New strategy to reduce tissue damage from flesh-eating bacteria

The study was led by Wei Xu, Ph.D., an assistant professor of biomedical sciences at the Marshall University Joan C. Edwards School of Medicine, and colleagues at Washington University School of Medicine and Central China Normal University. The team discovered that S. pyogenes manipulates the body's immune response through its aerobic mixed-acid fermentation process, which produces metabolic byproducts -- such as acetate and formate -- that impair immune cell function, delay bacterial clearance and slow wound healing.

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."

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).