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Scientists from NTU Singapore and the University of Geneva have discovered a new way to neutralise antibiotic‑resistant bacteria, helping chronic wounds heal more effectively.
Treating chronic wounds represents a major public health challenge, starting with diabetic foot ulcers, which affect an estimated 18.6 million people worldwide each year. A team from the University of Geneva (UNIGE) and Nanyang Technological University (NTU) in Singapore has uncovered how a common pathogen, Enterococcus faecalis, actively prevents these wounds from healing, and how neutralising this process—by blocking the harmful products it generates—can enable skin cells to regenerate and close the wound. The findings are published in Science Advances.
Chronic wounds are among the leading causes of lower-limb amputations. Often worsened by persistent infections, they struggle to heal, particularly in people with diabetes, whose elevated blood glucose levels impair the healing process.
In their recent study, researchers from UNIGE and NTU reveal how the widespread opportunistic bacterium Enterococcus faecalis actively disrupts tissue repair. They also demonstrate that neutralising this mechanism can restore the ability of skin cells to regenerate, thereby reducing the risk of complications and amputation.
Rather than trying to eliminate the bacterium with antibiotics—a strategy that is increasingly difficult and promotes resistance—we can now consider neutralising the harmful products it generates.
Jointly led by Guillaume Thibault, associate professor at NTU's School of Biological Sciences, and Kimberly Kline, full professor in the Department of Microbiology and Molecular Medicine at UNIGE's Faculty of Medicine and member of the SCELSE – Singapore Centre for Environmental Life Sciences and Engineering, the team discovered that the bacterium does not rely on a conventional toxin to interfere with healing. Instead, it hijacks a product of its own metabolism.
"E. faecalis uses a previously unrecognised metabolic process known as extracellular electron transport (EET), which continuously produces hydrogen peroxide, a highly reactive oxygen species that can damage living tissue," explains Aaron Tan, researcher at SCELSE and first author of the study.
Oxidative stress that paralyses skin cells
Hydrogen peroxide, widely known as an industrial disinfectant and bleaching agent, becomes problematic when generated directly within an infected wound. The researchers showed that this compound, produced by the bacterium, induces significant oxidative stress in keratinocytes—the skin cells responsible for tissue repair. This stress activates a cellular defence mechanism linked to misfolded proteins, ultimately paralysing the cells and preventing them from migrating to close the wound.
Neutralising hydrogen peroxide to restore healing
To confirm the central role of this process, the scientists used a genetically modified strain of E. faecalis lacking the EET pathway. As a result, hydrogen peroxide production dropped sharply, and the bacterium could no longer block wound healing.
The team then assessed whether neutralising hydrogen peroxide could reverse the damage. By treating skin cells with catalase—a naturally occurring antioxidant enzyme that breaks down hydrogen peroxide—they reduced cellular stress and restored the cells' ability to migrate and repair tissue.
"Our results show that the bacterium's own metabolism is its weapon—a surprising and previously unknown discovery," notes associate professor Thibault. "Rather than trying to eliminate the bacterium with antibiotics—a strategy that is increasingly difficult and promotes resistance—we can now consider neutralising the harmful products it generates, thereby restoring the healing process."
Towards new therapeutic approaches
The study establishes a direct link between bacterial metabolism and host cell dysfunction, opening the door to new therapeutic strategies for chronic wounds. It suggests that wound dressings enriched with antioxidants such as catalase could represent a promising approach. In the long term, these findings may lead to new treatments for patients suffering from non-healing wounds—a major public health concern.
