In vitro reconstitution of the polymicrobial community associated with cystic fibrosis airway infections

Project background

Patients with chronic respiratory diseases, such as asthma and cystic fibrosis (CF), are predisposed to microbial colonisation of the airways. Although these respiratory diseases are not caused by microbial infections, repeated infections can exacerbate the condition. It is now understood that the range of bacteria colonising patient airways extends beyond specialised respiratory pathogens and includes a wider range of taxa. Infections associated with chronic respiratory diseases are largely polymicrobial yet animal models are predominantly infected with one or two pathogens only.

Why we funded it

This PhD Studentship aims to replace the need for animal models in the study of polymicrobial infections by establishing an in vitro model to represent the polymicrobial community in the airways of CF patients. 

The most widely-used bronchopulmonary infection model involves introducing bacteria into the lower respiratory tract either via direct injection or surgery. Most of the current procedures modelling respiratory infection are classified as moderate or severe under the Animals (Scientific Procedures) Act 1986. With the developed in vitro model Dr Welch estimates that approximately 10% of current animal models relating to respiratory infection can be replaced.

Research methods

Bioreactor culture conditions will be established to allow the propagation of a stable polymicrobial community representative of the lung community in chronically-infected CF patients. Various growth conditions will be tested to establish a steady-state composition similar to that seen in CF patient sputa. The ability to sub-culture and lyophilise samples without impairing steady-state composition will also be explored. This will allow for the development of a bank of lyophilised stocks enabling reconstitution of a range of polymicrobial communities. The cultured polymicrobial communities will also be challenged with antibiotics to establish their response and whether steady-state compositions alter in response to clinically relevant treatments.   

O'Brien, T J & Welch, M (2019) A continuous-flow model for in vitro cultivation of mixed microbial populations associated with cystic fibrosis airway infections. Front. Microbiol. 10:2713. doi: 10.3389/fmicb.2019.02713

O'Brien, T J & Welch, M (2019) Recapitulation of polymicrobial communities associated with cystic fibrosis airway infections: a perspective. Future Microbiol. [Epub ahead of print] doi: 10.2217/fmb-2019-0200

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PhD Studentship

Institution

University of Cambridge

Grant reference number

NC/P001564/1

Award date

Oct 2017 - Mar 2021

Grant amount

£90,000