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.

pathogenic yeast

virulence factors

RNAi

gene library

macrophages

Candida glabrata

RNA interference

antifungal drugs

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 Knoell Inst

Lydia Kasper

Hans Knoell Inst

Sascha Brunke

Hans Knoell Inst

Bernhard Hube

Hans Knoell Inst

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

1664-302X (ISSN)

Vol. 10 1679

Ämneskategorier

Infektionsmedicin

Mikrobiologi

Mikrobiologi inom det medicinska området

DOI

10.3389/fmicb.2019.01679

PubMed

31396189

Mer information

Senast uppdaterat

2019-12-18