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In vitro and in situ structural characterization of the biofilm-associated functional amyloids in Pseudomonas aeruginosa bacteria

Project description

Targeting bacterial biofilms

Bacteria form dense communities known as biofilms. Biofilms pose a critical global health threat since they shield microbes from antibiotics and enhance antibiotic resistance. The bacterium Pseudomonas aeruginosa, linked to cystic fibrosis and hospital-acquired infections, forms biofilms supported by amyloid fibrils. These protein aggregates, known as functional amyloids of Pseudomonas (Faps), are poorly characterised in physiological situations. With the support of the Marie Skłodowska-Curie Actions programme, the FAPbulous project aims to uncover the structure and function of Faps and explore their role in biofilm formation. Using cutting-edge techniques, researchers will investigate basic mechanisms of bacterial resistance and lay the foundation for the development of new strategies against biofilm-associated infections.

Objective

Bacterial resistance to antibiotics poses a critical global threat and is partly due to the formation of stable biofilms which shield bacterial cells from antibiotics. Cystic fibrosis in lugs and some hospital-acquired infections caused by Pseudomonas aeruginosa are closely linked to the formation of biofilms and resistance mechanisms, which include the presence of amyloid fibrils. Amyloids are a class of proteins known for their ability to self-assemble into highly structured fibrils. Their pivotal role as major virulence factors in microbial pathogens makes them leading targets for developing novel antimicrobial treatments. However, our understanding of microbial amyloids is limited, especially in a physiological context. This gap is particularly pronounced for the Functional Amyloids in Pseudomonas (Faps). Detailed insights into their structures and how they interact within biofilms are still elusive, mostly due to the limits of imaging technologies. To address this knowledge gap, in the FAPbulous project, I will use a multidisciplinary approach by combining structural biology, biophysics and genetic engineering techniques to (1) determine the in vitro structures of Faps amyloid fibrils, (2) characterize their molecular mechanism within biofilms and (3) assess the effects of inhibitors known to prevent Faps fibrillation on biofilm formation and resilience. This highly innovative project will be achieved by using the recent advances in cryo-electron and super resolution fluorescence microscopies to gain unprecedented insights into the structural dynamics of Faps within medically relevant biofilms and unveil their detailed mechanism of action, paving the way for novel antimicrobial strategies. The interdisciplinarity of FAPbulous will massively improve my research profile, endowing me with the scientific and soft skills necessary to perform future multidisciplinary research at the interface of structural biology, host:pathogen interactions and protein aggregation.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

DEUTSCHES ELEKTRONEN-SYNCHROTRON DESY
Net EU contribution
€ 202 125,12
Address
NOTKESTRASSE 85
22607 Hamburg
Germany
Region
Hamburg Hamburg Hamburg
Activity type
Research Organisations
Links
Total cost
No data