Abstract
The pathogenic fungus Candida glabrata is thought to utilize extracellular sterols during infection, but there have been few reports on the sterol uptake mechanisms of this fungus. The addition of serum promoted the growth of C. glabrata cells in the presence of the sterol inhibitor fluconazole, probably as the result of incorporation of cholesterol from serum. We demonstrated that lipoprotein-deficient serum, in which most of the cholesterol was eliminated, could not rescue the growth of fluconazole-treated C. glabrata cells, but it successfully promoted the expression of the sterol transporter gene AUS1. After supplementation of free cholesterol to lipoprotein-deficient serum, the serum was again competent to promote the growth of fluconazole-treated C. glabrata. The serum-mediated growth rescue from fluconazole inhibition was observed in the nonpathogenic yeast Saccharomyces cerevisiae when it was followed by the activation of anaerobic sterol uptake. These results suggested that serum cholesterol was incorporated into yeast cells to compensate for sterol depletion when sterol uptake was activated. The uptake of serum cholesterol could support the growth of C. glabrata cells during bloodstream infections.
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Acknowledgments
This work was supported by JSPS KAKENHI Grant Number 24790428 (KT), 2459054 (NH), 21390305 (YM), 24.9439 (MN), the grant from the Ministry of Health, Labour and Welfare of Japan H22-shinko-ippan-008, H23-shinko-ippan-018, H23-shinko-ippan-007 and H24-shinko-ippan-013 (YM). We thank R. Fukuda for providing yeast strains. The authors thank Enago (http://www.enago.jp) for English language review.
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M. Nagi and K. Tanabe contributed equally to this work.
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Nagi, M., Tanabe, K., Nakayama, H. et al. Serum cholesterol promotes the growth of Candida glabrata in the presence of fluconazole. J Infect Chemother 19, 138–143 (2013). https://doi.org/10.1007/s10156-012-0531-3
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DOI: https://doi.org/10.1007/s10156-012-0531-3