Penn Study Identifies Microbes in Wound Healing That Can Lead to Foot Amputation

A University of Pennsylvania study, published April 18, 2019, in Cell Host and Microbe, finds whether wounds, including a diabetic foot ulcer, heal or progress to a worse outcome, including infection or even amputation, may depend on the microbiome within that wound. Researchers at the University’s Perelman School of Medicine identified specific strains of the Staphylococcus aureus (S. aureus), a common and difficult-to-treat

pathogen, are associated with wounds that do not heal. They also identified other common bacteria in these wounds that can impair or even improve healing. The observation suggests that monitoring the microbes of diabetic foot ulcers could provide physicians with information as to how to best treat these wound.

Diabetic Foot Ulcers Often Go Unnoticed

According to the researchers, about 10 percent of Americans have been diagnosed with diabetes, and one quarter of these patients will develop a wound that does not heal. In the worst-case outcome, occurring in up to 25 percent of these wound-developing patients, the wounds will require an amputation. Many diabetic patients who develop these ulcers may not notice the initial signs, since the high blood glucose of diabetes can lead to a lack of feeling and deformation of the feet. Thus, these diabetic patients commonly develop foot ulcers that may go unnoticed over time. Current treatments are insufficient, meaning patients can live with these wounds for months or even years without healing. The mortality rate associated with diabetic foot ulcers is equivalent to that of breast cancer and prostate cancer combined – higher than 70 percent when they lead to amputation.

“While wounds don’t receive the attention of other diseases, they’re incredibly common, and our study increases our understanding of how microbes impair or promote healing,” said the study’s senior author Elizabeth Grice, Ph.D., an associate professor of Dermatology in a statement announcing the published study. The lead author, Lindsay Kalan, Ph.D., now an assistant professor of Medical Microbiology and Immunology at the University of Wisconsin School of Medicine and Public Health, began this work as a postdoctoral researcher in Grice’s lab.

The researchers say previous studies have used lower resolution techniques to catalogue the microbes that reside in chronic wounds. But this study was built on that research by using higher resolution DNA sequencing to identify specific species and subspecies and how they are related to patient outcomes. Samples were collected from 46 patient ulcers every two weeks for a six-month period, until the wound healed or was amputated.

 S. aureus was found in the majority of wounds, say the researchers, noting that the presence of the bacteria itself did not predict whether or not a wound would heal. However, the high-resolution DNA sequencing used in this study showed certain strains of S. aureus were only in the wounds that did not heal over the course of the study. Further testing revealed that the “non-healing” strain was better equipped to cause tissue damage and evade antibiotic treatments. Researchers further validated this finding in mice.

Researchers Identified Microbe that May Benefit Wound Care

Researchers found that another common microbe found in diabetic wounds, Alcaligenes faecalis, was associated with quicker healing.

“It is possible there are bacteria that actually benefit the wound, and we can use what we learned in this study to develop new treatment strategies for non-healing wounds,” Grice said. “We hope this research will eventually help identify patients at risk for bad outcomes and lead to treatment innovations that these patients desperately need,” she said.

This study was supported by the National Institutes of Health through the National Institute of Nursing Research (R01-NR-009448, R01-NR-015639, P20 NR018081), the National Institute of Arthritis, Musculoskeletal, and Skin Disease (R01-AR-006663, R00-AR-060873), the Pennsylvania Department of Health, and the Linda Pechenik Montague Investigator Award.