RNAi as a Tool to Study Virulence in the Pathogenic Yeast Candida glabrata
Artikel i vetenskaplig tidskrift, 2019
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.
RNA interference
RNAi
virulence factors
gene library
macrophages
antifungal drugs
Candida glabrata
pathogenic yeast
Författare
Olena Ishchuk
Chalmers, Biologi och bioteknik, Systembiologi
Lunds universitet
Khadija Mohamed Ahmad
Lunds universitet
Katarina Koruza
Lunds universitet
Klara Bojanovic
Lunds universitet
Marcel Sprenger
Hans-Knoll-Institute (HKI)
Lydia Kasper
Hans-Knoll-Institute (HKI)
Sascha Brunke
Hans-Knoll-Institute (HKI)
Bernhard Hube
Hans-Knoll-Institute (HKI)
Friedrich-Schiller-Universität Jena
Torbjorn Sall
Lunds universitet
Thomas Hellmark
Lunds universitet
Birgitta Gullstrand
Lunds universitet
Christian Brion
Université de Strasbourg
Kelle Freel
Université de Strasbourg
Joseph Schacherer
Université de Strasbourg
Birgitte Regenberg
Köpenhamns universitet
Wolfgang Knechtts
Lunds universitet
Jure Piskur
Lunds universitet
Frontiers in Microbiology
1664302x (eISSN)
Vol. 10 1679Ämneskategorier
Infektionsmedicin
Mikrobiologi
Mikrobiologi inom det medicinska området
DOI
10.3389/fmicb.2019.01679
PubMed
31396189