Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?
Brogden, K. A. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1098 · Cited by 5,829 · see citing works
Impairment of starvation-induced and constitutive autophagy in <i>Atg7</i> -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331 · see citing works
Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T., & Ohsumi, Y. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-09-0704 · Cited by 2,323 · see citing works
Gutierrez, M. G., Master, S. S., Singh, S. B., Taylor, G. A., Colombo, M. I., & Deretic, V. (2004) · Cell · doi:10.1016/j.cell.2004.11.038 · Cited by 2,252 · see citing works
Nathan, C., & Shiloh, M. U. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.8841 · Cited by 1,469 · see citing works
Sturgill-Koszycki, S., Schlesinger, P. H., Chakraborty, P., Haddix, P. L., Collins, H. L., Fok, A. K., Allen, R. D., Gluck, S. L., Heuser, J., & Russell, D. G. (1994) · Science · doi:10.1126/science.8303277 · Cited by 1,302 · see citing works
Self-citationAutophagy Defends Cells Against Invading Group A Streptococcus
Nakagawa, I., Amano, A., Mizushima, N., Yamamoto, A., Yamaguchi, H., Kamimoto, T., Nara, A., Funao, J., Nakata, M., Tsuda, K., et al. (2004) · Science · doi:10.1126/science.1103966 · Cited by 1,091 · see citing works
Escape of Intracellular Shigella from Autophagy
Ogawa, M., Yoshimori, T., Suzuki, T., Sagara, H., Mizushima, N., & Sasakawa, C. (2004) · Science · doi:10.1126/science.1106036 · Cited by 830 · see citing works
Hicke, L., Schubert, H., & Hill, C. P. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1701 · Cited by 795 · see citing works
Mycobacterium tuberculosis: here today, and here tomorrow
Russell, D. G. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35085034 · Cited by 781 · see citing works
Self-citationImmune Control of Tuberculosis by IFN-γ-Inducible LRG-47
MacMicking, J. D., Taylor, G. A., & McKinney, J. D. (2003) · Science · doi:10.1126/science.1088063 · Cited by 685 · see citing works
Autophagy Controls Salmonella Infection in Response to Damage to the Salmonella-containing Vacuole
Birmingham, C. L., Smith, A. C., Bakowski, M. A., Yoshimori, T., & Brumell, J. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m509157200 · Cited by 658 · see citing works
Susceptibility to leprosy is associated with PARK2 and PACRG
Mira, M. T., Alcaïs, A., Thuc, N. V., Moraes, M. O., Flumeri, C. D., Thai, V. H., Phuong, M. C., Hương, N. T., Ba, N. N., Khoa, P. X., et al. (2004) · Nature · doi:10.1038/nature02326 · Cited by 467 · see citing works
Ciechanover, A. J. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401692 · Cited by 462 · see citing works
Schaible, U. E., Sturgill-Koszycki, S., Schlesinger, P. H., & Russell, D. G. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.3.1290 · Cited by 402 · see citing works
Self-citationEffects of cytokines on mycobacterial phagosome maturation
Via, L. E., Fratti, R. A., McFalone, M., Pagán-Ramos, E., Deretic, D., & Deretic, V. P. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.7.897 · Cited by 354 · see citing works
p62/SQSTM1: A Missing Link between Protein Aggregates and the Autophagy Machinery
Bjørkøy, G., Lamark, T., & Johansen, T. (2006) · Autophagy · doi:10.4161/auto.2.2.2405 · Cited by 322 · see citing works
Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation
Pethe, K., Swenson, D. L., Alonso, S., Anderson, J. L., Wang, C., & Russell, D. G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401657101 · Cited by 318 · see citing works
Self-citationDeretic, V. P., Singh, S., Master, S. S., Harris, J., Roberts, E. A., Kyei, G. B., Davis, A., Haro, S. A. D., Naylor, J., Lee, H.-H., et al. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00705.x · Cited by 306 · see citing works
Ubiquitin Ligases and the Immune Response
Liu, Y. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104813 · Cited by 283 · see citing works
Autophagy is an immediate macrophage response to Legionella pneumophila
Amer, A. O., & Swanson, M. S. (2005) · Cellular Microbiology · doi:10.1111/j.1462-5822.2005.00509.x · Cited by 279 · see citing works
Kamimoto, T., Shoji, S., Hidvegi, T., Mizushima, N., Umebayashi, K., Perlmutter, D. H., & Yoshimori, T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m509409200 · Cited by 259 · see citing works
E3 ubiquitin ligases as T cell anergy factors
Mueller, D. L. (2004) · Nature Immunology · doi:10.1038/ni1106 · Cited by 224 · see citing works
Exosomes contain ubiquitinated proteins
Buschow, S. I., Liefhebber, J. M. P., Wubbolts, R., & Stoorvogel, W. (2005) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2005.08.005 · Cited by 185 · see citing works
Human hemoglobin-derived peptides exhibit antimicrobial activity: a class of host defense peptides
Liepke, C., Baxmann, S., Heine, C., Breithaupt, N., Ständker, L., & Forssmann, W. (2003) · Journal of Chromatography B · doi:10.1016/s1570-0232(03)00245-9 · Cited by 145 · see citing works
Lim, K., Dawson, V. L., & Dawson, T. M. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.07.023 · Cited by 144 · see citing works
Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages
Hiemstra, P. S., van den Barselaar, M. T., Roest, M., et al. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.66.3.423 · Cited by 140 · see citing works
Macrophage Activation Downregulates the Degradative Capacity of the Phagosome
Yates, R. M., Hermetter, A., Taylor, G. A., & Russell, D. G. (2006) · Traffic · doi:10.1111/j.1600-0854.2006.00528.x · Cited by 134 · see citing works
Self-citationKuwata, H., Yip, T., Yip, C. L., TOMITA, M., & Hutchens, T. W. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8466 · Cited by 127 · see citing works
de Chastellier, C., & Thilo, L. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2005.00617.x · Cited by 118 · see citing works
Schaible, U. E., Schlesinger, P. H., Steinberg, T. H., Mangel, W. F., Kobayashi, T., & Russell, D. G. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.5.681 · Cited by 112 · see citing works
Self-citationThe N‐ and C‐terminal fragments of ubiquitin are important for the antimicrobial activities
Kieffer, A., Goumon, Y., Ruh, O., Chasserot‐Golaz, S., Nullans, G., Gasnier, C., Aunis, D., & Metz‐Boutigue, M. (2003) · The FASEB Journal · doi:10.1096/fj.02-0699fje · Cited by 102 · see citing works
Kim, H. S., Park, C. B., Kim, M. S., & Kim, S. C. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1814 · Cited by 81 · see citing works
Immunoelectron microscopic localization of ubiquitin in hepatoma cells.
Schwartz, A. L., Ciechanover, A. J., Brandt, R. A., et al. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb03158.x · Cited by 74 · see citing works
Shirk, A. J., Anderson, S. K., Hashemi, S. H., Chance, P. F., & Bennett, C. L. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20628 · Cited by 71 · see citing works
Antimicrobial polypeptides of the human colonic epithelium
Howell, S. J., Wilk, D. J., Yadav, S. P., et al. (2003) · Peptides · doi:10.1016/j.peptides.2003.07.028 · Cited by 64 · see citing works
Cervino, A. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.14.1599 · Cited by 64 · see citing works
Antibacterial peptides in stimulated human granulocytes
Wang, Y., Griffiths, W. J., Jörnvall, H., Agerberth, B., & Johansson, J. (2002) · European Journal of Biochemistry · doi:10.1046/j.0014-2956.2001.02675.x · Cited by 37 · see citing works
Svensson, I., Calles, K., Lindskog, E. K., et al. (2005) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-005-1958-6 · Cited by 12 · see citing works
Lőw, P., DOHERTY, F. J., Fellinger, E., et al. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00624-i · Cited by 12 · see citing works
Analysis of Mycobacterium-Infected Macrophages by Immunoelectron Microscopy and Cell Fractionation
Beatty, W. L., & Russell, D. G. (2003) · Humana Press eBooks · doi:10.1385/1-59259-147-7:281 · Cited by 3 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [6]Schaible UE, Sturgill-Koszycki S, Schlesinger PH, Russell DG. J Immunol. 1998;160:1290–1296. [PubMed] [Google Scholar]
Cited by
Sorted by citations
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Autophagy in infection, inflammation and immunity
Deretic, V., Saitoh, T., & Akira, S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3532 · Cited by 1,919 · see citing works
Macrophage defense mechanisms against intracellular bacteria
Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989 · see citing works
TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation
Pilli, M., Arko-Mensah, J., Ponpuak, M., Roberts, E., Master, S., Mandell, M. A., Dupont, N., Ornatowski, W., Jiang, S., Bradfute, S. B., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.04.015 · Cited by 655 · see citing works
Filimonenko, M., Stuffers, S., Raiborg, C., Yamamoto, A., Malerød, L., Fisher, E. M. C., Isaacs, A., Brech, A., Stenmark, H., & Simonsen, A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200702115 · Cited by 626 · see citing works
The ubiquitin ligase parkin mediates resistance to intracellular pathogens
Manzanillo, P. S., Ayres, J. S., Watson, R. O., Collins, A. C., Souza, G., Rae, C. S., Schneider, D. S., Nakamura, K., Shiloh, M. U., & Cox, J. S. (2013) · Nature · doi:10.1038/nature12566 · Cited by 588 · see citing works
A Family of IFN-γ–Inducible 65-kD GTPases Protects Against Bacterial Infection
Kim, B.-H., Shenoy, A. R., Kumar, P., Das, R., Tiwari, S., & MacMicking, J. D. (2011) · Science · doi:10.1126/science.1201711 · Cited by 494 · see citing works
Mycobacterial survival strategies in the phagosome: defence against host stresses
Ehrt, S., & Schnappinger, D. (2009) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01335.x · Cited by 448 · see citing works
Autophagy in Antimicrobial Immunity
Gomes, L. C., & Dikic, I. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.009 · Cited by 350 · see citing works
Modulation of inflammation by autophagy: Consequences for human disease
Netea-Maier, R. T., Plantinga, T. S., van de Veerdonk, F. L., Smit, J. W., & Netea, M. G. (2016) · Autophagy · doi:10.1080/15548627.2015.1071759 · Cited by 349 · see citing works
Interferon Gamma Activated Macrophages Kill Mycobacteria by Nitric Oxide Induced Apoptosis
Herbst, S., Schaible, U. E., & Schneider, B. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019105 · Cited by 277 · see citing works
Shiloh, M. U., & DiGiuseppe Champion, P. A. (2010) · Current Opinion in Microbiology · doi:10.1016/j.mib.2009.11.006 · Cited by 137 · see citing works
Innate immunity to mycobacteria: vitamin D and autophagy
Jo, E.-K. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01491.x · Cited by 98 · see citing works
Jung, J. W., Choi, J. C., Kim, J. Y., Park, I. W., Choi, B. W., Shin, J. W., & Christman, J. W. (2011) · Tuberculosis and Respiratory Diseases · doi:10.4046/trd.2011.70.2.113 · Cited by 2 · see citing works
- 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
- Publisher
- National Academy of Sciences
- Published
- 2007-04-03
- Volume
- 104
- Issue
- 14
- Pages
- 6031-6036
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1851611
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review