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

Author: Spano, Stefania; Gao, Xiang; Hannemann, Sebastian; Lara-Tejero, Mari­a; Galan, Jorge E.

Description: 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.

Subject headings: Animals; Bacterial Proteins; Host-Pathogen Interactions; Humans; Mice; Proteolysis; Salmonella Infections; Salmonella typhi; Salmonella typhimurium; Virulence; rab GTP-Binding Proteins; Rab GTPases; Rab32; Salmonella Typhi; Salmonella pathogenesis; Bacterial pathogenesis; Cell-autonomous defense; Innate immunity; Lysosome-related organelles; Lysosomes; Macrophages; Membrane traffic; Type III secretion; Typhoid fever

Publication year: 2016

Journal or book title: Cell Host & Microbe

Volume: 19

Issue: 2

Pages: 216-226

Find the full text: https://www.strategian.com/fulltext/Spano2016.pdf

Find more like this one (cited by): https://scholar.google.com/scholar?cites=18113053564506428044&as_sdt=5,26&sciodt=0,26&hl=en

Serial number: 3332

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