UVA’s Pires Lab to Lead Pioneering Antibiotic Research Effort

The University of Virginia’s Pires Lab has been awarded a major federal grant to lead research into one of the most urgent threats in modern medicine: drug-resistant bacteria. Chemistry professor Marcos Pires, who also holds appointments in microbiology, cancer and immunology at UVA’s Cancer Center, will head a multi-institutional team supported by a five-year, $6 million Research Project Grant (R01) from the National Institute of Allergy and Infectious Diseases.

The project focuses on Acinetobacter baumannii, a bacterium that has become notorious for causing deadly hospital-acquired infections. The World Health Organization classifies it as a “critical-priority pathogen” because of its ability to evade nearly all existing antibiotics.

Pires’ lab will lead efforts to understand what he calls the “chemical grammar of accumulation” — the rules governing how molecules get into bacterial cells. The approach assumes that if an antibiotic can’t reach its intended destination, it can’t work.

“If molecules can’t get into bacterial cells, they can’t be effective,” Pires said. “That’s the bottleneck we’re trying to solve.”

The NIH structured the grant as a partnership between academic labs and industry experts in drug discovery and AI experts. UVA will serve as the hub, working with collaborators at Genentech in California, the University of Massachusetts and Lehigh University. Together, they aim to generate the data needed to build artificial intelligence models that can predict which compounds will be able to penetrate resistant bacteria effectively, a process that involves studying thousands of compounds to identify those that have the potential to inform the development of more effective synthetic alternatives to natural antibiotics.

We are in the best position of any lab in the world now to be able to pull this off, and I believe we will.

“We’re driving the data that enables the machine learning,” Pires said. “It should be a perfect solution for identifying patterns at the kind of scale we’re working with.”

The grant will provide new resources for UVA’s labs, including advanced chemical libraries and additional support for graduate students and research scientists. “We’ll be able to buy the libraries we need, retain our full-time research scientists and add graduate students,” Pires said. “That’s what will make this possible.”

For Pires, the award is both a source of both excitement and heightened responsibility.

“It’s a burden — in a good way,” he said. “We’re operating as if this is a problem that’s going to get solved, and I think we’re in the right state of mind to take the challenge on.”

George Ongwae, a chemical biologist with the Pires Lab described the work as “pushing the boundaries of innovation.” 

“It’s troubling that pharmaceutical companies are showing less and less interest in investing in antibiotic discovery, Ongwae said. “That’s why it is encouraging to see the federal government step in to address this critical gap.”

“While we are thrilled that this award recognizes our contributions to antimicrobial research,” Ongwae added, “We are equally humbled by the responsibility it carries to transform taxpayers’ dollars into meaningful solutions that move us closer to solving the challenge Acinetobacter baumannii.”

Dean of Arts & Sciences Christa Acampora praised the award as both a recognition of UVA’s strengths and an investment in the College’s future. 

 “Professor Pires’ achievement exemplifies the kind of research that addresses some of the most urgent global challenges while expanding opportunities for our graduate students and faculty,” Acampora said. “This grant advances our priorities of discovery, community impact and preparing the next generation of citizen leaders.” 

Mark Esser, chief scientific officer and head of the Paul and Diane Manning Institute of Biotechnology, UVA’s new research and development center focused on advancing cellular, gene and immunotherapies, also acknowledged the importance of the project.

“I’m thrilled to see Marcos Pires and his team recognized with this important NIH grant, which unites chemistry, biology and artificial intelligence to pioneer the next generation of antibiotics against drug-resistant superbugs, a global health challenge we urgently need to solve,” Esser said.

Ultimately, the team hopes to generate an algorithm that can predict whether a molecule will accumulate inside bacterial cells — a tool that could accelerate the discovery of entirely new antibiotics, which could help in the fight against infections that claim thousands of lives each year and could bring the world closer to the next generation of life-saving antibiotics.

“At the very least, we are in the best position of any lab in the world now to be able to pull this off, and I believe we will,” Pires said.