Dynamics of microbe-microbe and microbe-host interactions in mixed-species biofilm infection

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

Bacteria often produce a sticky coat in order to glue themselves together into multicellular structures called biofilm. Biofilms are found in industrial settings (like liquid handling systems in factories) and in many chronic infections (like lung infections in people with cystic fibrosis, or diabetic foot ulcers). The biofilm coating allows bacteria to stick to surfaces and can prevent antibiotics and immune cells from reaching the bacteria to kills them. Also, biofilms are often a response to very specific environmental conditions that also change bacterial physiology. Bacteria in biofilms may express different genes and have quite different metabolism from bacteria growing as single, freely-moving cells in standard lab broth. These physiological changes can also increase the bacteria's resistance to antibiotics, and also allow different strains and species of bacteria to coexist and cooperate to protect one another from antibiotics. If we want to understand how bacteria behave in biofilms and why this makes them so hard to get rid of, we need laboratory models of the specific contexts in which bacteria from biofilms. These will allow us to study diverse biofilm communities of bacteria in an environment that is chemically and structurally similar to a real-world setting in which biofilms cause problems. In this PhD, I will use a model of bacterial biofilms in the lungs of people with cystic fibrosis to improve our understanding of the fundamental microbiology of bacterial biofilm formation, ecology and antibiotic resistance. I use pigs' lungs, supplied by a local butcher as a by-product of the meat industry, and carefully-constructed artificial CF lung mucus to mimic the lung environment. I will study how key species of bacteria interact and evolve in these biofilms, and assess how models like mine could be used to find better ways of dismantling biofilm.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 31/03/2024
1897887 Studentship BB/M01116X/1 02/10/2017 02/02/2022 Niamh Harrington
 
Description Our research so far has shown that a model using pig lung tissue that is a waste product from the meat industry is able to mimic key aspects of bacterial lung infections seen in humans. We have focused on the lung infections that affect people with the genetic condition Cystic Fibrosis (CF), and have shown that one of the major pathogens in the UK infects the pig lung model in the same way that it infects the CF lung. The model is allowing us to further understand the dynamics of these infections. It may facilitate research into these infections in a more realistic setting to bridge the gap between the laboratory and the clinic, and has potential to be used for the discovery of novel infection prevention methods and treatments.
Exploitation Route Development and hopefully publication of this model means that it can now be used by other research groups to develop it to study infections in other lung contexts. It may also be possible to develop it as a drug testing/development platform commercially.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description BBSRC Impact Acceleration Award via University of Warwick (PI) "Mesoporous materials for antibiotic delivery into bacterial biofilm" with industrial partner Brentapharm
Amount £3,996 (GBP)
Funding ID BB/S506783/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 02/2022 
End 03/2022
 
Description Microbiology Society Conference Grants - Annual Conference 2019
Amount £238 (GBP)
Funding ID GA001128 
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 02/2019 
End 04/2019
 
Title Ex vivo lung model - optimised / UKAS-accredited implementation 
Description In line with the aims of the grant, we have optimised and shared our ex vivo lung model. The current grant has allowed significant improvements and flexible re-optimisation of the model to make it more useful and tractable for colleagues, especially those in industry. We have successfully trained scientists from Perfectus Biomed Ltd. in the use of the model and helped them gain UKAS accreditation for its use in preclinical testing of antibiofilm agents. We have also published and open-access protocol for use of the model in antibiotic susceptibility testing (JoVE, video protocol to follow - delayed by COVID-19 restrictions). Please also refer to other sections of the ResearchFish submission for details of ongoing use and uptake, and the dedicated website at https://warwick.ac.uk/fac/sci/lifesci/people/fharrison/exvivolung 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact Accreditation of the model and Standard EN 1276 to ISO 17025 by our industrial collaborator Perfectus Biomed Ltd. for biocide testing on biofilms of P. aeruginosa. Now beiing used by Perfectus Biomoed Ltd. to test candidate antibiofilm agents for industrial clients. See https://perfectusbiomed.com/perfectus-biomed-elevate-method-testing-beyond-the-standard/ We have also published an open-access protocol for use of the model in antibiotic susceptibility testing for P. aeruginosa and S. aureus in JoVE (see Publications). We will continually monitor uptake of the model through the lifetime of the grant and beyond, an in particular record any concomitant reduction in animal usage by users of the model, and report on this at a later stage. 
URL https://www.jove.com/t/62187/antibiotic-efficacy-testing-an-ex-vivo-model-pseudomonas-aeruginosa
 
Description Getting Stuck into Antibiotics (British Science Festival) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Myself and our post-doc, Dr Marwa Hassan, ran a stall at the 2019 British Science Festival focused on the antimicrobial resistance crisis and demonstrating to the general public how this can occur in biofilm infections through a demonstration ('Getting Stuck into Antibiotics'). Guests were mainly adults of various age with some high school international students. Attendees tried to move some bacteria (represented by beads in a liquid) to explain how antibiotics bind to or interact with bacterial membranes. This gave us the chance to explain that antibiotic resistance develop in bacteria not humans. Then, they tried to get some bacteria out of a coloured slime, which represented biofilm infections in cystic fibrosis. This gave us the chance to talk about cystic fibrosis, biofilm infections, antibiotic tolerance in biofilms and our research in antibiotic tolerance and studying biofilm virulence. Feedback on the day was that people were learning new things from us and that we were conveying our information in an easy to understand way. The festival and outreach teams reported back that we ran a successful activity that engaged the attendees.
Year(s) Of Engagement Activity 2019
URL https://microbiologysociety.org/blog/getting-stuck-into-antibiotics-at-the-british-science-festival....
 
Description Primary School Visit (Solihull) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Myself and our post-doc, Dr Marwa Hassan, attended a primary school for a science day to run workshops about bacteria and infections. We held an assembly for the whole school (~120 pupils and teachers) to demonstrate the journey microbes take and then ran a workshop throughout the day which each class attended. This included a number of activities focused on antimicrobial resistance and the global spread of infectious diseases. This encouraged discussion and questions from the children and the school feedback was that all the pupils were very engaged and have requested more science days in the future.

Feedback from the school:
Please can you pass on huge thank you to all the staff and parents involved in science day. Parents on group messages and the playground have been talking non stop on what a good idea it was and how enthused the children were when they came home. It was a great idea. If the aim was to get them all talking about science it definitely achieved that! It was great to bring all he classes together with a theme and for them to have some joint learning. Huge thanks on behalf of lots of parents in being so creative today. Thanks.

Example feedback from a parent:
[My daughter] is always happy coming home from school but came home this evening so animated! She loved science day and we've had so much detail about all they have done today. It has been "the best school day ever" so a huge thank you to all involved.
Year(s) Of Engagement Activity 2019