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 multiple labs across the globe for over 50 years, this massive phage (e.g., megaphage) has now been fully mapped for the first time, thanks to this Charlotte-led effort. Due to the proximity of computer science and life sciences at UNC Charlotte’s Center for Computational Intelligence to Predict Health and Environmental Risks, also known as CIPHER, — the use of AI is coming to the fore in and is revolutionizing science to solve life-threatening problems such as multi-drug resistant bacteria.

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 Assistant Professor of Bioinformatics and Genomics Richard Allen White III, who is also affiliate faculty of the North Carolina Research Campus and the Charlotte Artificial Intelligence Institute. Instrumental in the effort were collaborators from three other institutions: Julie 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 been discovered only via computation on environmental DNA data. Typically, researchers have been unable to grow and culture these megaphages within laboratory conditions. In contrast, 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 and build the tools to drive the research and applications further.

Phages infect, kill and reproduce exclusively within bacteria. They do not cause disease directly in humans but can modify bacteria in ways that cause disease or promote health. Phages long have 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 with other phages — over three times larger physically than many. 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 computationally by environmental DNA analyses from the guts of moose. Oddly, Phage G doesn’t appear to use moose as a primary host. For decades, some scientists have shared the apocryphal story of an unknowing graduate student in Rome tracking the phage into their research lab. For now, the true origin of phage G is unknown. 

In terms of applications, phages can be used as an alternative or supplement to antibiotics to fight increasingly resilient diseases. "Phages have a lot of applications in health care 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 are a great way to transport genetic information to attack a target."

“Megaphages are present throughout our bodies and the environment. However, culturing has proved illusive. 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.

Thanks to the advanced computational techniques used by White with his students, including artificial intelligence-driven analysis methods to predict Phage G’s taxonomy, life cycle, and protein structure, UNC Charlotte researchers like Buchan and Wiedman are able to push their field forward with transformative applications to fight disease and promote health.

“Biological data is famous for its amount of noise, so all of these AI tools are really important to make sense of it all,” Wiedman said. “Working at UNC Charlotte, we’ve demonstrated the importance of these computational tools firsthand.”

Buchan, A., Wiedman, S., Lambirth, K., Bellanger-Perry, M., Figueroa, J., Wright, E., Suresh, P., Zhang, Q. Thomas, J., Serwer, P. and White, R.  Unlocking the genomic repertoire of a cultivated megaphage. Nature npj Viruses 3, 71 (2025). https://doi.org/10.1038/s44298-025-00150-9

https://www.nature.com/articles/s44298-025-00150-9