Tre-DST: A Drug Susceptibility Test for Mycobacterium tuberculosis Using Solvatochromic Trehalose Probes
Lilith A Schwartz1, Adriann L Brodeth2, Cara T Susilo2
1UCLA Department of Chemistry and Biochemistry, Los Angeles, California 90095, United States.
ACS Infectious Diseases
|December 19, 2025
Summary
A new trehalose probe assay (Tre-DST) rapidly detects drug-resistant tuberculosis (DR-TB) by identifying live mycobacteria. This cost-effective method offers results over two weeks faster than traditional culture methods.
Area of Science:
- Microbiology and Infectious Diseases
- Biotechnology and Diagnostics
Background:
- Tuberculosis (TB) affects millions globally, with a significant burden of drug-resistant TB (DR-TB).
- Current DR-TB diagnostics like culture and nucleic acid tests have limitations, including long turnaround times and high costs.
- Rapid and accurate diagnostics are crucial for timely treatment initiation and improved patient outcomes.
Purpose of the Study:
- To develop and evaluate a novel, rapid phenotypic drug susceptibility test for TB.
- To assess the feasibility of using cost-effective plate readers for this new diagnostic method.
- To demonstrate the assay's ability to detect drug resistance in a drug-agnostic manner.
Main Methods:
- Development of Tre-DST, a phenotypic test using metabolically incorporated trehalose probes to detect live mycobacteria.
- Utilized *Mycobacterium smegmatis* and attenuated/auxotrophic *Mycobacterium tuberculosis* strains for validation.
- Compared fluorescence detection using plate readers and flow cytometry; assessed time-to-result against colony-forming unit analysis.
Main Results:
- Strong correlation observed between plate reader and flow cytometry data, validating plate readers as suitable detectors.
- Tre-DST detected Mtb in 1 week, over 2 weeks earlier than traditional CFU analysis.
- The assay demonstrated drug-agnostic susceptibility reporting, detecting resistance to frontline drugs and bedaquiline, including RIF- and INH-resistant strains.
Conclusions:
- Tre-DST is a rapid, cost-effective phenotypic assay for detecting TB drug resistance.
- Its drug-agnostic nature suggests broad applicability for current and future DR-TB drugs in reference laboratories.
- This assay has the potential to significantly improve the speed and accessibility of DR-TB diagnostics.
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