Mycobacterium tuberculosis Type VII Secretion System Effectors Differentially Impact the ESCRT Endomembrane Damage Response
Open accessAbstract
Mycobacterium tuberculosis causes tuberculosis, which kills more people than any other infection. M. tuberculosis grows in macrophages, cells that specialize in engulfing and degrading microorganisms. Like many intracellular pathogens, in order to cause disease, M. tuberculosis damages the membrane-bound compartment (phagosome) in which it is enclosed after macrophage uptake. Recent work showed that when chemicals damage this type of intracellular compartment, cells rapidly detect and repair the damage, using machinery called the endosomal sorting complex required for transport (ESCRT). Therefore, we hypothesized that ESCRT might also respond to pathogen-induced damage. At the same time, our previous work showed that the EsxG-EsxH heterodimer of M. tuberculosis can inhibit ESCRT, raising the possibility that M. tuberculosis impairs this host response. Here, we show that ESCRT is recruited to damaged M. tuberculosis phagosomes and that EsxG-EsxH undermines ESCRT-mediated endomembrane repair. Thus, our studies demonstrate a battle between host and pathogen over endomembrane integrity.
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- Authors
- Mittal, E., Skowyra, M. L., Uwase, G., Tinaztepe, E., Mehra, A., Köster, S., Hanson, P. I., & Philips, J. A.
- Affiliations
- Washington University in St. Louis (US)
- New York University (US)
- Corresponding author
- Philips, Jennifer A.
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2018-12-21
- Volume
- 9
- Issue
- 6
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC6282207
- OpenAlex
- W2902814816
- Cited by
- 110
- References
- 73
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 15 · 2023: 17 · 2022: 7 · 2021: 17 · 2020: 14 · 2019: 11
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (R01 GM122434)
- HHS | NIH | National Institute of Allergy and Infectious Diseases (2R01 AI087682)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Mycobacterium tuberculosis, type VII secretion system, ESCRT, host-pathogen interaction, macrophages, intracellular pathogens, membrane integrity
- MeSH terms
- Type VII Secretion Systems, Animals, Antigens, Bacterial, Bacterial Proteins, Cell Line, Humans, Mycobacterium tuberculosis, Phagosomes, Protein Binding, Virulence Factors, Mice, Host-Pathogen Interactions, Endosomal Sorting Complexes Required for Transport
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