the mouth or the genitals, including thrush, which can be easily treated with over-the-counter antifungals.

However, Candida can cross into the bloodstream and produce long filaments that dig into tissues and even destroy them. And unfortunately, "there are only a few antifungal drugs, so it's particularly dangerous when drug resistance develops in Candida," Rao said, via the release. For that reason, she says, "we're always looking for new chinks in its armor."

Researchers looked for this detrimental issue in Candida cells known as the vacuole. The vacuole's work as a recycling center for cellular waste. Previous studies showed that antifungal drugs prevented the vacuole from becoming acidic, yet this led them to suspect that acidification of the area was caused by various genes with more than one version of a subunit.

The study concludes with the following, via the release: "Rao said first they altered Candida cells so that they could only use one or the other version of the subunit a gene. As expected, they found that inactivating either one had no effect because the other compensates in every function - except one. It turned out that acidification of the vacuole exclusively depended on one version of the gene. This allowed them to test the importance of the vacuole's acidity on virulence, separate from the many other functions of the V-ATPase. Unable to acidify the vacuole, the fungus could no longer form the tentacle-like filaments that characterize its deadly form. When the researchers injected healthy Candida into the bloodstream of mice, nearly all died within a week. In contrast, mice injected with the strain of fungus that was unable to acidify the vacuole remained healthy and survived.

"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."

More information regarding the study can be found via the The Journal of Biological Chemistry.