December 2017 | Issue 33
LKCMedicine scientists identify new biomarkers for non-healing wounds

Editor mug shot.jpgBy Nicole Lim, Senior Assistant Director, Communications & External Relations

Persistent redness, swelling and odour are some of the most common signals from the body that something has gone wrong in the wound healing process. By this point, the infection has taken hold and can lead to serious consequences, including amputation and even loss of life. But this could all change as scientists at LKCMedicine found a novel early biomarker that could allow doctors to identify infected wounds much earlier in the infection process.

In collaboration with researchers from NTU’s School of Biological Sciences and Lund University in Sweden, they studied wound fluids and found that bacterially infected wounds contain a different pattern of protein fragments than non-infected wounds.

After an injury to the skin, the body’s first response is to stop all bleeding, a phase known as coagulation. Thrombin, an enzyme essential throughout the wound healing process, is activated during this phase. Having completed its first tasks, which take a day or two, this enzyme is shredded into smaller protein fragments, known as peptides, that form a defence against foreign cells, such as bacteria while the wound continues to heal.

When studying these peptide patterns, the team of researchers found that human and bacterial enzymes cleave thrombin differently, each yielding different patterns. One of the resulting peptides is FYT21, which is cleaved from thrombin by two common bacteria – Staphylococcus aureus and Pseudomonas aeruginosa. This information may make it possible to detect a bacterial infection at an early stage, even without visible signs of infection.

These findings, published in Scientific Reports in October, are a proof-of-concept that peptide patterns can be used as a sensitive and specific biomarker.

LKCMedicine Postdoctoral Research Fellow Rathi Saravanan, who was the first author of the study, said, "The findings show a proof-of-principle that it is possible to define different peptide patterns that 'report' the existence of specific degrading enzymes in wounds. Since these patterns are different for acute, non-healing and infected wounds, we have found a novel way of diagnosing wound healing and infection risk."

Rathi pic (Custom).jpgArtur Schmidtchen (Custom).jpgLKCMedicine Postdoctoral Research Fellow Rathi Saravanan (left) and Prof Artur Schmidtchen (right) worked on this proof-of-principle study with collaborators from NTU's School of Biological Sciences and Lund University in Sweden

Non-healing wounds, such as leg ulcers which are common in diabetics, may require several years to heal, and some persist for decades. They can be very painful, reduce mobility, and cause social, emotional and physical distress. Eighty-five per cent of all major limb amputations were preceded by foot ulcers. For people with diabetes, who are prone to this type of ulcer, the outlook is particularly dire. In Singapore alone, four lower limb amputations are performed among people with diabetes in public hospitals every day (worldwide, the frequency is every 30 seconds), accounting for 70 per cent of all lower limb amputations.

​LKCMedicine Professor of Dermatology & Skin Biology Artur Schmidtchen said, "In my clinical practice, I often meet patients with various types of wounds - acute surgical wounds, and those that are chronic, such as diabetic or venous ulcers. Today, we lack reliable methods to objectively assess whether a given wound will heal properly, or whether there is a risk of infection. Our hope is that this discovery will help us to quickly assess wounds in the clinic in the future."