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Efficacy of 7-benzyloxyindole and other halogenated indoles to inhibit Candida albicans biofilm and hyphal formation.

ABSTRACT: Certain pathogenic bacteria and yeast form biofilms on biotic and abiotic surfaces including medical devices and implants. Hence, the development of antibiofilm coating materials becomes relevant. The virulence of those colonizing pathogens can be reduced by inhibiting biofilm formation rather than killing pathogens using excessive amounts of antimicrobials, which is touted as one of the main reasons for the development of drug resistance. Candida albicans is an opportunistic fungal pathogen, and the transition of yeast cells to hyphal cells is believed to be a crucial virulence factor. Previous studies have shown that indole and its derivatives possess antivirulence properties against various bacterial pathogens. In this study, we used various indole derivatives to investigate biofilm-inhibiting activity against C. albicans. Our study revealed that 7-benzyloxyindole, 4-fluoroindole and 5-iodoindole effectively inhibited biofilm formation compared to the antifungal agent fluconazole. Particularly, 7-benzyloxyindole at 0.02 mM (4.5 ?g ml-1 ) significantly reduced C. albicans biofilm formation, but had no effect on planktonic cells, and this finding was confirmed by a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay and three-dimensional confocal laser scanning microscopy. Scanning electron microscopy analyses revealed that 7-benzyloxyindole effectively inhibited hyphal formation, which explains biofilm inhibition. Transcriptomic analysis showed that 7-benzyloxyindole downregulated the expressions of several hypha/biofilm-related genes (ALS3, ECE1, HWP1 and RBT1). A C. albicans-infected Caenorhabditis elegans model system was used to confirm the antivirulence efficacy of 7-benzyloxyindole.

SUBMITTER: Manoharan RK

PROVIDER: S-EPMC6196399 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Efficacy of 7-benzyloxyindole and other halogenated indoles to inhibit Candida albicans biofilm and hyphal formation.

Manoharan Ranjith Kumar RK Lee Jin-Hyung JH Lee Jintae J

Microbial biotechnology 20180415 6

Certain pathogenic bacteria and yeast form biofilms on biotic and abiotic surfaces including medical devices and implants. Hence, the development of antibiofilm coating materials becomes relevant. The virulence of those colonizing pathogens can be reduced by inhibiting biofilm formation rather than killing pathogens using excessive amounts of antimicrobials, which is touted as one of the main reasons for the development of drug resistance. Candida albicans is an opportunistic fungal pathogen, an ...[more]

PMID: 29656577

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Project description:Candida albicans (C. albicans) is the most prevalent opportunistic human pathogenic fungus and can cause mucosal membrane infections and invade the blood. In the oral cavity, it can ferment dietary sugars, produce organic acids and therefore has a role in caries development. In this study, we examined whether the polyphenol rich extractions Polyphenon from green tea (PPFGT) and Padma Hepaten (PH) can inhibit the caries-inducing properties of C. albicans. Biofilms of C. albicans were grown in the presence of PPFGT and PH. Formation of biofilms was tested spectrophotometrically after crystal violet staining. Exopolysaccharides (EPS) secretion was quantified using confocal scanning laser microscopy (CSLM). Treated C. albicans morphology was demonstrated using scanning electron microscopy (SEM). Expression of virulence-related genes was tested using qRT-PCR. Development of biofilm was also tested on an orthodontic surface (Essix) to assess biofilm inhibition ability on such appliances. Both PPFGT and PH dose-dependently inhibited biofilm formation, with no inhibition on planktonic growth. The strongest inhibition was obtained using the combination of the substances. Crystal violet staining showed a significant reduction of 45% in biofilm formation using a concentration of 2.5mg/ml PPFGT and 0.16mg/ml PH. A concentration of 1.25?mg/ml PPFGT and 0.16?mg/ml PH inhibited candidal growth by 88% and EPS secretion by 74% according to CSLM. A reduction in biofilm formation and in the transition from yeast to hyphal morphotype was observed using SEM. A strong reduction was found in the expression of hwp1, eap1, and als3 virulence associated genes. These results demonstrate the inhibitory effect of natural PPFGT polyphenolic extraction on C. albicans biofilm formation and EPS secretion, alone and together with PH. In an era of increased drug resistance, the use of phytomedicine to constrain biofilm development, without killing host cells, may pave the way to a novel therapeutic concept, especially in children as orthodontic patients.

Dataset Information

Efficacy of 7-benzyloxyindole and other halogenated indoles to inhibit Candida albicans biofilm and hyphal formation.

Publications

Efficacy of 7-benzyloxyindole and other halogenated indoles to inhibit Candida albicans biofilm and hyphal formation.

Similar Datasets

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