NC State receives $1.8M defense grant to test molecule efficacy against antibiotic-resistant infections

A new $1.8 million grant from the Department of Defense will allow North Carolina State University researchers to work with the Walter Reed Institute of Research to further test the effectiveness of molecules that have shown great promise in combating antibiotic-resistant infections.

The two-and-a-half-year project will show the efficacy of molecules created by NC State's Dr. Christian Melander and Dr. John Cavanagh against different types of animal cells infected with bacteria - like methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Acinetobacter baumannii (MDRAB) and Pseudomonas aeruginosa - that wreak havoc across the globe.

"These three drug-resistant infections have been - until now - practically untreatable," Cavanagh says.

Published studies have shown the NC State molecules break up harmful bacterial accumulations called biofilms, causing them to revert to their single-celled state, where they can be destroyed by antibiotics. The molecules effectively take the "methicillin-resistant" out of MRSA, the NC State researchers say, and the "multi-drug resistant" out of MDRAB. Perhaps more importantly, the molecules appear to be non-toxic to cells and model organisms.

MRSA is a widespread and dangerous infection resistant to more than a dozen common antibiotics, including methicillin, penicillin and amoxicillin. MDRAB is arguably scarier. Up to 1,000 times more resistant than MRSA, it is found in hospitals and attacks patients who have compromised immune systems. Both, along with Pseudomonas, plague the military. Wounded soldiers are often more adversely affected by infections than the wounds themselves, the researchers say.

Which is where the Army's Defense Medical Research and Development Program comes in. Military wound infection experts at the Walter Reed Army Institute of Research want to see how the NC State molecules work in different conditions.

"There will be a massive effort between our two labs to identify the leading candidates that both make antibiotics work again and have a low toxicity profile," Melander says. "Our molecules will be tested against multiple animal models of infection."

Melander, an associate professor of chemistry, and Cavanagh, William Neal Reynolds Distinguished Professor of Molecular and Structural Biochemistry, created molecules that mimic ageliferin, a sea-sponge chemical compound that confounds biofilms. They started a company, Agile Sciences, to put these chemical compounds to use in medical, industrial and agricultural settings - where infections come in many different stripes but have the same result: death and destruction.