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Molecular mechanisms of fluconazole resistance in Candida parapsilosis isolates from a US surveillance system.
MedLine Citation:
PMID:  25451046     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Candida parapsilosis is the second or third most common cause of candidemia in many countries. The Infectious Disease Society of America recommends fluconazole as primary therapy for C. parapsilosis candidemia. Although fluconazole resistance among C. parapsilosis isolates is low in most US institutions, the resistance rate can be as high as 7.5%. This study was designed to assess the mechanisms of fluconazole resistance in 706 incident bloodstream isolates from US hospitals. We sequenced the ERG11 and MRR1 genes of 122 C. parapsilosis isolates with resistant (30 isolates; 4.2%), susceptible dose-dependent (37 isolates; 5.2%) and susceptible (55 isolates) fluconazole MIC values, and used RT-PCR on RNA from 17 isolates to investigate the regulation of MDR1. By comparing these isolates to fully fluconazole susceptible isolates we detected at least two mechanisms of fluconazole resistance: an amino acid substitution in the 14-α-demethylase gene ERG11, and overexpression of the efflux pump MDR1, possibly due to point mutations in the MRR1 transcription factor that regulates MDR1. The ERG11 single nucleotide polymorphism (snp) was found in 57% of the fluconazole resistant isolates and in no susceptible isolates. The MRR1 snps were more difficult to characterize, as not all resulted in overexpression of MDR1 and not all MDR1 overexpression was associated with a snp in MRR1. Further work to characterize the MRR1 snps and search for overexpression of other efflux pumps is needed.
Authors:
Nina T Grossman; Cau D Pham; Angela A Cleveland; Shawn R Lockhart
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-1
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  -     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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