Drug repurposing according to mechanism of action of an antifungal protein to inhibit Candida biofilms
As a consequence of the increasing number of fungal infections caused by antifungal drug-resistant
Candida
biofilms, there is an urgent need to develop new and effective biofilm inhibitory strategies against the most
prevalent clinically important species, such as Candida albicans and Candida auris. The Neosartorya
fischeri
antifungal protein 2 (NFAP2) is considered as a potential candidate for this purpose as it shows inhibitory and
eradication activities on Candida biofilms.
However, development of an NFAP2-based anti-biofilm drug is cost- and time-consuming. Drug repurposing
represents a time- and cost-effective straightforward strategy for identification of new applicability of
existing drugs beyond the original medical indication.
The announced PhD project focuses on these aspects, and aims to (1) investigate the biofilm inhibitory mechanism
of NFAP2 in C. albicans and C. auris, (2) identify the direct and indirect molecular components of
the Candida
biofilm inhibitory activity of NFAP2 to find protein targets for a drug repurposing strategy, (3) identify NFAP2
binding pockets of the directly targeted proteins, and search for molecules with binding affinity to these
pockets from approved drug, experimental drug and traditional Chinese medicine libraries, (4) investigate the
potential, safe, and future-proof applicability of the most promising candidate molecule.
These goals will be achieved with a multidisciplinary approach that integrates protein localization
investigation, transcriptome analysis, whole genome sequencing, in vitro protein-protein interaction analysis,
in silico protein-protein docking, structure-based virtual screening, antifungal susceptibility testing,
laboratory microevolution, acute toxicity testing. As a final outcome of the project, we will be able to make
suggestions for a new and effective Candida biofilm eradication strategy for the medicine.
Required skills:
Good communication in English. Basic knowledge in microbiology, protein works and bioinformatics.