Researchers have found a new explanation for why some chronic wounds refuse to heal despite antibiotic treatment — and the answer points toward a simpler solution than new drugs.
A study led by scientists at Nanyang Technological University (NTU) Singapore, in collaboration with the University of Geneva, has found that a common wound bacterium actively releases harmful molecules that overwhelm skin cells and stop tissue repair. The research was published in the journal Science Advances.
Chronic wounds are a significant and growing global health burden. Around 18.6 million people develop diabetic foot ulcers every year, and as many as one in three people with diabetes may experience a foot ulcer during their lifetime.
These wounds are among the leading causes of lower-limb amputations worldwide, with persistent infections trapping patients in cycles of delayed healing and repeated complications. In Singapore alone, more than 16,000 chronic wound cases are reported annually.
The study focused on Enterococcus faecalis (E. faecalis), a bacterium commonly found in long-lasting wounds. It frequently infects diabetic foot ulcers and is increasingly resistant to multiple antibiotics.
The researchers discovered that E. faecalis does not primarily disrupt healing through toxins. Instead, it releases reactive oxygen species — particularly hydrogen peroxide — as a byproduct of its normal metabolism.
The excess hydrogen peroxide creates intense stress inside human skin cells, triggering a protective process called the unfolded protein response. While this response normally helps cells survive damage, in chronic wounds it effectively paralyses them — preventing skin cells from migrating into the wound area, which is a critical step needed to close and repair damaged tissue.
To confirm the mechanism, the scientists tested a genetically modified strain of E. faecalis that lacked a key metabolic pathway. Without it, the bacteria produced far less hydrogen peroxide and could no longer block wound healing — directly linking bacterial metabolism to the disruption of skin repair.
The team then explored whether neutralising the hydrogen peroxide could reverse the damage. When stressed skin cells were treated with catalase — a naturally occurring antioxidant enzyme that breaks down hydrogen peroxide — cellular stress dropped significantly and the skin cells regained their ability to migrate and close wounds.
This approach sidesteps the problem of antibiotic resistance entirely. Rather than trying to eliminate the bacteria — which can drive further resistance — the strategy focuses on neutralising the harmful substances the bacteria produce.
The researchers believe future wound dressings infused with antioxidants like catalase could help restore healing even in infections caused by drug-resistant bacteria.
Because catalase is already widely used and well understood, this treatment strategy may move from laboratory to clinic faster than the development of entirely new antibiotics.
Since the experiments were conducted using human skin cells, the findings are directly relevant to human physiology. The research team is now refining delivery methods in animal studies, with human clinical trials planned as the next step.
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