Fungal cell membrane-promising drug target for antifungal therapy

Cai

et al. 2019

Plants

Pinocembroside (PiCB) isolated from Ficus hirta Vahl. fruit was studied herein with the aim to find the potential mechanism for significant inhibition of growth of Penicillium digitatum, a causative pathogen of citrus green mold disease. PiCB substantially inhibited mycelial growth of P. digitatum, with the observed half maximal effective concentration (EC 50 ), minimum inhibitory concentration (MIC), and minimum fungicidal concentration (MFC) of 120.3, 200, and 400 mg/L, respectively. Moreover, PiCB altered hyphal morphology and cellular morphology by breaking and shrinking of mycelia, decomposing cell walls, cytoplasmic inclusions. In addition to, a non-targeted metabolomics analysis by UHPLC-Q-TOF/MS was also performed, which revealed that PiCB treatment notably disrupted the metabolisms of amino acids, lipids, fatty acids, TCA, and ribonucleic acids, thereby contributing to membrane peroxidation. Current findings provide a new perception into the antifungal mechanism of PiCB treatment in inhibiting P. digitatum growth through membrane peroxidation.

Section: Effects Of Picb On the Metabolic Profiles Of P Digitatum Mymentioning

confidence: 99%

UHPLC-Q-TOF/MS-Based Metabolomics Approach Reveals the Antifungal Potential of Pinocembroside against Citrus Green Mold Phytopathogen

Cai

et al. 2019

Plants

“…In addition, it is essential to ensure the activity of membrane-bound enzymes. Owing to its essential role in fungal cells, many fungicides act by inhibiting its biosynthesis or binding it in the cell membrane (Sant et al, 2016). Phenols and aldehydes possess a sufficient hydrophobicity to pass the double phospholipid bilayer, to interact with ergosterol in the cell membrane, or to enter the nucleus and act as regulators for its biosynthesis.…”

Section: Effects On Cell Wall and Cell Membranementioning

confidence: 99%

Plant Bioactive Compounds in Pre- and Postharvest Management for Aflatoxins Reduction

et al. 2020

Aflatoxins (AFs) are secondary metabolites produced by Aspergillus spp., known for their hepatotoxic, carcinogenic, and mutagenic activity in humans and animals. AF contamination of staple food commodities is a global concern due to their toxicity and the economic losses they cause. Different strategies have been applied to reduce fungal contamination and AF production. Among them, the use of natural, plant-derived compounds is emerging as a promising strategy to be applied to control both Aspergillus spoilage and AF contamination in food and feed commodities in an integrated pre-and postharvest management. In particular, phenols, aldehydes, and terpenes extracted from medicinal plants, spices, or fruits have been studied in depth. They can be easily extracted, they are generally recognized as safe (GRAS), and they are foodgrade and act through a wide variety of mechanisms. This review investigated the main compounds with antifungal and anti-aflatoxigenic activity, also elucidating their physiological role and the different modes of action and synergies. Plant bioactive compounds are shown to be effective in modulating Aspergillus spp. contamination and AF production both in vitro and in vivo. Therefore, their application in pre-and postharvest management could represent an important tool to control aflatoxigenic fungi and to reduce AF contamination.

“…Fungal plasmalemma is a universal target explored extensively for the development of antifungal agents. This strategy has been proved fruitful by the pronounced success of antifungal drugs such as azoles and polyenes [99]. Consistent with the down regulation of most of membrane phospholipid synthesis was the overall trend of ergosterol biosynthesis of the membrane.…”

Section: Discussionmentioning

confidence: 90%

Cuminal Inhibits Trichothecium roseum Growth by Triggering Cell Starvation: Transcriptome and Proteome Analysis

Zhang

et al. 2020

Microorganisms

Trichothecium roseum is a harmful postharvest fungus causing serious damage, together with the secretion of insidious mycotoxins, on apples, melons, and other important fruits. Cuminal, a predominant component of Cuminum cyminum essential oil has proven to successfully inhibit the growth of T. roseum in vitro and in vivo. Electron microscopic observations revealed cuminal exposure impaired the fungal morphology and ultrastructure, particularly the plasmalemma. Transcriptome and proteome analysis was used to investigate the responses of T. roseum to exposure of cuminal. In total, 2825 differentially expressed transcripts (1516 up and 1309 down) and 225 differentially expressed proteins (90 up and 135 down) were determined. Overall, notable parts of these differentially expressed genes functionally belong to subcellular localities of the membrane system and cytosol, along with ribosomes, mitochondria and peroxisomes. According to the localization analysis and the biological annotation of these genes, carbohydrate and lipids metabolism, redox homeostasis, and asexual reproduction were among the most enriched gene ontology (GO) terms. Biological pathway enrichment analysis showed that lipids and amino acid degradation, ATP-binding cassette transporters, membrane reconstitution, mRNA surveillance pathway and peroxisome were elevated, whereas secondary metabolite biosynthesis, cell cycle, and glycolysis/gluconeogenesis were down regulated. Further integrated omics analysis showed that cuminal exposure first impaired the polarity of the cytoplasmic membrane and then triggered the reconstitution and dysfunction of fungal plasmalemma, resulting in handicapped nutrient procurement of the cells. Consequently, fungal cells showed starvation stress with limited carbohydrate metabolism, resulting a metabolic shift to catabolism of the cell's own components in response to the stress. Additionally, these predicaments brought about oxidative stress, which, in collaboration with the starvation, damaged certain critical organelles such as mitochondria. Such degeneration, accompanied by energy deficiency, suppressed the biosynthesis of essential proteins and inhibited fungal growth.fungicides to be used for postharvest treatment, reduced efficacy due to the emergence of pathogen resistance to these chemicals, and the growing public concerns over chemical residues in food and the environment have necessitated the seeking of alternative solutions to control the fungal spoilage and to guarantee food safety and consumer health [8].Essential oils (EOs), generally recognized as safe by the US Food and Drug Administration [9], are natural substances with established antimicrobial activities [10,11] and are a candidate instrument for controlling postharvest disease [12,13]. Nonetheless, this candidacy is compromised by the expensiveness of these natural substances due to their generally low yields. However, exploring their mode of actions is valuable to the development of novel alternatives.The multicomponent EOs attribute their mode of act...