In chronic wounds, a bacterium was identified that is not only resistant to medications but also releases molecules that negatively affect skin cells and slow down the tissue healing process.
Research has shown that using antioxidants to neutralize these molecules promotes skin cell recovery and activates healing.
The problem of chronic wounds is becoming increasingly relevant on a global scale. Every year, about 18.6 million people worldwide suffer from diabetic foot ulcers. One-third of diabetes patients will develop a foot ulcer in their lifetime.
These persistent wounds often lead to amputations of the lower limbs, as infections hinder healing, creating a vicious cycle of complications.
In Singapore, there is a rise in cases of chronic wounds, such as diabetic ulcers, pressure sores, and venous leg ulcers. More than 16,000 new cases are reported each year, particularly among the elderly and people with diabetes.
The study showed that the bacterium Enterococcus faecalis actively hinders the healing process. The team also established that blocking its action allows skin cells to recover and heal.
E. faecalis is an opportunistic pathogen often associated with chronic infections, such as diabetic ulcers. These wounds are difficult to treat and often remain unhealed, increasing the risk of severe complications and amputations.
The resistance of this bacterium to antibiotics exacerbates the situation. Some strains of E. faecalis no longer respond to many common antibiotics, making the fight against infections more challenging.
Although doctors have long noted that infections slow down wound healing, the mechanisms of this process remained unclear until now.
The research was conducted under the guidance of NTU Associate Professor Guillaume Thibault 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 researchers found that E. faecalis behaves differently from other bacteria that infect wounds. Instead of releasing toxins, the bacterium produces reactive oxygen species that disrupt the normal function of skin cells.
The lead author of the study, Dr. Aaron Tan, discovered that E. faecalis uses a process known as extracellular electron transfer, which leads to the continuous production of hydrogen peroxide—a reactive oxygen species capable of damaging living tissues.
The presence of E. faecalis in the wound leads to oxidative stress in skin cells. Laboratory experiments showed that this stress activates protective mechanisms in keratinocytes responsible for healing.
Typically, such a reaction helps cells cope with damage, slowing down the processes necessary for recovery. However, in this case, this reaction effectively blocks the cells, preventing them from moving to the wound area.
To confirm the importance of this mechanism, the scientists tested a genetically modified strain of E. faecalis that lacked the extracellular electron transfer pathway. These bacteria produced significantly less hydrogen peroxide and could not hinder healing.
The results confirmed that the metabolic process is critically important for E. faecalis's disruption of skin recovery. The team also investigated whether neutralizing hydrogen peroxide could aid in cell recovery.
Treating skin cells with catalase, a natural antioxidant enzyme that breaks down hydrogen peroxide, reduced cellular stress levels and restored their ability to migrate and heal wounds.
This approach represents an alternative solution for combating infections caused by antibiotic-resistant E. faecalis. Instead of destroying bacteria with antibiotics, the strategy focuses on neutralizing the harmful molecules they release.
“Our results show that bacterial metabolism is a weapon, which was an unexpected discovery previously unknown to scientists,” noted Associate Professor Thibault. “Instead of focusing on destroying bacteria with antibiotics, which complicates matters and leads to future antibiotic resistance, we can neutralize them by blocking harmful products and restoring wound healing. We are targeting not the source but the true cause of chronic wounds—reactive oxygen species.”
This research establishes a link between bacterial metabolism and human cell dysfunction, opening new horizons for therapeutic treatment of chronic wounds.
The researchers suggest that future dressings containing antioxidants, such as catalase, could improve the healing process.
Since antioxidants like catalase are already well-studied and widely used, the team believes that this approach could be implemented in clinical practice more quickly than the development of new drugs.
As the mechanism of action has been demonstrated on human skin cells, the findings are directly relevant to human physiology and may lead to new treatment methods for patients with non-healing wounds.
In the future, the researchers plan to conduct clinical trials after determining the most effective ways to deliver antioxidants, based on current studies in animal models.
