Researchers at Cold Spring Harbor Laboratory and Scripps Research have restored the effectiveness of vancomycin, one of medicine's last-resort antibiotics, by pairing it with a small molecule called pghi-4. The compound blocks a bacterial enzyme, secreted antigen A (SagA), that vancomycin-resistant Enterococcus faecium relies on to fend off the drug.
In lab tests, adding pghi-4 stripped resistant bacteria of that defense, letting vancomycin kill strains that had previously survived treatment. Pghi-4 was first identified in 2020 from a screen of more than 150 compounds in Professor John Moses' lab at Cold Spring Harbor, working with Professor Howard Hang's team at Scripps.
The approach belongs to a growing category of antibiotic adjuvants: molecules that are not antibiotics themselves but restore the punch of existing drugs. Researchers say the same strategy could eventually help revive treatments for other resistant infections, including drug-resistant tuberculosis, offering a faster route to fighting superbugs than developing entirely new antibiotics from scratch.