Cited by 318Tuberculosis Research and EpidemiologyAutophagy in Disease and TherapyUbiquitin and proteasome pathways

Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy

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Alonso, Sylvie, Pethe, Kevin, Russell, David G., Purdy, Georgiana E.·2007·Proceedings of the National Academy of Sciences

Abstract

Mycobacterium tuberculosis parasitizes resting macrophages yet is killed by activated macrophages through both oxidative and nonoxidative mechanisms. Nonoxidative mechanisms are linked to the maturation of the bacteria-containing phagosome into an acidified, hydrolytically active compartment. We describe here a mechanism for killing Mycobacteria in the lysosomal compartment through the activity of peptides generated by the hydrolysis of ubiquitin. The induction of autophagy in infected macrophages enhanced the delivery of ubiquitin conjugates to the lysosome and increased the bactericidal capacity of the lysosomal soluble fraction. The accumulation of ubiquitinated proteins in the autophagolysosome provides one possible mechanism behind the antimicrobial activities observed for a range of pathogens in autophagous host cells.

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Crossref · 10.1073/pnas.0700036104

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  • Killing of bacteria within the auto-phagolysosome has been attributed in part to ubiquitin-derived AMP generated by cathepsin D-mediated proteolysis.

    “Killing of bacteria within this compartment has been attributed in part to ubiquitin-derived AMP generated by cathepsin D-mediated proteolysis (78).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [78]

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Research works printed but not linked: 1

  1. [6]Schaible UE, Sturgill-Koszycki S, Schlesinger PH, Russell DG. J Immunol. 1998;160:1290–1296. [PubMed] [Google Scholar]

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Authors
Alonso, S., Pethe, K., Russell, D. G., & Purdy, G. E.
Affiliations
  • Cornell University (US)
  • Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
Venue
Proceedings of the National Academy of Sciences
Published
2007-04-03
Volume
104
Issue
14
Pages
6031-6036
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2036167259
Cited by
318
References
41
Citations by year
2026: 6 · 2025: 6 · 2024: 4 · 2023: 12 · 2022: 6 · 2021: 12 · 2020: 11 · 2019: 15 · 2018: 10 · 2017: 20 · 2016: 29 · 2015: 16 · 2014: 20 · 2013: 18 · 2012: 33
FWCI
15.10
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI067027, AI 067027, R01AI057086, AI057086)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
Mycobacterium tuberculosis, autophagy, autophagolysosomes, macrophages, phagosome maturation, ubiquitin conjugates, antimicrobial activity
MeSH terms
Amino Acid Sequence, Anti-Bacterial Agents, Autophagy, Chromatography, High Pressure Liquid, Lysosomes, Macrophages, Molecular Sequence Data, Mycobacterium tuberculosis, Peptides, Mass Spectrometry, Sequence Homology, Amino Acid, Ubiquitin

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