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TFEB and MCOLN1 are important for Coxiella burnetii egress via lysosomal exocytosis.

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Τίτλος: TFEB and MCOLN1 are important for Coxiella burnetii egress via lysosomal exocytosis.
Συγγραφείς: Rinkel S; Mikrobiologisches Institut, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Schulze-Luehrmann J; Mikrobiologisches Institut, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Kadavil Baburaj B; Mikrobiologisches Institut, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Weber F; Mikrobiologisches Institut, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Liebler-Tenorio EM; Friedrich-Loeffler-Institut, Institut für Molekulare Pathogenese, Jena, Germany., Lührmann A; Mikrobiologisches Institut, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Πηγή: Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2026 Aug 14; Vol. 16, pp. 1835140. Date of Electronic Publication: 2026 Aug 14 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Frontiers Media SA Country of Publication: Switzerland NLM ID: 101585359 Publication Model: eCollection Cited Medium: Internet ISSN: 2235-2988 (Electronic) Linking ISSN: 22352988 NLM ISO Abbreviation: Front Cell Infect Microbiol Subsets: MEDLINE
Imprint Name(s): Original Publication: Lausanne : Frontiers Media SA
Ιατρικοί όροι (MeSH): Coxiella burnetii*/physiology , Coxiella burnetii*/pathogenicity , Lysosomes*/metabolism , Lysosomes*/microbiology , Transient Receptor Potential Channels*/metabolism , Transient Receptor Potential Channels*/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors*/genetics , Q Fever*/microbiology , Q Fever*/metabolism , Exocytosis*, Vacuoles/microbiology ; Vacuoles/metabolism ; Calcium/metabolism ; Animals ; Humans ; Host-Pathogen Interactions ; Autophagy
Περίληψη: Coxiella burnetii is a Gram-negative, obligate intracellular pathogen and the causative agent of the zoonotic disease Q fever. Resident alveolar macrophages are the first target cells, but C. burnetii spreads to other cell types. While we have information about C. burnetii uptake and the establishment of the replication-competent phagolysosomal-like C. burnetii-containing vacuole (CCV), it is not well studied how C. burnetii exits its host cell. Here, we show that an infection with C. burnetii also triggers the activation of TFEB, a master regulator of autophagy and lysosomal development. The activation occurs in a time-dependent manner and depends on the size of the CCV. Crucially, TFEB activation during C. burnetii infection depends on MCOLN1, which channels Ca2+ across the lysosomal membrane into the cytosol. Knock-down of MCOLN1 resulted in reduced TFEB activation and smaller CCVs, while MCOLN1 activation boosted bacterial egress. Indeed, peripheral CCVs are positive for LAMP1/2 and release bacteria, without inducing host cell death. Importantly, LAMP1/2 and C. burnetii were stainable in non-permeabilized cells at sites of bacterial release, demonstrating fusion of the lysosome with the plasma membrane. Crucially, while replication of C. burnetii is not inhibited in cells lacking LAMP1/2, egress is impaired. Taken together, our data indicates that with increasing CCV size, TFEB is activated by the release of Ca2+ from lysosomes via the MCOLN1 channel, which in turn enables further CCV development and damage of the CCV membrane. This triggers lysosomal exocytosis and egress of C. burnetii without cell death induction.
(Copyright © 2026 Rinkel, Schulze-Luehrmann, Kadavil Baburaj, Weber, Liebler-Tenorio and Lührmann.)
Competing Interests: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author AL declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
Σχόλια: Erratum in: Front Cell Infect Microbiol. 2026 Sep 07;16:1974473. doi: 10.3389/fcimb.2026.1974473.. (PMID: 42769642)
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Contributed Indexing: Keywords: Coxiella burnetii; Egress; LAMP; MCOLN1; Q fever; TFEB; lysosomal exocytosis; type IV secretion system
Substance Nomenclature: 0 (Transient Receptor Potential Channels)
0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
0 (TFEB protein, human)
SY7Q814VUP (Calcium)
Entry Date(s): Date Created: 20260829 Date Completed: 20260829 Latest Revision: 20260923
Update Code: 20260923
PubMed Central ID: PMC13521786
DOI: 10.3389/fcimb.2026.1835140
PMID: 42666149
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2235-2988
DOI:10.3389/fcimb.2026.1835140