# Characterizing the requirement of the mycobacterial BrkB ortholog in TB pathogenesis

> **NIH NIH R16** · LAKE FOREST COLLEGE · 2024 · $130,776

## Abstract

Project Summary / Abstract:
 Due to the rise of antibiotic resistant tuberculosis and the long treatment time of current anti-tuberculosis
therapies, there is an immediate need for new drug targets against tuberculosis. My lab has identified the
mycobacterial BrkB ortholog as a likely drug target. We have already observed that mutation of mycobacterial
BrkB greatly attenuates growth of our model organism Mycobacterium marinum in its natural host, the zebrafish.
Furthermore, we have observed that this organism is attenuated for growth in both intracellular and extracellular
spaces, making it particularly attractive because extracellular mycobacteria are especially present in late-stage
TB and contribute to TB transmission, and because there is a specific need to target mycobacteria in the
extracellular niche.
 While BrkB is found throughout the bacterial kingdom, the function of BrkB remains elusive. I propose to
characterize the biochemical function of mycobacterial BrkB and resolve its role in virulence by completing the
following three specific aims: (1) Identify mycobacterial BrkB channel substrate(s) and test for protein
interactions, (2) identify mechanism of BrkB extracellular growth requirement, and (3) Measure mycobacterial
BrkB growth under late-stage infection conditions. Towards this end, I have purified recombinant tuberculosis
BrkB from E. coli. In collaboration with Dr. Paul DeCaen (Northwestern Univ.), my students and I will test BrkB
for channel function. My lab has extensive experience with the biochemistry, microbiology, and organismal
biology required to complete aims 1,2, and 3 respectively. With the biophysical expertise of the DeCaen lab, we
collectively share the expertise to solve the role of BrkB in the mycobacterial cell and in the context of infection.
 This project will serve as the foundation of a sustainable research platform that will empower undergraduates
to test independent hypotheses about mycobacterial virulence factors and host susceptibility factors. Students
will have the tools necessary to investigate the biochemical functions of these functions, to work at biosafety
level 2 to investigate mycobacterial cellular biology, and to test their molecular hypotheses at the organismal
level using the zebrafish Mycobacterium marinum model of infection.

## Key facts

- **NIH application ID:** 10936733
- **Project number:** 1R16AI184352-01
- **Recipient organization:** LAKE FOREST COLLEGE
- **Principal Investigator:** William Henry Conrad
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $130,776
- **Award type:** 1
- **Project period:** 2024-09-04 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936733

## Citation

> US National Institutes of Health, RePORTER application 10936733, Characterizing the requirement of the mycobacterial BrkB ortholog in TB pathogenesis (1R16AI184352-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10936733. Licensed CC0.

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