# Gerome Wide Association Study of Bacterial Determinants of Clinical Response in Tuberculosis

> **NIH NIH U19** · HARVARD MEDICAL SCHOOL · 2022 · $990,349

## Abstract

Summary Project 1
The premise of this project is that Mycobacteria tuberculosis (MTB) drug resistance
phenotypes as measured by standard in vitro DSTs on conventional media may not
encompass the full range of responses to drug therapy that affect patient outcomes. In
previous work, we have identified MTB mutations that confer drug tolerance and
conditional drug tolerance among “drug resistant” clinical strains. We hypothesize that
patients who do not manifest early and vigorous clinical responses to treatment may be
infected with strains with mutations that confer these phenotypes. If this is shown to be
true, the early detection of these mutations through the use of rapid diagnostic tools
which would allow clinicians to modify drug treatment to achieve better outcomes.
The goals of this study are to identify bacterial genetic determinants of 1) sub-optimal
patient response to TB treatment. We will further characterize strains from people who
respond and do not respond to TB treatment in terms of their ability to be grown on
alternate non-conventional media, their mean inhibitory concentrations on alternate
media, and their transcriptional signatures. We expect to identify specific mutations and
transcriptional signatures that are associated with different growth characteristics and that
these will be related to antibiotic tolerance and resistance phenotypes.
We will conduct this longitudinal study at two field sites in different countries (Peru and
Mongolia), enrolling active TB patients whom we will follow for interim and final
treatment outcomes as measured by clinical criteria. Almost all previous studies of
clinical treatment outcomes have relied on microbiological assays to determine treatment
response so there are no well established norms to assess treatment response that do not
include microbiological results. We propose here a panel of clinical assessments designed
to measure pulmonary function, inflammatory response and respiratory symptoms, all of
which we expect to improve over the first two months of effective TB treatment. Once
we identify and isolate TB strains from people with sub-optimal responses to treatment,
we will sequence these strains and perform a genome wide association study to identify
specific variants associated with these outcomes.

## Key facts

- **NIH application ID:** 10390299
- **Project number:** 5U19AI142793-04
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** MEGAN B MURRAY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $990,349
- **Award type:** 5
- **Project period:** 2019-04-18 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390299

## Citation

> US National Institutes of Health, RePORTER application 10390299, Gerome Wide Association Study of Bacterial Determinants of Clinical Response in Tuberculosis (5U19AI142793-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10390299. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*