New Finding for Diabetic Wounds Has Potential for Use in Developing New Therapeutics

The bacteria Alcaligenes faecalis (A faecalis) can be useful in healing difficult-to-treat wounds for individuals with diabetes, according to results of a study in Science Advances. A faecalis promotes skin cell movement essential for wound closure, and investigators established it inhibited enzymes that are over-expressed for those with diabetes.^1,2

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“This research builds heavily on our previous research where we profiled the bacteria found in diabetic foot ulcers over time and studied how these bacteria influence healing outcomes,” said Elizabeth Grice, PhD, Sandra J Lazarus professor in dermatology at the Perelman School of Medicine at the University of Pennsylvania, said in a news release. “We did not expect to find that a bacterium would be able to promote healing, but this surprising finding motivated further studies of A faecalis.”¹

In a study published in Medicina (Kaunas), it is estimated the diabetic wounds that have impaired healing affects approximately 25% of patients with diabetes. Diabetic wounds are categorized as chronic, often taking more than 3 months to heal. This can cause lower limb amputation and is also associated with high economic and psychosocial costs. The authors stated that hyperglycemia can contribute to wound closure by impairing various skin cell functions. Furthermore, it can also contribute to the development of atherosclerosis, which prevents circulating nutrients from reaching wounds.^3,4

Current therapies include removal of damaged tissues and dressing the wound, transcutaneous electrical nerve stimulation, nanomedicine, shockwave therapy, hyperbaric and topical oxygen therapy, and photobiomodulation. There are several OTC and prescription recommendations for diabetic foot wounds, including antibiotics for infection. However, pharmacists should counsel patients on not self-treating with salicylic acid when calluses and corns appear; instead patients should soak them in warm water to soften dead tissues for removal. Counseling on proper nail trimming to prevent ingrown nails is also important.^4,5

Treatment primarily focuses around preventing lower limb amputation. Pharmacists should be aware of foot and wound complications due to diabetes and incorporate information into counseling points. In an article by PharmD candidate Karisse Lora, Lora explains how many pharmacists and patients are unaware of this complication. Prevention methods, including foot screenings and education on foot hygiene, are essential for patients to know, and pharmacists should communicate these prevention methods with all patients.^4,5

Investigators performed quantitative cultures to identify microbial bioburden that could be associated with clinical outcomes for wound healing. They found that A faecalis comprises up to 28% of the mean relative abundance in culture-positive diabetic foot ulcer, ranking at the fifth mean relative abundance overall, according to the authors. They added that there was no association with diabetic foot ulcer outcome, even with the prevalence.²

The authors said that they directed the study to focus on the impact of A. faecalis on diabetic wound healing by using a 12-week-old db/db (diabetic) mouse model. They photographed and measured wounds at days 0, 3, 7, 14, and 21. They found that A faecalis accelerated wound closure at day 3 compared with the vehicle-related controls, and there were no signs of infection. They also found that A faecalis also caused keratinocytes, which is the dominate wound healing cell type, and closed the wounds more than the untreated cells.^1,2

Furthermore, they found that the bacteria was linked to the activation of leukocytes, including T cells, which affect the immune system’s defense. It also deregulated matrix metalloproteinases, responsible for collagen breakdown and has been shown to be overexpressed for patients with diabetes, leading to improper wound healing.^1,2

“Bacterial-based wound therapies are an exciting new frontier,” Grice said in the news release. “There are many different ways to take advantage of our findings and future work on the wound microbiome. It may be possible to isolate the pro-healing molecules secreted by A faecalis or target the pathways that are downstream of the bacteria’s effects. The better we understand the whole process, the more likely we can translate our findings to ultimately help patients with wound and skin repair problems.”¹

Investigators of the study hope that the research could be explored to facilitate the development of therapeutics that are centered around wound care, specifically for diabetes.¹

REFERENCES

1. Penn researchers reveal how a bacterium supports healing of chronic diabetic wounds. News release. University of Pennsylvania School of Medicine. July 25, 2024. Accessed August 7, 2024. https://www.eurekalert.org/news-releases/1052632

2, White EK, Uberoi A, Pan JT, et al. Alcaligenes faecalis corrects aberrant matrix metalloproteinase expression to promote reepithelialization of diabetic wounds. Sci Adv. 2024;10(26):eadj2020. doi:10.1126/sciadv.adj2020

3, Burgess JL, Wyant WA, Abdo Abujamra B, Kirsner RS, Jozic I. Diabetic Wound-Healing Science. Medicina (Kaunas). 2021;57(10):1072. Published 2021 Oct 8. doi:10.3390/medicina57101072

4. Oyebode OA, Jere SW, Houreld NN. Current Therapeutic Modalities for the Management of Chronic Diabetic Wounds of the Foot. J Diabetes Res. 2023;2023:1359537. Published 2023 Feb 10. doi:10.1155/2023/1359537

5. Lora K. Foot Care Is Essential for Patients With Diabetes. Pharmacy Times. August 25, 2022. Accessed August 8, 2024. https://www.pharmacytimes.com/view/foot-care-is-essential-for-patients-with-diabetes