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Phenotypic drug susceptibility testing for Mycobacterium tuberculosis variant bovis BCG in 12 hours

Author

Listed:
  • Buu Minh Tran

    (Uppsala University)

  • Jimmy Larsson

    (Uppsala University)

  • Anastasia Grip

    (Uppsala University)

  • Praneeth Karempudi

    (Uppsala University)

  • Johan Elf

    (Uppsala University)

Abstract

Drug-resistant tuberculosis (DR-TB) kills ~200,000 people every year. A contributing factor is the slow turnaround time (TAT) associated with drug susceptibility diagnostics. The prevailing gold standard for phenotypic drug susceptibility testing (pDST) takes at least two weeks. Here we show that growth-based pDST for slow-growing mycobacteria can be conducted in 12 h. We use Mycobacterium tuberculosis variant bovis Bacillus Calmette-Guérin (BCG) and Mycobacterium smegmatis as the mycobacterial pathogen models and expose them to antibiotics used in (multidrug-resistant) tuberculosis (TB) treatment regimens - i.e., rifampicin (RIF), isoniazid (INH), ethambutol (EMB), linezolid (LZD), streptomycin (STR), bedaquiline (BDQ), and levofloxacin (LFX). The bacterial growth in a microfluidic chip is tracked by time-lapse phase-contrast microscopy. A deep neural network-based segmentation algorithm is used to quantify the growth rate and to determine how the strains responded to drug treatments. Most importantly, a panel of susceptible and resistant M. bovis BCG are tested at critical concentrations for INH, RIF, STR, and LFX. The susceptible strains could be identified in less than 12 h. These findings are comparable to what we expect for pathogenic M. tuberculosis as they share 99.96% genetic identity.

Suggested Citation

  • Buu Minh Tran & Jimmy Larsson & Anastasia Grip & Praneeth Karempudi & Johan Elf, 2025. "Phenotypic drug susceptibility testing for Mycobacterium tuberculosis variant bovis BCG in 12 hours," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59736-9
    DOI: 10.1038/s41467-025-59736-9
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    References listed on IDEAS

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    1. Vinodh Kandavalli & Praneeth Karempudi & Jimmy Larsson & Johan Elf, 2022. "Rapid antibiotic susceptibility testing and species identification for mixed samples," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
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