Synthetic Polymers May Help Stop Deadly Fungal Infections
Washington, DC – May 23, 2018 – Researchers who develop novel treatments for treatment-resistant fungal infections have found a new ally: Synthetic polymers. This week in mSphere, an interdisciplinary team reports on three nylon polymers that inhibit the growth of a spectrum of diverse pathogenic fungi, including many resistant strains. Those included Rhizopus arrhizus, which can cause a life-threatening disease called mucormycosis in immunocompromised patients, and Scedosporium prolificans, an emerging pathogen that's intrinsically resistant to available drugs and causes often-fatal infections.
Based on their previous studies, the researchers knew the polymers could inhibit some pathogenic species, but say they were surprised to see how many species responded in the new work. “The fungi are very spread out, in a biochemical way,” says microbiologist Nancy Keller at the University of Wisconsin-Madison, who co-led the study. “There was no way of predicting the polymers would be active against such a wide breadth of taxa.” (image: Rhizopus zygospores, Wikimedia commons)
The researchers measured the minimum concentration of the polymer that halted the growth of the fungi in 41 species, representing 18 genera. They compared the concentrations of the polymers to those of azoles, which are common anti-fungal drugs. The polymers inhibited fungal growth in 24 species, including some that are resistant to azoles. Consistent with earlier studies, the researchers found that species in the Aspergillus genus, a common mold that can cause problems in people with lung problems, did not respond to the polymers.
Keller collaborated with microbiologist Christina Hull and chemist Samuel Gellman, all at the University of Wisconsin. Chemist Leslie Rank, who works in Gellman's lab, led the study. She and her colleagues developed the polymers, which have been previously investigated for their promising antibacterial properties. Very few therapeutics currently use polymers to treat disease, says Gellman, but perhaps that should change in light of the antifungal and antibacterial activity of these compounds. “Observations of this type should encourage the community to consider polymers as potentially useful biomedical agents,” he says.
The new paper also reports finding synergistic effects that emerged between the polymers and existing antifungals. The combination of the agents caused most of the tested resistant strains to become resensitized to treatment. That finding suggests infections that don't respond to the polymers alone might still be treated with a combination of multiple antifungal agents.
Synthetic polymers might also be useful for curbing the devastating effects of fungal infections in other species, including bats and snakes. The current study reports that the polymers effectively inhibit the growth of Pseudogymnoascus destructans, the fungus that causes white nose syndrome in bats, which has devastated bat populations across the United States. Keller, who works with wildlife biologists on emerging fungal infections, says that's an encouraging step toward helping the bats – though it will be difficult to find a way to administer any therapeutic.
Gellman says the researchers became interested in the polymers as a way to mimic the action of peptides produced by the immune system to fight microbial infections. Peptides are a kind of biological polymer, which is a long chain of connected molecules. Using those as a model, researcher in Gellman's lab began assembling synthetic polymers. “There are more structures than we can imagine,” he says. However, he says that even though polymers in the current study show antifungal activity, it's unlikely that they work like the body's defense peptides. “We don't really know how they work,” he says.
# # #
The American Society for Microbiology is the largest single life science society, composed of more than 30,000 scientists and health professionals. ASM's mission is to promote and advance the microbial sciences.
ASM advances the microbial sciences through conferences, publications, certifications and educational opportunities. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.