The Inhibitory Effect of Validamycin A on<i>Aspergillus flavus</i>

Plabutong, Napasawan; Ekronarongchai, Supanuch; Niwetbowornchai, Nattarika; Edwards, Steven W.; Virakul, Sita; Chiewchengchol, Direkrit; Thammahong, Arsa

doi:10.1155/2020/3972415

Cited by 15 publications

(18 citation statements)

References 69 publications

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“…Validamycin A, a well-known trehalase inhibitor, is already used in food crops to prevent fungal infections [ 91 ]. This compound showed to have weak antifungal activity against C. albicans whereas a strong effect was observed against A. flavus [ 92 , 93 ]. Based on this work, we propose to test different structural analogues of trehalose for their antifungal activity against C. glabrata .…”

Section: Discussionmentioning

confidence: 99%

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The involvement of the Candida glabrata trehalase enzymes in stress resistance and gut colonization

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…albicans whereas a strong effect was observed against A. flavus[92,93]. Based on this propose to test different structural analogues of trehalose for their antifungal activity against C. glabrata.…”

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confidence: 99%

The involvement of the Candida glabrata trehalase enzymes in stress resistance and gut colonization

et al. 2021

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“…The FICI is calculated using the sum of the fractional inhibitory concentration (FIC 1 ) of the first compound, which is MIC 1 + 2 of the combination of the first and the second compounds divided by MIC 1 of the first compound alone, and the FIC 2 of the second compound [184,185]. Synergistic, additive, indifferent, and antagonistic effects are defined by FICI ≤0.5; >0.5-1; >1-4; and > 4, respectively [184][185][186]. For the cytotoxicity effects on human epithelial cells, many in vitro colorimetric assays, including mammalian tissue culture systems and vital dyes, are used, such as Alamar blue, MTT, XTT (tetrazolium) assays [181].…”

Section: Management Of Azole-resistant Aspergillus and Novel Antifungal Candidatesmentioning

confidence: 99%

“…Validamycin A is one of the inhibitors of trehalase enzymes and was first demonstrated its strong antifungal activity against a plant fungal pathogen, Rhizoctonia solani [266][267][268][269]. Furthermore, validamycin A has antifungal activity against Candida albicans and Aspergillus flavus [186,270]. Validamycin A also possesses combinatorial effects with conventional amphotericin B against A. flavus [186].…”

Section: Management Of Azole-resistant Aspergillus and Novel Antifungal Candidatesmentioning

confidence: 99%

“…Furthermore, validamycin A has antifungal activity against Candida albicans and Aspergillus flavus [186,270]. Validamycin A also possesses combinatorial effects with conventional amphotericin B against A. flavus [186]. Nevertheless, in vivo experiments are still necessary to verify an antifungal activity of validamycin A. Additionally, the high-osmolarity glycerol (HOG)-mitogen-activated protein kinase (MAPK) signaling pathway is associated with trehalose production and stress response in A. fumigatus [271][272][273][274].…”

Section: Management Of Azole-resistant Aspergillus and Novel Antifungal Candidatesmentioning

confidence: 99%

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Aspergillus-Human Interactions: From the Environment to Clinical Significance

Thammahong¹

2022

The Genus Aspergillus - Pathogenicity, Mycotoxin Production and Industrial Applications

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Aspergillus species are ubiquitous fungi found in the environment worldwide. The most common Aspergillus species causing diseases in humans are A. fumigatus, A. flavus, A. niger, and A. terreus. However, species causing human infections are also depending on human immune status. Host immune status and previous underlying diseases are important factors leading to different clinical manifestations and different disease spectra of Aspergillus infections. The most severe form of Aspergillus infections is invasive aspergillosis in human tissue, especially invasive pulmonary aspergillosis (IPA), which has high morbidity and mortality in immunocompromised patients. ICU patients with influenza infections and COVID-19 infections are recently risk factors of invasive pulmonary aspergillosis. New diagnostic criteria include galactomannan antigen assays, nucleic acid amplification assays, and lateral flow assays for early and accurate diagnosis. Voriconazole and the newest azole, isavuconazole, are antifungals of choice in IPA. Nevertheless, azole-resistant Aspergillus strains are increasing throughout the world. The etiology and spreading of azole-resistant Aspergillus strains may originate from the widespread use of fungicides in agriculture, leading to the selective pressure of azole-resistant strains. Therefore, there is a necessity to screen Aspergillus antifungal susceptibility patterns for choosing an appropriate antifungal agent to treat these invasive infections. In addition, mutations in an ergosterol-producing enzyme, i.e., lanosterol 14-α demethylase, could lead to azole-resistant strains. As a result, the detection of these mutations would predict the resistance to azole agents. Although many novel azole agents have been developed for invasive Aspergillus infections, the rate of novel antifungal discovery is still limited. Therefore, better diagnostic criteria and extensive antifungal resistant Aspergillus screening would guide us to better manage invasive Aspergillus infections with our existing limited resources.

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Trehalase inhibition by validamycin A may be a promising target to design new fungicides and insecticides

García

Argüelles

2021

Pest Management Science

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The introduction of insecticides and fungicides in agriculture has improved crop yields and, consequently, the quality of life for many people, especially in what is widely considered as the ‘first world’. However, the indiscriminate use of dangerous chemical insecticides has led to pest resistance, human and animal poisoning and environmental pollution. Biochemical and genetic evidence concludes that the non‐reducing disaccharide trehalose plays an essential role in the pathobiology of many insects and fungi. Both organisms share identical pathway for trehalose biosynthesis (the TPS/TPP pathway), while a high degree of homology in their trehalose hydrolysis capacity (trehalase activities) has also been demonstrated. In the search for new, effective and environmentally sustainable compounds, a set of trehalase inhibitors has emerged as a potentially interesting antifungal and insecticidal target. In particular, the trehalose analogue, Validamycin A, which has a strong inhibitory effect on several trehalases, has been successfully introduced for the treatment of various diseases caused by insects and fungi. Herein, we review the main features of the specific interaction between Validamycin A and trehalase as well as the expected advantages of the applications based on trehalase inhibition as insecticides and fungicides. © 2021 Society of Chemical Industry.

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The Inhibitory Effect of Validamycin A onAspergillus flavus

Cited by 15 publications

References 69 publications

The involvement of the Candida glabrata trehalase enzymes in stress resistance and gut colonization

The involvement of the Candida glabrata trehalase enzymes in stress resistance and gut colonization

Aspergillus-Human Interactions: From the Environment to Clinical Significance

Trehalase inhibition by validamycin A may be a promising target to design new fungicides and insecticides

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