The Anaplasma phagocytophilum-occupied vacuole selectively recruits Rab-GTPases that are predominantly associated

Bernice Huang1, Andree Hubber, Justin A McDonough

  • 1Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.

Cellular Microbiology
|March 30, 2010
PubMed

Insights

Anaplasma phagocytophilum manipulates host cell vacuoles by recruiting specific Rab GTPases, primarily from recycling endosomes, to evade lysosomal fusion and ensure intracellular survival. Bacterial proteins may regulate Rab10 on the vacuole.

Area of Science:

  • Cell Biology
  • Microbiology
  • Molecular Biology

Background:

  • Anaplasma phagocytophilum is an obligate intracellular bacterium that infects neutrophils.
  • The bacterium resides in a unique vacuole (ApV) that avoids lysosomal maturation and fusion.
  • Rab GTPases are key regulators of intracellular membrane trafficking.

Purpose of the Study:

  • To investigate how A. phagocytophilum modulates the ApV's interaction with the host endocytic pathway.
  • To identify specific Rab GTPases involved in the biogenesis and maintenance of the ApV.

Main Methods:

  • Utilized green fluorescent protein (GFP) or red fluorescent protein (RFP)-tagged Rab GTPases in infected HL-60 cells.
  • Examined the intracellular localization of 20 different Rab GTPases in A. phagocytophilum-infected cells.
  • Assessed the impact of tetracycline treatment and GTPase-deficient mutants on Rab localization.

Main Results:

  • Several Rab GTPases, including Rab1, Rab4A, Rab10, Rab11A, Rab14, Rab22A, and Rab35, were found to localize to the ApV.
  • Recruitment of Rab GTPases to the ApV occurs upon its formation and persists throughout infection.
  • GTPase-dependent and -independent recruitment mechanisms were observed, with Rab10 recruitment being guanine nucleotide-independent.

Conclusions:

  • A. phagocytophilum selectively recruits Rab GTPases, particularly those involved in recycling endosomes, to establish and maintain its intracellular niche.
  • This selective recruitment is crucial for the bacterium's survival within the host cell.
  • Bacterial effector proteins are implicated in modulating Rab GTPase activity, specifically Rab10, on the ApV.

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