PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection

Catherine M. Buckley, Victoria L. Heath, Aurélie Guého, Cristina Bosmani, Paulina Knobloch, Phumzile Sikakana, Nicolas Personnic, Stephen K. Dove, Robert H. Michell, Roger Meier, Hubert Hilbi, Thierry Soldati, Robert H. Insall, Jason S. King

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
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By engulfing potentially harmful microbes, professional phagocytes are continually at risk from intracellular pathogens. To avoid becoming infected, the host must kill pathogens in the phagosome before they can escape or establish a survival niche. Here, we analyse the role of the phosphoinositide (PI) 5-kinase PIKfyve in phagosome maturation and killing, using the amoeba and model phagocyte Dictyostelium discoideum. PIKfyve plays important but poorly understood roles in vesicular trafficking by catalysing formation of the lipids phosphatidylinositol (3,5)-bisphosphate (PI(3,5)2) and phosphatidylinositol-5-phosphate (PI(5)P). Here we show that its activity is essential during early phagosome maturation in Dictyostelium. Disruption of PIKfyve inhibited delivery of both the vacuolar V-ATPase and proteases, dramatically reducing the ability of cells to acidify newly formed phagosomes and digest their contents. Consequently, PIKfyve- cells were unable to generate an effective antimicrobial environment and efficiently kill captured bacteria. Moreover, we demonstrate that cells lacking PIKfyve are more susceptible to infection by the intracellular pathogen Legionella pneumophila. We conclude that PIKfyve-catalysed phosphoinositide production plays a crucial and general role in ensuring early phagosomal maturation, protecting host cells from diverse pathogenic microbes.

Original languageEnglish
Article numbere1007551
Pages (from-to)e1007551
Number of pages26
JournalPLoS pathogens
Issue number2
Publication statusPublished - 17 Feb 2019


  • Adenosine Triphosphatases
  • Animals
  • Cell Line
  • Dictyostelium/metabolism
  • Humans
  • Hydrolases/metabolism
  • Legionella pneumophila/pathogenicity
  • Legionellosis/metabolism
  • Macrophages
  • Phagocytosis
  • Phagosomes
  • Phosphatidylinositol 3-Kinases/metabolism
  • Phosphatidylinositol Phosphates/metabolism
  • Phosphatidylinositols
  • Protein Transport
  • Protozoan Infections/metabolism


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