Model of SNX3-dependent processing of borreliae by macrophages. B. burgdorferi is internalized by macrophages through uptake into Rab22a-decorated phagosomes that are contacted by Rab5a vesicles that also contain SNX3. SNX3 enables docking of Rab5a vesicles to phagosomes by binding to PI(3)P on the phagosomal surface, which is enriched at sites of high curvature due to the helical shape of the spirochete. SNX3 also recruits, by its C-terminal region, a second subset of vesicles positive for galectin-9. Both Rab5a and galectin-9 contribute to phagosome compaction and phagolysosome maturation, leading to the elimination of spirochetes by human macrophages. PM, plasma membrane.