Unlike other tetracycline drugs, sarecycline binds to mRNA in bacterial ribosomes.

Researchers at Yale and the University of Illinois-Chicago have discovered how Sarecycline’s unique chemical structure makes it so effective against acne.

Unlike other tetracycline drugs, sarecycline binds to messenger RNA (mRNA) in bacterial ribosomes.  Sarecycline and other tetracyclines treat acne by inhibiting bacterial protein synthesis. They block ribosome function in Cutibacterium acnes. “We show that the structure of sarecycline matters,” says  Christopher Bunick, MD, PhD, associate professor of dermatology at Yale and co-corresponding author of the study, in a news release. “This mode of action has never been seen before in this class of antibiotics, and suggests that sarecycline has unique properties among the tetracycline class.”

Importantly, the researchers found an explanation for why sarecycline has such a low drug-resistance profile, boosting its effectiveness. Sarecycline thwarts TetM, a ribosome guardian protein that protects bacteria from outside interference.  Their findings appear in the Proceedings of the National Academy of Science.

 Bunick and his team said the broader implication of the study is that structural knowledge of tetracycline compounds could be used to engineer better antibiotics.

 “This could result in therapies with better or longer-lasting efficacy, fewer side effects, and lower drug resistance,” Bunick says. “Future agents could be used not just in acne, but potentially in other skin disorders and infections as well.”

The co-corresponding author of the study was Yury Polikanov of the University of Illinois-Chicago. Zahra Batool of UIC was first author of the study and Ivan Lomakin of Yale was a co-author. The National Institutes of Health, State of Illinois startup funds, and a research grant from Almirall funded the research. Bunick has received honoraria for consulting and speaking for Almirall.