A nanocompartment system contributes to defense against oxidative stress in Mycobacterium tuberculosis

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Abstract

Encapsulin nanocompartments are an emerging class of prokaryotic protein-based organelle consisting of an encapsulin protein shell that encloses a protein cargo. Genes encoding nanocompartments are widespread in bacteria and archaea, and recent works have characterized the biochemical function of several cargo enzymes. However, the importance of these organelles to host physiology is poorly understood. Here, we report that the human pathogen Mycobacterium tuberculosis (Mtb) produces a nanocompartment that contains the dye-decolorizing peroxidase DyP. We show that this nanocompartment is important for the ability of Mtb to resist oxidative stress in low pH environments, including during infection of host cells and upon treatment with a clinically relevant antibiotic. Our findings are the first to implicate a nanocompartment in bacterial pathogenesis and reveal a new mechanism that Mtb uses to combat oxidative stress.

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All data generated or analysed during this study are included in the manuscript and supporting file

Article and author information

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Katie A Lien

Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Kayla Dinshaw

Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Robert J Nichols

Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8476-0554
Caleb Cassidy-Amstutz

Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Matthew Knight

Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Rahul Singh

The University of British Columbia, Vancouver, Canada

Competing interests
The authors declare that no competing interests exist.
Lindsay D Eltis Prof.

The University of British Columbia, Vancouver, Canada

Competing interests
The authors declare that no competing interests exist.
David F Savage

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0042-2257
Sarah A Stanley

School of Public Health and Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
sastanley@berkeley.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4182-9048

Funding

Center for Emerging and Neglected Disease (Graduate Student Award)

Katie A Lien

National Institute of General Medical Sciences (R01GM129241)

David F Savage

National Institute of Allergy and Infectious Disease (1R01AI143722)

Sarah A Stanley

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures involving the use of mice were approved by the University of California, Berkeley Institutional Animal Care and Use Committee (protocol no. R353-1113B). All protocols conform to federal regulations, the National Research Council's Guide for the Care and Use of Laboratory Animals, and the Public Health Service's Policy on Humane Care and Use of Laboratory Animals.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.