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Infection Biology

Characterising pathogen interactions with the host at an atomic, molecular, and tissue level to tackle infection and antimicrobial resistance

Intrinsic and extrinsic constrains to plasmid-born antibiotic resistance dissemination

The continuous spread of antibiotic resistant pathogens is one of the biggest challenges of modern medicine. Despite the strong research focus on antibiotic resistance, a common limitation is that the phenotypic penetrance of resistance genes can depend on intrinsic (e.g., genomic background) and extrinsic factors (e.g., microbial communities). Large-scale studies following a wholistic approach are needed to identify drivers and inhibitors of resistance spread relevant under natural conditions. To this end, I propose to extensively screen the dynamics of multidrug resistance plasmid dissemination across a large set of E. coli isolates and identify genes that influence plasmid acquisition and maintenance by construction of genome-wide transposon knockout libraries. Plasmid maintenance in these libraries will furthermore be quantified in different microbial community contexts, uncovering genes involved in community competitiveness in presence or absence of resistance plasmids. If awarded, this project will provide a roadmap to systematically probe resistance dissemination across wide and relevant settings, reveal genetic interactions that will seed research projects on their mechanistic exploration and provide the foundation for future grant applications on my road to independence.

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