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

被引：60
作者：
Brodmann, Maj [1 ]
Dreier, Roland F. [1 ]
Broz, Petr [1 ]
Basler, Marek [1 ]
机构：
[1] Univ Basel, Biozentrum, Focal Area Infect Biol, Klingelbergstr 50-70, CH-4056 Basel, Switzerland
来源：
NATURE COMMUNICATIONS | 2017年 / 8卷
基金：
瑞士国家科学基金会;
关键词：
TULARENSIS PATHOGENICITY ISLAND; INTRACELLULAR LIFE-CYCLE; AIM2; INFLAMMASOME; UNIQUE PHENOTYPE; INNATE IMMUNITY; AAA+ PROTEASES; SPIKE PROTEIN; INFECTION; NOVICIDA; ACTIVATION;
D O I：
10.1038/ncomms15853
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：12
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