Short-Term Antifungal Treatments of Caprylic Acid with Carvacrol or Thymol Induce Synergistic 6-Log Reduction of Pathogenic Candida albicans by Cell Membrane Disruption and Efflux Pump Inhibition

Bae, Yoon Seol; Rhee, Min Suk

doi:10.33594/000000139

Cited by 23 publications

(8 citation statements)

References 51 publications

(68 reference statements)

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“…Interestingly, in vitro analysis of fungal membrane fluidity upon treatment with CAP suggested large scale decrease in the bilayer order which was not seen upon exposure to LRA. This observation of fungal membrane perturbation by CAP aligns with existing literature reports of membrane damage caused by CAP in C. albicans and S. cerevisiae (Liu et al, 2013;Bae and Rhee, 2019). Further, our in vitro time kill assays and electron microscopy data show CAP and 2 http://www.who.int/mediacentre/factsheets/fs194/en/ its ester derivative, propylene glycol monocaprylate (PGMC), to have potent membrane disruptive actions against various fungal pathogens.…”

Section: Introductionsupporting

confidence: 89%

Mechanistic Insight Into the Antifungal Effects of a Fatty Acid Derivative Against Drug-Resistant Fungal Infections

et al. 2020

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The prevalence of drug-resistant pathogenic fungi is a major global health challenge. There is an urgent need for novel drugs that can exert a potent antifungal activity and overcome resistance. Newly discovered anti-fungal properties of existing compounds can potentially offer a rapid solution to address this persistent threat. We rationalized that structures which disrupt the fungal cell membrane could address the above unmet need. As fatty acids underpin the formation and stability of cell membranes, we used computational simulations to evaluate the interactions between selected short chain fatty acids and a model cell membrane. Here, we report that caprylic acid could penetrate and perturb the membrane in silico. Based on the in silico findings, we identified a derivative of this fatty acid that disrupts fungal membranes as detected using steady-state fluorescence anisotropy. We show that this fatty acid derivative is potent against a variety of fungal pathogens like Candida and Trichophyton. We further demonstrated the ability of this fatty acid derivative to potentiate some azoles in vitro and enhance the efficacy of antifungal formulations in vivo. Our data suggests the emergence of a novel therapy for effective disease management and overcoming anti-fungal drug resistance.

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Section: Introductionsupporting

confidence: 89%

Mechanistic Insight Into the Antifungal Effects of a Fatty Acid Derivative Against Drug-Resistant Fungal Infections

et al. 2020

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“…This result suggests that our peptide could indirectly affect membrane integrity. It is widely reported that fatty acids, depending on their properties (i.e., chain length, degree, position and orientation of unsaturation) as well as those of their target, are able to interact with cell membranes ( Bhattacharyya et al, 2020 ), provoking structural perturbation and the consequent loss of functionality ( Liu et al, 2013 ; Bae and Rhee, 2019 ). The upregulation of genes encoding fatty acid synthases in treated P. oryzae cells correlates with membrane rearrangement of to form vesicles and autophagic bodies ( Polyansky et al, 2020 ), observed through the TEM analysis.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic and Ultrastructural Analyses of Pyricularia Oryzae Treated With Fungicidal Peptaibol Analogs of Trichoderma Trichogin

et al. 2021

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Eco-friendly analogs of Trichogin GA IV, a short peptaibol produced by Trichoderma longibrachiatum, were assayed against Pyricularia oryzae, the causal agent of rice blast disease. In vitro and in vivo screenings allowed us to identify six peptides able to reduce by about 70% rice blast symptoms. One of the most active peptides was selected for further studies. Microscopy analyses highlighted that the treated fungal spores could not germinate and the fluorescein-labeled peptide localized on the spore cell wall and in the agglutinated cytoplasm. Transcriptomic analysis was carried out on P. oryzae mycelium 3 h after the peptide treatment. We identified 1,410 differentially expressed genes, two-thirds of which upregulated. Among these, we found genes involved in oxidative stress response, detoxification, autophagic cell death, cell wall biogenesis, degradation and remodeling, melanin and fatty acid biosynthesis, and ion efflux transporters. Molecular data suggest that the trichogin analogs cause cell wall and membrane damages and induce autophagic cell death. Ultrastructure observations on treated conidia and hyphae confirmed the molecular data. In conclusion, these selected peptides seem to be promising alternative molecules for developing effective bio-pesticides able to control rice blast disease.

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“…TEM images following singular treatments with CAR and NaCl showed disrupted membranes with damage to the cytoplasm and a decrease in the density of the cytoplasm, respectively. However, most of those cells maintained their morphological characteristics despite the slight increases in damaged cells observed by flow cytometry, highlighting that membrane damage caused by singular treatments using low quantity of EOs with short-term exposure was reversible and insufficient for affecting viability [9]. The combined treatments showed evidence of irreversible damage or cell death by both analytical methods (flow cytometry and TEM) based on the increases in the population of damaged/dead cells and highly deformed membranes allowing the leakage of cellular material from the cells, respectively.…”

Section: Antimicrobial Mechanisms Of Eo Complex Against Pathogensmentioning

confidence: 94%

“…In addition, EOs have been shown to have antibacterial [6,7], antifungal [8,9], antiviral [10], antimycotic [11], antiparasitic [12], and insecticidal activities [13]. Along with the drastically increased interests from consumers in the use of natural agents for the development of antimicrobial products (e.g., disinfectants, preservatives, and food additives), natural compounds including EOs are preferred and the role of EOs as alternatives to synthetic chemical agents has been emphasized [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Application of Antibacterial Complexes Using Essential Oils

Cho

Park

et al. 2020

Molecules

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Although antibacterial spectrum of essential oils (EOs) has been analyzed along with consumers’ needs on natural biocides, singular treatments generally require high concentration of EOs and long-term exposures to eliminate target bacteria. To overcome these limitations, antibacterial complex has been developed and this review analyzed previous reports regarding the combined antibacterial effects of EOs. Since unexpectable combined effects (synergism or antagonism) can be derived from the treatment of antibacterial complex, synergistic and antagonistic combinations have been identified to improve the treatment efficiency and to avoid the overestimation of bactericidal efficacy, respectively. Although antibacterial mechanism of EOs is not yet clearly revealed, mode of action regarding synergistic effects especially for the elimination of pathogens by using low quantity of EOs with short-term exposure was reported. Whereas comprehensive analysis on previous literatures for EO-based disinfectant products implies that the composition of constituents in antibacterial complexes is variable and thus analyzing the impact of constituting substances (e.g., surfactant, emulsifier) on antibacterial effects is further needed. This review provides practical information regarding advances in the EO-based combined treatment technologies and highlights the importance of following researches on the interaction of constituents in antibacterial complex to clarify the mechanisms of antibacterial synergism and/or antagonism.

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Short-Term Antifungal Treatments of Caprylic Acid with Carvacrol or Thymol Induce Synergistic 6-Log Reduction of Pathogenic Candida albicans by Cell Membrane Disruption and Efflux Pump Inhibition

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 23 publications

References 51 publications

Mechanistic Insight Into the Antifungal Effects of a Fatty Acid Derivative Against Drug-Resistant Fungal Infections

Mechanistic Insight Into the Antifungal Effects of a Fatty Acid Derivative Against Drug-Resistant Fungal Infections

Transcriptomic and Ultrastructural Analyses of Pyricularia Oryzae Treated With Fungicidal Peptaibol Analogs of Trichoderma Trichogin

Recent Advances in the Application of Antibacterial Complexes Using Essential Oils

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