Rapid detection of FKS-associated echinocandin resistance in Candida glabrata

Yanan Zhao, Yoji Nagasaki, Milena Kordalewska, Ellen G. Press, Ryan K. Shields, M. Hong Nguyen, Cornelius J. Clancy, David S. Perlin

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

A novel and highly accurate diagnostic assay platform was established for rapid identification of FKS mutations associated with echinocandin resistance in Candida glabrata. The assay platform uses allele-specific molecular beacon and DNA melt analysis following asymmetric PCR. A dual assay for FKS1 and FKS2 was developed to identify within 3 h the most common and clinically relevant resistance-associated mutations, including 8 FKS1 HS1 (wild type [WT], S629P, F625S, D632Y, D632E [T1896G], D632E [T1896A], I634V, and F625F) and 7 FKS2 HS1 (WT, F659del, F659S, F659V, F659L, S663P, and S663F) genotypes. A blinded panel of 188 C. glabrata clinical isolates was tested by both assays. The molecular diagnostic results from the dual assay were 100% concordant with data obtained from DNA sequencing. This platform has the potential to overcome the deficiencies of existing in vitro susceptibility-based assays to identify echinocandin-resistant C. glabrata and holds promise as a surrogate diagnostic method to better direct echinocandin therapy.

Original languageEnglish
Pages (from-to)6573-6577
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

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Echinocandins
Candida glabrata
Mutation
Molecular Pathology
DNA Sequence Analysis
Alleles
Genotype
Polymerase Chain Reaction
DNA
Therapeutics
echinocandin C
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Zhao, Y., Nagasaki, Y., Kordalewska, M., Press, E. G., Shields, R. K., Nguyen, M. H., ... Perlin, D. S. (2016). Rapid detection of FKS-associated echinocandin resistance in Candida glabrata. Antimicrobial Agents and Chemotherapy, 60(11), 6573-6577. https://doi.org/10.1128/AAC.01574-16

Rapid detection of FKS-associated echinocandin resistance in Candida glabrata. / Zhao, Yanan; Nagasaki, Yoji; Kordalewska, Milena; Press, Ellen G.; Shields, Ryan K.; Nguyen, M. Hong; Clancy, Cornelius J.; Perlin, David S.

In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 11, 01.11.2016, p. 6573-6577.

Research output: Contribution to journalArticle

Zhao, Y, Nagasaki, Y, Kordalewska, M, Press, EG, Shields, RK, Nguyen, MH, Clancy, CJ & Perlin, DS 2016, 'Rapid detection of FKS-associated echinocandin resistance in Candida glabrata', Antimicrobial Agents and Chemotherapy, vol. 60, no. 11, pp. 6573-6577. https://doi.org/10.1128/AAC.01574-16
Zhao, Yanan ; Nagasaki, Yoji ; Kordalewska, Milena ; Press, Ellen G. ; Shields, Ryan K. ; Nguyen, M. Hong ; Clancy, Cornelius J. ; Perlin, David S. / Rapid detection of FKS-associated echinocandin resistance in Candida glabrata. In: Antimicrobial Agents and Chemotherapy. 2016 ; Vol. 60, No. 11. pp. 6573-6577.
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