Recent research has revealed that a specific bacterium, Alcaligenes faecalis (A. faecalis), can aid in the healing process of difficult-to-treat wounds in individuals with diabetes. While many studies have focused on harmful bacteria in wounds, this research demonstrates that A. faecalis, which is commonly found in various types of chronic wounds, actually enhances the healing of diabetic wounds. The study shows that this beneficial bacterium promotes essential skin cell movements for wound closure by inhibiting certain enzymes that tend to be overproduced in diabetics.
There are several crucial reasons to maintain the cleanliness of cuts and sores, but new findings from the Perelman School of Medicine at the University of Pennsylvania indicate that a specific bacterium, Alcaligenes faecalis (A. faecalis), can support the healing of challenging wounds in those with diabetes. Unlike numerous studies that examine potentially dangerous bacteria in wounds, researchers found that A. faecalis, which appears in various chronic wounds, actually promotes the healing of diabetic ulcers. This bacterium aids in moving skin cells needed for effective wound closure by inhibiting enzymes that are excessively produced in diabetic patients. The results of this study are detailed in Science Advances, led by Elizabeth Grice, PhD, the Sandra J. Lazarus Professor in Dermatology at Penn, and Ellen K. White, a MD-PhD student at Penn.
The research team believes that understanding how A. faecalis aids healing may lead to new therapies for diabetic wounds.
“This work builds significantly on our previous research where we analyzed the bacteria present in diabetic foot ulcers over time and studied how these microbes affect healing outcomes,” explained Dr. Grice. “We didn’t anticipate discovering a bacterium that promotes healing, but this unexpected result inspired further investigations of A. faecalis.”
Chronic wounds, characterized by sores, ulcers, or lacerations that do not heal or heal at a very slow rate, are prevalent among diabetes patients. These wounds can be painful, increase the risk of additional infections, and are associated with higher morbidity and mortality rates. There is an urgent need for novel therapies to treat these debilitating wounds, but advancements in treatment options have been limited, mainly involving surgical removal of dead tissue and standard dressings.
To explore how A. faecalis affects the healing of diabetic wounds, the researchers conducted a series of tests involving diabetic mice, their skin cells, and samples from human diabetic skin. Initially, they discovered that applying A. faecalis to diabetic mice with wound healing issues resulted in faster healing without any signs of infection. They then found that introducing A. faecalis to the wounds caused keratinocytes—the key cells involved in wound healing in the epidermis—to grow and move more effectively compared to untreated cells. Furthermore, skin samples from diabetics cultured with A. faecalis exhibited a significantly greater outgrowth of keratinocytes after 10 days.
The researchers also observed that wounds in diabetic mice treated with A. faecalis activated genes related to leukocyte function, including T cells crucial for immune defense. They noticed a downregulation of genes involved in collagen breakdown, specifically matrix metalloproteinases (MMPs). Excess MMPs in diabetics have been shown to impede proper wound healing. The study focused on MMP-10, expressed by keratinocytes, which was reduced in wounds treated with A. faecalis.
“MMPs are vital enzymes that break down cellular connections to allow movement. However, in diabetic patients, MMP levels are excessively high,” White noted. “Our study indicated that A. faecalis rebalances MMP expression in wounds, facilitating quicker closure. In future research, we aim to discover more about how this bacterium interacts with skin cells and how A. faecalis coexists with other bacteria in wounds.”
This innovative research highlights areas where scientists can seek potential new treatments. By focusing not only on the microbes present in chronic wounds but also on their specific interactions, researchers may develop more advanced wound care options.
“Bacterial-based therapies for wounds are an exciting emerging field,” stated Grice. “There are various approaches we can pursue based on our findings and future exploration of the wound microbiome. It might be possible to isolate the healing molecules secreted by A. faecalis or to target the pathways influenced by the bacterium. The better we understand the entire process, the more likely we are to convert our research into practical help for patients with skin and wound repair issues.”
This research was sponsored by the NIH Institute of Nursing Research (R01NR009448, R01NR015639), National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR069589, F31AR079852, T32AR007465, K99AR081404, F31AR079845), Prevent Cancer Foundation, Penn SBDRC Pilot and Feasibility Grant (P30AR069589), Penn Blavatnik Family Fellowship, NIH National Institute of Allergy and Infectious Diseases (5T32AI141393), and the NIH National Institute of General Medical Sciences (R25GM071745-19).
