Researchers at the University of North Carolina Asheville, led by Associate Professor of Biology Melinda R. Grosser alongside a team of undergraduate students, published a study in the peer-reviewed Journal of Bacteriology identifying a potential new drug target in Staphylococcus aureus. By disabling the YqeK enzyme, the team found they could strip the drug-resistant bacteria of its toxicity without using conventional antibiotics.
Antibiotic resistance remains a major bottleneck in modern clinical microbiology. Traditional bactericidal therapeutics rely on directly killing pathogenic strains or halting their replication.
The UNC Asheville research team took a fundamentally different architectural approach. Instead of engineering a molecule to destroy the pathogen, they focused on disarming its pathogenesis machinery.
Targeting the YqeK Enzyme Pathway
At the center of the discovery is YqeK, an intracellular enzyme that Staphylococcus aureus uses to clear out toxic stress-signaling molecules. Under normal, highly controlled laboratory growth conditions, the bacteria can function without this enzyme. But inside a human host, the cellular microenvironment turns hostile, volatile, and metabolically stressful.
When the research team removed YqeK from the bacterial genome, the organism struggled significantly under those simulated host-like conditions. Furthermore, the crippled bacteria lost much of their hemolytic capability—specifically, their destructive effect on red blood cells.
“We were excited to find that this enzyme hardly matters during normal growth but becomes critical during conditions bacteria would face in a host,” Professor Grosser explained, according to university disclosures. That exact vulnerability transforms YqeK into an ideal therapeutic target. Inhibiting it could blunt disease severity during an active infection while drastically reducing the selective evolutionary pressure that drives resistance.
Undergraduate-Led Discovery and Academic Collaboration
The published findings represent a four-year investigative effort housed inside the Department of Biology at UNC Asheville, paired with cross-departmental collaboration from Caitlin McMahon, Ph. D. in the Department of Chemistry & Biochemistry. Notably, the project relied heavily on undergraduate researchers.
Recent graduate Jenna Vidaud, who finished her studies at UNC Asheville with a double major in Biology and Chemistry & Biochemistry, led the project as part of her undergraduate research track. Vidaud and several peers anchored their senior theses to the data generated in Grosser’s lab.
Jackson Coker, an early contributor to the research group and now a medical student at East Tennessee State University, authored an initial thesis that laid critical groundwork for securing early project funding. In total, 12 undergraduate students contributed as co-authors on the Journal of Bacteriology paper, which was published by the American Society for Microbiology.
Funding and Future Therapeutic Implications
The four-year study received primary funding from an American Heart Association award granted to Grosser in 2023. Additional financial support came from the UNC Asheville Undergraduate Research and Creative Activity Program, the Steve and Frosene Zeis Professorship, the Forrest Fund for Undergraduate Research, and the Chemistry Scholars Program Early Undergraduate Research Fellowship via NSF S-STEM Grant 1833604.
As academic laboratories and pharmaceutical pipelines look beyond traditional small-molecule antibiotics, anti-virulence strategies like the YqeK disruption model offer a promising blueprint. By targeting mechanisms of disease rather than mechanisms of survival, researchers may soon outmaneuver the evolutionary adaptability of dangerous hospital- and community-acquired pathogens.
