Building a new antimicrobial medication with inspiration from nature

Roughly 40 years ago, researchers isolated a molecule from Turkish soil that would become daptomycin, an invaluable treatment for skin, bloodstream, and other infections. Now, a team of researchers based at Rowan University hope to improve on nature’s chemistry to better treat potentially dangerous infections like these. 

With funding from the National Institutes of Health (NIH), Gregory Caputo, a professor in the departments of Chemistry & Biochemistry and Biological & Biomedical Sciences in the College of Science & Mathematics, and his colleagues plan to draw on the best features of daptomycin to create a more versatile medication that could replace existing drugs that have become ineffective. 

“It's important that we continue to develop new antimicrobials because bacteria are continuing to develop new ways to fight them,” Caputo said. “We have to keep ahead of the curve.”

The NIH grant, totaling $474,363 over three years, will support work in his lab and in those of his collaborators at Cooper Medical School of Rowan University (CMSRU) and Howard University. 

Every year, antimicrobial medications, including antibiotics, save millions of lives. But inevitably, germs evolve the means to evade them. The Centers for Disease Control and Prevention has estimated that more than 2.8 million infections each year involve medication-resistant bacteria and fungi, and that more than 35,000 people die as a result. 

Daptomycin, a naturally derived peptide, is one type of molecule currently approved to treat certain bacterial infections, including those resistant to other drugs. However, more infections are failing to respond to it as well. 

Originally made by soil bacteria to attack one another, daptomycin binds to calcium on the surface of bacterial cells, then it attaches to and disrupts these cells’ membranes. Although effective, this strategy only works on a type of bacteria known as gram-positive, not their counterparts, gram-negative bacteria.  

Daptomycin has other drawbacks, too. Its chemistry makes it difficult to synthesize in the lab and, because the digestive system readily breaks it down, patients must receive it intravenously.

Caputo and his team hope to overcome these challenges in part by combining pieces of this molecule with another peptide called C18G. Unlike daptomycin, C18G fights both ram-positive and gram-negative bacteria, and it is easier to make in the lab.  

His collaborator Jacqueline Smith, an associate professor of chemistry at Howard University, and her lab will work to alter these compounds so they could be administered in pill form. To accomplish this, her group plans to swap out the chemical building blocks of C18G and daptomycin, known as amino acids, to make them better able to withstand digestion.  

After initial tests in bacteria that do not cause disease, Caputo’s lab intends to send the most promising candidates to another collaborator, Valerie Carabetta, an assistant professor of biomedical sciences at CMSRU. Her lab will evaluate their ability to fight their true targets: disease-causing bacteria isolated from patients’ clinical samples. 

Caputo has hired four undergraduates for the project and intends to bring on a master’s student. These student researchers will build skills in chemistry and microbiology because they will learn how to make molecules and characterize their chemical properties, while also testing their antibacterial activity, he said. “They are going to get both sides of the coin.”