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Infect. Immun. doi:10.1128/IAI.00588-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Analysis of PRA1 and its relationship to Candida-macrophage interactions

Genetics Group, Biotechnology Research Institute, National Research Council of Canada, Montreal, Québec H4P 2R2

^* To whom correspondence should be addressed. Email: anne.marcil{at}cnrc-nrc.gc.ca.

	Abstract

Phagocytosis of Candida albicans by either primary bone marrow-derived mouse macrophages or RAW264.7 cells up-regulated transcription of PRA1, which encodes a cell wall/membrane associated antigen previously described as a fibrinogen binding protein. However, a pra1 null mutant was still able to bind fibrinogen, showing that Pra1p is not uniquely required for fibrinogen binding. As well, Pra1-GFP did not co-localize with AlexaFluor 546 labeled human fibrinogen, and while PRA1 expression was inhibited when Candida was grown in FBS containing medium, Candida binding to fibrinogen was activated by these conditions. Therefore it appears that Pra1p can play at most a minor role in fibrinogen binding to C. albicans. PRA1 gene expression is induced in vitro by alkaline pH, and therefore its activation in phagosomes suggested that phagosome maturation was suppressed by the presence of Candida cells. LysoTracker red-labeled organelles failed to fuse with phagosomes containing live Candida, while phagosomes containing dead Candida undergo a normal phagosome to phagolysosome maturation. Immunofluorescence staining with the early/recycling endosomal marker transferrin receptor (CD71) suggests that live Candida may escape macrophage destruction through inhibition of phagolysosomal maturation.