In late August, the University of North Carolina will be celebrating its modern and historical ties with Ireland through a week-long series of academic, cultural, sports, and business events in Dublin. The week will then end in true Tar Heel fashion: with a football game against Texas Christian University at Aviva Stadium.
Ireland's influence runs deep in North Carolina's history. Scots-Irish settlers were among the first to establish communities in the Appalachians and along the coast. Today, Ireland continues to shape the Tar Heel State's future through biomedical and pharmacological research.
Microbiologists Brian Conlon, PhD, and his wife Sarah Rowe-Conlon, PhD, embody this connection through their innovative approaches to combat antibiotic tolerance. The Irish-born husband and wife duo first arrived at the University of North Carolina - Chapel Hill 10 years ago to establish a lab, drawn by its strong scientific ecosystem and proximity to their motherland.
"Ireland has long been a real strength in the Staphylococcus aureus research," said Conlon, who is a professor of microbiology and immunology at the UNC School of Medicine. "We came here to continue that work because this is not a problem unique to Ireland. This is a global problem that is in desperate need of a solution."
Colorized scanning electron micrograph of methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Credit: National Institute of Allergy and Infectious Diseases
Their research focuses on combatting difficult-to-treat infections caused by Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. Antibiotics, which are designed to kill the bacteria or keep them from reproducing, don't always work.
Some bacteria can evolve and evade lethal doses of antibiotics. But there is rising evidence that other factors, like our own immune systems, might also be contributing to antibiotic failure. The complex problem typically manifests in patient populations who frequently experience chronic wounds and reoccurring infections, such as those with diabetes.
According to the World Health Organization (WHO), antibiotic-resistant bacterial infections cause about 1.5 million deaths worldwide each year. To improve antibiotic use and help prevent further harm, Conlon and Rowe-Conlon have launched several research projects:
When the Immune System Gets in the Way
Last year, the Conlon lab uncovered an unexpected way the body's own immune response can contribute to antibiotic treatment failure. Their study, published in the Proceedings of the National Academy of Sciences, showed that a major innate immune protein sequesters essential metals, inadvertently protecting bacteria from killing by β-lactam antibiotics, including penicillin and amoxicillin. The lab is now developing therapeutic strategies to prevent this host-driven antibiotic tolerance and improve the effectiveness of existing antibiotics.
A New Strategy to Prevent Antibiotic Failure
In a study published in Nature Microbiology, the Conlon lab identified a small molecule that restores the ability of antibiotics to kill dormant bacteria in models of Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella infections. Rather than targeting the bacteria directly, the molecule "wakes up" dormant bacteria residing within immune cells, making them susceptible to antibiotic treatment. The lab is now working to develop this approach into a new therapeutic strategy that could improve treatment of persistent bacterial infections.
New and Innovative Ways to Kill MRSA
The cover art illustrates ultrasound-mediated drug delivery into a biofilm-infected wound. Illustration by Ella Marushchenko.
Rowe-Conlon has been working on a different approach. In 2023, she joined forces with researchers at the Lampe Joint Department of Biomedical Engineering to help remove the physical defensive barriers surrounding methicillin-resistant Staphylococcus aureus (MRSA) cells.
The new method uses non-invasive ultrasound to agitate biofilm - a slick, slimy forcefield that neither immune cells nor antibiotics can penetrate through. The mechanical action of the ultrasound creates spaces in the biofilm that drugs can squeeze through to kill the bacteria within.
"This therapeutic strategy has the potential to improve outcomes and reduce relapse of chronic wound infections in patients," said senior author Rowe-Conlon, an associate professor in the Department of Microbiology and Immunology. "We are excited about the potential of translating this to the clinic, and that's what we're exploring right now."
Understanding an Emerging Superbug
In a study published in the Proceedings of the National Academy of Sciences (PNAS), Rowe-Conlon's team discovered that antibiotics successfully reach therapeutic concentrations within Klebsiella pneumoniae liver abscesses, yet still fail to eliminate the bacteria. The finding revealed that antibiotic tolerance-not poor drug penetration-is a major driver of treatment failure, reshaping how researchers think about these life-threatening infections.
Irish Homecomings
Bringing their work full circle, Conlon and Rowe-Conlon returned to Northern Ireland last year to discuss biofilms with researchers at Queen's University Belfast, where they shared their latest findings, toured facilities, and connected with other researchers in the field.
When the opportunity arises, the couple also takes advantage of North Carolina's direct flights to Ireland to visit friends and loved ones back home. There, they enjoy the things they miss most about Ireland - including its high-quality seafood - with their nine-year-old son, Patrick, and seven-year-old daughter, Ciara.
