James Fraser, PhD, chair and professor in the UCSF School of Pharmacy’s Department of Bioengineering and Therapeutic Sciences, is harnessing the power of synchrotron X-rays to fight one of the most urgent global threats in modern medicine: antibiotic resistance.  

By capturing high-resolution images of bacterial enzymes that blunt the effects of certain antibiotics, Fraser’s lab has uncovered new ways to restore the potency of drugs that had been losing their effectiveness.

The findings, published in Structure, mark an important step toward designing therapies that can revive existing antibiotics rather than relying solely on creating new ones, and demonstrate how combining structural biology with drug discovery can open new pathways to outpace antibiotic resistance.

Working with collaborators at the Stanford Synchrotron Radiation Lightsource and the Advanced Light Source at Lawrence Berkeley National Laboratory, Fraser’s team identified small molecules that bind to a bacterial enzyme known as VatD, which interferes with the activity of streptogramin antibiotics. By pinpointing previously hidden binding sites, they developed a promising compound that could block VatD and, in turn, allow streptogramins to work again against resistant bacteria.