4.6 Article

Chitin Deacetylase, a Novel Target for the Design of Agricultural Fungicides

Journal

JOURNAL OF FUNGI
Volume 7, Issue 12, Pages -

Publisher

MDPI
DOI: 10.3390/jof7121009

Keywords

chitin; chitin deacetylase; chitin-triggered immunity; EDTA; Podosphaera xanthii; powdery mildews; RNAi silencing

Ask authors/readers for more resources

The study suggests that chitin deacetylase (CDA) could be a suitable target for antifungals. RNAi silencing of PxCDA resulted in a significant reduction in fungal growth and rapid elicitation of chitin-triggered immunity. The chelating agent EDTA showed promising disease-suppression activity against a variety of phytopathogenic fungi.
Fungicide resistance is a serious problem for agriculture. This is particularly apparent in the case of powdery mildew fungi. Therefore, there is an urgent need to develop new agrochemicals. Chitin is a well-known elicitor of plant immunity, and fungal pathogens have evolved strategies to overcome its detection. Among these strategies, chitin deacetylase (CDA) is responsible for modifying immunogenic chitooligomers and hydrolysing the acetamido group in the N-acetylglucosamine units to avoid recognition. In this work, we tested the hypothesis that CDA can be an appropriate target for antifungals using the cucurbit powdery mildew pathogen Podosphaera xanthii. According to our hypothesis, RNAi silencing of PxCDA resulted in a dramatic reduction in fungal growth that was linked to a rapid elicitation of chitin-triggered immunity. Similar results were obtained with treatments with carboxylic acids such as EDTA, a well-known CDA inhibitor. The disease-suppression activity of EDTA was not associated with its chelating activity since other chelating agents did not suppress disease. The binding of EDTA to CDA was confirmed by molecular docking studies. Furthermore, EDTA also suppressed green and grey mould-causing pathogens applied to oranges and strawberries, respectively. Our results conclusively show that CDA is a promising target for control of phytopathogenic fungi and that EDTA could be a starting point for fungicide design.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Chemistry, Medicinal

How Molecular Topology Can Help in Amyotrophic Lateral Sclerosis (ALS) Drug Development: A Revolutionary Paradigm for a Merciless Disease

Maria Galvez-Llompart, Riccardo Zanni, Ramon Garcia-Domenech, Jorge Galvez

Summary: Despite being considered an orphan disease, amyotrophic lateral sclerosis (ALS) is seeing a rapid increase in prevalence, making it difficult to find effective treatments. Computational methods based on receptors or ligands have the potential to improve the success rate of potential drug candidates and reduce resources and time. This study presents a computational strategy based on Molecular Topology to create a reliable tool for identifying and repurposing potential drugs for ALS treatment in the early stages.

PHARMACEUTICALS (2022)

Article Biochemistry & Molecular Biology

COVID-19 and the Importance of Being Prepared: A Multidisciplinary Strategy for the Discovery of Antivirals to Combat Pandemics

Maria Galvez-Llompart, Riccardo Zanni, Jorge Galvez, Subhash C. Basak, Sagar M. Goyal

Summary: This study demonstrates the potential of drug repurposing in tackling pandemics. The researchers identified molecules with anti-SARS-CoV-2 activity through in silico screening and validated their effectiveness in vitro.

BIOMEDICINES (2022)

Article Agriculture, Multidisciplinary

Rational Design of Chitin Deacetylase Inhibitors for Sustainable Agricultural Use Based on Molecular Topology

Riccardo Zanni, Jesus Martinez-Cruz, Maria Galvez-Llompart, Dolores Fernandez-Ortuno, Diego Romero, Ramon Garcia-Domenech, Alejandro Perez-Garcia, Jorge Galvez

Summary: Fungicide resistance is a serious issue in modern agriculture, and the development of new and environmentally friendly chemicals is in high demand. In this study, a computational strategy based on quantitative structure-activity relationship (QSAR) and molecular topology (MT) was used to discover potential chitin deacetylase (CDA) inhibitors. The identified inhibitors showed fungicidal activity and the ability to stimulate the plant immune system, making them promising candidates for combating resistant fungal species.

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY (2022)

Article Microbiology

Suppression of Chitin-Triggered Immunity by a New Fungal Chitin-Binding Effector Resulting from Alternative Splicing of a Chitin Deacetylase Gene

Jesus M. Martinez-Cruz, Alvaro Polonio, Laura Ruiz-Jimenez, Alejandra Vielba-Fernandez, Jesus Hierrezuelo, Diego Romero, Antonio de Vicente, Dolores Fernandez-Ortuno, Alejandro Perez-Garcia

Summary: Phytopathogenic fungi have evolved mechanisms to manipulate plant defenses by preventing chitin recognition, with the CDA gene playing a crucial role in powdery mildew fungi. A new fungal chitin-binding effector, CHBE, has been identified as involved in the manipulation of chitin-triggered immunity in powdery mildew fungi.

JOURNAL OF FUNGI (2022)

Article Biochemistry & Molecular Biology

Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays

Angela Garcia-Garcia, Jesus Vicente de Julian-Ortiz, Jorge Galvez, David Font, Carles Ayats, Maria del Remedio Guna Serrano, Carlos Munoz-Collado, Rafael Borras, Jose Manuel Villalgordo

Summary: A method for identifying molecular scaffolds active against Mycobacterium tuberculosis complex (MTBC) has been developed. A mathematical model based on topological descriptors was constructed and validated, with an accuracy of over 86% in discriminating active and inactive compounds. The model was also effective in selecting potential antituberculosis compounds and several new compounds showed activity in vitro.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Review Biochemistry & Molecular Biology

RNAi Technology: A New Path for the Research and Management of Obligate Biotrophic Phytopathogenic Fungi

Isabel Padilla-Roji, Laura Ruiz-Jimenez, Nisrine Bakhat, Alejandra Vielba-Fernandez, Alejandro Perez-Garcia, Dolores Fernandez-Ortuno

Summary: RNA interference (RNAi) technology plays a crucial role in the study and management of powdery mildew and rust fungi by allowing gene function analysis and potential disease control approaches.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Microbiology

Sporulation Activated via σW Protects Bacillus from a Tse1 Peptidoglycan Hydrolase Type VI Secretion System Effector

Alicia I. Perez-Lorente, Carlos Molina-Santiago, Antonio de Vicente, Diego Romero

Summary: The study examines the competition dynamics between Pseudomonas and Bacillus and the mechanism by which a T6SS toxin modifies Bacillus physiology. The researchers found that Pseudomonas triggers Bacillus sporulation by injecting a toxin called Tse1 through T6SS, which degrades Bacillus peptidoglycan and damages Bacillus membrane functionality.

MICROBIOLOGY SPECTRUM (2023)

Article Biotechnology & Applied Microbiology

Digestive exophagy of biofilms by intestinal amoeba and its impact on stress tolerance and cytotoxicity

Eva Zanditenas, Meirav Trebicz-Geffen, Divya Kolli, Laura Dominguez-Garcia, Einan Farhi, Liat Linde, Diego Romero, Matthew Chapman, Ilana Kolodkin-Gal, Serge Ankri

Summary: The human protozoan parasite Entamoeba histolytica is capable of invading and degrading biofilms formed by bacteria, which could potentially provide a new approach for treating biofilms. The parasite's cysteine proteinases play a crucial role in the degradation process and also contribute to parasite adhesion to the biofilm. These proteinases are also involved in degrading biofilms formed by other enteric pathogens. Additionally, biofilms can protect the parasite against oxidative stress and products derived from the parasite have been shown to restore antibiotic sensitivity to biofilm cells. Probiotic biofilms, on the other hand, can act as a protective shield for mammalian cells, hindering parasite progression.

NPJ BIOFILMS AND MICROBIOMES (2023)

Article Biotechnology & Applied Microbiology

Molecular characterization of the N-terminal half of TasA during amyloid-like assembly and its contribution to Bacillus subtilis biofilm formation

Jesus Camara-Almiron, Laura Dominguez-Garcia, Nadia El Mammeri, Alons Lends, Birgit Habenstein, Antonio de Vicente, Antoine Loquet, Diego Romero

Summary: This study demonstrates that recombinantly purified RcTasA retains the biochemical properties of the entire protein and shows that two aggregation-prone stretches and imperfect amino acid repeats in RcTasA contribute to its amyloid-like capacity. The study also identifies the critical role of residues D64, K68, and D69 in the structural function of TasA. Experiments with mutant versions of TasA reveal a partial loss of function in the assembly of the extracellular matrix or the stability of the core and amyloid-like properties. Overall, these findings provide insights into the polymerization process of TasA and the sequence determinants that govern the behavior of protein filaments in bacteria.

NPJ BIOFILMS AND MICROBIOMES (2023)

Review Microbiology

Suppression of Chitin-Triggered Immunity by Plant Fungal Pathogens: A Case Study of the Cucurbit Powdery Mildew Fungus Podosphaera xanthii

Nisrine Bakhat, Alejandra Vielba-Fernandez, Isabel Padilla-Roji, Jesus Martinez-Cruz, Alvaro Polonio, Dolores Fernandez-Ortuno, Alejandro Perez-Garcia

Summary: Fungal pathogens pose a growing threat to crop production worldwide, and chitin-induced immunity plays a crucial role in plant defense against these pathogens. However, fungi have developed various strategies to evade chitin-triggered immunity, including the secretion of effector proteins that modify or degrade chitin oligomers. This review provides an overview of chitin-triggered immune signaling and the mechanisms employed by fungi to suppress it, using powdery mildew fungi as an example.

JOURNAL OF FUNGI (2023)

Article Chemistry, Applied

Incorporation of bioactive compounds from avocado by-products to ethyl cellulose-reinforced paper for food packaging applications

Maria A. Acquavia, Jos e J. Benitez, Giuliana Bianco, Maria A. Crescenzi, Jesus Hierrezuelo, Montserrat Grife-Ruiz, Diego Romero, Susana Guzman-Puyol, Jose A. Heredia-Guerrero

Summary: Reinforced films were produced by impregnating paper with ethyl cellulose solutions, improving the mechanical and barrier properties. Avocado by-products extract, rich in phenolic compounds and flavonoids, was incorporated into the reinforced paper, reducing water absorption, increasing biodegradability, and acting as a barrier for bacteria. These films demonstrated potential for food packaging with low migrations and similar food preservation to polyethylene.

FOOD CHEMISTRY (2023)

Article Food Science & Technology

Elucidating the mechanism of action of mycotoxins through machine learning-driven QSAR models: Focus on lipid peroxidation

Maria Galvez-Llompart, Riccardo Zanni, Lara Manyes, Giuseppe Meca

Summary: Machine learning models based on quantitative structure-activity relationship (QSAR) were used to predict the lipid peroxidation activity of mycotoxins. Two algorithms, Linear Discriminant Analysis (LDA) and Artificial Neural Networks (ANNs), were trained and achieved high classification rates. These models provide a fast, accurate, and cost-effective means to assess mycotoxin toxicity and mechanism of action.

FOOD AND CHEMICAL TOXICOLOGY (2023)

No Data Available