New drug candidate discovered for fungal lung infections

New drug candidate discovered for fungal lung infections

There are an estimated 100,000 Histoplasma infections in the U.S. each year.

Humans and fungi share similar proteins. This biological bond makes curing fungal infections difficult and expensive. The current cost of treatment for these infections can be around $50,000 per patient and no new anti-fungal drugs that can treat systemic infections have been introduced for about 20 years.

According to a new press release, however, researchers at The Ohio State University Wexner Medical Center have discovered a new compound that could potentially be developed into an anti-fungal drug to treat histoplasmosis and cryptococcosis, two types of fungal infections that are naturally drug resistant.

In general, people with a weakened immune system are more likely to develop life threatening fungal infections, but the airborne fungus Histoplasma capsulatum, which causes histoplasmosis, can infect completely healthy individuals too.

“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 and in the Department of Microbial Infection and Immunity at Ohio State’s College of Medicine. “So this is an unrecognized public health threat that’s needed better treatment options for some time.”

There are an estimated 100,000 Histoplasma infections in the U.S. each year. Most are contained by the body’s own immune system, but each year a few thousand people will develop chronic or life threatening histoplasmosis that requires hospitalization and anti-fungal treatment. Currently prescribed anti-fungals can have some very toxic side effects so close monitoring is required. The course of treatment can also last several weeks or even months.

Histoplasma is particularly good at avoiding detection by the body’s immune system and surviving the immune response,” said Jessica Edwards, PhD, a postdoctoral researcher at Ohio State University.

Rappleye’s research team searched a library of commercially available small molecules used by other investigators to find new antivirals or anticancer drugs. They performed a high-throughput phenotypic screen of 3,600 compounds looking for agents that inhibited fungal cells without effecting human cells.

To speed up the process, the researchers engineered Histoplasma cells with a fluorescent protein that made them glow red while inside of a living macrophage, the type of immune cell that Histoplasma attacks and reproduces in.

The research team narrowed their search to a primary candidate called 41F5, which is 60 times more toxic to fungal cells than human cells.

This research work was published in the September issue of Antimicrobial Agents and Chemotherapy.

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