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A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP.

Abstract：

:Cell-autonomous defense mechanisms are potent strategies that protect individual cells against intracellular pathogens. The Rab-family GTPase Rab32 was previously shown to restrict the intracellular human pathogen Salmonella Typhi, but its potential broader role in antimicrobial defense remains unknown. We show that Rab32 represents a general cell-autonomous, antimicrobial defense that is counteracted by two Salmonella effectors. Mice lacking Rab-32 or its nucleotide exchange factor BLOC-3 are permissive to S. Typhi infection and exhibit increased susceptibility to S. Typhimurium. S. Typhimurium counters this defense pathway by delivering two type III secretion effectors, SopD2, a Rab32 GAP, and GtgE, a specific Rab32 protease. An S. Typhimurium mutant strain lacking these two effectors exhibits markedly reduced virulence, which is fully restored in BLOC-3-deficient mice. These results demonstrate that a cell-autonomous, Rab32-dependent host defense pathway plays a central role in the defense against vacuolar pathogens and describe a mechanism evolved by a bacterial pathogen to counter it.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Spanò S,Gao X,Hannemann S,Lara-Tejero M,Galán JE

doi

10.1016/j.chom.2016.01.004

subject

Has Abstract

pub_date

2016-02-10 00:00:00

pages

216-26

issue

2

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(16)30003-8

journal_volume

19

pub_type

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