# Drifting to victory: resolving the paradox of M. tuberculosis evolution

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $459,734

## Abstract

PROJECT SUMMARY/ABSTRACT
Tuberculosis (TB) is the leading cause of death due to an infectious disease worldwide. Although TB is treatable,
treatments are prolonged, complex, and difficult for many people to tolerate. Mycobacterium tuberculosis (M. tb)
also readily acquires drug resistance and global efforts to control TB are threatened by the increasing problem
of drug resistance. M. tb is capable of assembling into biofilm communities capable of withstanding lethal doses
of antibiotics and this phenomenon likely contributes to difficulties in treating and controlling TB. We have
developed an in vitro system to study adaptation M. tb within biofilms. Leveraging analyses of these experimental
populations with those of a well characterized natural population of M. tb, we discovered that M. tb strains
separated by a small number of genetic differences exhibit a surprising array of phenotypic differences. Our
preliminary data point to regulatory mechanisms underlying these changes. Contextualizing these data with our
recent discoveries in M.tb evolutionary population genomics at regional and global scales, we hypothesize that
M. tb adaptation occurs at the scale of individual hosts while large scale phenomena act primarily as a constraint
on adaptation. Our major objective now is to delineate the mechanisms underlying observed phenotypic
differences in these natural and experimental populations.

## Key facts

- **NIH application ID:** 10101604
- **Project number:** 5R01AI113287-07
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Caitlin S Pepperell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $459,734
- **Award type:** 5
- **Project period:** 2015-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101604

## Citation

> US National Institutes of Health, RePORTER application 10101604, Drifting to victory: resolving the paradox of M. tuberculosis evolution (5R01AI113287-07). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10101604. Licensed CC0.

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