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A Phosphatidylinositol 3-Kinase Effector Alters Phagosomal Maturation to Promote Intracellular Growth of Francisella.

Cell host & microbe | 2018

Many pathogenic intracellular bacteria manipulate the host phago-endosomal system to establish and maintain a permissive niche. The fate and identity of these intracellular compartments is controlled by phosphoinositide lipids. By mechanisms that have remained undefined, a Francisella pathogenicity island-encoded secretion system allows phagosomal escape and replication of bacteria within host cell cytoplasm. Here we report the discovery that a substrate of this system, outside pathogenicity island A (OpiA), represents a family of wortmannin-resistant bacterial phosphatidylinositol (PI) 3-kinase enzymes with members found in a wide range of intracellular pathogens, including Rickettsia and Legionella spp. We show that OpiA acts on the Francisella-containing phagosome and promotes bacterial escape into the cytoplasm. Furthermore, we demonstrate that the phenotypic consequences of OpiA inactivation are mitigated by endosomal maturation arrest. Our findings suggest that Francisella, and likely other intracellular bacteria, override the finely tuned dynamics of phagosomal PI(3)P in order to promote intracellular survival and pathogenesis.

Pubmed ID: 30057173 RIS Download

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI093646
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI129992
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI130798
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI055396
  • Agency: Wellcome Trust, United Kingdom
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM077349
  • Agency: Howard Hughes Medical Institute, United States

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