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What to expect of ExPEC: is the success of extraintestinal pathogenic E. coli linked to specific genomic and cellular properties?

Project description

Uncovering genomic drivers of pathogenic E. coli

Extraintestinal pathogenic Escherichia coli (ExPEC) is a subset of E. coli strains that can cause infections outside the intestinal tract, unlike typical E. coli. ExPEC strains are a leading cause of healthcare-associated infections and often resistant to common antibiotics, making infections harder to treat. With the support of the Marie Skłodowska-Curie Actions programme, the EXCELLGEN project aims to explore genomic features that may influence ExPEC’s physiology, growth and metabolism. The research team will create a database of ExPEC-specific regions to conduct a large-scale comparison with other E. coli genomes, identifying regions unique to ExPEC. The impact of these regions on phenotype and the underlying molecular mechanisms will provide essential insights into ExPEC physiology and management.

Objective

Extraintestinal pathogenic E. coli (ExPEC) are one of the greatest challenges for the healthcare system, with a frightening prognosis for the future. Despite being heavily studied in recent years, no unifying principle explaining their success has been identified. Only limited attention has been paid to the additional genomic properties of ExPEC strains that are not virulence factors or antimicrobial resistance genes. I aim to demonstrate that these additional genomic features lead to alterations in cellular features (related to physiology, growth ability and metabolism) that contribute to ExPEC (pathogenic) success. To do so, I will first setup a database of ExPEC specific regions and use this to perform an unbiased large-scale screen comparing them to publicly available E. coli genomes. This analysis will yield specific genomic regions that can be confidently assigned to ExPEC or ExPEC subgroups. To further demonstrate the biological significance of these regions, high-throughput single-cell phenomics will be employed to quantitatively examine specific strains of interest across different growth conditions and identify the genes or groups of genes present in the ExPEC specific regions associated with specific phenotypic alterations. Finally, the identified genomic regions will be further characterized using a deep mutational scanning approach to uncover the exact molecular mechanisms that underlie phenotypic alterations of pathogenic strains in comparison to their non-pathogenic counterparts. I expect this project to bring much-needed insights into ExPEC physiology, linking it with its specific genomic background. Such fundamental knowledge will contribute to managing ExPEC more effectively in the future.

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-2022-PF-01

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Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN
Net EU contribution
€ 191 078,00
Address
OUDE MARKT 13
3000 Leuven
Belgium
Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
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Total cost
No data