Professor of Biology Melinda GrosserA staph infection, caused by the bacterium Staphylococcus aureus (S. aureus), is a fairly common skin infection. Most cases resolve on their own or with antibiotics. But for people who are immunocompromised, have a long-term medical device in their bodies, or are recovering from surgery, the infection can spread to their blood and key organs, including their hearts with often devastating consequences. In fact, staph infections kill more than 20,000 Americans each year.
University of North Carolina Asheville Professor of Biology Melinda Grosser is working on a project that may help researchers understand how to best treat staph infections. In collaboration with Assistant Professor of Chemistry Caitlin McMahon, Grosser has been awarded an American Heart Association (AHA) Institutional Research Enhancement Award (AIREA) grant for $153,998 for this study, titled “The contribution of YqeK, a diadenosine tetraphosphate hydrolase, to pathogenic traits of Staphylococcus aureus.”
This enhancement award is specifically given to institutions that are primarily undergraduate and don’t receive much federal funding. For the next two years, it will allow Grosser to hire four full-time undergraduate students each summer, fund supplies and sequencing and an academic collaborator.
Grosser started working on Staphylococcus aureus and how it interacts with the human immune system in graduate school. “Staph can infect basically any tissue of the body,” she says. “If the body isn’t able to contain it at the site of infection, then it can escape into the bloodstream and colonize other sites in the body.” Sometimes it forms a biofilm where the bacteria live in a community that is much harder for the immune system to clear. “They secrete a matrix of proteins and polysaccharide sugars and other stuff that protects them from antibiotics and your immune system.”
In her research, Grosser and her team deleted a gene, yqeK, that degrades a signaling molecule called diadenosine tetraphosphate (Ap4A) inside the individual S. aureus cells. For this new study, they will take strains of S. aureus with more or less of the signaling molecule and perform RNA sequencing to test how bacteria behave both without yqeK and with an excess of yqeK.
“We’re trying to figure out what the signal, AP4A, is doing inside the cell,” she says. “We think some of the signal is contributing to its ability to survive in those biofilms. But we don’t know how.” The study will help them better understand how these biofilms form and how they can be weakened.
“Our results will lay the groundwork for new treatment ideas,” Grosser says.
Grosser and her team will recreate conditions that closely resemble that of a staph infection in the heart by creating biofilm communities in the lab. To more closely mimic a human taking antibiotics, they’re also setting up a new simulated endocardial vegetation model to mix S. aureus with human serum, platelets, and clotting factors from human blood to form a mass of bacteria and proteins. This is similar to what grows on heart valves. Finally, to model the circulatory system, they will also have a pump system in place. Although this model has been used previously to test drug efficacy, researchers haven’t used this sort of set-up much in the context of looking at the bacterial genes and proteins important to the infection process. “It’s a lot more representative of a real infection condition than growing staph in a test tube, and we’re going to be using it in a unique way.”
Drug resistant strains of staph are on the rise, and this work will be important to combating them in the future. According to Grosser, “understanding staph physiology is going to be important to leading us to new drug targets that people haven’t explored before.”
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