title: Candida albicans adhesin Als3p is dispensable for virulence in the mouse model of disseminated candidiasis.
abstract: The presence of specific proteins, including Ece1p, Hwp1p and Als3p, distinguishes the Candida albicans hyphal cell wall from that of yeast-form cells. These proteins are thought to be important for the ability of C. albicans 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 C. albicans interactions with endothelial cells. Using an in vitro 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 ALS3 in a wild-type C. albicans strain. In agreement with previous studies, our als3Δ null strain formed hyphae normally but was defective in biofilm formation. Whilst ALS3 was not expressed in our null strain, hypha-specific genes such as ECE1 and HWP1 were still induced appropriately. Both the yeast form and the hyphal form of the als3Δ 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 als3Δ remained as virulent as the wild-type parent strain.
authors: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA.
authors: Ian A
authors: IA
authors: Cleary
authors: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA.
authors: Sara M
authors: SM
authors: Reinhard
authors: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA.
authors: C Lindsay
authors: CL
authors: Miller
authors: Academic Unit of Oral and Maxillofacial Medicine and Surgery, University of Sheffield, Sheffield, UK.
authors: Craig
authors: C
authors: Murdoch
authors: Academic Unit of Oral and Maxillofacial Medicine and Surgery, University of Sheffield, Sheffield, UK.
authors: Martin H
authors: MH
authors: Thornhill
authors: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA.
authors: Anna L
authors: AL
authors: Lazzell
authors: Departmento de Patología, Facultad de Medicina y Odontología, Universidad de Valencia, 46010 Valencia, Spain.
authors: Carlos
authors: C
authors: Monteagudo
authors: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA.
authors: Derek P
authors: DP
authors: Thomas
authors: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA.
authors: Stephen P
authors: SP
authors: Saville
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000382:microbiology; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D025301:Hyphae / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014774:Virulence / Q000235:genetics
chemical_list: C113620:ALS3 protein, Candida albicans; D005656:Fungal Proteins