SNX3 drives maturation of Borrelia phagosomes by forming a hub for PI(3)P, Rab5a, and galectin-9

J Cell Biol. 2019 Sep 2;218(9):3039-3059. doi: 10.1083/jcb.201812106. Epub 2019 Jul 23.


The spirochete Borrelia burgdorferi, the causative agent of Lyme disease, is internalized by macrophages and processed in phagolysosomes. Phagosomal compaction, a crucial step in phagolysosome maturation, is driven by contact of Rab5a-positive vesicles with the phagosomal coat. We show that the sorting nexin SNX3 is transported with Rab5a vesicles and that its PX domain enables vesicle-phagosome contact by binding to PI(3)P in the phagosomal coat. Moreover, the C-terminal region of SNX3 recruits galectin-9, a lectin implicated in protein and membrane recycling, which we identify as a further regulator of phagosome compaction. SNX3 thus forms a hub for two distinct vesicle populations, constituting a convergence point for the endosomal recycling machinery, to contribute to phagosome maturation and intracellular processing of borreliae. These data also suggest that the helical shape of B. burgdorferi itself, providing sites of high curvature and thus local PI(3)P enrichment at phagosomes, may be one of the driving elements underlying the efficient elimination of spirochetes by immune cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Borrelia burgdorferi / metabolism*
  • Galectins / metabolism*
  • Humans
  • Lyme Disease / metabolism*
  • Lyme Disease / pathology
  • Monocytes* / metabolism
  • Monocytes* / microbiology
  • Monocytes* / pathology
  • Phagosomes* / metabolism
  • Phagosomes* / microbiology
  • Phagosomes* / pathology
  • Phosphatidylinositol Phosphates / metabolism*
  • Sorting Nexins / metabolism*
  • rab5 GTP-Binding Proteins / metabolism*


  • Galectins
  • LGALS9 protein, human
  • Phosphatidylinositol Phosphates
  • SNX3 protein, human
  • Sorting Nexins
  • phosphatidylinositol 3-phosphate
  • RAB5C protein, human
  • rab5 GTP-Binding Proteins

Associated data

  • RefSeq/NM_009587