Format

Send to

Choose Destination
Cell Host Microbe. 2017 Sep 13;22(3):302-316.e7. doi: 10.1016/j.chom.2017.07.020. Epub 2017 Aug 31.

Legionella pneumophila Modulates Mitochondrial Dynamics to Trigger Metabolic Repurposing of Infected Macrophages.

Author information

1
Institut Pasteur, Biologie des Bactéries Intracellulaires, Paris 75724, France; CNRS UMR 3525, Paris 75724, France.
2
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, 59000 Lille, France.
3
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
4
Institut Pasteur, Unité d'Analyse d'Images Biologiques, CNRS UMR 3691, Paris, France.
5
VIB-UGent Center for Medical Biotechnology, Ghent University, 9000 Ghent, Belgium; VIB Proteomics Core, Ghent University, 9000 Ghent, Belgium; Department of Biochemistry, Ghent University, 9000 Ghent, Belgium.
6
Institut Pasteur, Biologie des Bactéries Intracellulaires, Paris 75724, France; CNRS UMR 3525, Paris 75724, France. Electronic address: cbuch@pasteur.fr.

Abstract

The intracellular bacteria Legionella pneumophila encodes a type IV secretion system (T4SS) that injects effector proteins into macrophages in order to establish and replicate within the Legionella-containing vacuole (LCV). Once generated, the LCV interacts with mitochondria through unclear mechanisms. We show that Legionella uses both T4SS-independent and T4SS-dependent mechanisms to respectively interact with mitochondria and induce mitochondrial fragmentation that ultimately alters mitochondrial metabolism. The T4SS effector MitF, a Ran GTPase activator, is required for fission of the mitochondrial network. These effects of MitF occur through accumulation of mitochondrial DNM1L, a GTPase critical for fission. Furthermore mitochondrial respiration is abruptly halted in a T4SS-dependent manner, while T4SS-independent upregulation of cellular glycolysis remains elevated. Collectively, these alterations in mitochondrial dynamics promote a Warburg-like phenotype in macrophages that favors bacterial replication. Hence the rewiring of cellular bioenergetics to create a replication permissive niche in host cells is a virulence strategy of L. pneumophila.

KEYWORDS:

DNM1L; Legionella pneumophila; bioenergetics; host-pathogen interactions; live cell imaging; mitochondrial dynamics; virulence

Comment in

PMID:
28867389
DOI:
10.1016/j.chom.2017.07.020
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center