Researchers at Ohio State University’s Departments of Microbiology and Microbial Infection and Immunity recently discovered a new compound that could be developed as an antifungal drug to treat drug-resistant fungal infections, according to a study published in Antimicrobial Agents and Chemotherapy.
The airborne fungus Histoplasma capsulatum causes histoplasmosis, which manifests with flu-like symptoms, increasing the difficulty of diagnosis. Histoplasma capsulatum spores are found across a broad stretch of the Midwest and southern United States. Experts estimate that 80% of people who live in the region have been exposed, and that nearly 10 to 25% of all AIDS patients living in these areas will develop a histoplasmosis infection.
Once inhaled, the fungal cells can cause symptoms similar to an upper respiratory infection, and disease severity is dependent on how many spores are inhaled. In rare cases, histoplasmosis can cause blindness, joint pain, or life-threatening complications including meningitis and heart problems.
“Histoplasmosis is an unusual fungal disease because anyone can be infected, not just people with compromised immune systems. Like tuberculosis, Histoplasma infects healthy hosts, attacks their lungs, and can lie dormant in immune cells for years, later causing reactivation disease,” said Chad Rappleye, PhD, a microbiologist in the Center for Microbial Interface Biology at Ohio State’s Wexner Medical Center. “So this is an unrecognized public health threat that’s needed better treatment options for some time.”
In its efforts to find a new drug that could target the fungus without harming the human host, the team performed a high-throughput phenotypic screen of 3,600 compounds looking for agents that inhibited fungal, but not human, cells. They narrowed the number down to a primary candidate called 41F5, which is 60 times more toxic to fungal cells than human cells.
“There are people here in the U.S. and around the world suffering from varying degrees of histoplasmosis that need a safer and better treatment option,” said Rappleye. “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.”