The inhibition of trans-cinnamaldehyde on the virulence of Candida albicans via enhancing farnesol secretion with low potential for the development of resistance

Li, Ying; Shan, Mingzhu; Yan, Mengmeng; Xu, Ye; Wang, Yuechen; Chen, Ying; Gu, Bing; Li, Hongchun; Zhu, Zhaohui

doi:10.1016/j.bbrc.2019.05.165

Cited by 15 publications

(14 citation statements)

References 23 publications

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“…The phosphatase Dpp3 is a critical protein for farnesol biosynthesis (Ying et al . 2019) and Dpp3 expression was strongly inhibited by berberine and amphotericin B, thus breaking farnesol synthesis and subsequently hindering the crosstalk between C. albicans and S. aureus .…”

Section: Discussionmentioning

confidence: 99%

Enhanced in vitro antimicrobial activity of amphotericin B with berberine against dual‐species biofilms of Candida albicans and Staphylococcus aureus

Gao

Zhang

2020

J Appl Microbiol

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Aims Multi‐species biofilms formed by fungi and bacteria are clinically common and confer the commensal micro‐organisms with protection against antimicrobial therapies. Previously, the plant alkaloid berberine was reported to show antimicrobial efficacy to eliminate bacterial and fungal biofilms. In this study, the combination of berberine and amphotericin B, an antifungal agent, was evaluated against dual‐species Candida albicans/Staphylococcus aureus biofilms. Methods and Results Combinatorial treatment by berberine and amphotericin B significantly reduced the biomass and viability of residing species in biofilms. Moreover, morphological examination revealed hyphal filamentation of C. albicans and coadhesion between C. albicans/S. aureus were considerably impaired by the treatment. These effects coincided with the reduced expression of cell surface components and quorum‐sensing‐related genes in both C. albicans and S. aureus. Additionally, in C. albicans, the core transcription factors for controlling biofilm formation together with a crucial component of dual‐species biofilms were also downregulated. Conclusions These results demonstrated synergistic effects of berberine and amphotericin B against C. albicans/S. aureus dual‐species biofilms. Significance and Impact of the Study This study confirms the potential of berberine and amphotericin B for treating the C. albicans/S. aureus biofilms related infections and reveals molecular basis for the efficacy of combinatorial treatment.

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Section: Discussionmentioning

confidence: 99%

Enhanced in vitro antimicrobial activity of amphotericin B with berberine against dual‐species biofilms of Candida albicans and Staphylococcus aureus

Gao

Zhang

2020

J Appl Microbiol

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“…The MIC values of KPA against various genotypes C. albicans were detected by the broth microdilution method as previously described (M27-E4) (Li et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

“…The effect of KPA on C. albicans adhesion was evaluated by the XTT reduction assay as previously described (Li et al, 2019), using AMB (2 μg/mL) as positive control. After culture and wash, treated YEM30 cells were observed directly under a microscope (Olympus IX71, Olympus, Tokyo, Japan) in the bright field mode.…”

Section: Methodsmentioning

confidence: 99%

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Anticandidal Activity of Kalopanaxsaponin A: Effect on Proliferation, Cell Morphology, and Key Virulence Attributes of Candida albicans

Shan

Yan

et al. 2019

Front. Microbiol.

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BackgroundThe pathogenicity of Candida albicans is attributed to various virulence factors including adhesion to the surface of epithelial cells or mucosa, germ tube formation, hyphal morphogenesis, development of drug resistant biofilms, and so on. The objective of this study was to investigate the effects of Kalopanaxsaponin A (KPA) on the virulence of C. albicans.MethodsThe effect of KPA on the virulence of C. albicans was characterized by an XTT reduction assay and fluorescent microscopic observation. The action mechanism was further explored using GC/MS system and BioTek Synergy2 spectrofluorophotometry. The cytotoxicity and therapeutic effect of KPA were evaluated by the Caenorhabditis elegans-C. albicans infection model in vivo.ResultsThe minimum inhibitory concentration (MIC) of KPA was 8∼16 μg/mL for various genotypes of C. albicans. The compound was identified as having remarkable effect on the adhesion, morphological transition and biofilm formation of C. albicans. The results of fluorescent microscopy and GC/MS system suggested that KPA could promote the secretion of farnesol by regulating the expression of Dpp3 and decrease the intracellular cAMP level, which together inhibited morphological transition and biofilm formation. Notably, KPA showed low toxicity in vivo and a low possibility of developing resistance.ConclusionOur results demonstrated that KPA had remarkable efficacy against C. albicans pathogenicity, suggesting that it could be a potential option for the clinical treatment of candidiasis.

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“…Trans -cinnamaldehyde is a yellow oil with a sweet taste and the odor of cinnamon and is primarily used as a flavoring agent as well as used in medical products, cosmetics, and perfumes ( Brackman et al, 2008 ; Doyle and Stephens, 2019 ). Furthermore, trans -cinnamaldehyde has also been documented to have antibiofilm and anti-quorum sensing activity against Vibrio harveyi ( Niu et al, 2006 ), enterohemorrhagic and uropathogenic Escherichia coli strains ( Kim et al, 2015 ; Kot et al, 2015 ), methicillin-resistant Staphylococcus aureus strains ( Kavanaugh and Ribbeck, 2012 ; Kot et al, 2018 ), Pseudomonas aeruginosa ( Kavanaugh and Ribbeck, 2012 ), Pseudomonas fluorescens ( Li et al, 2018 ), Cronobacter sakazakii ( Amalaradjou and Venkitanarayanan, 2011 ), Streptococcus pyogenes ( Beema Shafreen et al, 2014 ), Salmonella typhimurium ( Silva et al, 2018 ), and against the pathogenic fungus C. albicans ( Ying et al, 2019 ; Miranda-Cadena et al, 2021 ). In addition, cinnamaldehyde analogs are known to have an array of bioactivities, which include antibacterial ( Firmino et al, 2018 ), antifungal ( Da Nobrega Alves et al, 2020 ), antiviral ( Hayashi et al, 2007 ), antiulcer ( Tabak et al, 1999 ), antioxidant ( Mathew and Abraham, 2006 ), antidiabetic ( Im et al, 2014 ), anti-inflammatory ( Srisook et al, 2019 ), anticancer ( Fang et al, 2004 ) activities and insecticidal ( Cheng et al, 2009 ; Lu et al, 2020 ), larvicidal ( Cheng et al, 2004 ), nematicidal ( Ferreira Barros et al, 2021 ), and anthelmintic ( Williams et al, 2015 ) effects.…”

Section: Introductionmentioning

confidence: 99%

Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents

et al. 2022

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Cinnamaldehyde has a broad range of biological activities, which include antibiofilm and anthelmintic activities. The ever-growing problem of drug resistance and limited treatment options have created an urgent demand for natural molecules with antibiofilm and anthelmintic properties. Hence, we hypothesized that molecules with a scaffold structurally similar to that of cinnamaldehyde might act as dual inhibitors against fungal biofilms and helminths. In this regard, eleven cinnamaldehyde analogs were tested to determine their effects on fungal Candida albicans biofilm and nematode Caenorhabditis elegans. α-Methyl and trans-4-methyl cinnamaldehydes efficiently inhibited C. albicans biofilm formation (>90% inhibition at 50 μg/mL) with minimum inhibitory concentrations (MICs) of ≥ 200 μg/mL and 4-bromo and 4-chloro cinnamaldehydes exhibited anthelmintic property at 20 μg/mL against C. elegans. α-Methyl and trans-4-methyl cinnamaldehydes inhibited hyphal growth and cell aggregation. Scanning electron microscopy was employed to determine the surface architecture of C. albicans biofilm and cuticle of C. elegans, and confocal laser scanning microscopy was used to determine biofilm characteristics. The perturbation in gene expression of C. albicans was investigated using qRT-PCR analysis and α-methyl and trans-4-methyl cinnamaldehydes exhibited down-regulation of ECE1, IFD6, RBT5, UCF1, and UME6 and up-regulation of CHT4 and YWP1. Additionally, molecular interaction of these two molecules with UCF1 and YWP1 were revealed by molecular docking simulation. Our observations collectively suggest α-methyl and trans-4-methyl cinnamaldehydes are potent biofilm inhibitors and that 4-bromo and 4-chloro cinnamaldehydes are anthelmintic agents. Efforts are required to determine the range of potential therapeutic applications of cinnamaldehyde analogs.

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The inhibition of trans-cinnamaldehyde on the virulence of Candida albicans via enhancing farnesol secretion with low potential for the development of resistance

Cited by 15 publications

References 23 publications

Enhanced in vitro antimicrobial activity of amphotericin B with berberine against dual‐species biofilms of Candida albicans and Staphylococcus aureus

Enhanced in vitro antimicrobial activity of amphotericin B with berberine against dual‐species biofilms of Candida albicans and Staphylococcus aureus

Anticandidal Activity of Kalopanaxsaponin A: Effect on Proliferation, Cell Morphology, and Key Virulence Attributes of Candida albicans

Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents

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