A Genome-Wide Screening of Potential Target Genes to Enhance the Antifungal Activity of Micafungin in Schizosaccharomyces pombe

19Citations
Citations of this article
37Readers
Mendeley users who have this article in their library.

Abstract

Micafungin is a non-reversible inhibitor of 1, 3-β-D-glucan synthase and interferes with fungal cell wall synthesis. Clinically, micafungin has been shown to be efficacious for the treatment of invasive candidiasis and invasive aspergillosis. However, considering its relatively restricted antifungal spectrum, combination therapy with micafungin plus other agents should be considered in critically ill patients. To identify potential therapeutic targets for syncretic drug combinations that potentiate micafungin action, we carried out a genome-wide screen for altered sensitivity to micafungin by using the model yeast Schizosaccharomyces pombe mutant library. We confirmed that 159 deletion strains in the library are micafungin sensitive and classified them into various functional categories, including cell wall biosynthesis, gene expression and chromatin remodeling, membrane trafficking, signaling transduction, ubiquitination, ergosterol biosynthetic process and a variety of other known functions or still unknown functions. On the other hand, we also investigated the growth inhibitory activities of some well-known drugs in combination with micafungin including antifungal drug amphotericin B, fluconazole and immunosuppressive drug FK506. We found that amphotericin B in combination with micafungin showed a more potent inhibitory activity against wild-type cells than that of micafungin alone, whereas fluconazole in combination with micafungin did not. Also, the immunosuppressive drug FK506 showed synergistic inhibitory effect with micafungin on the growth of wild-type cells, whereas it decreased the inhibitory effect of micafungin in Δpmk1 cells, a deletion mutant of the cell wall integrity mitogen-activated protein kinase (MAPK) Pmk1. Altogether, our findings provide useful information for new potential drug combinations in the treatment of fungal infections. © 2013 Zhou et al.

Cite

CITATION STYLE

APA

Zhou, X., Ma, Y., Fang, Y., gerile, W., Jaiseng, W., Yamada, Y., & Kuno, T. (2013). A Genome-Wide Screening of Potential Target Genes to Enhance the Antifungal Activity of Micafungin in Schizosaccharomyces pombe. PLoS ONE, 8(5). https://doi.org/10.1371/journal.pone.0065904

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free