# Bacterial Determinants of Treatment Response in Mycobacteria Tuberculosis

> **NIH NIH U19** · HARVARD MEDICAL SCHOOL · 2020 · $2,936,284

## Abstract

Summary: Overview
The recent development of rapid molecular diagnostics promises to revolutionize TB
control. Such tests can be performed directly on sputum or other clinical samples and
rely on the rapid detection of Mycobacteria tuberculosis (MTB) genetic signatures as well
as drug resistance- associated mutations. Clinical studies demonstrate that they perform
better than sputum smear microscopy and reliably identify resistance to several first line
drugs. However, these tools suffer from two important limitations. First, current platforms
are limited in their ability to extract MTB DNA directly from clinical samples. And
secondly, there are major gaps in our knowledge of the genetic determinants of poor
treatment responses. Here, we propose to address these gaps through a multi-
disciplinary collaboration emphasizing discovery of new biomarkers of drug resistance
and tolerance, the identification of optimal clinical sampling strategies directed toward
detection of MTB DNA and the development of a sensitive micro-array based rapid
diagnostic. Our long-term goal is to develop a diagnostic strategy that will improve the
diagnosis of DR TB and stem the further spread of the disease. The immediate aims of
this projects are to 1) discover and characterize novel biomarkers of TB drug resistance
both through human studies and by phenotyping isogenic strains with introduced
mutations; 2) continue late stage development of a novel diagnostic with which to detect
MTB DR, 3) develop the most promising clinical sampling strategies with which to detect
DNA from MTB and 4) develop and optimize a micro-array based near Point of Care
diagnostic designed to detect adult and pediatric MTB and its drug resistance mutations.

## Key facts

- **NIH application ID:** 9918252
- **Project number:** 5U19AI142793-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** MEGAN B MURRAY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,936,284
- **Award type:** 5
- **Project period:** 2019-04-18 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918252

## Citation

> US National Institutes of Health, RePORTER application 9918252, Bacterial Determinants of Treatment Response in Mycobacteria Tuberculosis (5U19AI142793-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9918252. Licensed CC0.

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