6533b828fe1ef96bd1289114

RESEARCH PRODUCT

Candida albicans adhesin Als3p is dispensable for virulence in the mouse model of disseminated candidiasis

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The presence of specific proteins, including Ece1p, Hwp1p and Als3p, distinguishes theCandida albicanshyphal cell wall from that of yeast-form cells. These proteins are thought to be important for the ability ofC. albicanscells to adhere to living and non-living surfaces and for the cell-to-cell adhesion necessary for biofilm formation, and also to be pivotal in mediatingC. albicansinteractions with endothelial cells. Using anin vitroflow adhesion assay, we previously observed that yeast cells bind in greater numbers to human microvascular endothelial cells than do hyphal or pseudohyphal cells. This is consistent with previous observations that, in a murine model of disseminated candidiasis, cells locked in the yeast form can efficiently escape the bloodstream and invade host tissues. To more precisely explore the role of Als3p in adhesion and virulence, we deleted both copies ofALS3in a wild-typeC. albicansstrain. In agreement with previous studies, ourals3Δ null strain formed hyphae normally but was defective in biofilm formation. WhilstALS3was not expressed in our null strain, hypha-specific genes such asECE1andHWP1were still induced appropriately. Both the yeast form and the hyphal form of theals3Δ strain adhered to microvascular endothelial cells to the same extent as a wild-type strain under conditions of flow, indicating that Als3p is not a significant mediator of the initial interaction between fungal cells and the endothelium. Finally, in a murine model of haematogenously disseminated candidiasis the mutantals3Δ remained as virulent as the wild-type parent strain.