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

Rinkel S, Schulze-Lührmann J, Kadavil Baburaj B, Weber F, Liebler-Tenorio EM, Lührmann A (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Frontiers in Cellular and Infection Microbiology Frontiers Media

Book Volume: 16

Article Number: 1835140

DOI: 10.3389/fcimb.2026.1835140

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.

Authors with CRIS profile

Sven Rinkel Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Jan Schulze-Lührmann Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Bhavyalakshmi Kadavil Baburaj Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Frederik Weber Medizinische Fakultät Anja Lührmann Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

Friedrich-Loeffler-Institut (FLI), Bundesforschungsinstitut für Tiergesundheit DE Germany (DE)

How to cite

APA:

Rinkel, S., Schulze-Lührmann, J., Kadavil Baburaj, B., Weber, F., Liebler-Tenorio, E.M., & Lührmann, A. (2026). TFEB and MCOLN1 are important for Coxiella burnetii egress via lysosomal exocytosis. Frontiers in Cellular and Infection Microbiology, 16. https://doi.org/10.3389/fcimb.2026.1835140

MLA:

Rinkel, Sven, et al. "TFEB and MCOLN1 are important for Coxiella burnetii egress via lysosomal exocytosis." Frontiers in Cellular and Infection Microbiology 16 (2026).

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