Role of Fks1p and matrix glucan on C. albicans biofilm resistance to an echinocandin, pyrimidine, and polyene

Department of Medicine, University of Wisconsin, 600 Highland Ave., H4/572 Clinical Sciences Center, Madison, WI 53792, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.45). 08/2010; 54(8):3505-8. DOI: 10.1128/AAC.00227-10
Source: PubMed

ABSTRACT Candida infections frequently involve drug-resistant biofilm growth on device surfaces. Glucan synthase gene FKS1 has been linked to triazole resistance in Candida biofilms. We tested the impact of FKS1 modulation on susceptibility to additional antifungal classes. Reduction of FKS1 expression rendered biofilms more susceptible to amphotericin B, anidulafungin, and flucytosine. Increased resistance to anidulafungin and amphotericin B was observed for biofilms overexpressing FKS1. These findings suggest that Candida biofilm glucan sequestration is a multidrug resistance mechanism.

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Available from: Karen Marchillo, Jan 15, 2014
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    • " glabrata , C . parapsilosis , C . tropicalis , and C . dubliniensis ( Silva et al . 2009 ) . A key biofilm constituent is b - 1 , 3 - glucan , which is produced by glucan syn - thase . Downstream components of the yeast PKC pathway , including Smi1 , Rlm1 , Rho1 , and Fsk1 , regulate b - 1 , 3 - glucan biosynthesis and biofilm matrix production ( Nett et al . 2010a , b , 2011 ; Desai et al . 2013 ) . Other cellular proteins , such as the transcription factor Zap1 , alcohol dehydrogenases Adh5 , Csh1 , and Ifd6 , as well as glucoamylases , CaGca1 and CaGca2 , also affect matrix production and resistance pheno - types ( Nobile et al . 2009 ) ."
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    • "Firstly, the gene FKS1, encoding a b-1,3-glucan synthase which is the target for the echinocandin class of antifungals, was shown to be necessary for resistance, since viability of cells in a biofilm produced by a heterozygous deletion mutant which showed a 30 % reduction in b-1,3-glucans content, was reduced with 80 % after 48 h of treatment with 250 lg/ml fluconazole . A similar effect was not observed in planktonic cells (Nett et al. 2010). Furthermore, genes involved in the protein kinase C cell-wall integrity pathway, which controls cell-wall glucan content in response to stress, namely SMI1 and RLM1, were shown to be essential for C. albicans matrix and cell-wall b-1,3-glucan content (Nett et al. 2011). "
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