Genome-Wide Screen for Saccharomyces cerevisiae Genes Contributing to Opportunistic Pathogenicity in an Invertebrate Model Host
| Autor: | Kaitlyn L. Norman, Lucas A. Michelotti, Sujal Phadke, Timothy Y. James, Anuj Kumar, Calum J. Maclean, Serena Zhao, Emmi A. Mueller |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genotype bulk segregant analysis Quantitative Trait Loci 030106 microbiology Saccharomyces cerevisiae Virulence Investigations Moths Quantitative trait locus Biology QH426-470 medicine.disease_cause 03 medical and health sciences pseudohyphae Cell Wall medicine Genetics Animals Molecular Biology Gene Alleles Genetics (clinical) 2. Zero hunger Mutation Innate immune system hybrid Molecular Sequence Annotation barseq biology.organism_classification Phenotype Immunity Innate Yeast Mitochondria virulence Gene Ontology 030104 developmental biology Larva Host-Pathogen Interactions Tyrosine Genome Fungal Genome-Wide Association Study |
| Zdroj: | G3: Genes, Genomes, Genetics, Vol 8, Iss 1, Pp 63-78 (2018) G3: Genes|Genomes|Genetics |
| ISSN: | 2160-1836 |
| DOI: | 10.1534/g3.117.300245 |
| Popis: | Environmental opportunistic pathogens can exploit vulnerable hosts through expression of traits selected for in their natural environments. Pathogenicity is itself a complicated trait underpinned by multiple complex traits, such as thermotolerance, morphology, and stress response. The baker’s yeast, Saccharomyces cerevisiae, is a species with broad environmental tolerance that has been increasingly reported as an opportunistic pathogen of humans. Here we leveraged the genetic resources available in yeast and a model insect species, the greater waxmoth Galleria mellonella, to provide a genome-wide analysis of pathogenicity factors. Using serial passaging experiments of genetically marked wild-type strains, a hybrid strain was identified as the most fit genotype across all replicates. To dissect the genetic basis for pathogenicity in the hybrid isolate, bulk segregant analysis was performed which revealed eight quantitative trait loci significantly differing between the two bulks with alleles from both parents contributing to pathogenicity. A second passaging experiment with a library of deletion mutants for most yeast genes identified a large number of mutations whose relative fitness differed in vivovs.in vitro, including mutations in genes controlling cell wall integrity, mitochondrial function, and tyrosine metabolism. Yeast is presumably subjected to a massive assault by the innate insect immune system that leads to melanization of the host and to a large bottleneck in yeast population size. Our data support that resistance to the innate immune response of the insect is key to survival in the host and identifies shared genetic mechanisms between S. cerevisiae and other opportunistic fungal pathogens. |
| Databáze: | OpenAIRE |
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