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Unraveling the multidrug resistance, drug tolerance, and collateral sensitivity in the emergent nosocomial fungus C. auris using experimental evolution and multi-omics analysis.

Antifungal resistance is rising on an unprecedented scale. Invasive, multidrug-resistant (MDR) fungal infections are threatening public health, and are further complicated by the availability of only three major antifungal drug classes. The novel species C. auris embodies this antifungal resistance crisis. Since its first identification in 2009, this opportunistic pathogen has emerged worldwide in various hospital outbreaks and it has shown resistance to an extent that has not been observed in other fungi. Despite being the first fungus to be considered an urgent threat by the CDC, an understanding of the molecular mechanisms underlying its MDR is still missing. Traditionally, antifungal resistance has been studied by whole genome sequencing of clinical isolates. This is however challenging and genome association studies of C. auris are not able to resolve the extensive MDR seen in the clinic. In this project, we will overcome these limitations by performing in vitro and in vivo experimental evolution followed by multi-omics analysis and recently optimized gene-editing tools. Additionally, we will assess the role of tolerance in the development of drug resistance and we aim to validate whether collateral sensitivity exists in C. auris. Eventually, this project will result in the elucidation of the molecular mechanisms which govern (multi) drug resistance in C. auris and possibly provide indications towards new treatment strategies and druggable targets.
Date:1 Nov 2021 →  Today
Keywords:Drug resistance, Experimental evolution, Fungal pathogen
Disciplines:Mycology, Proteomics, Genomics, Transcriptomics, Infectious diseases
Project type:PhD project