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Do Candida albicans Isolates with Borderline Resistant Micafungin MICs Always Harbor FKS1 Hot Spot Mutations?
Kathrin Spettel1, Sonia Galazka1, Richard Kriz2
1Division of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
Abstract:
Antifungal susceptibility testing is important in guiding patient therapy due to an increasing number of resistant Candida isolates. In the clinical strain collection of the Austrian resistance report (AURES), a high number of micafungin-resistant C. albicans isolates (18.2% 49/269) was detected in seven different centres in Austria from 2011-2016. Most of these isolates showed a micafungin MIC value that was just above the clinical breakpoint (CB) established by EUCAST (0.016 mg/L). The aim of this study was to analyse whether C. albicans strains showing a micafungin MIC value of 1-2 dilutions above the CB (0.032 mg/L and 0.064 mg/L) are associated with mutations in FKS1 hotspot (HS) regions. 115 C. albicans candidemia strains showing a micafungin MIC one or two dilutions above the EUCAST CB (0.032 mg/L and 0.064 mg/L) were categorized as borderline resistant and screened for mutations in FKS1 HS1, HS2, and HS3 regions, which are known locations for the development of echinocandin resistance. For this purpose, we implemented targeted resequencing utilizing a next generation sequencing technology. No missense mutations could be detected in FKS1 HS1, HS2, and HS3 in any of the 115 isolates, which indicated that resistance conferred by alteration of FKS1 seems unlikely.
Insights
Borderline micafungin resistance in Candida albicans was investigated. Mutations in FKS1 hotspot regions were screened in resistant isolates, but none were found, suggesting FKS1 alterations are unlikely causes of this resistance.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Molecular Biology
Background:
- Increasing antifungal resistance in Candida isolates necessitates effective patient therapy guidance.
- High rates of micafungin-resistant Candida albicans were observed in Austrian clinical settings (2011-2016).
- Many resistant isolates exhibited minimum inhibitory concentration (MIC) values slightly above the EUCAST clinical breakpoint (CB).
Purpose of the Study:
- To investigate the association between borderline micafungin resistance in Candida albicans and mutations in FKS1 hotspot regions.
- To analyze strains with micafungin MICs of 0.032 mg/L and 0.064 mg/L (1-2 dilutions above CB).
Main Methods:
- Targeted resequencing using next-generation sequencing technology.
- Screening of 115 Candida albicans candidemia strains for mutations in FKS1 hotspot regions (HS1, HS2, HS3).
Main Results:
- No missense mutations were detected in the FKS1 HS1, HS2, or HS3 regions of any of the 115 analyzed isolates.
- The observed borderline resistance to micafungin in these isolates is unlikely to be conferred by alterations in FKS1.
Conclusions:
- FKS1 mutations are not the likely mechanism for borderline micafungin resistance in the studied Candida albicans isolates.
- Further research is needed to elucidate the genetic basis of echinડોcandin resistance in Candida albicans.
