1. Microbiology and Infectious Disease
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ODELAM Rapid sequence-independent detection of drug resistance in isolates of Mycobacterium tuberculosis

  1. Thurston Herricks
  2. Magdalena Donczew  Is a corresponding author
  3. Fred D Mast
  4. Tige Rustad
  5. Robert Morrison
  6. Timothy R Sterling
  7. David R Sherman  Is a corresponding author
  8. John D Aitchison  Is a corresponding author
  1. Seattle Children's Research Institute, United States
  2. University of Washington, United States
  3. Vanderbilt University, United States
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Cite this article as: eLife 2020;9:e56613 doi: 10.7554/eLife.56613

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.

Article and author information

Author details

  1. Thurston Herricks

    Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0247-7967
  2. Magdalena Donczew

    Department of Microbiology, University of Washington, Seattle, United States
    For correspondence
    mdonczew@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
  3. Fred D Mast

    Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tige Rustad

    Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert Morrison

    Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Timothy R Sterling

    Division of Infectious Disease, Department of Medicine, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. David R Sherman

    Department of Microbiology, University of Washington, Seattle, United States
    For correspondence
    dsherman@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
  8. John D Aitchison

    Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States
    For correspondence
    John.Aitchison@seattlechildrens.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9153-6497

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.

Reviewing Editor

  1. Miles P Davenport, University of New South Wales, Australia

Publication history

  1. Received: March 3, 2020
  2. Accepted: May 12, 2020
  3. Accepted Manuscript published: May 13, 2020 (version 1)

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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