#FEMSmicroBlog: Bacterial biofilms impacting the wound healing process

22-09-2021

Sometimes wounds do not heal properly and turn into “chronic” wounds. These have become growing problems worldwide as they leave patients with extensive pain and open to serious infections that may even require hospitalization. Common underlying causes for chronic wounds include diabetes, vascular diseases, limited mobility and bacterial infections. The article “The effects of Staphylococcus aureus biofilm conditioned media on 3T3 fibroblasts” published in FEMS Microbes explores this pathogen’s secretion factors that impact the molecular mechanisms of wound healing. David Becker explains for the #FEMSmicroBlog how Staphylococcus aureus biofilms inhibit the wound healing process. #FascinatingMicrobes

 

Chronic wounds are a growing health concern

The number of patients suffering from chronic wounds is reaching epidemic proportions due to an ageing and increasingly obese population. Diabetic foot ulcers, pressure ulcers – also known as bedsores – and venous leg ulcers all can lead to wounds not healing properly and pain for the patient.

An estimate from the US put the healthcare costs associated with chronic wounds at $28B USD a year; a heavy financial burden. Under normal circumstances, the process of wound healing involves multiple steps including stopping of bleeding (haemostasis); inflammation; cells dividing and crawling into the wound to replace damaged cells (proliferation and migration); and scar formation (remodelling).

Normally, the wound healing process happens quickly and without incident. In chronic wounds, however, the process stalls; often in the inflammatory state. This means that wounds can remain open for months or even years.

In chronic wounds, the wound healing process stalls in the inflammation phase making them susceptible for bacterial infections.

 

Chronic wounds due to bacterial biofilms

The problem is that about 60-78% of chronic wounds contain bacterial biofilms, in which bacteria band together and stick to the surface of the open wound. After establishing a bacterial biofilm, bacteria produce a slimy substance to protect them from the person’s immune system and antibiotics.

Staphylococcus aureus is the most common type of microorganism in bacterial biofilms in chronic wounds. As such, bacteria in biofilms secrete substances that are bad for human cells. However, it is not clear how these substances affect the wound healing process. This is what the study “The effects of Staphylococcus aureus biofilm conditioned media on 3T3 fibroblasts” published in FEMS Microbes set out to understand.

The study aims to simulate a wound using a fibroblast cell line, as fibroblasts are key cells in the wound healing process. The work focuses on a Staphylococcus aureus strain that was originally isolated from a chronic wound.

Bacteria were grown as biofilms and their secreted fractions used in the investigation. Diluted secretion fractions helped understand how much of the secretions would impact the fibroblasts.

workflow to analyse how bacterial biofilms impact wounds healing
The workflow to analyse how bacterial biofilms impact wound healing. By Madden et al. in FEMS Microbes (2021).

Using this simulation of a wound, the study investigated how bacterial secretion factors impact the ability of fibroblasts to migrate and divide. It further looked at a number of proteins known to be important in the fibroblast’s role in wound healing.

 

Bacteria impact the fibroblast’s behavior in wound healing

When treating fibroblasts with secreted bacterial biofilm fractions, the cells changed their shapes. Long treatments reduced the rates of fibroblasts dividing (proliferation) and their abilities to move (migration). Shorter treatments increased the number of contacts between adjacent fibroblasts and changed the locations and/or proteins associated with adhesion.

This means that fibroblasts on the edge of chronic wounds that are exposed to the secretions of Staphylococcus aureus may suffer similar effects. The bacterial secretion factors can reduce the fibroblast’s proliferation and migration and thus contribute to the delayed healing of chronically infected wounds.

Taken together, results from the study suggest that Staphylococcus aureus biofilms inhibit wound healing via several mechanisms. These include stopping cell division and migration and increasing the fibroblasts “stickiness” (adhesion) to fibroblasts around them.

Bacterial biofilms inhibit the wound healing process via several mechanisms including stopping cell division and migration.

Unfortunately, some of these effects, such as inhibiting cell division, may be irreversible. These cells would need to be cut away (debridement) for the wound to heal normally.

Based on these findings, the study concludes that preventing biofilm infections in chronic wounds should be a key aim in helping the healing process. As such, removing bacteria and their biofilms will be required for successful wound healing.

 

About the author of this blog

David Becker obtained his BSc in Biology in 1985 and his PhD in 1988 at University College London. In 1994 he was awarded a Royal Society Research Fellowship and in 2008 was made full Professor at UCL. In 2013 he moved to Singapore to join the newly formed Lee Kong Chian School of Medicine at Nanyang Technological University, Singapore. For his translational research, he has 30 worldwide patents pending and granted. In 2006 he was a founding scientist of CoDaTherapeutics Inc, (now Ocunexus) to develop Nexagon, a drug that promotes wound healing in skin and the cornea.

About this blog section

The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.

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