Scientists Discover New Drug Candidate for Dangerous Fungal Lung Infections

Fungal infections are some of the most difficult and expensive to cure. On a molecular level, both humans and fungi share similar proteins, a biological bond that complicates treatments. In fact, current methods can top $50,000 per patient. Now, though, scientists may have developed a new compound that could combat these fungal infections. It could be used as an antifungal drug to treat both histoplasmosis and cryptococcosis.

Generally, people with weakened immune systems are more likely to develop life-threatening fungal infections. Yet the airborne fungus, Histoplasma capsulatum, which causes histoplasmosis, can also infect healthy people. Complicating matters is the fact that both histoplasmos and crytococcosis are two types of fungal infections that are naturally drug resistant.

"Histoplasmosis is an unusual fungal disease because anyone can be infected, not just people with compromised immune systems," said Chad Rappleye, one of the researchers, in a news release. "Like tuberculosis, Histoplasma infects healthy hosts, attacks their lungs, and can lie dormant in immune cells for years, later causing reactivation disease. So this is an unrecognized public health threat that's needed better treatment options for some time."

That's why scientists decided to focus their efforts on designing a new way to treat these fungi. The researchers searched a library of commercially-available small molecules used by other investigators in order to find new antivirals or anticancer drugs. The scientists then performed a high-throughput phenotypic screen of 3,600 compounds looking for agents that inhibited fungal, but not human, cells. In order to speed this selection process, the researchers engineered Histoplasma cells with a fluorescent protein that made the cells glow red while inside of a living macrophage, the type of mammaliam immune cell that the fungus attacks.

So what did they find? They discovered a primary candidate to treat the fungi called 41F5, which is 60 times more toxic to fungal cells than human cells. Currently, the researchers hope to see if the selectivity and toxicity profile can be enhanced further for additional testing.

"There are people in the U.S. and around the world suffering from varying degrees of histoplasmosis that need a safer and better treatment option," said Rappleye in a news release. "Our pilot study outcomes and methods are very encouraging, and I'm hopeful that with additional funding from the National Institutes of Health, we'll be able to keep moving at this accelerated pace."