# The role of nanocompartments in M. tuberculosis pathogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $381,061

## Abstract

Contact PD/PI: Stanley, Sarah A
Project Summary. The bacterial pathogen Mycobacterium tuberculosis is highly resistant to oxidative stress
encountered in the host, however defense mechanisms remain poorly characterized. This proposal seeks to
characterize a nanocompartment system in M. tuberculosis that we propose contributes to defense against
oxidative stress. Nanocompartments are protein-based organelles that encapsulate an enzymatic cargo, often
an enzyme related to oxidative defense. Although genes encoding nanocompartments are widespread in
bacteria and archaea, their endogenous functions are not well understood and it is not clear what benefit the
encapsulation of specific enzymes provides. We have discovered that M. tuberculosis has a bacterial
nanocompartment system that is required for defense against oxidative stress. This system consists of the
encapsulin protein Cfp29 and the cargo protein DypB, a dye decolorizing peroxidase. Our hypothesis is that
the M. tuberculosis DypB nanocompartment system is required for resisting oxidative stresses encountered in
host macrophages. Building on preliminary data in which we show that DypB encapsulin mutants are
attenuated for growth in macrophages, and that these mutants are also susceptible to H2O2 at pH 4.5 in axenic
culture we test this hypothesis in three aims. 1) Determine whether encapsulation promotes DypB stability and
function; 2) Determine whether the M. tuberculosis DypB encapsulin system is required for defense against
lipid peroxides; 3) Determine the role of the DypB nanocompartment in virulence of M. tuberculosis. If
successful, the proposed experiments will provide the first link between a nanocompartment system and
bacterial virulence, advancing our understanding of how M. tuberculosis, and possibly other pathogens, defend
against diverse oxidative stresses encountered in the host. In addition, these studies will provide insights into
the function of encapsulin systems and the specific role of the shell protein. Finally, these studies will advance
our understanding of the endogenous functions of DyP peroxidases, which are widespread throughout
bacteria, archaea, and eukaryotes
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Project Summary/Abstract

## Key facts

- **NIH application ID:** 10020315
- **Project number:** 5R01AI143722-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Sarah A Stanley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,061
- **Award type:** 5
- **Project period:** 2019-09-18 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020315

## Citation

> US National Institutes of Health, RePORTER application 10020315, The role of nanocompartments in M. tuberculosis pathogenesis (5R01AI143722-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020315. Licensed CC0.

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