Rich Reservoir of Antifungal Drug Combinations Unveiled at McMaster

Researchers at McMaster University have identified promising leads in the fight against drug-resistant fungal infections.

The discovery comes at a time when there is a scarcity of new drugs to treat systemic fungal pathogens, which have emerged as a leading cause of human mortality. Fungal pathogens are especially deadly in patients undergoing cancer chemotherapy.

In a paper published this week in the journal Cell Reports, researchers from the Michael G. DeGroote Institute for Infectious Disease Research, along with colleagues from McGill and Duke Universities, describe how they tested approximately 86,000 unique drug combinations for activity against a variety of species of fungi.

The resulting dataset, called the Antifungal Combination Matrix (ACM), is the first of its kind and contains hundreds of chemical combinations that blocked fungal growth – the starting point for the development of potential new drugs.

The ACM is a unique and valuable resource of potential antifungal therapies, the authors write, “and it will continue to be exploited for both fundamental biological research and as an approach to accelerate drug discovery.”

A subsequent analysis of the ACM led researchers to profile clofazimine – an old antibiotic used as a combination agent to treat leprosy – as a new candidate to enhance the activity of known antifungal drugs.

“We discovered that clofazimine improved the efficacy of caspofungin, a common antifungal medication used to treat Candida albicans,” says Dr. Nicole Robbins, a postdoctoral fellow in the Wright Lab and the paper’s lead author.

“This particular pathogen is arguably the most problematic in the medical community, especially given its ability to acquire resistance to current medications in the clinic. We hope our study will lead to additional treatment options for C. albicans and other harmful pathogens.”

In 2013, the Centers for Disease Control and Prevention (CDC) identified drug-resistant C. albicans as a “serious threat” to human health.