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1.
J Appl Microbiol ; 127(1): 68-77, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31013388

ABSTRACT

AIMS: Candida albicans biofilms are commonly associated with severe oral infections. We previously discovered that a crude extract from the Solidago virgaurea plant (SV extract) was a potent inhibitor of C. albicans biofilm formation. Here, we further investigate the mechanisms underlying C. albicans biofilm inhibition by the SV extract. METHODS AND RESULTS: The SV extract was shown to inhibit laboratory and clinical C. albicans isolates adherence and hyphal transition on inert support and epithelial human cells, without affecting viability and growth of planktonic yeasts. Interestingly, RT-PCR-based experiments demonstrated that some key genes involved in adhesion and hyphal morphological switch (e.g. Hwp1p, Ece1p, Als3p) were strongly down-regulated by the SV extract. Moreover, antimicrobial synergy testing (checkerboard assay) demonstrated that antifungal effects of miconazole, nystatin or a common antiseptic mouthwash were synergistically improved when used in combination with the SV extract. CONCLUSIONS: The SV extract prevents C. albicans biofilm formation through direct inhibition of key adherence and hyphae-associated genes. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofilm is considered as a key virulence factor of C. albicans infection. Our discovery of an inhibitor specifically acting on genes involved in biofilm formation paves the way for the future development of a new class of antifungal product.


Subject(s)
Biofilms/drug effects , Candida albicans/drug effects , Candida albicans/genetics , Plant Extracts/pharmacology , Solidago/chemistry , Antifungal Agents/pharmacology , Cells, Cultured , Drug Synergism , Gene Expression/drug effects , Humans , Hyphae/drug effects , Miconazole/pharmacology , Nystatin/pharmacology , Plant Extracts/chemistry
2.
Rapid Commun Mass Spectrom ; 25(15): 2141-8, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21710593

ABSTRACT

We have investigated the synthesis of a new antifungal agent with a polymerisable moiety for the prevention of denture stomatisis. Nystatin (antifungal polyene) is modified in one step by reaction with isocyanatoethylmethacrylate to afford a new polymerisable antifungal agent in good yield (90%). In order to prove the monografting of the acrylate derivative and to localise the new group in the skeleton of the molecule, a rapid and efficient analytical method involving electrospray ionisation mass spectrometry (ESI-MS) was developed for the study. In view of the structures of such antifungal agents, their complexation with metal cations was investigated by Coordination-Ion Spray Mass Spectrometry (CIS-MS). This mass spectrometry study covers two aspects: improving the MS signal to overcome the low ionisation efficiency in ESI-MS and exploring the complexation behaviour of the induced structure to optimise the antifungal properties.


Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/chemical synthesis , Isocyanates/chemistry , Methacrylates/chemistry , Nystatin/chemistry , Nystatin/chemical synthesis , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, High Pressure Liquid , Copper/chemistry , Nitrates/chemistry , Polymerization , Zinc Compounds/chemistry
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