According to a 2013 report given by the Centers for Disease Control and Prevention, 2 million people are infected with antibiotic-resistant bacteria each year.
Worse still, 23,000 of those 2 million people die as a direct result of their infections.
“Antibiotic resistance is a growing problem, and people are not necessarily aware,” said Penn State Ph.D. candidate Erica Schwalm. “We go to the doctor, we get a set of antibiotics, and we feel better, but bacteria evolve very quickly to combat the mechanisms we make to kill them, and eventually the mechanisms we have to treat infections are going to stop working. Pushing research into antibiotic development is essential.”
Schwalm, a UA chemistry alumna, has been studying antibiotic-resistant enzymes for the last six years, and in 2016, when she was just 26 years old, one of her groundbreaking collaborations on the topic was featured in Science, the leading scientific magazine in the world.
“My research focuses on two enzymes that modify RNA in the ribosome, which is where proteins are made,” Schwalm said. “We are interested in these enzymes not only because they do difficult chemistry, but they’re also implicated in antibiotic resistance.”
The two enzymes, evolutionarily related to one another, are RlmN and Cfr. The Cfr enzyme is one of the mechanisms responsible for modifying bacteria so that they are antibiotic resistant, but until Schwalm’s research, scientists did not have an avenue for understanding how.
To get a clue into the process, Schwalm and her colleagues ventured to capture an image of RlmN in the process of modifying RNA because RlmN is structurally similar to Cfr. First, the team grew E. Coli cells with the RlmN protein, then crystalized the protein, and used high-energy x-rays to see a snapshot of what is going on.
After analyzing hundreds of samples into the middle of the night, Schwalm identified the image they’d been searching for at 2 a.m. in the morning.
“I was very excited,” Schwalm said. “After months and months of work, we finally had something that could answer our question and tell us what we were looking for.”
Schwalm, who has already been hired to work for Merck Pharmaceuticals after graduation, says that now that the RlmN structure has been identified, scientists will be able to design countermeasures to the Cfr enzyme and the bacteria it modifies by theoretically designing molecules that will cause the enzymes not to work.
“A lot of drug design comes from being able to look at an enzyme and see what interactions are important,” Schwalm said. “By knowing the structure, we can theoretically design molecules that would bind in a certain orientation and cause these enzymes to not work anymore.”
“I knew, starting the project, that it was important to people and it would be high-impact if we could get the right results, but I had never thought, starting grad school, that I would have a Science publication when I was done.”
Schwalm successfully defended her dissertation and earned her PhD in chemistry from Penn State University in spring 2018. That summer, she moved to Rahway, NJ to work for Merck as a senior scientist in the Small Molecule Analytical Research and Development Department. Here, she focuses on developing analytical methods for potential small molecule pharmaceuticals as they move through the development pipeline.
“We work to create methods and perform testing that will allow a full understanding of the synthetic process,” Schwalm said. “It is highly collaborative work that involves a lot of problem solving and troubleshooting in order to drive pharmaceutical development to provide patients with novel medications.”
Schwalm is currently working with islatravir, which is used to treat and potentially prevent HIV. In 2019, the compound was highlighted in The New York Times and Science. Schwalm and her team are currently working to characterize parts of the biocatalytic cascade and the enzymes involved.