UNC Charlotte researchers use AI to map out world’s largest cultivated bacteria-killing virus
Through cutting-edge methods and advanced artificial intelligence analysis, UNC Charlotte researchers leading a multidisciplinary team across four universities have successfully resolved the entire genome of “phage G,” the largest bacterial virus (aka bacteriophages or phages) ever cultivated in a physical lab environment.
Studied by labs across the globe for over fifty years, this massive phage (i.e., megaphage) has now been fully mapped-out for the first time thanks to this Charlotte-led effort. This unprecedented analysis will be a boon for scientists working to solve life-threatening problems tied to multi-drug resistant bacteria the world over.
Published Sept. 30 in leading journal Nature’s NPJ Viruses, the study was led by UNC Charlotte College of Computing and Informatics Bioinformatics and Genomics master’s students Andra Buchan and Stephanie Wiedman along with UNC Charlotte Assistant Professor of Bioinformatics and Genomics Richard Allen White III, affiliate faculty of the North Carolina Research Campus, the Center for Computational Intelligence to Predict Health & Environmental Risks and the Charlotte Artificial Intelligence Institute. Also instrumental in the effort were collaborators from three other institutions: Juile A. Thomas from Rochester Institute of Technology’s Gosnell School of Life Science, Qibin Zhang from the University of North Carolina at Greensboro and Philip Serwer from UT Health San Antonio.
Environmental DNA sequencing has shown that megaphages are extremely prevalent — from deep in the guts of humans to natural ecosystems — but historically have only been discovered digitally. So far, researchers have been unable to grow and culture these megaphages within laboratory conditions. Phage G is the only megaphage that scientists can grow in laboratories and the first of its kind that can be observed physically within the lab. This allows researchers to conduct direct experiments, providing a new model system to study megaphages.
Photo credit: Kayla Lenz and Richard Allen White III.
Phages evolved specifically to infect, kill and reproduce exclusively within bacteria, and cause no known disease in humans. They’ve long been a subject of interest for scientists, including Buchan, Wiedman, and their fellow researchers in White’s UNC Charlotte research lab.
Phage G is massive in size compared to other phages over 3-times larger physically compared to common phages. Its massive size is proportional to the level of mystery by which it is surrounded; Phage G shares much in common with another megaphage found digitally by DNA sequencing data inside the guts of moose, but doesn’t appear to be moose-borne itself. For decades, some scientists have shared the apocryphal story that an unknowing Italian graduate student tracked the phage into their research lab, but the true origin of phage G is unknown.
Phages could be used as an alternative or supplement to antibiotics to fight increasingly resilient diseases. “Phages could have a lot of applications in healthcare right now, especially in light of the ongoing antimicrobial resistance crisis,” Buchan said. “Think of them as packages of DNA that you can deliver to a source. We believe they could be a great way to transport genetic information to a target.”
The laboratory history of phage G, spanning 50 years of cultivation in multiple labs.
“Megaphages are present throughout our bodies and the environment. However, none have ever been cultured. Thus, G phage offers us an invaluable model to study megaphages in the lab,” said White. “We’re fundamentally trying to determine what ecology drives viruses to evolve to this size, and what selection provides a niche that allows them to coexist with smaller, more rapidly growing viruses under massive competition,” said White.
Lifecycle model of phage G within its bacterial host. Illustration by Andra Buchan.
Thanks to the advanced computational techniques used by White with his students, including state of the art artificial intelligence-assisted analysis methods, UNC Charlotte scholars like Buchan and Wiedman are able to push their field forward with potentially transformative applications for global health.
“Biological data is famous for its amount of noise, so all of these advanced tools are really important,” Wiedman said. “Working at UNC Charlotte, we’ve experienced the importance of these computational tools firsthand.”
Buchan, A., Wiedman, S., Lambirth, K. et al. Unlocking the genomic repertoire of a cultivated megaphage. Nature npj Viruses 3, 71 (2025). https://doi.org/10.1038/s44298-025-00150-9