Microbiology Editor’s Choice: biofilm formation prevents colistin entry in cystic fibrosis
Posted on January 6, 2021 by Microbiology Society
Each month, a manuscript published in our flagship journal Microbiology is chosen by a member of the Editorial Board. This month, the paper is titled ‘Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa’ and was chosen by Dr Jen Cavet.
Biofilm infections remain problematic to treat due to their extensive antibiotic tolerance. Key issues hampering the treatment of in vivo biofilms include the inability of antibiotics to penetrate the biofilm extracellular matrix and poor concordance between antibiotic susceptibility testing in diagnostic laboratories and patient outcomes.
Pseudomonas aeruginosa is highly prevalent in chronic biofilm lung infections of patients suffering from cystic fibrosis (CF), whilst the drug colistin is commonly prescribed to treat these infections. However, this study reveals that the ability of colistin to enter the biofilm matrix and kill bacteria is low when P. aeruginosa is grown as a CF-like bronchiolar biofilm. The authors compared the tolerance of P. aeruginosa to colistin in generic in vitro biofilm assays and in an ex vivo CF model. They show that P. aeruginosa has increased tolerance when grown in a synthetic medium that mimics CF sputum compared to standard medium and has drastically increased tolerance when grown in an ex vivo model that combines the synthetic CF sputum medium with porcine bronchiolar tissue. Using fluorescently labelled colistin they demonstrate that the increased drug tolerance in the ex vivo model is indeed due to poor penetration of the biofilm matrix.
This study highlights the limitations of generic in vitro biofilm assays that are commonly used to test antibiotic efficacy and provides a tractable model for improved modelling of the CF lung environment and for monitoring drug entry into the biofilm matrix. This study thereby offers aid for antibiotic susceptibility testing in both diagnostics and drug development in the future.'
Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa
We aimed to reproduce the environment inside the lungs of people with cystic fibrosis (CF), where bacteria called Pseudomonas aeruginosa stick themselves together to make structures called biofilms. We used pieces of pig lung and artificial mucus. We showed that it’s possible to use our lung model to test the anti-biofilm activity of antibiotics, potentially getting a more realistic measure of how much different antibiotics could help a person with CF. We also used a fluorescent dye to measure how well an antibiotic could penetrate the biofilm. These techniques could help researchers find new drugs to treat cystic fibrosis lung infections.
We spoke with the authors Dr Freya Harrison and Dr Esther Sweeney to find out more:
What is your institution and how long have you been there?
We are both based at the University of Warwick. Freya moved to Warwick set up her first independent research group in August 2016, and Esther joined the lab as its first member in February 2017.
What is your research area?
Models of polymicrobial and chronic infections, particularly biofilms associated with the cystic fibrosis lung and with non-healing wounds. Our team tries to understand how the fundamental biology of bacteria changes when they establish these infections and to find new antimicrobial molecules that could be developed into badly needed drugs to prevent or treat them.
What inspired you to research this topic?
Antimicrobial resistance remains one of the biggest threats to future global health. We need to understand it better and find alternative approaches to treating infections that will be effective when antibiotics are not. Bacteria are very flexible, and the same species of bacteria can have quite different biology in an infected host and in a test tube – and also in different types of infection. So, building more accurate models of infection, that closely reflect a clinical situation, is one of the essential means to achieve the goal of finding new ways to treat antibiotic-resistant bacteria.
What is the most rewarding part of your research?
Esther: Model development can be labour intensive and primarily trial and error or troubleshooting. It isn’t often that you see ‘rapid results’, but I love the creative process and when you notice something novel or intriguing happening in your model it is always exciting.
Freya: Creativity and problem-solving is also the main attraction for me. I enjoy the fact that being a scientist involves a lot of talking to people to work together and exchange ideas and expertise. The most rewarding aspect of this particular research, though, has been seeing other research groups and even a company adopt and use the lung model to test potential new treatments for CF lung infections. It’s fantastic to see that all of our hard work has produced something useful.
What would you be doing if you weren't a scientist?
Esther: Telling the world about science! Perhaps teaching creativity to children in order to inspire innovation in the next generation and, if money was no object, I’d be travelling the world, finding spectacular, natural landscapes to inspire my love for abstract acrylic painting.
Freya: I’d enjoy working in a science centre or a museum, engaging people in hands-on activities to learn new things. I like building and making things, so I’d especially enjoy making props and replicas for people to handle to learn about science or history.
Follow the authors Freya, Esther and Dr Andrew Edwards on Twitter.
