title: Candida albicans Als1p: an adhesin that is a downstream effector of the EFG1 filamentation pathway.
abstract: Filamentation and adherence to host cells are critical virulence factors of Candida albicans. Multiple filamentation regulatory pathways have been discovered in C. albicans using Saccharomyces cerevisiae as a model. In S. cerevisiae, these pathways converge on Flo11p, which functions as a downstream effector of filamentation and also mediates cell-cell adherence (flocculation). In C. albicans, such effector(s) have not yet been identified. Here, we demonstrate that the cell surface protein Als1p is an effector of filamentation in C. albicans. We show that Als1p expression is controlled by the transcription factor Efg1p, which is known to be a key regulator of filamentation in C. albicans. Further, disruption of ALS1 inhibited filamentation, and autonomous expression of Als1p restored filamentation in an efg1 homozygous null mutant. Thus, Als1p functions as a downstream effector of the EFG1 filamentation pathway. In addition, we found that Als1p mediates both flocculation and adherence of C. albicans to endothelial cells in vitro. As a cell surface glycoprotein that mediates filamentation and adherence, Als1p has both structural and functional similarity to S. cerevisiae Flo11p. Consistent with our in vitro results, Als1p was required for both normal filamentation and virulence in the mouse model of haematogenously disseminated candidiasis.
authors.affiliation: Division of Infectious Diseases, St John's Cardiovascular Research Center, Harbor-UCLA Research and Education Institute, Bldg. RB2, 1124 West Carson St., Torrance, CA 90502, USA. Fue_Yu@humc.edu
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: Donald C
authors.initials: DC
authors.lastname: Sheppard
authors.forename: Yee-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.forename: Jim E
authors.initials: JE
authors.lastname: Cutler
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.forename: John E
authors.initials: JE
authors.lastname: Edwards
mesh_terms: D002176:Candida albicans / Q000235:genetics* / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D004730:Endothelium, Vascular / Q000382:microbiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C093538:ALS1 protein, Candida albicans; D017931:DNA Primers; D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D014157:Transcription Factors