Peptides May Provide Key to Identifying Biomarkers for Healing, Infection

Peptides found in wound fluids were found to be useful in analyzing peptide pattern differences in surgical patients, suggesting their potential use to identify biomarkers for wound healing and infection, according to a study published in eLife.

“The peptidomics data generated here provides previously undisclosed data on proteolytic fragmentation patterns during wounding, which may aid in the discovery of novel bioactive peptides and elucidation of their biological roles during wound healing,” wrote the investigators.

Typically, wound healing is associated with proteolytic events, and as the downstream reporters of these actions, peptides may serve as a potential tool for wound diagnosis. The present study, from Sweden, is the first to characterize the peptidome of human wound fluid, which encompasses both the peptides created by the body and those created by bacteria in a wound.

Surgical-site infections (SSIs) are the second most frequent nosocomial infections in Europe and the United States. In European hospitals, the rate of SSIs ranges between 3% and 4% for most surgical patients and could exceed 10% for patients undergoing procedures using skin grafts or biomaterials.

Expenses for wound treatments are expected to rise as antimicrobial entities continue to become resistant to antibiotics and as the incidence of obesity and diabetes continues to increase in Western countries.

The investigators said that predicting infection risk and improving early detection could reduce the impact of wounds and make them easier to treat.

“There are many obvious signs of advanced infection, including redness, heat, swelling, purulent exudate, smell, and pain, but the challenge is to translate these observations to objective and sensitive methods that correctly evaluate wound status and, in particular, the associated inflammation, before wounds even reach this dysfunctional state,” said the investigators.

To analyze wound peptidomes, the investigators collected plasma from 3 healthy donors, sterile acute wound fluids from 5 donors who had undergone mastectomies that required surgical drainage post operation, and wound fluids from 6 donors who underwent facial full-thickness skin grafting.

The investigators used 2 methods to analyze the collected samples: sodium dodecyl sulphate–polyacrylamide gel electrophoresis and liquid chromatography–tandem mass spectrometry.

The results demonstrated that sterile postsurgical wound fluid samples contained higher degrees of peptides compared with the healthy plasma samples. When pooling the results from both methods for each fluid type, the wound fluids had 6.8 times as many peptides and more than 5 times as many proteins vs the healthy plasma samples.

Additionally, the investigators found that wound fluids contained more small peptides and larger peptides were more prevalent in plasma.

They divided the patients who underwent facial full-thickness skin grafts into 2 group: a low-inflammation group (n = 3), which included patients who were healing well 7 days after surgery, and a high-inflammation group (n = 3), which included patients who had an inflamed and infected wound.

Evaluation of wound dressings revealed increased levels of interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor alpha in the high-inflammation group compared with the low-inflammation group. The high-inflammation group also demonstrated higher protein degradation and enzymatic activity, which were found to be positively correlated with one another.

When pooling the results from both groups, the investigators found 163 proteins (n = 2666 peptides) in both groups, but not necessarily in every patient. There were 156 proteins (n = 5273 peptides) specific to the low-inflammation group and 90 proteins (n = 4661 peptides) specific to the high-inflammation group, which suggests that a there is a higher degree of proteolysis in the high-inflammation group compared with the low-inflammation group.

“Combining the use of such new peptides as biomarkers along with classical analyses of cytokines and [matrix metalloproteinases] could yield higher diagnostic sensitivity and specificity with respect to wound status and infection risk,” wrote the investigators.

Reference

van der Plas, Cai J, Petrlova J, Saleh K, Kjellström S, Schmidtchen A. Method development and characterisation of the low-molecular-weight peptidome of human wound fluids. eLife. Published online July 6, 2021. doi:10.7554/eLife.66876