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Ex vivo Lung Model

A flexible, realistic and ethical model for studying chronic lung infections

Our ex vivo model of chronic bacterial lung infection avoids some key drawbacks of in vitro or animal models of lung infection. We source pig lungs from a local butcher (they are a byproduct of the meat industry) and dissect small sections of tissue. These are combined with bespoke culture media designed to mimic human lung secretions. This provides a clinically valid structural and chemical environment, in which microbial communities may be cultured for several weeks in standard multiwell tissue culture plates. The system is cheap, high throughput and highly flexible, providing an opportunity to replace the use of live animals in infection research. We are keen to discuss potential collaboration or knowledge transfer to further research into antibiotic-resistant infections.

Access to the model and our team's expertise for biofilm research and early-stage antibiofilm R&D is available via collaboration, and we can offer screening of in-development antimicrobial agents via the Warwick Antimicrobial Screening Facility. For later-stage commercial biocide testing, our industrial partners Perfectus Biomed offer access to the model under ISO17025 / EN 1276.

For more information please contact Dr Freya Harrison.

Aggregates of P. aeruginosa in the alveolae of ex vivo pig lung. By Dr Sheyda Azimi.

Chronic lung infections are life-limiting or even life-threatening. They cause fatal respiratory failure in 90% of people with the genetic condition cystic fibrosis (CF) and also affect people who have COPD, HIV or who are receiving mechanical ventilation. Our ability to understand the formation and persistence of polymicrobial, highly antibiotic tolerant microbial communities (biofilm) in these conditions severely limits our ability to treat them.

"The ex vivo lung infection model will be extremely useful to study the impact of quorum sensing inhibitors on Pseudomonas aeruginosa virulence, also enabling the performance of histology studies to determine the effect these inhibitors have on the attenuation of damage to the host."

Prof. Miguel Cámara, School of Life Sciences, University of Nottingham and Co-Director of the National Biofilms Innovation Centre 

Biofilms of P. aeruginosa grown on ex vivo pig bronchiole. By Dr Freya Harrison

We are actively seeking opportunities to share this system with colleagues from academia and industry. Pig lung tissue, airway surface liquid and immune responses are highly similar to those of humans; when combined with culture medium tailored to reflect the unique chemistry of lung secretions characteristic of specific infection contexts, this model allows the culture of microbes in environments with enhanced clinical validity when compared with standard surface-attached biofilm platforms or acute animal models.

TOF-SIMS image showing presence of bacteria and the candidate antimicrobial gallium on a section of pig bronchus. By Dr Sarah Davies.

“We have had extensive discussions with Dr Harrison about potential translational uses of the ex vivo lung model, and two of our microbiologists have received training at Warwick in the use of the model. We are excited by our recent collaborative funding from the National Biofilms Innovation Centre, which will enable us to work together to assess a novel method to detect how well antibiotics penetrate biofilms in chronic lung infections."

Dr Samantha Westgate, CEO, Perfectus Biomed Ltd.

We are keen to discuss potential collaboration or knowledge transfer with colleagues seeking a reliable platform to address fundamental microbiological questions about chronic infection, or for R&D testing of novel antimicrobial agents. While our lab’s work focusses on chronic bacterial biofilm in cystic fibrosis, we are able to work with colleagues to adapt an optimise the ex vivo lung model for use in a variety of contexts

“This open approach to research is very welcome. I felt privileged to be invited to visit and actively learn how best to set up the model, then share that knowledge to others in my research centre. I have plans to use it in future research.”

Dr Chloë James, Senior Lecturer in Medical Microbiology, School of Environment and Life Sciences, University of Salford

Dissecting lung tissue. Photograph courtesy of the Microbiology Society

Pig lungs do not enter the human food chain. By using this waste product from the meat industry, we are able to conduct experiments which use real lung tissue but which do not require the slaughter or infection of live animals. We hope that this approach will help researchers explore different aspects of chronic lung infection microbiology while reducing reliance on animal experiments. You can watch a video about the model to hear more about our approaches to studying infection and reducing animal use in research.

"We have an ongoing collaboration through my PhD student Stefano Gualdi, using the pig lung model to extend his research into the microbiology of Burkholderia cenocepacia."

Prof. Leo Eberl, Department of Plant and Microbial Biology, University of Zürich

"After receiving training in the model, we plan to use it in several Pseudomonas projects in the future"

Dr Jacob Malone, Project Leader, John Innes Centre

Key publications from our lab

Harrington NE, Sweeney E & Harrison F (2020) Building a better biofilm - Formation of in vivo-like biofilm structures by Pseudomonas aeruginosa in a porcine model of cystic fibrosis lung infection. Biofilm 2:100024 (From publisher, OA)

Sweeney, E, Sabnis, A, Edwards, AM & Harrison, F (2020) Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill P. aeruginosa. Microbiology 166:1171 (From publisher, OA)

Harrison, F & Diggle, SP (2016) An ex vivo lung model to study bronchioles infected with Pseudomonas aeruginosa biofilms. Microbiology 162:1755 (From publisher) (bioRxiv pre-print, OA)

Sweeney, E, Hassan, MH, Harrington, NE, Smyth, AR, Hurley, MN, Tormao-Mas, MA & Harrison, F (2020) An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic S. aureus infection. Microbiology, AOP (From publisher; bioRxiv preprint, OA).

Davies, SK, Fearn, S, Allsopp, LP, Harrison, F, Ware, E, Diggle, SP, Filloux, A, McPhail, DS & Bundy, JG (2017) Visualizing antimicrobials in bacterial biofilms: three-dimensional biochemical imaging using TOF-SIMS. mSphere 2:e00211-17 (From publisher, OA)

Collaboration highlight: ECR fellowship

Air pollution is the world’s largest single environmental health risk, causing increased chronic, infectious respiratory diseases. The ground breaking work by Dr. Julie Morrissey's interdisciplinary team at the University of Leicester has shown that exposure to air pollution has a major impact on respiratory tract bacteria. Along with new WTISSF fellow Dr Jo Purves, they are now using the ex vivo pig lung model to investigate the impact of air pollution on the colonisation of bacteria with an important role in respiratory diseases including community acquired pneumonia & chronic obstructive pulmonary disease (COPD).

Citation highlight

Roberts, AEL et al. (2019) Anti-pseudomonad activity of manuka honey and antibiotics in a specialized ex vivo model simulating cystic fibrosis lung infection. Frontiers in Microbiology 10:869 (From publisher).

In this article, ex vivo pig bronchioles and alveolar tissue are used, along with synthetic CF sputum, to test the antibacterial efficacy of Manuka honey alone and in combination with standard antibiotics. Honey shows anti-pseudomonas potential in this model of chronic biofilm infection.