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Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains
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Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains
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Journal Article
Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains
2021
Overview
Candida auris
is an emerging healthcare-associated pathogen of global concern. Recent reports have identified
C. auris
isolates that grow in cellular aggregates or filaments, often without a clear genetic explanation. To investigate the regulation of
C. auris
morphogenesis, we applied an
Agrobacterium
-mediated transformation system to all four
C. auris
clades. We identified aggregating mutants associated with disruption of chitin regulation, while disruption of
ELM1
produced a polarized, filamentous growth morphology. We developed a transiently expressed Cas9 and sgRNA system for
C. auris
that significantly increased targeted transformation efficiency across the four
C. auris
clades. Using this system, we confirmed the roles of
C. auris
morphogenesis regulators. Morphogenic mutants showed dysregulated chitinase expression, attenuated virulence, and altered antifungal susceptibility. Our findings provide insights into the genetic regulation of aggregating and filamentous morphogenesis in
C. auris
. Furthermore, the genetic tools described here will allow for efficient manipulation of the
C. auris
genome.
Some isolates of the emerging fungal pathogen
Candida auris
can form cellular aggregates or filaments. Here, Santana and O’Meara use
Agrobacterium
-mediated transformation and a CRISPR-Cas9 system to identify several genes that regulate
C. auris
morphogenesis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45
/ 45/23
/ 45/41
/ 45/70
/ 45/77
/ Animals
/ Antifungal Agents - pharmacology
/ Candida auris - drug effects
/ Chitin
/ CRISPR
/ Drug Resistance, Fungal - drug effects
/ Gene Expression Regulation, Fungal
/ Genomes
/ Humanities and Social Sciences
/ Morphogenesis - drug effects
/ Moths
/ Mutants
/ Mutation
/ Science
