Droplet microfluidics–based detection of rare antibiotic-resistant subpopulations in Escherichia coli from bloodstream infections

IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Sagar N. Agnihotri, Nikos Fatsis-Kavalopoulos, Jonas Windhager, Maria Tenje, Dan I. Andersson
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Abstract

Population heterogeneity in bacterial phenotypes, such as antibiotic resistance, is increasingly recognized as a medical concern. Heteroresistance occurs when a predominantly susceptible bacterial population harbors a rare resistant subpopulation. During antibiotic exposure, these resistant bacteria can be selected and lead to treatment failure. Standard antibiotic susceptibility testing methods often fail to reliably detect these subpopulations due to their low frequency, highlighting the need for improved diagnostic approaches. Here, we present a droplet microfluidics method where bacteria are encapsulated in droplets containing growth medium and antibiotics. The growth of rare resistant cells is detected by observing droplet shrinkage under microscopy. We validated this method for three clinically important antibiotics in Escherichia coli isolates obtained from bloodstream infections and showed that it can detect resistant subpopulations as infrequent as 10−6 using only 200 to 300 droplets. In addition, we designed a multiplex microfluidic chip to increase the throughput of the assay.

Abstract Image

基于微流控液滴的血液感染大肠杆菌罕见耐药亚群检测
细菌表型的群体异质性,如抗生素耐药性,越来越被认为是一个医学问题。当主要易感菌群中含有罕见的耐药亚群时,就会发生异耐药。在抗生素暴露期间,这些耐药细菌可以被选择并导致治疗失败。标准的抗生素药敏试验方法往往不能可靠地检测到这些亚群,因为它们的频率低,强调需要改进诊断方法。在这里,我们提出了一种微流体方法,其中细菌被封装在含有生长介质和抗生素的液滴中。在显微镜下通过观察液滴收缩来检测罕见耐药细胞的生长。我们对从血液感染中获得的大肠杆菌分离株的三种临床重要抗生素进行了验证,结果表明,仅使用200至300个液滴就可以检测到罕见的10 - 6个耐药亚群。此外,我们设计了一个多路微流控芯片,以提高分析的通量。
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来源期刊
Science Advances
Science Advances 综合性期刊-综合性期刊
CiteScore
21.40
自引率
1.50%
发文量
1937
审稿时长
29 weeks
期刊介绍: Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.
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