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- W3205771144 abstract "Abstract Phenotypic variations between individual microbial cells play a key role in the resistance of microbial pathogens to pharmacotherapies. Nevertheless, little is known about cell individuality in antibiotic accumulation. Here we hypothesize that phenotypic diversification can be driven by fundamental cell-to-cell differences in drug transport rates. To test this hypothesis, we employed microfluidics-based single-cell microscopy, libraries of fluorescent antibiotic probes and mathematical modelling. This approach allowed us to rapidly identify phenotypic variants that avoid antibiotic accumulation within populations of Escherichia coli, Pseudomonas aeruginosa, Burkholderia cenocepacia and Staphylococcus aureus . Crucially, we found that fast growing phenotypic variants avoid macrolide accumulation and survive treatment without genetic mutations. These findings are in contrast with the current consensus that cellular dormancy and slow metabolism underlie bacterial survival to antibiotics. Our results also show that fast growing variants display significantly higher expression of ribosomal promoters before drug treatment compared to slow growing variants. Drug-free active ribosomes facilitate essential cellular processes in these fast growing variants, including efflux that can reduce macrolide accumulation. Using this new knowledge, we phenotypically engineered bacterial populations by eradicating variants that displayed low antibiotic accumulation through the chemical manipulation of their outer membrane inspiring new avenues to overcome current antibiotic treatment failures." @default.
- W3205771144 created "2021-10-25" @default.
- W3205771144 creator A5020735646 @default.
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- W3205771144 creator A5070122398 @default.
- W3205771144 date "2021-10-19" @default.
- W3205771144 modified "2023-09-23" @default.
- W3205771144 title "Fast bacterial growth reduces antibiotic accumulation and efficacy" @default.
- W3205771144 cites W1577922858 @default.
- W3205771144 cites W1938292773 @default.
- W3205771144 cites W1972074942 @default.
- W3205771144 cites W1972271331 @default.
- W3205771144 cites W1974053222 @default.
- W3205771144 cites W1981267913 @default.
- W3205771144 cites W1981457705 @default.
- W3205771144 cites W1985161570 @default.
- W3205771144 cites W1996666978 @default.
- W3205771144 cites W1996764065 @default.
- W3205771144 cites W2000812746 @default.
- W3205771144 cites W2024596209 @default.
- W3205771144 cites W2035164474 @default.
- W3205771144 cites W2038186289 @default.
- W3205771144 cites W2038727507 @default.
- W3205771144 cites W2045825103 @default.
- W3205771144 cites W2048128158 @default.
- W3205771144 cites W2049862828 @default.
- W3205771144 cites W2053460598 @default.
- W3205771144 cites W2074771787 @default.
- W3205771144 cites W2081183202 @default.
- W3205771144 cites W2087920996 @default.
- W3205771144 cites W2107600014 @default.
- W3205771144 cites W2110881003 @default.
- W3205771144 cites W2119608865 @default.
- W3205771144 cites W2120061656 @default.
- W3205771144 cites W2121209300 @default.
- W3205771144 cites W2121581360 @default.
- W3205771144 cites W2127999800 @default.
- W3205771144 cites W2131170296 @default.
- W3205771144 cites W2139861245 @default.
- W3205771144 cites W2144190398 @default.
- W3205771144 cites W2148323109 @default.
- W3205771144 cites W2150693438 @default.
- W3205771144 cites W2154513384 @default.
- W3205771144 cites W2167244112 @default.
- W3205771144 cites W2167495799 @default.
- W3205771144 cites W2296621547 @default.
- W3205771144 cites W2322777826 @default.
- W3205771144 cites W2325687759 @default.
- W3205771144 cites W2336625825 @default.
- W3205771144 cites W2341166238 @default.
- W3205771144 cites W2346347138 @default.
- W3205771144 cites W2463945839 @default.
- W3205771144 cites W2474289722 @default.
- W3205771144 cites W2506731899 @default.
- W3205771144 cites W2563408447 @default.
- W3205771144 cites W2577537660 @default.
- W3205771144 cites W2600724618 @default.
- W3205771144 cites W2613613983 @default.
- W3205771144 cites W2614889529 @default.
- W3205771144 cites W2744332922 @default.
- W3205771144 cites W2745506379 @default.
- W3205771144 cites W2760639581 @default.
- W3205771144 cites W2777170042 @default.
- W3205771144 cites W2778327699 @default.
- W3205771144 cites W2785225429 @default.
- W3205771144 cites W2788772064 @default.
- W3205771144 cites W2796472927 @default.
- W3205771144 cites W2804284370 @default.
- W3205771144 cites W2804696912 @default.
- W3205771144 cites W2809703987 @default.
- W3205771144 cites W2810380367 @default.
- W3205771144 cites W2810727101 @default.
- W3205771144 cites W2886495199 @default.
- W3205771144 cites W2902168927 @default.
- W3205771144 cites W2903562424 @default.
- W3205771144 cites W2910584283 @default.
- W3205771144 cites W2920362129 @default.
- W3205771144 cites W2932368306 @default.
- W3205771144 cites W2940117744 @default.
- W3205771144 cites W2941980995 @default.
- W3205771144 cites W2945944428 @default.
- W3205771144 cites W2955249862 @default.
- W3205771144 cites W2956541422 @default.
- W3205771144 cites W2972649058 @default.
- W3205771144 cites W2973182801 @default.
- W3205771144 cites W2977389456 @default.
- W3205771144 cites W2978705707 @default.
- W3205771144 cites W2980146749 @default.
- W3205771144 cites W2993083022 @default.
- W3205771144 cites W3007309629 @default.
- W3205771144 cites W3023088732 @default.
- W3205771144 cites W3028082238 @default.
- W3205771144 cites W3035398086 @default.