Unraveling bacterial complexity at the single-cell level through cryo-electron microscopy and microfluidics

Nida Ali (University of Cambridge, UK)

14:30 - 14:45 Wednesday 15 April Afternoon

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Abstract

The rise of antimicrobial-resistant bacterial strains has created an urgent need for new antibacterial approaches. Bacteria use sophisticated molecular networks to control their behaviour and adapt to changing environments, including antibiotic stress.  The different mechanisms for resistance involve efflux pumps, target modifications, RNA regulation and cleaving enzymes. Diverse resistance mechanisms also come into play at once, and not all resistance are simply based on a single gene. Some of these are well studied in bacteria by bulk-level experiments, but remain largely unexplored at the single-cell level. This is important as heterogeneity has a huge impact on responses to antimicrobials in the population and the capacity of a subset of cells to temporarily evade bactericidal action and to rebound after exposure. I am currently exploring different methodologies to study spatiotemporal organisation, function, and relationship of all these mechanisms to each other and to antibiotic resistance. These results will lead to a significant shift in our understanding of bacterial cell-to-cell heterogeneity and survival mechanisms. The study applies cryo-electron microscopy, biochemistry, and microfluidics-based single-cell techniques. The microfluidics enables precise environmental control and multigenerational live-cell imaging and fluorescence tracking. The results lead to a better understanding of cell-to-cell heterogeneity and survival mechanisms related to responses to antimicrobials in the population.

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