Document Detail


Small-molecule suppressors of Candida albicans biofilm formation synergistically enhance the antifungal activity of amphotericin B against clinical Candida isolates.
MedLine Citation:
PMID:  23387427     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A new class of fungal biofilm inhibitors represented by shearinines D (3) and E (4) were obtained from a Penicillium sp. isolate. The inhibitory activities of 3 and 4 were characterized using a new imaging flow-cytometer technique, which enabled the rapid phenotypic analysis of Candida albicans cell types (budding yeast cells, germ tube cells, pseudohyphae, and hyphae) in biofilm populations. The results were confirmed by experimental data obtained from three-dimensional confocal laser scanning microscopy and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assays. These data indicate that 3 and 4 inhibited C. albicans biofilm formation by blocking the outgrowth of hyphae at a relatively late stage of biofilm development (IC50 = 8.5 and 7.6 μM, respectively). However, 3 and 4 demonstrated comparatively weak activity at disrupting existing biofilms. Compounds 3 and 4 also exhibited synergistic activities with amphotericin B against C. albicans and other clinical Candida isolates by enhancing the potency of amphotericin B up to 8-fold against cells in both developing and established biofilms. These data suggest that the Candida biofilm disruption and amphotericin B potentiating effects of 3 and 4 could be mediated through multiple biological targets. The shearinines are good tools for testing the potential advantages of using adjunctive therapies in combination with antifungals.
Authors:
Jianlan You; Lin Du; Jarrod B King; Brian E Hall; Robert H Cichewicz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-14
Journal Detail:
Title:  ACS chemical biology     Volume:  8     ISSN:  1554-8937     ISO Abbreviation:  ACS Chem. Biol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-10-17     Revised Date:  2014-04-22    
Medline Journal Info:
Nlm Unique ID:  101282906     Medline TA:  ACS Chem Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  840-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amphotericin B / pharmacology*
Antifungal Agents / pharmacology*
Biofilms*
Candida albicans / drug effects*,  physiology
Drug Synergism
Indole Alkaloids / pharmacology*
Microbial Sensitivity Tests
Microscopy, Confocal
Small Molecule Libraries*
Grant Support
ID/Acronym/Agency:
R01 AI085161/AI/NIAID NIH HHS; R01AI085161/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antifungal Agents; 0/Indole Alkaloids; 0/Small Molecule Libraries; 7XU7A7DROE/Amphotericin B
Comments/Corrections

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