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Lack of Acidification in Mycobacterium Phagosomes Produced by Exclusion of the Vesicular Proton-ATPase
Abstract
The success of Mycobacterium species as pathogens depends on their ability to maintain an infection inside the phagocytic vacuole of the macrophage. Although the bacteria are reported to modulate maturation of their intracellular vacuoles, the nature of such modifications is unknown. In this study, vacuoles formed around Mycobacterium avium failed to acidify below pH 6.3 to 6.5. Immunoelectron microscopy of infected macrophages and immunoblotting of isolated phagosomes showed that Mycobacterium vacuoles acquire the lysosomal membrane protein LAMP-1, but not the vesicular proton-adenosine triphosphatase (ATPase) responsible for phagosomal acidification. This suggests either a selective inhibition of fusion with proton-ATPase-containing vesicles or a rapid removal of the complex from Mycobacterium phagosomes.
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“The early phagosome lacks the proton pumping vesicular ATPase (vATPase) and is therefore characterized by a mildly acidic pH of 6–6.5 (21).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [21]
In the citing paper
“NRAMP1 is a transmembrane transporter expressed in late phagosomes, where it exerts multiple functions including regulation of phagosome acidification, which is, however, exerted mainly by v-ATPase [144] along with pH-dependent shuttling of divalent metals, including Fe, zinc and manganese, across the phagolysosomal membrane [145-147] (Fig 3).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [144]
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Weiss, D. J., Evanson, O. A., Deng, M., & Abrahamsen, M. S. (2004) · Veterinary Pathology · doi:10.1354/vp.41-4-326 · Cited by 54
Yuk, J., & Jo, E. (2014) · Clinical and Experimental Vaccine Research · doi:10.7774/cevr.2014.3.2.155 · Cited by 55
Pathogenesis of Human Immunodeficiency Virus-Mycobacterium tuberculosis Co-Infection
Wong, K., Nguyen, J., Blair, L., Banjanin, M., Grewal, B., Bowman, S., Boyd, H., Gerstner, G., Cho, H. J., Panfilov, D., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9113575 · Cited by 53
Metadata
- Authors
- 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.
- Affiliations
- Washington University Medical Center (US)
- University of Hawaiʻi at Mānoa (US)
- ORCID
- Venue
- Science
- Published
- 1994-02-04
- Volume
- 263
- Issue
- 5147
- Pages
- 678-681
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2147251439
- Cited by
- 1,302
- References
- 26
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 15 · 2023: 21 · 2022: 24 · 2021: 37 · 2020: 34 · 2019: 38 · 2018: 25 · 2017: 42 · 2016: 37 · 2015: 39 · 2014: 67 · 2013: 39 · 2012: 45
- FWCI
- 47.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01ai034207-01, 5r01ar042370-04, 5r01ai026889-03)
- National Institute of Allergy and Infectious Diseases (AI 26889, AI 34207)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 42370)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Mycobacterium avium, phagosome acidification, phagosome maturation, macrophages, LAMP1, lysosomal membrane proteins, intracellular bacterial survival, mycobacterial pathogenesis
- MeSH terms
- Animals, Proton-Translocating ATPases, Hydrogen-Ion Concentration, Leishmania mexicana, Macrophages, Membrane Fusion, Membrane Glycoproteins, Mycobacterium avium, Mycobacterium tuberculosis, Phagosomes, Vacuoles, Antigens, CD, Microscopy, Immunoelectron, Mice, Lysosomal Membrane Proteins
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