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Deciphering Aspergillus fumigatus - Pseudomonas aeruginosa synergistic interactions in coinfection


Project Description

Pathogen-pathogen interactions in polymicrobial infections are known to directly impact, often to worsen, disease outcomes.
Aspergillus fumigatus is the most common fungal pathogen and Pseudomonas aeruginosa one of the most prevalent bacterial pathogens of the human lung. These microbes are commonly found in long term pulmonary disorders such as COPD or cystic fibrosis. In fact, A. fumigatus and P. aeruginosa are the most prevalent fungal and bacterial pathogens isolated from the cystic fibrosis airways. Co-infection is common and results in an overall worse prognosis.
Interaction during co-infection may affect their virulence potential and therefore have an impact on disease outcome. Using an invertebrate model of infection we have described a synergistic association, based on the production of volatile sulphur compounds, that results in enhanced fungal and bacterial burdens and higher mortality. Furthermore, using an in vitro infection model with an epithelial cystic fibrosis cell line we have confirmed that co-infection enhances fungal and bacterial growth in infection settings.
The objective of this PhD project is to decipher the mechanisms that underpin the increase of pathogenicity in co-infection. To this aim the student will investigate gene expression of fungal and bacterial cells that are in close proximity, but not in direct contact. We will then scrutinize relevant traits by constructing mutant strains and characterising their virulence potential in single and co-infection using both in vitro and in vivo models of infection. We will further determine which volatile compounds trigger the long distance signalling responsible for the intermicrobial interaction and investigate how such communication can be prevented. Finally, we will explore if those volatiles can be detected in infected patients, which will be the basis for the translation of our results into clinical application.
Therefore, our findings will have the potential to drive the development of novel strategies to manage co-infected patients.

Candidates are expected to hold a minimum of a good first degree (upper second class or better) from a UK university or an equivalent qualification if obtained outside the UK. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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