A breakthrough study led by Nanyang Technological University (NTU) in Singapore has revealed a surprising reason why some chronic wounds resist healing, even with antibiotic treatment. Scientists found a common bacterium, Enterococcus faecalis, not only resists drugs but actively releases harmful molecules that overwhelm skin cells, preventing tissue repair.
This critical discovery, detailed on ScienceDaily.com on January 20, 2026, sheds light on the complex biological mechanisms underlying persistent non-healing wounds. Neutralizing these damaging molecules with antioxidants allowed skin cells to recover and resume the vital healing process in laboratory settings.
Chronic wounds represent a significant global health challenge, affecting millions annually. For instance, approximately 18.6 million people worldwide develop diabetic foot ulcers each year, with as many as one in three individuals with diabetes experiencing such an ulcer in their lifetime. These persistent wounds are a leading cause of lower limb amputations and often trap patients in a cycle of repeated complications, exacerbated by ongoing infections and growing antibiotic resistance.
The bacterial saboteur and its mechanism
The research, published in Science Advances, identified Enterococcus faecalis (E. faecalis) as a primary culprit. This opportunistic pathogen frequently appears in chronic infections like diabetic foot ulcers, which are notoriously difficult to treat. While infections have long been known to impede wound healing, the precise biological mechanism remained unclear until now.
Jointly led by NTU Associate Professor Guillaume Thibault and Professor Kimberly Kline from the University of Geneva, the team found that E. faecalis utilizes a metabolic process called extracellular electron transport (EET). This pathway continuously generates hydrogen peroxide, a highly reactive oxygen species (ROS). When present in a wound, this hydrogen peroxide induces oxidative stress in nearby human skin cells, specifically keratinocytes, which are crucial for wound repair.
Laboratory experiments conducted by first author Dr. Aaron Tan, an NTU Research Fellow, showed that this oxidative stress triggers a protective, yet ultimately detrimental, response in keratinocytes known as the “unfolded protein response.” Normally, this response helps cells survive damage by slowing protein production. However, in this context, it paralyzes the cells, preventing their migration into the wound area—a critical step for tissue sealing and healing. Genetically modified E. faecalis strains lacking the EET pathway produced less hydrogen peroxide and could not block wound healing, confirming the pathway’s central role.
A new path for chronic wound healing
The findings suggest a promising avenue beyond conventional antibiotic treatments, especially given the rising challenge of antibiotic resistance in many E. faecalis strains. Researchers investigated whether neutralizing the hydrogen peroxide could reverse the damage and restart healing.
When stressed skin cells were treated with catalase, a naturally occurring antioxidant enzyme that breaks down hydrogen peroxide, cellular stress levels significantly dropped. Consequently, these cells regained their ability to migrate and heal the wound. This approach highlights the potential for non-antibiotic interventions that target bacterial metabolic byproducts rather than the bacteria themselves.
This discovery offers substantial hope for patients suffering from chronic wounds, which often lead to severe complications and reduced quality of life. Future research may focus on developing topical treatments or dressings containing antioxidants to directly counteract the bacterial sabotage, potentially revolutionizing how persistent wounds are managed and healed.
