title: Does Candida albicans Als5p amyloid play a role in commensalism in Caenorhabditis elegans?
abstract: Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors, including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates and is upregulated during commensal interactions but is downregulated during active C. albicans infections. An amyloid-forming core sequence at residues 325 to 331 is important for Als5p function, because a single-amino-acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence. We evaluated the role of Als5p in host-microbe interactions by using Caenorhabditis elegans nematodes as a host model and feeding them Saccharomyces cerevisiae expressing Als5p on the surface. Als5p-expressing yeast had 8.5- and 3.5-fold-increased intestinal accumulation rates compared to Als5p-nonexpressing S. cerevisiae or yeast expressing amyloid-deficient Als5p(V326N), respectively. Surprisingly, this accumulation delayed S. cerevisiae-induced killing of C. elegans. The median survival time was nearly twice as long as that of nematodes fed nonexpressing or non-amyloid-forming Als5p(V326N)-expressing S. cerevisiae. Treatment with the amyloid-inhibiting dye Congo red or repression of Als5p expression abrogated the protective effect of Als5p. Furthermore, Als5p had no effect on oocyte quantity or quality, since nematodes fed either empty vector (EV)- or Als5p(V326N)-expressing S. cerevisiae had similar egg-laying and egg-hatching rates. This study is the first, to our knowledge, to show that expression of an amyloid-forming protein can attenuate pathogenicity in C. elegans.
authors.affiliation: Molecular Cellular and Developmental Biology Program, Graduate Center of the City University of New York, New York, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bois
authors.forename: Sean
authors.initials: S
authors.lastname: Singh
authors.forename: Alyssa
authors.initials: A
authors.lastname: Samlalsingh
authors.forename: Peter N
authors.initials: PN
authors.lastname: Lipke
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Garcia
mesh_terms: D000682:Amyloid / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000382:microbiology*; D002176:Candida albicans / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000235:genetics; D054884:Host-Pathogen Interactions; D007422:Intestines / Q000382:microbiology; D009865:Oocytes / Q000502:physiology; D009866:Oogenesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000472:pathogenicity
chemical_list: C109455:ALA1 protein, Candida albicans; D000682:Amyloid; D015815:Cell Adhesion Molecules; D005656:Fungal Proteins; D011994:Recombinant Proteins