Francisella requires dynamic type VI secretion system and ClpB to deliver effectors for phagosomal escape

Francisella tularensis is an intracellular pathogen that causes the fatal zoonotic disease tularaemia. Critical for its pathogenesis is the ability of the phagocytosed bacteria to escape into the cell cytosol. For this, the bacteria use a non-canonical type VI secretion system (T6SS) encoded on the...

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Bibliographic Details
Published in:	Nature communications 2017-06, Vol.8 (1), p.15853-15853, Article 15853
Main Authors:	Brodmann, Maj, Dreier, Roland F, Broz, Petr, Basler, Marek
Format:	Article
Language:	eng
Subjects:	Animals Assembly Bacteria Bacterial Proteins - genetics Bacterial Proteins - immunology Bacterial Proteins - metabolism ClpB protein Coding Cytosol Delivery contracts Dismantling Effectors Endopeptidase Clp - genetics Endopeptidase Clp - immunology Endopeptidase Clp - metabolism Escape systems Female Francisella tularensis - genetics Francisella tularensis - immunology Francisella tularensis - metabolism Gene Expression Regulation, Bacterial Humans In vitro methods and tests Inflammasomes Macrophages Mice Mice, Inbred C57BL Pathogenesis Pathogenicity Pathogens Phagosomes - immunology Phagosomes - microbiology Rupture Secretion Sheaths Tularemia - immunology Tularemia - microbiology Type VI Secretion Systems - genetics Type VI Secretion Systems - immunology Type VI Secretion Systems - metabolism Zoonoses
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Summary:	Francisella tularensis is an intracellular pathogen that causes the fatal zoonotic disease tularaemia. Critical for its pathogenesis is the ability of the phagocytosed bacteria to escape into the cell cytosol. For this, the bacteria use a non-canonical type VI secretion system (T6SS) encoded on the Francisella pathogenicity island (FPI). Here we show that in F. novicida T6SS assembly initiates at the bacterial poles both in vitro and within infected macrophages. T6SS dynamics and function depends on the general purpose ClpB unfoldase, which specifically colocalizes with contracted sheaths and is required for their disassembly. T6SS assembly depends on iglF, iglG, iglI and iglJ, whereas pdpC, pdpD, pdpE and anmK are dispensable. Importantly, strains lacking pdpC and pdpD are unable to escape from phagosome, activate AIM2 inflammasome or cause disease in mice. This suggests that PdpC and PdpD are T6SS effectors involved in phagosome rupture.
ISSN:	2041-1723 2041-1723