ODELAM Rapid sequence-independent detection of drug resistance in isolates of Mycobacterium tuberculosis
- Seattle Children's Research Institute, United States
- University of Washington, United States
- Vanderbilt University, United States
Abstract
Antimicrobial-resistant Mycobacterium tuberculosis (Mtb) causes over 200,000 deaths each year. Current assays of antimicrobial resistance need knowledge of mutations that confer drug resistance, or long periods of culture time to test growth under drug pressure. We present ODELAM (One-cell Doubling Evaluation of Living Arrays of Mycobacterium), a time-lapse microscopy-based method that observes individual cells growing into microcolonies. ODELAM enables rapid quantitative measures of growth kinetics in as little as 30 hours under a wide variety of environmental conditions. We demonstrate ODELAM's utility by identifying ofloxacin resistance in cultured clinical isolates of Mtb and benchmark its performance with standard minimum inhibitory concentration (MIC) assays. In Mtb isolate, ODELAM identified ofloxacin heteroresistance and identifies the presence of drug resistant colony forming units (CFUs) at 1 per 1000 CFUs in as little as 48 hours. ODELAM is a powerful new tool that can rapidly evaluate Mtb drug resistance in a laboratory setting.
Data availability
MATLAB data *.mat files and MATLAB *.m files utilized for generating figures in this submission are posted at Dryad. Additional source code has been made available at https://github.com/AitchisonLab/
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ODELAM: Rapid sequence-independent detection of drug resistance in clinical isolates of Mycobacterium tuberculosisDryad Digital Repository, doi:10.5061/dryad.b8gtht78q.
Article and author information
Author details
Funding
National Institutes of Health (U19 AI135976)
- David R Sherman
- John D Aitchison
National Institutes of Health (U19 AI111276)
- John D Aitchison
National Institutes of Health (R01 AI141953)
- John D Aitchison
National Institutes of Health (P41 GM109824)
- John D Aitchison
National Institutes of Health (R01 AI063200)
- Timothy R Sterling
National Institutes of Health (R56 AI118361)
- Timothy R Sterling
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Herricks et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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ODELAM Rapid sequence-independent detection of drug resistance in isolates of Mycobacterium tuberculosis
eLife 9:e56613.
https://doi.org/10.7554/eLife.56613
