Dataset Information

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.

SUBMITTER: Bois M

PROVIDER: S-EPMC3647779 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Does Candida albicans Als5p amyloid play a role in commensalism in Caenorhabditis elegans?

Bois Michael M Singh Sean S Samlalsingh Alyssa A Lipke Peter N PN Garcia Melissa C MC

Eukaryotic cell 20130308 5

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 ( ...[more]

PMID: 23475704

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Project description:Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ~1.6% of the genome) many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through "pattern recognition," an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs). This study provides new information on the evolution and regulation of the innate immune response to divergent pathogens and demonstrates that nematodes selectively mount specific antifungal defenses at the expense of antibacterial responses.

Dataset Information

Does Candida albicans Als5p amyloid play a role in commensalism in Caenorhabditis elegans?

Publications

Does Candida albicans Als5p amyloid play a role in commensalism in Caenorhabditis elegans?

Similar Datasets

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