Disease and wounding
Skin is our main defensive barrier and it’s there to keep us protected and healthy. However, when we get cuts on our skin this barrier is broken, increasing the risk of pathogens getting in and causing infections. Biofilms make disease and wounding infections more resistant.
Skin that is damaged due to an injury isn’t the only way that infection can get in. People with skin conditions like acne and eczema also have a higher chance of getting skin infections, because their skin is slightly weaker or damaged.
Usually our body can fight minor infections off, as we have a built-in response in our immune system that recognises when our skin gets damaged or when bacteria living on the skin travel from the top skin layers to deeper ones.
However, if bacteria on the skin organise themselves into layers called a biofilm, it can be a lot harder for us to fight them off. In some cases, biofilms in disease and wounding can make skin conditions worse, or stop skin wounds healing correctly.
Wounds are an ideal environment for the formation of biofilms due to their susceptibility to contamination and the availability of substrate and surface for biofilm attachment. Biofilm infections form preferentially on dead or damaged tissue. These infections develop gradually and may be slow to produce obvious symptoms. Once established, however, biofilm infections persist. They are rarely resolved by host defence mechanisms. Biofilm infections are treated with antibiotics.
Chronic wound infections share two important attributes with other biofilm diseases: persistent infection that is not cleared by the host immune system, and resistance to systemic and topical antimicrobial agents. These similarities between biofilms in disease and wounding are important when considering treatments.
Frequent debridement is one of the most clinically effective treatments to help heal chronic wounds. This may be an effective treatment because it removes the biofilm from the wound. This is similar to However, direct evidence of biofilm involvement in chronic wound infections is scarce. Using a porcine model, Serralta et. al. demonstrated that Pseudomonas aeruginosa inoculated onto wounds do indeed form biofilm. These researchers also demonstrated that a P. aeruginosa strain isolated from a burn wound rapidly formed biofilms in-vitro. The CBE recently conducted a microscopic examination of clinical specimens of chronic and acute wounds for the presence of biofilm. Overall, preliminary evidence indicate polymicrobial biofilm forms on chronic wounds and clinical aspects of chronic wound infections resemble those of other biofilm infections. However, the role of biofilms in preventing wound healing and mechanisms involved have yet to be determined.
Wounds can be home to lots of different bacteria. When skin is damaged by wounding, a healing process occurs that moves through four key stages:
i) Scab formation ii) increased inflammation (felt as swelling, redness and heat) iii) a creation of new skin cells to cover the wound iv) final scar formation.
Inflammation is needed to help kill off any infectious bacteria that may be in the wound, but some skin wounds get ‘stuck’ in this inflammation stage and cannot heal properly. If they don’t heal within 3 months they are considered as chronic wounds; examples of these include diabetic foot ulcers. Bacteria, especially when they are growing together in layers called biofilms, increase the inflammatory response. This is because, while our bodies are very effective at detecting these bacteria, they struggle to remove them. This slows down the wound healing response (Attinger and Wolcott, 2012)
A study in 2020 found that 59% of chronic wounds healed if there was no infection present, but this rate dropped to 45% in infected chronic wounds. Infected chronic wounds can have severe consequences – from the risk of amputation of the infected limb, to the additional care costs on the NHS. Treating non-healing chronic wounds cost the NHS £5.8 billion in 2017 alone (Guest et al., 2020)
The skin is generally considered as a hostile place for bacteria to survive. The wide ranges in temperature and humidity, as well as the factors our bodies secrete onto the skin all serve to limit bacterial growth (Grice and Segre, 2012) . Upon wounding, our body releases factors known as Damage Associated Molecular Patterns (DAMPs) that alert the body to losses in epidermal barrier integrity(Ridiandries et al., 2018). Bacteria express Pathogen Associated Molecular Patterns (PAMPs); our body recognises these and in response stimulates our immune response to secrete pro-inflammatory factors like cytokines (Sun et al., 2019). In infected wounds the DAMPs and the PAMPs synergise to increase inflammation.
The reason that wounds support the development of bacterial biofilms is due to the moist, nutrient-rich environment caused by wound exudates (Oh et al., 2014). A prolonged or uncontrolled host inflammatory response results in host tissue damage which enables the bacteria within the biofilm to gain more nutrients from the wound (Percival et al., 2012). Typically, wound biofilms are polymicrobial in nature and are more robust than single-species biofilms (Gontcharova et al., 2010). Polymicrobial biofilms can support bacterial growth over a wider range of environments through co-operation between species with different attributes. For example, cooperation between aerobes and anaerobes allowing biofilm growth over a wide range of oxygen concentrations (Mayrand, and McBride, 1980). In chronic wounds specifically, it is thought that 80% of wound infections are due to biofilms (Hurlow and Bowler, 2012).
Further reading on biofilms in disease and wounding
Attinger, C. and Wolcott, R. (2012) ‘Clinically Addressing Biofilm in Chronic Wounds’, Advances in Wound Care, vol. 1(3), pp. 127-32, https://doi-org.uea.idm.oclc.org/10.1089/wound.2011.0333.
Grice E. A. and Segre J. A. (2012) ‘Interaction of the Microbiome with the Innate Immune Response in Chronic Wounds’ In: Lambris J., Hajishengallis G. (eds) Current Topics in Innate Immunity II. Advances in Experimental Medicine and Biology, vol. 946. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0106-3_4.
Gontcharova, V., Youn, E., Sun, Y., Wolcott, R. D. and Dowd, S. E. (2010) ‘A comparison of bacterial composition in diabetic ulcers and contralateral intact skin’, Open Microbiology Journal, vol. 4, pp. 8-19, https://doi.org/10.2174/1874285801004010008 .
Guest, J. F., Fuller, G. W. and Vowden, P. (2020) ‘Cohort study evaluating the burden of wounds to the UK’s National Health Service in 2017/2018: update from 2012/2013’, BMJ Open, vol. 10(12), e045253, https://doi.org/10.1136/bmjopen-2020-045253.
Hurlow, J. and Bowler, P. G. (2012) ‘Potential implications of biofilm in chronic wounds: A case series’, Journal of Wound Care, vol. 21(3), pp. 109-19, https://doi.org/10.12968/jowc.2012.21.3.109.
Mayrand, D. and McBride, B. C. (1980) ‘Ecological relationships of bacteria involved in a simple, mixed anaerobic infection’ Infection and Immunity, vol. 27(1). pp. 44-50, https://doi.org/10.1128/iai.27.1.44-50.1980.
Oh, J., Byrd, A. L., Deming, C., Conlan, S., Kong, H. H. and Segre, J. A (2014) ‘Biogeography and individuality shape function in the human skin metagenome’, Nature, vol. 514, pp. 59-64, https://doi.org/10.1038/nature13786.
Percival, S. L., Emanuel, C., Cutting, K. F. and Williams, D. W. (2012) ‘Microbiology of the skin and the role of biofilms in infection’ International Wound Journal, vol. 9(1), pp. 14–32. https://doi.org/10.1111/j.1742-481X.2011.00836.x.
Ridiandries, A., Tan, J. T. M. and Bursill, C. A. (2018) ‘The role of chemokines in wound healing’, International Journal of Molecular Sciences, vol. 19(10) https://doi.org/10.3390/ijms19103217.
Sun, L., Liu, W. and Zhang, L. J. (2019) ‘The role of Toll-like receptors in skin host defense, psoriasis, and atopic dermatitis’, Journal of Immunology Research, https://doi.org/10.1155/2019/1824624.