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

Authors

Sven Rinkel, Jan Schulze-Luehrmann, Bhavyalakshmi Kadavil Baburaj, Fiona Weber, Elisabeth M Liebler-Tenorio, Anja Lührmann

Published in

Frontiers in cellular and infection microbiology. Volume 16. Pages 1835140. Epub Aug 14, 2026.

Abstract

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.

PMID:
42666149
Bibliographic data and abstract were imported from PubMed on 29 Aug 2026.

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