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Low prevalence of fks1 hot spot 1 mutations in a worldwide collection of Candida strains
Journal article   Open access   Peer reviewed

Low prevalence of fks1 hot spot 1 mutations in a worldwide collection of Candida strains

Mariana Castanheira, Leah N Woosley, Daniel J Diekema, Shawn A Messer, Ronald N Jones and Michael A Pfaller
Antimicrobial agents and chemotherapy, Vol.54(6), pp.2655-2659
06/2010
DOI: 10.1128/AAC.01711-09
PMCID: PMC2876398
PMID: 20368396
url
https://doi.org/10.1128/AAC.01711-09View
Published (Version of record) Open Access

Abstract

We evaluated the prevalence of fks1 hot spot (HS) 1 mutations among 133 Candida strains from six species displaying various caspofungin MIC values (from < or =0.008 to >8 microg/ml). Only 4 (2.9%) strains displayed FKS1 HS1 amino acid substitutions: 1 C. albicans (F641Y) among 32 isolates tested (3.1%), 1 C. glabrata (S645P) among 34 isolates tested (2.9%), and 2 C. tropicalis (F641S) among 12 isolates tested (16.7%). The 4 isolates displaying FKS1 HS1 alterations showed elevated caspofungin MIC results (1 to >8 microg/ml) but lower anidulafungin and micafungin MIC values (0.12 to 4 microg/ml and 0.25 to 4 microg/ml, respectively) in some instances within the wild-type MIC population, as determined using the epidemiologic cutoff values (ECV). Candida krusei, C. parapsilosis, and C. guilliermondii isolates tested showed no FKS1 HS1 alterations regardless of echinocandin MIC result. We additionally analyzed 8 C. albicans and 7 C. glabrata strains for mutations on other HS regions of fks1 and fks2. Three C. glabrata strains showed alterations on FKS2 HS1 (two S645P and one L644W). In general, strains displaying S645P alteration showed higher echinocandin MIC values than strains harboring other mutations. Overall, Candida spp. strains showing caspofungin MIC values within the ECV did not display fks HS mutations. In contrast, strains showing alterations in this region displayed anidulafungin and/or micafungin MIC values within the wild-type population, suggesting that caspofungin could be the most sensitive agent for detection of these resistance mutations. Furthermore, results from this large, geographically diverse Candida spp. collection demonstrated that fks1 HS1 mutations remain uncommon among isolates with various echinocandin MIC levels.
 DNA, Fungal - genetics Species Specificity Humans Molecular Sequence Data Candidiasis - microbiology Candida albicans - genetics Microbial Sensitivity Tests Candida - classification Candida albicans - drug effects Candidiasis - drug therapy Base Sequence Candida albicans - isolation & purification Genes, Fungal Echinocandins - pharmacology Antifungal Agents - pharmacology Amino Acid Sequence Candida - genetics Drug Resistance, Fungal - genetics Fungal Proteins - genetics Candida - isolation & purification Sequence Homology, Amino Acid Candida glabrata - isolation & purification Candida - drug effects Mutation Candida glabrata - genetics In Vitro Techniques Amino Acid Substitution Candida glabrata - drug effects

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