Significant differences in the cell-wall mannans from three Candida glabrata strains correlate with antifungal drug sensitivity

Department of Infection and Host Defense, Tohoku Pharmaceutical University, Aoba-ku, Sendai, Japan.
FEBS Journal (Impact Factor: 4). 03/2012; 279(10):1844-56. DOI: 10.1111/j.1742-4658.2012.08564.x
Source: PubMed


Candida glabrata is often the second or third most common cause of candidiasis after Candida albicans. C. glabrata infections are difficult to treat, often resistant to many azole antifungal agents and are associated with a high mortality rate in compromised patients. We determined the antigenic structure of the cell-wall mannoproteins from three C. glabrata strains, NBRC 0005, NBRC 0622 and NBRC 103857. (1)H NMR and methylation analyses of the acetolysis products of these mannoproteins showed a significant difference in the amount of the β-1,2-linked mannose residue and side-chain structure. The C. glabrata NBRC 103857 strain contained up to the triose side chains and the nonreducing terminal of the triose was predominantly the β-1,2-linked mannose residue. By contrast, the mannans of the two former strains possessed up to the tetraose side chains and the amount of the β-1,2-linked mannose residue was very low. Larger oligosaccharides than tetraose in the acetolysis products of these mannans were identified as incomplete cleavage fragments by analyzing methylation, (1)H NMR spectra and the α1-2,3 mannosidase degradation reaction. Resistance to the antifungal drugs itraconazole and micafungin was significantly different in these strains. Interestingly, the NBRC 103857 strain, which involved a large amount of the β-1,2-linked mannose residues, exhibited significant sensitivity to these antifungal drugs.

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    • "It is considered innately resistant to the most common antifungal group, the azoles [3]. The yeast cell wall mannoprotein architecture influences antifungal susceptibility [4]. "
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    • "Finally, Takahashi and colleagues reported that acquired triazole and echinocandin resistance in C. glabrata was associated with significant changes in the antigenic cell wall mannoprotein structure of C. glabrata.53 Specifically, C. glabrata isolates exhibiting resistance to both itraconazole and micafungin contained very low cell concentrations of β-1,2-linked mannose residues relative to susceptible strains. "
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