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- W2806248497 abstract "Bacteria population density modulates the effectiveness of antibiotic treatment. Better understanding of the dynamics between bacteria density and antibiotics helps designing improved treatment strategies, and prevent emergence and spread of drug resistance. In here we describe a droplet microfluidic platform designed for parallel analysis of multiple bacteria inoculum densities. We generate a color-coded series of bacteria inoculum densities, split them into 2nL droplets, and pool them together for incubation and analysis. During cefotaxime treatment of bacteria we observed strong inoculum effect, often associated with beta-lactam antibiotics. The technology also revealed two types of phenotypic heterogeneity in our test strain. Firstly, we observed heterogeneity in growth inhibition in samples starting from single bacteria. At sub-inhibitory antibiotic concentrations only a ~10% fraction of bacteria manage to start viable colony in droplet. That hints for a phenotypical differences in molecular mechanisms responsible for reducing effects of beta-lactams. Secondly, we saw intensive clumping of bacteria that is modulated by the inoculum density and antibiotic concentration. The clumping is most intensive at sub-inhibitory concentrations of cefotaxime. Such diversity in population heterogeneity would have been difficult to spot with conventional cytometry or microscopy methods. This demonstrates that the technology we describe here opens up new possibilities in modern microbiology, especially in investigating antibiotic susceptibility and drug resistance." @default.
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- W2806248497 date "2018-06-04" @default.
- W2806248497 modified "2023-09-24" @default.
- W2806248497 title "Multiplex droplet assay reveals coinciding inoculum effect and phenotypic heterogeneity during beta-lactam treatment of bacteria" @default.
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