Antibiotic tolerance of biofilms emerging from multicellular effects of antibiotic efflux

•  Prof Dr Rosalind J Allen  Friedrich-Schiller Universität Jena, Institute für Mikrobiologie.
• Dr Frank Schreiber Bundesanstalt für Materialforschung und –Prüfung.

© GH-FS, BAM

This project seeks to elucidate the link between multi-drug efflux pumping of bacterial cells, their multicellular structure, and the emergent function of antibiotic tolerance of biofilms.

Biofilms are multicellular assemblies of bacteria in which cell-cell interactions via metabolism and signalling lead to emergent structural and functional properties. Biofilms are notoriously difficult to kill with antimicrobial substances, a phenomenon that is known as tolerance. This is an emergent multicellular trait since biofilms show much greater tolerance than planktonic cells. Tolerance is distinct from antimicrobial resistance, but it can be a stepping stone on the pathway to resistance.

Our project focuses on the mechanisms that lead to emerging antimicrobial tolerance in biofilms. Previous studies suggest a key role for multi-drug efflux pumps. Efflux pumps are protein complexes that cross the bacterial membrane and can pump toxic substances out of the cell.

We aim to develop a predictive, mathematical model for efflux-mediated antimicrobial tolerance in bacterial multicellular assemblies. Experimental data will provide important parameters for the model and confirm its predictions. Our central hypothesis is that efflux pump activity causes emergent antibiotic tolerance of multicellular bacterial populations, through the interplay of efflux-mediated spatial interactions and induction of non-growing, highly tolerant persister cells.

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