Microfluidic Evolution‐On‐A‐Chip Reveals New Mutations that Cause Antibiotic Resistance

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 17; no. 10; pp. e2007166 - n/a
• Main Authors: Zoheir, Ahmed E., Späth, Georg P., Niemeyer, Christof M., Rabe, Kersten S.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.03.2021
• Subjects: Acid resistance; Adaptation; adaptive laboratory evolution; antibiotic resistance; Antibiotics; biofilms; Drug resistance; E coli; Evolution; gradients; lab‐on‐a‐chip; Microfluidic devices; Microorganisms; Mutation; mutations; Nanotechnology; mutations; adaptive laboratory evolution; antibiotic resistance; gradients; biofilms; lab-on-a-chip
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202007166

Microfluidic devices can mimic naturally occurring microenvironments and create microbial population heterogeneities ranging from planktonic cells to biofilm states. The exposure of such populations to spatially organized stress gradients can promote their adaptation into complex phenotypes, which are otherwise difficult to achieve with conventional experimental setups. Here a microfluidic chip that employs precise chemical gradients in consecutive microcompartments to perform microbial adaptive laboratory evolution (ALE), a key tool to study evolution in fundamental and applied contexts is described. In the chip developed here, microbial cells can be exposed to a defined profile of stressors such as antibiotics. By modulating this profile, stress adaptation in the chip through resistance or persistence can be specifically controlled. Importantly, chip‐based ALE leads to the discovery of previously unknown mutations in Escherichia coli that confer resistance to nalidixic acid. The microfluidic device presented here can enhance the occurrence of mutations employing defined micro‐environmental conditions to generate data to better understand the parameters that influence the mechanisms of antibiotic resistance. Applying stress to bacterial populations can accelerate their evolutionary adaptation. In particular, the development of antibiotic resistance has significant health and economic implications. With the help of a new type of microfluidic device, bacterial cells can be exposed to defined stress gradients in complex microenvironments, which lead to accelerated adaptation and the occurrence of new mutations that induce antibiotic resistance.