1887

Abstract

The presence of specific proteins, including Ece1p, Hwp1p and Als3p, distinguishes the hyphal cell wall from that of yeast-form cells. These proteins are thought to be important for the ability of cells 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 mediating interactions with endothelial cells. Using an flow 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 of in a wild-type strain. In agreement with previous studies, our Δ null strain formed hyphae normally but was defective in biofilm formation. Whilst was not expressed in our null strain, hypha-specific genes such as and were still induced appropriately. Both the yeast form and the hyphal form of the Δ 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 mutant Δ remained as virulent as the wild-type parent strain.

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2011-06-01
2019-08-23
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