scholarly journals The Small GTPase CsRAC1 Is Important for Fungal Development and Pepper Anthracnose in Colletotrichum scovillei

2021 ◽  
Vol 37 (6) ◽  
pp. 607-618
Author(s):  
Noh-Hyun Lee ◽  
Teng Fu ◽  
Jong-Hwan Shin ◽  
Yong-Won Song ◽  
Dong-Cheol Jang ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Fungal Growth ◽  
Pathogenic Fungi ◽  
Fruit Production ◽  
Small Gtpase ◽  
Fungal Development ◽  
Functional Roles ◽  
Pepper Fruit ◽  
Colletotrichum Scovillei ◽  
Reduced Rate

The pepper anthracnose fungus, Colletotrichum scovillei, causes severe losses of pepper fruit production in the tropical and temperate zones. RAC1 is a highly conserved small GTP-binding protein in the Rho GTPase family. This protein has been demonstrated to play a role in fungal development, and pathogenicity in several plant pathogenic fungi. However, the functional roles of RAC1 are not characterized in C. scovillei causing anthracnose on pepper fruits. Here, we generated a deletion mutant (ΔCsrac1) via homologous recombination to investigate the functional roles of CsRAC1. The ΔCsrac1 showed pleiotropic defects in fungal growth and developments, including vegetative growth, conidiogenesis, conidial germination and appressorium formation, compared to wild-type. Although ΔCsrac1 was able to develop appressoria, it failed to differentiate appressorium pegs. However, ΔCsrac1 still caused anthracnose disease with significantly reduced rate on wounded pepper fruits. Further analyses revealed that ΔCsrac1 was defective in tolerance to oxidative stress and suppression of host-defense genes. Taken together, our results suggest that CsRAC1 plays essential roles in fungal development and pathogenicity in C. scovillei-pepper fruit pathosystem.

scholarly journals Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 737
Author(s):  
Marina Pekmezovic ◽  
Melina Kalagasidis Krusic ◽  
Ivana Malagurski ◽  
Jelena Milovanovic ◽  
Karolina Stępień ◽  
...  
Keyword(s):  
Fungal Growth ◽  
Pathogenic Fungi ◽  
Trichophyton Mentagrophytes ◽  
Microsporum Gypseum ◽  
Medium Chain Length ◽  
Gold Drugs ◽  
Growth Inhibitory Activity ◽  
Transdermal Application ◽  
Antifungal Efficiency

Novel biodegradable and biocompatible formulations of “old” but “gold” drugs such as nystatin (Nys) and amphotericin B (AmB) were made using a biopolymer as a matrix. Medium chain length polyhydroxyalkanoates (mcl-PHA) were used to formulate both polyenes (Nys and AmB) in the form of films (~50 µm). Thermal properties and stability of the materials were not significantly altered by the incorporation of polyenes in mcl-PHA, but polyene containing materials were more hydrophobic. These formulations were tested in vitro against a panel of pathogenic fungi and for antibiofilm properties. The films containing 0.1 to 2 weight % polyenes showed good activity and sustained polyene release for up to 4 days. A PHA monomer, namely 3-hydroxydecanoic acid (C10-OH), was added to the films to achieve an enhanced synergistic effect with polyenes against fungal growth. Mcl-PHA based polyene formulations showed excellent growth inhibitory activity against both Candida yeasts (C. albicans ATCC 1023, C. albicans SC5314 (ATCC MYA-2876), C. parapsilosis ATCC 22019) and filamentous fungi (Aspergillus fumigatus ATCC 13073; Trichophyton mentagrophytes ATCC 9533, Microsporum gypseum ATCC 24102). All antifungal PHA film preparations prevented the formation of a C. albicans biofilm, while they were not efficient in eradication of mature biofilms, rendering them suitable for the transdermal application or as coatings of implants.

scholarly journals Double Gamers—Can Modified Natural Regulators of Higher Plants Act as Antagonists against Phytopathogens? The Case of Jasmonic Acid Derivatives

2020 ◽  
Vol 21 (22) ◽  
pp. 8681
Author(s):  
Nicolò Orsoni ◽  
Francesca Degola ◽  
Luca Nerva ◽  
Franco Bisceglie ◽  
Giorgio Spadola ◽  
...  
Keyword(s):  
Jasmonic Acid ◽  
Plant Pathogens ◽  
Higher Plants ◽  
Fungal Growth ◽  
Pathogenic Fungi ◽  
Inhibitory Effect ◽  
Fungal Species ◽  
Phytopathogenic Fungi ◽  
Phaeomoniella Chlamydospora ◽  
Horticultural Crops

As key players in biotic stress response of plants, jasmonic acid (JA) and its derivatives cover a specific and prominent role in pathogens-mediated signaling and hence are promising candidates for a sustainable management of phytopathogenic fungi. Recently, JA directed antimicrobial effects on plant pathogens has been suggested, supporting the theory of oxylipins as double gamers in plant-pathogen interaction. Based on these premises, six derivatives (dihydrojasmone and cis-jasmone, two thiosemicarbazonic derivatives and their corresponding complexes with copper) have been evaluated against 13 fungal species affecting various economically important herbaceous and woody crops, such as cereals, grapes and horticultural crops: Phaeoacremonium minimum, Neofusicoccum parvum, Phaeomoniella chlamydospora, Fomitiporia mediterranea, Fusarium poae, F. culmorum, F. graminearum, F. oxysporum f. sp. lactucae,F. sporotrichioides, Aspergillus flavus, Rhizoctonia solani,Sclerotinia spp. and Verticillium dahliae. The biological activity of these compounds was assessed in terms of growth inhibition and, for the two mycotoxigenic species A. flavus and F. sporotrichioides, also in terms of toxin containment. As expected, the inhibitory effect of molecules greatly varied amongst both genera and species; cis-jasmone thiosemicarbazone in particular has shown the wider range of effectiveness. However, our results show that thiosemicarbazones derivatives are more effective than the parent ketones in limiting fungal growth and mycotoxins production, supporting possible applications for the control of pathogenic fungi.

scholarly journals Calcineurin Controls Growth, Morphology, and Pathogenicity in Aspergillus fumigatus

2006 ◽  
Vol 5 (7) ◽  
pp. 1091-1103 ◽  
Author(s):  
William J. Steinbach ◽  
Robert A. Cramer ◽  
B. Zachary Perfect ◽  
Yohannes G. Asfaw ◽  
Theodor C. Sauer ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Clinical Observation ◽  
Immunocompromised Patient ◽  
Fungal Growth ◽  
Pathogenic Fungi ◽  
Wild Type ◽  
Therapeutic Approaches ◽  
Growth Morphology ◽  
Different Types ◽  
Hyphal Morphology

ABSTRACT Calcineurin is implicated in a myriad of human diseases as well as homeostasis and virulence in several major human pathogenic microorganisms. The fungus Aspergillus fumigatus is a leading cause of infectious death in the rapidly expanding immunocompromised patient population. Current antifungal treatments for invasive aspergillosis are often ineffective, and novel therapeutic approaches are urgently needed. We demonstrate that a mutant of A. fumigatus lacking the calcineurin A (cnaA) catalytic subunit exhibited defective hyphal morphology related to apical extension and polarized growth, which resulted in drastically decreased filamentation. The ΔcnaA mutant lacked the extensive lattice of invading hyphae seen with the wild-type and complemented strains. Sporulation was also affected in the ΔcnaA mutant, including morphological conidial defects with the absence of surface rodlets and the added presence of disjunctors creating long conidial chains. Infection with the ΔcnaA mutant in several distinct animal models with different types of immunosuppression and inoculum delivery led to a profound attenuation of pathogenicity compared to infection with the wild-type and complemented strains. Lung tissue from animals infected with the ΔcnaA mutant showed a complete absence of hyphae, in contrast to tissue from animals infected with the wild-type and complemented strains. Quantitative fungal burden and pulmonary infarct scoring confirmed these findings. Our results support the clinical observation that substantially decreasing fungal growth can prevent disease establishment and decrease mortality. Our findings reveal that calcineurin appears to play a globally conserved role in the virulence of several pathogenic fungi and yet plays specialized roles in each and can be an excellent target for therapeutic intervention.

scholarly journals Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1990
Author(s):  
Inmaculada Navarro-Lérida ◽  
Miguel Sánchez-Álvarez ◽  
Miguel Ángel del Pozo
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Protein Complexes ◽  
Specific Protein ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Post Translational Modification ◽  
Functional Regulation ◽  
Subcellular Compartmentalization ◽  
Cellular Compartments

Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression—a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP–GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.

Antifungal activity of chitinolytic bacteria isolated from airtight stored cereal grain

1998 ◽  
Vol 44 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Emma Frändberg ◽  
Johan Schnürer
Keyword(s):  
Streptomyces Coelicolor ◽  
Fungal Growth ◽  
Pathogenic Fungi ◽  
Dual Culture ◽  
Chitinolytic Activity ◽  
Bacterial Colony ◽  
Chitinolytic Bacteria ◽  
Cereal Grain ◽  
Antifungal Chitinase ◽  
Streptomyces Halstedii

Chitinolytic bacteria are used as biocontrol agents of plant pathogenic fungi. They might also potentially inhibit growth of molds, e.g., Aspergillus spp. and Penicillium spp., in stored plant material. We isolated chitinolytic bacteria from airtight stored cereal grain and evaluated their antifungal capacity. Between 0.01 and 0.5% of the total aerobic counts were chitinolytic bacteria. Gram-negative bacteria, mainly Pseudomonadaceae, constituted approximately 80% of the chitinolytic population. Gram-positive isolates belonged predominantly to the Corynebacterium-Arthrobacter group, Streptomyces, and Bacillus. Chitinolytic activity was evaluated using culture filtrates from chitin-grown isolates as the release of p-nitrophenol from p-nitrophenyl N,N'-diacetylchitobiose and as the formation of clearing zones on chitin agar. No correlation between chitinolytic activity and antifungal effects was found when challenging Penicillium roqueforti Dierckx with bacterial isolates on chitin agar in a dual culture bioassay. Fungal hyphae frequently grew seemingly unaffected through the bacterial colony of a high chitinase producer on colloidal chitin. Only 4% of the chitinolytic isolates had strong effects on fungal growth. Among these, Streptomyces halstedii (K122) and Streptomyces coelicolor (K139) inhibited growth of a broad range of fungi. Streptomyces halstedii affected hyphal morphology and decreased the radial growth rate of all fungi investigated. These effects were not caused by volatile metabolites, polyenes, or N-carbamoyl-D-glucosamine.Key words: antifungal, chitinase, Streptomyces halstedii, Streptomyces coelicolor.

scholarly journals Identification and characterization of a new isoform of small GTPase RhoE

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yuan Dai ◽  
Weijia Luo ◽  
Xiaojing Yue ◽  
Wencai Ma ◽  
Jing Wang ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Biological Functions ◽  
Coding Region ◽  
Alternative Translation ◽  
Rho Family ◽  
Binding Capability ◽  
Identification And Characterization

Abstract The Rho family of GTPases consists of 20 members including RhoE. Here, we discover the existence of a short isoform of RhoE designated as RhoEα, the first Rho GTPase isoform generated from alternative translation. Translation of this new isoform is initiated from an alternative start site downstream of and in-frame with the coding region of the canonical RhoE. RhoEα exhibits a similar subcellular distribution while its protein stability is higher than RhoE. RhoEα contains binding capability to RhoE effectors ROCK1, p190RhoGAP and Syx. The distinct transcriptomes of cells with the expression of RhoE and RhoEα, respectively, are demonstrated. The data propose distinctive and overlapping biological functions of RhoEα compared to RhoE. In conclusion, this study reveals a new Rho GTPase isoform generated from alternative translation. The discovery provides a new scope of understanding the versatile functions of small GTPases and underlines the complexity and diverse roles of small GTPases.

Nanofiber curvature with Rho GTPase activity increases mouse embryonic fibroblast random migration velocity

2022 ◽  
Author(s):  
Daniel T Bowers ◽  
Justin L Brown
Keyword(s):  
Stem Cell ◽  
Flat Surface ◽  
Rho Gtpase ◽  
Kinase Inhibitor ◽  
Single Cells ◽  
Stem Cell Differentiation ◽  
Migration Velocity ◽  
Embryonic Cell ◽  
Small Gtpase ◽  
Curved Surface

Abstract Mechanotransduction arises from information encoded in the shape of materials such as curvature. It induces activation of small GTPase signaling affecting cell phenotypes including differentiation. We carried out a set of preliminary experiments to test the hypothesis that curvature (1/radius) would also affect cell motility due to signal pathway crosstalk. High molecular weight poly (methyl methacrylate) straight nanofibers were electrospun with curvature ranging from 41 to 1 μm−1 and collected on a passivated glass substrate. The fiber curvature increased mouse mesenchymal stem cell aspect ratio (P < 0.02) and decreased cell area (P < 0.01). Despite little effect on some motility patterns such as polarity and persistence, we found selected fiber curvatures can increase normalized random fibroblastic mouse embryonic cell (MEF) migration velocity close to 2.5 times compared with a flat surface (P < 0.001). A maximum in the velocity curve occurred near 2.5 μm−1 and may vary with the time since initiation of attachment to the surface (range of 0–20 h). In the middle range of fiber curvatures, the relative relationship to curvature was similar regardless of treatment with Rho-kinase inhibitor (Y27632) or cdc42 inhibitor (ML141), although it was decreased on most curvatures (P < 0.05). However, below a critical curvature threshold MEFs may not be able to distinguish shallow curvature from a flat surface, while still being affected by contact guidance. The preliminary data in this manuscript suggested the large low curvature fibers were interpreted in a manner similar to a non-curved surface. Thus, curvature is a biomaterial construct design parameter that should be considered when specific biological responses are desired. Statement of integration, innovation, and insight  Replacement of damaged or diseased tissues that cannot otherwise regenerate is transforming modern medicine. However, the extent to which we can rationally design materials to affect cellular outcomes remains low. Knowing the effect of material stiffness and diameter on stem cell differentiation, we investigated cell migration and signaling on fibrous scaffolds. By investigating diameters across orders of magnitude (50–2000 nm), we identified a velocity maximum of ~800 nm. Furthermore, the results suggest large fibers may not be interpreted by single cells as a curved surface. This work presents insight into the design of constructs for engineering tissues.

scholarly journals Preliminary Study on the Activity of Phycobiliproteins against Botrytis cinerea

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 600
Author(s):  
Hillary Righini ◽  
Ornella Francioso ◽  
Michele Di Foggia ◽  
Antera Martel Quintana ◽  
Roberta Roberti
Keyword(s):  
Spore Germination ◽  
Plant Pathogens ◽  
Disease Incidence ◽  
Fungal Growth ◽  
Pathogenic Fungi ◽  
Gray Mold ◽  
Fungal Plant Pathogens ◽  
Ft Ir ◽  
Preliminary Study ◽  
Ft Raman

Phycobiliproteins (PBPs) are proteins of cyanobacteria and some algae such as rhodophytes. They have antimicrobial, antiviral, antitumor, antioxidative, and anti-inflammatory activity at the human level, but there is a lack of knowledge on their antifungal activity against plant pathogens. We studied the activity of PBPs extracted from Arthrospiraplatensis and Hydropuntiacornea against Botrytiscinerea, one of the most important worldwide plant-pathogenic fungi. PBPs were characterized by using FT-IR and FT-Raman in order to investigate their structures. Their spectra differed in the relative composition in the amide bands, which were particularly strong in A. platensis. PBP activity was tested on tomato fruits against gray mold disease, fungal growth, and spore germination at different concentrations (0.3, 0.6, 1.2, 2.4, and 4.8 mg/mL). Both PBPs reduced fruit gray mold disease. A linear dose–response relationship was observed for both PBPs against disease incidence and H. cornea against disease severity. Pathogen mycelial growth and spore germination were reduced significantly by both PBPs. In conclusion, PBPs have the potential for being also considered as natural compounds for the control of fungal plant pathogens in sustainable agriculture.

Chimaerins: GAPs that bridge diacylglycerol signalling and the small G-protein Rac

2007 ◽  
Vol 403 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Chengfeng Yang ◽  
Marcelo G. Kazanietz
Keyword(s):  
G Protein ◽  
Rho Gtpase ◽  
System Development ◽  
Tumour Progression ◽  
Biological Properties ◽  
Nervous System Development ◽  
Small Gtpase ◽  
Gtpase Activating Proteins ◽  
Tumour Promoters ◽  
The Central Nervous System

Chimaerins are the only known RhoGAPs (Rho GTPase-activating proteins) that bind phorbol ester tumour promoters and the lipid second messenger DAG (diacylglycerol), and show specific GAP activity towards the small GTPase Rac. This review summarizes our knowledge of the structure, biochemical and biological properties of chimaerins. Recent findings have established that chimaerins are regulated by tyrosine kinase and GPCRs (G-protein-coupled receptors) via PLC (phospholipase C) activation and DAG generation to promote Rac inactivation. The finding that chimaerins, along with some other proteins, are receptors for DAG changed the prevalent view that PKC (protein kinase C) isoenzymes are the only cellular molecules regulated by DAG. In addition, vigorous recent studies have begun to decipher the critical roles of chimaerins in the central nervous system, development and tumour progression.

scholarly journals Structure-guided approaches to targeting stress responses in human fungal pathogens

2020 ◽  
Vol 295 (42) ◽  
pp. 14458-14472
Author(s):  
Emmanuelle V. LeBlanc ◽  
Elizabeth J. Polvi ◽  
Amanda O. Veri ◽  
Gilbert G. Privé ◽  
Leah E. Cowen
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Small Gtpase ◽  
Ecological Niches ◽  
Attractive Alternative ◽  
Response Regulators ◽  
Fungal Virulence

Fungi inhabit extraordinarily diverse ecological niches, including the human body. Invasive fungal infections have a devastating impact on human health worldwide, killing ∼1.5 million individuals annually. The majority of these deaths are attributable to species of Candida, Cryptococcus, and Aspergillus. Treating fungal infections is challenging, in part due to the emergence of resistance to our limited arsenal of antifungal agents, necessitating the development of novel therapeutic options. Whereas conventional antifungal strategies target proteins or cellular components essential for fungal growth, an attractive alternative strategy involves targeting proteins that regulate fungal virulence or antifungal drug resistance, such as regulators of fungal stress responses. Stress response networks enable fungi to adapt, grow, and cause disease in humans and include regulators that are highly conserved across eukaryotes as well as those that are fungal-specific. This review highlights recent developments in elucidating crystal structures of fungal stress response regulators and emphasizes how this knowledge can guide the design of fungal-selective inhibitors. We focus on the progress that has been made with highly conserved regulators, including the molecular chaperone Hsp90, the protein phosphatase calcineurin, and the small GTPase Ras1, as well as with divergent stress response regulators, including the cell wall kinase Yck2 and trehalose synthases. Exploring structures of these important fungal stress regulators will accelerate the design of selective antifungals that can be deployed to combat life-threatening fungal diseases.

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