Professors from the colleges of Agriculture and Pharmacy are working on a project to discover treatments for fungal infections through Purdue's One Health strategic initiative.
Fungal infections are problematic for people who have chronic health conditions or are immunocompromised. This is a growing issue due to the rising population of people who have health concerns like diabetes or are taking immunosuppressing drugs for autoimmune disease, according to an article from the college of Agriculture.
"Fungal infections kill almost four million people a year around the world," said Mark Hall, a professor and associate department head of biochemistry. "More people now die from fungal infections than from malaria and tuberculosis combined."
Additionally, Hall noted that many deaths from COVID-19 were a result of secondary infections such as those caused by aspergillus, a kind of fungus that infects the lungs.
One of the problems with treating fungal infections is that these pathogens are increasingly developing resistance to the drugs currently being used. Some scientists suggest agriculture practices are a cause of this drug resistance.
"One of the most widely used classes of antifungal drugs are called azoles and they're often used in agricultural settings as an antifungal pesticide.
The azoles would eliminate most of the fungus but resistant fungi would survive and become harder to treat with current drugs, he said.
"There's a hypothesis that some of the resistance is coming from (agricultural practices) and not just from applications in healthcare settings."
According to the article, a study published in Frontiers in Microbiology led by Zhong-Yin Zhang, a professor of medicinal chemistry, showed the Cdc14 enzyme is critically important for a pathogen to infect a host.
"Through a collaboration here at Purdue, we discovered by chance that when fungal pathogens don't have this enzyme, they're unable to establish an infection in their target host," Hall said. "We originally saw it in a plant pathogen that affects crops ... we then decided to look in human pathogens to see if the same thing was true."
In a later study published in the Journal of Medicinal Chemistry, the Zhang lab identified a compound that specifically targets Cdc14 and could potentially be helpful in preventing fungal infections, though this research has only been demonstrated in animal models.
Research on the Cdc14 enzyme may also be significant for cancer patients, according to Hall, who noted that a potential drug might protect high risk patients from fungal infection.
"Fungal pathogens mostly infect people with compromised immune systems. Healthy people rarely get fungal infections but cancer patients are often taking aggressive chemotherapy treatments that suppress the immune system, which is why you commonly see fungal infections with chemotherapy patients," Hall said. "The drug could be used to help prevent this."
Zhang, whose lab published the enzyme study, has been involved in drug discovery for other diseases, but this new collaboration is his first work on fungal infections.
"The goal is to improve upon the molecule that we have already tested. I would call it a first-generation Cdc14 inhibitor," Zhang said.
Jinhong Chen, a synthetic chemist, is collaborating with Hall and Zhang to improve the effectiveness of the first generation inhibitor by improving the design of the molecule. His research involves using two different molecular design strategies: fragment based design and structure based design.
Fragment based design is a ground-up approach of creating a new molecule. While, structure based design involves developing a new molecule by refining a preexisting molecule.
"Then we synthesize these (molecules), purify them, characterize them and test them (to only target the Cdc14 protein)," Chen said.
"There are hundreds of proteins in the human genome, plants and other organisms," Zhang said. "We want to make sure they're specific for the target."
Campus
Students band together to stop the stigma around substance use disorder
* By JOHN MILES Staff Reporter
Campus
Astronaut Scholarship launches 3 Purdue students to new heights