An international team of scientists, led by Nanyang Technological University, Singapore (NTU Singapore), has unveiled a groundbreaking method that could accelerate the healing of chronic wounds infected by antibiotic-resistant bacteria. This discovery is poised to address a significant global health challenge, as chronic wounds affect millions worldwide.
Chronic wounds, such as diabetic foot ulcers, represent a major health burden, with an estimated 18.6 million people developing these ulcers annually. In Singapore alone, over 16,000 cases are reported each year, primarily affecting older adults and individuals with diabetes. These wounds often lead to severe complications, including lower-limb amputations, due to persistent infections that hinder healing.
Understanding the Mechanism of Disruption
Published in Science Advances, the study conducted in collaboration with the University of Geneva, Switzerland, reveals the role of the bacterium Enterococcus faecalis (E. faecalis) in impeding wound healing. Unlike other bacteria that produce toxins, E. faecalis generates a metabolic product known as reactive oxygen species (ROS), which disrupts the healing process of human skin cells.
E. faecalis, an opportunistic pathogen, is frequently found in chronic infections like diabetic foot ulcers. The bacterium’s increasing antibiotic resistance complicates treatment, making it a formidable challenge for healthcare providers. The study, led by NTU Associate Professor Guillaume Thibault and Professor Kimberly Kline from the University of Geneva, sheds light on the biological mechanism that has long puzzled scientists.
The Role of Reactive Oxygen Species
NTU Research Fellow Dr. Aaron Tan, the study’s first author, discovered that E. faecalis utilizes a metabolic process called extracellular electron transport (EET), which continuously produces hydrogen peroxide, a highly reactive oxygen species. This substance causes oxidative stress, damaging human skin cells and triggering a cellular defense mechanism known as the “unfolded protein response” in keratinocytes, cells responsible for skin repair.
This response, while typically protective, effectively paralyzes the cells, preventing them from migrating to close the wound. The researchers demonstrated that using a genetically modified strain of E. faecalis lacking the EET pathway resulted in reduced hydrogen peroxide production, thereby restoring the cells’ ability to heal.
Potential Solutions Beyond Antibiotics
The study’s findings suggest a novel approach to treating infections caused by antibiotic-resistant E. faecalis. By using catalase, a naturally occurring antioxidant enzyme that breaks down hydrogen peroxide, researchers were able to reduce cellular stress and restore healing capabilities. This strategy offers an alternative to traditional antibiotics, which are becoming less effective due to rising resistance.
“Our findings show that the bacteria’s metabolism itself is the weapon, which was a surprise finding previously unknown to scientists,” said Assoc Prof Thibault.
Instead of targeting the bacteria directly, this method neutralizes the harmful products they generate, offering a promising new therapeutic strategy for chronic wounds.
Implications and Future Directions
The study establishes a direct link between bacterial metabolism and host cell dysfunction, paving the way for innovative treatments. Researchers suggest that wound dressings infused with antioxidants like catalase could be an effective treatment in the future. Given that antioxidants are already widely used and understood, this approach could expedite the transition from laboratory research to clinical application.
The team plans to advance towards human clinical trials, aiming to determine the most effective delivery method for antioxidants through ongoing studies in animal models. As the findings are based on human skin cells, they hold significant relevance to human physiology and could lead to new treatments for patients with non-healing wounds.
This development follows growing concerns over antibiotic resistance, highlighting the need for alternative strategies in treating infections. The breakthrough by NTU Singapore and its collaborators represents a significant step forward in the global fight against superbugs, offering hope for millions affected by chronic wounds.
