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

Abstract

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.