UNC Asheville Faculty Amanda Wolfe and Ryan Steed Receive NIH Award To Develop New Antibiotic Addressing Drug-Resistant Strains of Bacteria

February 21, 2022

At the University of North Carolina Asheville, 2022-2027 GlaxoSmithKline Distinguished Professor in Molecular and Chemical Biology Amanda Wolfe (PI) and Assistant Professor of Chemistry Ryan Steed (CO-PI) are combining their individual research specialties of Medicinal Chemistry and Biomolecular Chemistry, respectively, to potentially turn the pharmaceutical industry on its head. Their goal is to develop a new antibiotic that treats a form of bacteria that is currently antibiotic treatment-resistant. Their initial research, conducted entirely with UNC Asheville undergraduate research students, has been promising. So promising that the team has received a National Institutes of Health Academic Research Enhancement Award of over $380,000 to continue developing their research, and support six students with stipends to work on the project full time over the next three summers.

Pseudomonas aeruginosa is a type of bacteria spread in hospitals and health care environments. This antibiotic-resistant strain of bacteria is transmitted through water or soil and spreads from person to person via contaminated hands, surfaces, and equipment. For those already immune-compromised, the infection from Pseudomonas aeruginosa in the blood, lungs, or other parts of the body post-surgery can be deadly. In the U.S., between 32-33k people may contract this bacteria in a hospital setting, with 2,700 deaths reported annually.

2022-2027 GlaxoSmithKline Distinguished Professor in Molecular and Chemical Biology Amanda Wolfe

So far, very little work has been done to target ATP synthase in Pseudomonas aeruginosa. This new antibiotic would be able to eliminate drug-resistant strains of Pseudomonas aeruginosa because it works in a novel way,” explains Wolfe regarding the new antibiotic that her team is developing. “Our approach is unique from how other antibiotics function because most target parts of the bacterial cell that have evolved over time to be less affected by current antibiotics. We are developing a series of antibiotics that selectively target ATP synthase in Pseudomonas aeruginosa and cause bacterial cell death. Bacteria will have no defense against it.”

Explains Steed, “Pseudomonas aeruginosa, and other similar bacteria, are very good at keeping toxic molecules from entering the cell. Part of this research aims to address this barrier by improving the penetration of antibiotics into the bacterial cell. If we find a successful molecular strategy, it could be applied to other drug-resistant bacteria.”

Assistant Professor of Chemistry Ryan Steed

Drug-resistant bacteria are on the rise and are labeled a severe threat by the CDC. And according to WHO, if no action is taken, drug-resistant diseases could account for 10 million deaths each year by 2050. With infectious diseases becoming increasingly more challenging to treat, humans will become progressively exposed to harmful bacteria that can be transmitted during routine medical procedures.

“There is a great need for the constant development of new and unique antibiotics since bacteria will always evolve and become resistant to current antibiotics,” says Wolfe. “This work will help with the current bacterial resistance issue by developing novel antibiotics that target ATP synthase while also developing new molecular technology for delivering the antibiotics to the interior of the bacterial cell.”

The development of a new antibiotic not only has the potential of helping individuals that have contracted Pseudomonas aeruginosa, but also common bacteria that is currently on a trajectory to becoming antibiotic-resistant.

Teamwork at UNC Asheville is the crux of this noteworthy research. “Because it spans the fields of medicinal chemistry and biophysical chemistry, this type of project wouldn’t be possible without collaboration,” says Wolfe. The project was piloted in an upper-level laboratory course; chemistry undergraduates collected data over multiple semesters to provide preliminary data to submit for the NIH grant proposal. “This aspect is pretty unique and demonstrates the type of applied and cutting edge education-focused research that we provide our chemistry majors at UNC Asheville.”