High-throughput screening of antibiotic-resistant bacteria in picodroplets

被引:90
作者
Liu, X. [1 ]
Painter, R. E. [2 ]
Enesa, K. [1 ]
Holmes, D. [1 ]
Whyte, G. [3 ]
Garlisi, C. G. [2 ]
Monsma, F. J., Jr. [2 ]
Rehak, M. [1 ]
Craig, F. F. [1 ]
Smith, C. A. [1 ]
机构
[1] Sphere Fluid Ltd, Jonas Webb Bldg,Babraham Res Campus, Cambridge CB22 3AT, England
[2] Merck & Co Inc, Merck Res Labs, 2015 Galloping Hill Rd,K15, Kenilworth, NJ 07033 USA
[3] Heriot Watt Univ, Inst Biol Chem Biophys & Bioengn, Sch Engn & Phys Sci, Edinburgh EH14 4AS, Midlothian, Scotland
关键词
SUSCEPTIBILITY;
D O I
10.1039/c6lc00180g
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The prevalence of clinically-relevant bacterial strains resistant to current antibiotic therapies is increasing and has been recognized as a major health threat. For example, multidrug-resistant tuberculosis and methicillin-resistant Staphylococcus aureus are of global concern. Novel methodologies are needed to identify new targets or novel compounds unaffected by pre-existing resistance mechanisms. Recently, water-in-oil picodroplets have been used as an alternative to conventional high-throughput methods, especially for phenotypic screening. Here we demonstrate a novel microfluidic-based picodroplet platform which enables high-throughput assessment and isolation of antibiotic-resistant bacteria in a label-free manner. As a proof-of-concept, the system was used to isolate fusidic acid-resistant mutants and estimate the frequency of resistance among a population of Escherichia coli (strain HS151). This approach can be used for rapid screening of rare antibiotic-resistant mutants to help identify novel compound/target pairs.
引用
收藏
页码:1636 / 1643
页数:8
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