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RNAi as a Tool to Study Virulence in the Pathogenic Yeast Candida glabrata

Ishchuk, Olena P LU ; Ahmad, Khadija Mohamed LU ; Koruza, Katarina LU ; Bojanovič, Klara; Sprenger, Marcel; Kasper, Lydia; Brunke, Sascha; Hube, Bernhard; Säll, Torbjörn LU and Hellmark, Thomas LU , et al. (2019) In Frontiers in Microbiology 10. p.1679-1679
Abstract

The yeast Candida glabrata is a major opportunistic pathogen causing mucosal and systemic infections in humans. Systemic infections caused by this yeast have high mortality rates and are difficult to treat due to this yeast's intrinsic and frequently adapting antifungal resistance. To understand and treat C. glabrata infections, it is essential to investigate the molecular basis of C. glabrata virulence and resistance. We established an RNA interference (RNAi) system in C. glabrata by expressing the Dicer and Argonaute genes from Saccharomyces castellii (a budding yeast with natural RNAi). Our experiments with reporter genes and putative virulence genes showed that the introduction of RNAi resulted in 30 and 70% gene-knockdown for the... (More)

The yeast Candida glabrata is a major opportunistic pathogen causing mucosal and systemic infections in humans. Systemic infections caused by this yeast have high mortality rates and are difficult to treat due to this yeast's intrinsic and frequently adapting antifungal resistance. To understand and treat C. glabrata infections, it is essential to investigate the molecular basis of C. glabrata virulence and resistance. We established an RNA interference (RNAi) system in C. glabrata by expressing the Dicer and Argonaute genes from Saccharomyces castellii (a budding yeast with natural RNAi). Our experiments with reporter genes and putative virulence genes showed that the introduction of RNAi resulted in 30 and 70% gene-knockdown for the construct-types antisense and hairpin, respectively. The resulting C. glabrata RNAi strain was used for the screening of a gene library for new virulence-related genes. Phenotypic profiling with a high-resolution quantification of growth identified genes involved in the maintenance of cell integrity, antifungal drugs, and ROS resistance. The genes identified by this approach are promising targets for the treatment of C. glabrata infections.

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@article{7de59110-0e3e-4e48-a85f-084701511b93,
  abstract     = {<p>The yeast Candida glabrata is a major opportunistic pathogen causing mucosal and systemic infections in humans. Systemic infections caused by this yeast have high mortality rates and are difficult to treat due to this yeast's intrinsic and frequently adapting antifungal resistance. To understand and treat C. glabrata infections, it is essential to investigate the molecular basis of C. glabrata virulence and resistance. We established an RNA interference (RNAi) system in C. glabrata by expressing the Dicer and Argonaute genes from Saccharomyces castellii (a budding yeast with natural RNAi). Our experiments with reporter genes and putative virulence genes showed that the introduction of RNAi resulted in 30 and 70% gene-knockdown for the construct-types antisense and hairpin, respectively. The resulting C. glabrata RNAi strain was used for the screening of a gene library for new virulence-related genes. Phenotypic profiling with a high-resolution quantification of growth identified genes involved in the maintenance of cell integrity, antifungal drugs, and ROS resistance. The genes identified by this approach are promising targets for the treatment of C. glabrata infections.</p>},
  author       = {Ishchuk, Olena P and Ahmad, Khadija Mohamed and Koruza, Katarina and Bojanovič, Klara and Sprenger, Marcel and Kasper, Lydia and Brunke, Sascha and Hube, Bernhard and Säll, Torbjörn and Hellmark, Thomas and Gullstrand, Birgitta and Brion, Christian and Freel, Kelle and Schacherer, Joseph and Regenberg, Birgitte and Knecht, Wolfgang and Piškur, Jure},
  issn         = {1664-302X},
  language     = {eng},
  pages        = {1679--1679},
  publisher    = {Frontiers},
  series       = {Frontiers in Microbiology},
  title        = {RNAi as a Tool to Study Virulence in the Pathogenic Yeast Candida glabrata},
  url          = {http://dx.doi.org/10.3389/fmicb.2019.01679},
  volume       = {10},
  year         = {2019},
}