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

Stefania Spano, Xiang Gao, Sebastian Hanneman, Maria Lara-Tejero, Jorge E. Galan

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)216-226
Number of pages11
JournalCell Host & Microbe
Issue number2
Publication statusPublished - 10 Feb 2016

Bibliographical note

We thank members of the J.E.G. laboratory for careful review of this manuscript. We thank Jana Kamanova and Hui Sun for technical advice and reagents. X.G. was supported in part by a James Hudson Brown-Alexander Brown Coxe Postdoctoral Fellowship. This work was supported by National Institute of Allergy and Infectious Diseases grants AI055472 and AI079022 (to J.E.G.).


  • bacterial pathogenesis
  • cell-autonomous defense
  • type III secretion
  • RAB GTpases
  • Rab32
  • membrane traffic
  • macrophages
  • innate immunity
  • lysosomes
  • lysosome-related organelles
  • salmonella pathogenesis
  • Salmonella typhi
  • typhoid fever


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