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Journal article
Sphingolipids Mediate Differential Echinocandin Susceptibility in Candida albicans and Aspergillus nidulans
Antimicrobial agents and chemotherapy, v 59(6), pp 3377-3384
14 May 2015
PMID: 25824222
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The cell wall synthesis-inhibiting echinocandins, including caspofungin and micafungin, play important roles in the treatment of candidiasis and aspergillosis. Previous studies revealed that, in the haploid yeast Candida glabrata, sphingolipid biosynthesis pathway mutations confer caspofungin reduced susceptibility (CRS) but micafungin increased susceptibility (MIS). Here, we describe one Candida albicans strain (of 10 tested) that similarly yields CRS-MIS mutants at relatively high frequency. Mutants demonstrated increased levels of long-chain bases (sphingolipid pathway intermediates) and, unique to this strain, loss of His104/Pro104 heterozygosity in the TSC13-encoded enoyl reductase. CRS-MIS was similarly observed in a C. albicans homozygous fen1Δ fen12Δ laboratory strain and in diverse wild-type strains following exogenous long-chain-base treatment. Analogous to these results, CRS-MIS was demonstrated in an Aspergillus nidulans basA mutant encoding defective sphingolipid C4-hydroxylase and in its wild-type parent exposed to long-chain bases. Sphingolipids likely modulate echinocandin interaction with their Fks membrane target in all susceptible fungi, with potential implications for optimizing therapy with existing antifungals and the development of novel agents.
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Details
- Title
- Sphingolipids Mediate Differential Echinocandin Susceptibility in Candida albicans and Aspergillus nidulans
- Creators
- Kelley R Healey - Drexel UniversityKrishna K Challa - Drexel UniversityThomas D Edlind - MicrobiType LLC, Plymouth Meeting, Pennsylvania, USA.Santosh K Katiyar - Drexel University
- Publication Details
- Antimicrobial agents and chemotherapy, v 59(6), pp 3377-3384
- Publisher
- American Society for Microbiology
- Number of pages
- 8
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000358623200052
- Scopus ID
- 2-s2.0-84973363319
- Other Identifier
- 991019168008904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy