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Πέμπτη 31 Αυγούστου 2017

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

Publication date: Available online 31 August 2017
Source:Cell Host & Microbe
Author(s): Pedro Escoll, Ok-Ryul Song, Flávia Viana, Bernhard Steiner, Thibault Lagache, Jean-Christophe Olivo-Marin, Francis Impens, Priscille Brodin, Hubert Hilbi, Carmen Buchrieser
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.

Graphical abstract

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Teaser

Escoll et al. show that L. pneumophila establishes transient and highly dynamic contacts with mitochondria in a T4SS-independent manner, while secretion of the T4SS effector MitF induces mitochondrial fragmentation. L. pneumophila-induced modulation of mitochondrial dynamics promotes a switch in the metabolism of the infected cell that favors bacterial replication.


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