# A Rapid Phenotypic Drug Susceptibility Testing System for Tuberculosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $675,156

## Abstract

Abstract
Tuberculosis (TB) is second only to COVID-19 as the most lethal cause of death from a single infectious agent.
In 2020, an estimated 10 million people developed TB, nearly half a million of which were infected with drug-
resistant tuberculosis (DR-TB). Early detection of infection and drug resistance is critical to controlling
DR-TB as this enables rapid engagement into effective care. Unfortunately, only 71% of newly diagnosed
TB patients are ever tested for rifampicin resistance, and even fewer receive more comprehensive testing.
Additionally, despite improved treatment success rates for DR-TB globally, these success rates do not reflect
upstream losses resulting from undiagnosed (missing cases) and untreated patients. Currently, bacterial culture
and nucleic acid testing remain the primary methods for diagnosing infection, with smear microscopy being
phased out. However, these methods present significant limitations for diagnosing drug resistance such as
lengthy time-to-result for phenotypic tests, as well as the need for a priori knowledge of resistance mutations and
prohibitive cost for molecular tests. Clearly, there remains a critical need for a fast, accurate, and cost-effective
DST, particularly for resource-limited settings. To address this, we propose to design and develop a rapid
phenotypic drug susceptibility test that can be easily adapted in TB endemic regions. The trehalose-
based DST, termed Tre-DST, is based on novel trehalose probes, which require metabolic conversion to emit
fluorescent signals, giving them their unique ability to specifically detect live Mycobacterium tuberculosis
(Mtb). Agnostic to mechanism(s) of drug resistance, Tre-DST can be used with all WHO-recommended DRTB
drugs, as well as any future TB drugs as a companion diagnostic. In Aim 1, we will develop, characterize,
and optimize a family of novel fluorescent trehalose probes (3HC-Tre and RMR-Tre) that are specifically
designed to improve performance over DMN-Tre and to distinguish live Mtb, making them ideal as biomarkers
of drug susceptibility. We will also evaluate probe specificity to TB and probe performance across a variety of
bacteria typically present in oral mucosa. In Aim 2, we will develop and optimize Tre-DST as a multi-drug DST
for first- and second-line TB drugs. We will evaluate Tre-DST’s performance in accurately determining drug
resistance using drug susceptible and drug resistant Mtb strains, treated singly and in combination with the anti-
TB drugs that fulfill the WHO Target Product Profile (TPP) for next generation DST. We will also evaluate several
point-of-care (POC)-friendly detection methods to optimize efficiency and cost-effectiveness. Lastly, in Aim 3,
we will perform preliminary evaluation using banked clinical isolates in Johannesburg, South Africa to assess
the performance of Tre-DST in the field. We will evaluate pre-validated readout methods in this clinical study,
benchmarking the performance of Tre-DST against bact...

## Key facts

- **NIH application ID:** 10777490
- **Project number:** 1R01AI179891-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Mireille Kamariza
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $675,156
- **Award type:** 1
- **Project period:** 2024-08-23 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10777490

## Citation

> US National Institutes of Health, RePORTER application 10777490, A Rapid Phenotypic Drug Susceptibility Testing System for Tuberculosis (1R01AI179891-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10777490. Licensed CC0.

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