Breakthrough Study Reveals New Path to Heal Chronic Wounds

An international team of scientists has identified a groundbreaking approach to accelerate the healing of chronic wounds infected by antibiotic-resistant bacteria. The research, led by a team at Nanyang Technological University (NTU Singapore) in collaboration with the University of Geneva, highlights the behavior of the bacterium Enterococcus faecalis as a crucial factor in impeding wound healing.

In their preclinical study, published in the journal Science Advances, the researchers focused on how E. faecalis affects human skin cells. Unlike other bacteria that produce toxins, this bacterium generates reactive oxygen species (ROS), which significantly disrupt the healing process. The study showed that ROS activates the unfolded protein response (UPR) in epithelial cells, hindering their ability to migrate and heal wounds.

Understanding the Mechanism of Impairment

The team, co-led by NTU’s Guillaume Thibault, PhD, and Kimberly Kline, PhD, from the University of Geneva, established a direct link between bacterial metabolism and dysfunction in host cells. Their findings suggest that extracellular electron transport (EET) is a previously unrecognized mechanism through which E. faecalis produces ROS, leading to impaired wound healing.

In their research, they noted, “Our findings establish EET as a virulence mechanism that links bacterial redox metabolism to host cell stress and impaired repair, offering new avenues for therapeutic intervention in chronic infections.” This new understanding could pave the way for innovative treatments targeting chronic wounds, which affect an estimated 18.6 million people worldwide each year, particularly those with diabetes.

The situation is pressing; in Singapore alone, there are over 16,000 cases of chronic wounds annually, including diabetic foot ulcers, which are a leading cause of lower-limb amputations. The implications of this research extend beyond Singapore, addressing a global health challenge prevalent in many regions.

Potential Therapeutic Strategies

The researchers’ experiments revealed that a genetically modified strain of E. faecalis, lacking the EET pathway, produced significantly less hydrogen peroxide and did not inhibit wound healing. This finding confirmed the central role of the metabolic pathway in the bacterium’s ability to disrupt skin repair.

By neutralizing the harmful effects of hydrogen peroxide with catalase—a naturally occurring antioxidant enzyme—the team successfully restored the migration and healing capabilities of skin cells. This approach suggests a promising therapeutic strategy that moves beyond traditional antibiotics to address antibiotic-resistant strains of E. faecalis.

Thibault emphasized the novel approach: “Instead of focusing on killing the bacteria with antibiotics, which is becoming increasingly difficult and leads to future antibiotic resistance, we can now neutralize it by blocking the harmful products it generates.” This signifies a paradigm shift in treating chronic wounds, as researchers target the underlying cause of the issue rather than the bacteria itself.

The findings underscore the potential for wound dressings infused with antioxidants like catalase, which could expedite the transition from laboratory research to clinical application. As the study utilized human skin cells, the implications may directly translate to human physiology, paving the way for new treatments for patients with non-healing wounds.

Future studies are planned to explore the role of EET in live organisms and assess its impact in polymicrobial environments. The researchers aim to advance towards human clinical trials following further investigations in animal models, focusing on effective delivery methods for antioxidants.

In summary, this research offers a promising new direction in the fight against chronic wounds, particularly those complicated by antibiotic-resistant bacteria. By elucidating the metabolic mechanisms at play, scientists are poised to develop innovative therapeutic strategies that may significantly enhance healing outcomes for millions of patients worldwide.