An international team of scientists, spearheaded by Nanyang Technological University, Singapore (NTU Singapore), has unveiled a groundbreaking approach to accelerate the healing of chronic wounds infected by antibiotic-resistant bacteria. This discovery holds significant promise for millions worldwide who suffer from persistent infections that hinder recovery.
Chronic wounds, such as diabetic foot ulcers, pose a major global health challenge, affecting an estimated 18.6 million people annually. In Singapore alone, over 16,000 cases are reported each year, predominantly among older adults and individuals with diabetes. These wounds are a leading cause of lower-limb amputations, often exacerbated by infections that resist conventional treatment.
Revealing the Biological Mechanism
Published in the journal Science Advances, the study conducted in collaboration with the University of Geneva, Switzerland, sheds light on the role of the bacterium Enterococcus faecalis (E. faecalis) in impeding wound healing. The research team demonstrated how neutralizing a specific biological process can facilitate skin cell recovery and wound closure.
E. faecalis is frequently found in chronic infections and is notorious for its antibiotic resistance. The bacterium’s ability to delay healing has long puzzled scientists, but the study reveals that E. faecalis produces a metabolic byproduct, reactive oxygen species (ROS), that disrupts the healing process of human skin cells.
Mechanism that Disrupts Wound Healing
Dr. Aaron Tan, a research fellow at NTU and the study’s first author, discovered that E. faecalis employs extracellular electron transport (EET) to continuously produce hydrogen peroxide, a reactive oxygen species that damages living tissue. This oxidative stress triggers a cellular defense mechanism known as the “unfolded protein response” in keratinocytes, the skin cells responsible for repair.
“Once activated, the stress response effectively paralyses the cells, preventing them from moving to close the wound, a process known as migration,” explained Dr. Tan.
The researchers found that using a genetically modified strain of E. faecalis lacking the EET pathway resulted in significantly less hydrogen peroxide production, allowing the wound healing process to proceed unhindered. This confirmed the central role of the metabolic pathway in disrupting skin repair.
Potential Solution Beyond Antibiotics
In a promising development, the team discovered that treating affected skin cells with catalase, an antioxidant enzyme that breaks down hydrogen peroxide, reduced cellular stress and restored the cells’ ability to heal. This approach offers an alternative to combating antibiotic-resistant strains by neutralizing harmful byproducts rather than relying on antibiotics.
“Our findings show that the bacteria’s metabolism itself is the weapon, which was a surprise finding previously unknown to scientists,” said Assoc Prof Guillaume Thibault of NTU. “Instead of focusing on killing the bacteria with antibiotics, we can now neutralise it by blocking the harmful products it generates and restoring wound healing.”
The study establishes a direct link between bacterial metabolism and host cell dysfunction, suggesting a new therapeutic strategy for treating chronic wounds. The researchers propose that wound dressings infused with antioxidants like catalase could serve as an effective treatment in the future.
Implications for Future Treatments
Given that antioxidants such as catalase are already widely used and understood, this strategy could expedite the transition from laboratory research to clinical application, potentially offering relief to patients with non-healing wounds sooner than developing new drugs.
As the study utilized human skin cells to demonstrate the mechanism, the findings are directly applicable to human physiology. The research team is now focused on advancing towards human clinical trials, exploring the most effective methods for delivering antioxidants through ongoing studies in animal models.
This development follows a growing global concern over antibiotic resistance, highlighting the need for innovative solutions in medical treatment. The NTU-led study not only provides a novel approach to tackling superbugs but also underscores the importance of understanding bacterial metabolism in developing future therapies.
