During the study, a bacterium commonly found in chronic wounds was identified, which not only exhibits antibiotic resistance but also releases harmful molecules that suppress skin cell functions and hinder tissue repair.
The scientists noted that using antioxidants to neutralize these molecules helps skin cells recover and activates the healing process.
The issue of chronic wounds is becoming increasingly relevant in healthcare. According to statistics, approximately 18.6 million people worldwide suffer from diabetic foot ulcers each year. One in three people with diabetes may develop a foot ulcer during their lifetime.
These prolonged wounds often lead to amputations of the lower limbs. Infections arising from these ulcers exacerbate the situation, creating a vicious cycle of recurring complications.
In Singapore, the number of cases of chronic wounds, such as diabetic ulcers, pressure sores, and venous ulcers, is on the rise. Each year, over 16,000 new cases are recorded, particularly among the elderly and diabetics.
The study showed that the bacterium Enterococcus faecalis can significantly impede the healing process. The team also demonstrated that blocking the negative effects of this bacterium allows skin cells to recover and close wounds.
E. faecalis is an opportunistic pathogen often found in chronic infections, such as diabetic foot ulcers. Treating such ulcers is challenging, and their persistence increases the risk of serious complications and amputations.
The antibiotic resistance of this bacterium adds complexity to the fight against infections. Some strains of E. faecalis do not respond to many commonly used antibiotics, making the treatment of infections more complicated.
Although medical professionals have long known that infections slow healing, the precise biological mechanisms of this process have remained unclear.
The research involved Associate Professor Guillaume Thibault from NTU's School of Biological Sciences and Professor Kimberly Klein from the University of Geneva, who is also a visiting professor at the Singapore Centre for Environmental Life Sciences Engineering at NTU.
The results showed that E. faecalis behaves differently from other pathogenic bacteria. Instead of using toxins, it releases reactive oxygen species that disrupt normal skin cell healing processes.
Dr. Aaron Tan, the lead author of the study, found that E. faecalis employs a process known as extracellular electron transfer, which continuously produces hydrogen peroxide—a highly reactive molecule capable of damaging living tissues.
The presence of E. faecalis in the wound leads to oxidative stress in skin cells, activating protective responses in keratinocytes, the cells responsible for healing. This response, known as the unfolded protein response, slows down the processes necessary for repair.
However, in this case, this response effectively blocks the cells, hindering their movement to the damage site for healing.
To confirm their hypothesis, the researchers tested a genetically modified strain of E. faecalis that lacked the extracellular electron transfer pathway. These modified bacteria produced significantly less hydrogen peroxide and did not interfere with wound healing.
This result confirmed the importance of the metabolic pathway in how E. faecalis disrupts skin repair. The team then explored the possibility of neutralizing hydrogen peroxide to restore damage.
In experiments where skin cells were treated with catalase—a natural antioxidant enzyme that breaks down hydrogen peroxide—the level of cellular stress decreased. This allowed the cells to regain their ability to migrate and heal.
The proposed approach could become an alternative method for combating infections caused by antibiotic-resistant E. faecalis bacteria. Instead of destroying the bacteria with antibiotics, the new strategy focuses on neutralizing their harmful products.
“Our results show that bacterial metabolism is a weapon, which was an unexpected discovery for us,” noted Associate Professor Thibault, who also serves as the Deputy Dean for International Relations at the College of Science. “Instead of focusing on destroying bacteria, which is becoming increasingly difficult and leads to antibiotic resistance, we can neutralize them by blocking the harmful products they release and restoring the wound healing process. We are targeting not the source, but the true cause of chronic wounds—reactive oxygen species.”
The study links bacterial metabolism with the disruption of human cellular functions, opening new horizons in the therapy of chronic wounds.
The authors of the study suggest that future dressings containing antioxidants, such as catalase, could promote healing.
Since antioxidants, including catalase, are already well-studied, the team believes that this method could be implemented in clinical practice more quickly than the development of a new drug.
The results obtained, based on human skin cells, are directly relevant to physiology and may lead to new therapeutic methods for treating patients with non-healing wounds.
In the future, researchers plan to move on to clinical trials in humans, determining the most effective ways to deliver antioxidants following current studies in animal models.
