Journal article
Role for Fks1 in the Intrinsic Echinocandin Resistance of Fusarium solani as Evidenced by Hybrid Expression in Saccharomyces cerevisiae
Antimicrobial agents and chemotherapy, v 53(5), pp 1772-1778
May 2009
PMID: 19258277
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 hot spot 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
hot spot 1 and flanking residues. Hybrid construction was accomplished by a PCR-based method that was validated by studies with Fks1 sequences from EC-susceptible
Aspergillus fumigatus
and paired EC-susceptible and -resistant
Candida glabrata
isolates. In support of our hypothesis, hybrid Fks1 incorporating
F. solani
hot spot 1 conferred significantly reduced EC susceptibility, 4- to 8-fold less than that of wild-type
S. cerevisiae
and 8- to 32-fold less than that of the same hybrid with an F639 mutation. We propose that Fks1 sequences represent determinants of intrinsic EC resistance in
Fusarium
and
Scedosporium
species and, potentially, other fungi.
Metrics
Details
- Title
- Role for Fks1 in the Intrinsic Echinocandin Resistance of Fusarium solani as Evidenced by Hybrid Expression in Saccharomyces cerevisiae
- Creators
- Santosh K Katiyar - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaThomas D Edlind - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- Antimicrobial agents and chemotherapy, v 53(5), pp 1772-1778
- Publisher
- American Society for Microbiology (ASM)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000265528700008
- Scopus ID
- 2-s2.0-66149144294
- Other Identifier
- 991014878042204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy