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J. Biol. Chem., Vol. 278, Issue 15, 13086-13093, April 11, 2003

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Candida albicans Phospholipomannan Promotes Survival of Phagocytosed Yeasts through Modulation of Bad Phosphorylation and Macrophage Apoptosis^*

Stella Ibata-Ombetta^§, Thierry Idziorek^¶, Pierre-André Trinel, Daniel Poulain, and Thierry Jouault

From the  Laboratoire de Mycologie Fondamentale et Appliquée, Inserm EMI0360, Université de Lille II, and ^¶ Inserm U459, Faculté de Médecine H. Warembourg, Place Verdun, 59037 Lille Cedex, France

The surface of the pathogenic yeast Candida albicans is coated with phospholipomannan (PLM), a phylogenetically unique glycolipid composed of -1,2-oligomannosides and phytoceramide. This study compared the specific contribution of PLM to the modulation of signaling pathways linked to the survival of C. albicans in macrophages in contrast to Saccharomyces cerevisiae. C. albicans endocytosis by J774 and disregulation of the ERK1/2 signal transduction pathway was associated downstream with a reduction in Bad Ser-112 phosphorylation and disappearance of free Bcl-2. This suggested an apoptotic effect, which was confirmed by staining of phosphatidylserine in the macrophage outer membrane. The addition of PLM to macrophages incubated with S. cerevisiae mimicked each of the disregulation steps observed with C. albicans and promoted the survival of S. cerevisiae. Externalization of membranous phosphatidylserine, loss of mitochondrial integrity, and DNA fragmentation induced by PLM showed that this molecule promoted yeast survival by inducing host cell death. These findings suggest strongly that PLM is a virulence attribute of C. albicans and that elucidation of the relationship between structure and apoptotic activity is an innovative field of research.

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