Antifungal proteins - Investigation of antifungal mechanism and biological
role for new therapeutic approaches (OTKA FK 134343)
Principal Investigator: László Galgóczy
Duration: 48 moths (2020-2024)
In the consequence of the emerging number of drug-resistant fungal strains the
incidences of fungal infections dramatically increased worldwide. The
facts that only a few classes of antifungal drugs are available and that
they can cause serious side-effects and damage the host’s organs
permanently hamper patient management. Therefore, there is a substantial
demand for development of fundamental new, effective and safely applicable
antifungal strategies to prevent and treat fungal infections.
The features of the small molecular weight, cysteine-rich, cationic antifungal proteins
secreted by the filamentous ascomycete, Neosartorya (Aspergillus) fischeri
(crAFPs) correspond well to these challenges.
One of the key steps in their application as antifungals drugs is an understanding the molecular
mechanisms behind the antifungal activity.
The present project focuses to
this aspect, (1) investigation of their antifungal mechanism in human
pathogenic fungi and biological role in the native producer, and (2)
identification the molecular components of these mechanisms. Furthermore,
to (3) identify or design potential drug candidate compounds acting on
these molecular components, and (4) prove their safe applicability in the
clinical therapy.
These goals will be achieved by young and senior
scientists, and supervised university students applying a
multidisciplinary approach that integrates transcriptome meta-analysis,
virtual ligand screenings and docking techniques, antifungal and toxicity
tests.
As a final outcome of the accomplished project, we will be able to
make suggestions for a new and effective crAFP target-based antifungal
strategy.
Supported by Hungarian National Research, Development and
Innovation Office.
Biofungicide and bioactivator potential of novel
defensin-like proteins from Solanum lycopersicum L. (OTKA PD 134284)
Principal Investigator: Liliána Tóth
Duration: 36 moths (2020-2023)
As a consequence of the worldwide increase of enormous crop losses by pesticide
resistant plant-pathogenic fungi, there is a substantial demand to develop
new antifungal strategies in
agriculture to support the increasing global
calorie consumption in the next decades.
Antifungal proteins and peptides, including plant defensins are already considered as potential
biofungicides; however, several factors still limit their direct topical
agricultural application to treat of prevent fungal infections. These
limitations are the high costs of production, narrow antifungal spectrum,
and potential detrimental effects on plant development and human/animal
health.
The present project aims at proving the safe and effective
applicability of novel defensin-like proteins from tomato plant (Solanum
lycopersicum L.) and their rational designed γ-core peptide derivatives as
biofungicide agents in plant protection by investigating their antifungal
efficacy against plant pathogenic filamentous fungi and the toxicity
against different human cell lines
and plant seedling; furthermore, their
application as protective or therapeutic agents against fungal infections
on plants leaves and roots. The cost-effective heterologous production of
these tomato plant-derived defensins applying a fungal expression system
is also in the focus of present project.
In addition, present project
aimed to reveal the antifungal mechanisms of these defensins in sensitive
fungi, and their potential bioactivator role in the host to trigger the
self-defence mechanisms
or modulate the plant development as responses to
fungal infection.
Supported by Hungarian National Research, Development
and Innovation Office.