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Katiyar SK and Edlind TD  (2009) Role for Fks1 in the intrinsic echinocandin resistance of Fusarium solani as evidenced by hybrid expression in Saccharomyces cerevisiae. Antimicrob Agents Chemother 53(5):1772-8

Abstract: The opportunistic mold Fusarium solani is intrinsically resistant to cell wall synthesis-inhibiting echinocandins (ECs) including caspofungin and micafungin. Mutations that confer acquired EC resistance in Saccharomyces cerevisiae and other normally susceptible yeast species have been mapped to the Fks1 gene; among these is the mutation of residue 639 from Phe to Tyr (F639Y) within a region designated hotspot 1. Fks1 sequence analysis identified the equivalent of Y639 in F. solani, as well as in Scedosporium prolificans, another intrinsically EC-resistant mold. To test its role in intrinsic EC resistance, we constructed Fks1 hybrids in S. cerevisiae that incorporate F. solani hotspot 1 and flanking residues. Hybrid construction was accomplished by a PCR-based method which was validated by studies with Fks1 sequences from EC-susceptible Aspergillus fumigtus and paired EC-susceptible and resistant Candida glabrata. In support of our hypothesis, hybrid Fks1 incorporating F. solani hotspot 1 conferred significantly reduced EC susceptibility: 4 to 8-fold compared to wild-type S. cerevisiae and 8 to 32-fold compared to the same hybrid substituted with F639. We propose that Fks1 sequences represent determinants of intrinsic EC resistance in Fusarium and Scedosporium species, and potentially other fungi.

Status: Published

Type: Journal Article

PubMed ID: 19258277

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Katiyar SK Edlind TD Papers in SGD Colleagues in SGD PubMed Google Scholar

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