Cytosolic Access of Mycobacterium tuberculosis: Critical Impact of Phagosomal Acidification Control and Demonstration of Occurrence In Vivo
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Mycobacterium tuberculosis (Mtb) uses efficient strategies to evade the eradication by professional phagocytes, involving--as recently confirmed--escape from phagosomal confinement. While Mtb determinants, such as the ESX-1 type VII secretion system, that contribute to this phenomenon are known, the host cell factors governing this important biological process are yet unexplored. Using a newly developed flow-cytometric approach for Mtb, we show that macrophages expressing the phagosomal bivalent cation transporter Nramp-1, are much less susceptible to phagosomal rupture. Together with results from the use of the phagosome acidification inhibitor bafilomycin, we demonstrate that restriction of phagosomal acidification is a prerequisite for mycobacterial phagosomal rupture and cytosolic contact. Using different in vivo approaches including an enrichment and screen for tracking rare infected phagocytes carrying the CD45.1 hematopoietic allelic marker, we here provide first and unique evidence of M. tuberculosis-mediated phagosomal rupture in mouse spleen and lungs and in numerous phagocyte types. Our results, linking the ability of restriction of phagosome acidification to cytosolic access, provide an important conceptual advance for our knowledge on host processes targeted by Mtb evasion strategies.
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Due to the absence of ESX-1, BCG does not gain access to the host cell cytosol and thus lacks the induction of certain immune signaling pathways.
“Due to the absence of ESX-1, BCG does not gain access to the host cell cytosol and thus lacks the induction of certain immune signaling pathways (74,86).”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [86]
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Self-citation
- Authors
- Simeone, R., Sayes, F., Song, O., Gröschel, M. I., Brodin, P., Brosch, R., & Majlessi, L.
- Affiliations
- Institut Pasteur (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Brosch, Roland
- Majlessi, Laleh
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-02-06
- Volume
- 11
- Issue
- 2
- Pages
- e1004650
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC4450080
- OpenAlex
- W1992799735
- Cited by
- 198
- References
- 77
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 15 · 2021: 16 · 2020: 21 · 2019: 25 · 2018: 26 · 2017: 25 · 2016: 26 · 2015: 15
- FWCI
- 23.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
- Funders
- Jan Kornelis de Cock Stichting
- Equipex
- European Commission (260872, 241745)
- Fondation pour la Recherche Médicale (DEQ20130326471)
- FP7 Ideas: European Research Council (260901)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- Mycobacterium tuberculosis, phagosome acidification, bafilomycin, macrophages, host-pathogen interaction, phagosome escape, ESX-1 secretion system
- MeSH terms
- Natural Resistance-associated Macrophage Protein 1, Animals, Humans, Hydrogen-Ion Concentration, Macrophages, Mice, Mutant Strains, Mycobacterium tuberculosis, Phagosomes, Tuberculosis, Leukocyte Common Antigens, Cation Transport Proteins, Cell Line, Tumor, Mice, Bacterial Secretion Systems
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 ›
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