Treatment Game-Changer: Scientists Discover a Metabolic Weakness in Flesh-Eating Bacteria

Researchers discovered that targeting S. pyogenes metabolism with a pyruvate dehydrogenase inhibitor reduces tissue damage and improves immune response in necrotizing fasciitis.

A study published in Nature Communications introduces a new strategy for reducing tissue damage caused by Streptococcus pyogenes, the bacterium responsible for severe infections like necrotizing fasciitis. The research demonstrates that targeting bacterial metabolism can enhance the body’s ability to tolerate infection and promote healing.

Led by Wei Xu, Ph.D., assistant professor of biomedical sciences at the Marshall University Joan C. Edwards School of Medicine, in collaboration with researchers from Washington University School of Medicine and Central China Normal University, the study reveals how S. pyogenes alters the immune response. The bacterium’s aerobic mixed-acid fermentation process generates metabolic byproducts—such as acetate and formate—that weaken immune cell function, hinder bacterial clearance, and delay wound healing.

Targeting Bacterial Metabolism to Reduce Tissue Damage

By inhibiting this bacterial metabolic pathway with a pyruvate dehydrogenase inhibitor, the team successfully reduced tissue damage in a mouse model of necrotizing skin infection. These findings suggest that reprogramming bacterial metabolism could serve as a novel therapeutic approach, not only to improve host tolerance but also as a potential adjuvant therapy alongside antibiotics. This strategy could enhance the effectiveness of existing treatments, particularly in severe infections where antibiotic resistance or excessive inflammation worsens patient outcomes.

“This study sheds light on how bacterial metabolism influences the immune system,” Xu said. “By understanding these interactions, we can develop new treatment strategies that protect tissues, enhance antibiotic efficacy, and improve patient outcomes.”

Reference: “Reprogramming aerobic metabolism mitigates Streptococcus pyogenes tissue damage in a mouse necrotizing skin infection model” by Wei Xu, Tara R. Bradstreet, Zongsen Zou, Suzanne Hickerson, Yuan Zhou, Hongwu He, Brian T. Edelson and Michael G. Caparon, 15 March 2025, Nature Communications.
DOI: 10.1038/s41467-025-57348-x

The research was supported by the National Institutes of Health (R56 AI070759, R21 AI163825, and R01 AI132653) and the National Natural Science Foundation of China (21472062 and 21907035).