Wound care
that, these wounds are prone to bacterial colonisation of the most pernicious kind – the formation of a biofilm. “It hasn’t necessarily been proven that it’s the presence of a biofilm that causes an acute infection to develop into a chronic infection, but they certainly do worsen wound healing,” says Barbara Conway, head of pharmacy at the University of Huddersfield, UK, and co-director of the Institute of Skin Integrity and Infection Prevention. “It’s that combination of a chronic wound in a non-healing state, and the presence of the biofilm that together provides a real problem.”
Why are biofilms such a problem? In their free-living, ‘planktonic’ state, bacteria are easy enough for the body to deal with. Rampaging phagocytes (a type of white blood cell) engulf the bacteria and chew them up. However, bacteria have found a way to defend themselves within hostile environments: they adhere to surfaces, where they organise themselves into fortress-like structures known as biofilms.
“The bacteria tend to grow together in large groups and surround themselves with a sticky, slimy matrix,” says Sarah Rowe-Conlon, a research associate professor in the Department of Microbiology and Immunology at the University of North Carolina. “This matrix is the biofilm, and it acts like a forcefield protecting the encased bacteria from our immune systems and other assaults, such as antibiotics.” Sometimes described as ‘cities for microorganisms’, biofilms are complex communities in which members work together to fend off attacks. Like any other city, they are cosmopolitan in nature – composed not just of bacteria, but of a mixture of different entities, including polysaccharides, proteins and DNA. “You get them on all sorts of surfaces,” says Conway.
“You get them on medical devices, you get them in natural environments like rocks and rivers, and you also get them in other places within the human body. We’re disturbing and removing a biofilm every time we brush our teeth.” Unfortunately, the biofilms that form in chronic wounds aren’t as easy to dispel as dental plaque. Even once the wound has been debrided (physically scraped out), cells can remain, and the bacterial ‘city’ can start to rebuild its walls. Forty percent of diabetic foot ulcers will have reappeared within a year, rising to 65% within five years.
“I often compare the current therapeutic strategy to removing a weed in your garden by cutting the stem off using scissors,” says Rowe-Conlon. “You can cut it off, but you're going expect to it to grow back, and it might grow back in the same place or it might proliferate somewhere else.”
While healthcare professionals do administer antibiotics, this tends to bring mixed success. For one thing, certain classes of drugs can struggle to
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penetrate the biofilm. For another, sluggishly growing ‘persister cells’ within the biofilm can tolerate very high concentrations of antibiotics. Biofilms are even known to contribute to antibiotic resistance, which can happen when bacteria of different species swap genetic material.
“For example, the first reported incidence of a strain of Staphylococcus aureus acquiring vancomycin resistance from Enterococcus was from a patient who had a diabetic foot ulcer and was co-infected with both pathogens,” says Rowe-Conlon “This is an example of bacteria sharing resistance mechanisms within biofilms.”
The research community is responding Evidently, we need approaches that get rid of the biofilm altogether. Some researchers are looking at strategies that disperse biofilm communities, while others are more interested in stopping the biofilm from forming in the first place. “It’s important to understand the biofilm lifecycle, from early colonisation through to maturity, because the approach that is needed will be determined by the stage it has reached,” says Conway. “You can either try to stop the adhesion and the formation of the biofilm, or you can try to destroy it after it’s already in existence. People are working on targeting entities within the biofilm like the polysaccharides and proteins.” Conway herself works within pharmaceutical formulation, designing drug delivery systems that target drugs towards the sites where they’re needed. In the context of wound care, she is particularly interested in strategies involving nanomaterials, in which the microbial agent is encased in tiny particles and (to continue the city analogy) smuggled through the city walls.
Biofilms contain bacteria cells, but also other biological materials like proteins and DNA.
94%
The percentage reduction in MRSA infection achieved in the wounds of diabetic mice using the sonotherapy approach.
Huddersfield University 41
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