Analysis ofPRA1and Its Relationship toCandida albicans- Macrophage Interactions

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Abstract
Phagocytosis ofCandida albicansby either primary bone marrow-derived mouse macrophages or RAW 264.7 cells upregulated transcription ofPRA1, which encodes a cell wall/membrane-associated antigen previously described as a fibrinogen binding protein. However, apra1null mutant was still able to bind fibrinogen, showing that Pra1p is not uniquely required for fibrinogen binding. As well, Pra1 tagged with green fluorescent protein did not colocalize with AlexaFluor 546-labeled human fibrinogen, and whilePRA1expression was inhibited whenCandidawas grown in fetal bovine serum-containing medium,Candidabinding to fibrinogen was activated by these conditions. Therefore, it appears that Pra1p can play at most a minor role in fibrinogen binding toC. albicans. PRA1gene expression is induced in vitro by alkaline pH, and therefore its activation in phagosomes suggested that phagosome maturation was suppressed by the presence ofCandidacells. LysoTracker red-labeled organelles failed to fuse with phagosomes containing liveCandida, while phagosomes containing deadCandidaunderwent a normal phagosome-to-phagolysosome maturation. Immunofluorescence staining with the early/recycling endosomal marker transferrin receptor (CD71) suggested that liveCandidamay escape macrophage destruction through the inhibition of phagolysosomal maturation.