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 language | English |
|---|---|
| Pages (from-to) | 6573-6577 |
| Number of pages | 5 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 60 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2016 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
Cite this
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 journal › Article
}
TY - JOUR
T1 - Rapid detection of FKS-associated echinocandin resistance in Candida glabrata
AU - Zhao, Yanan
AU - Nagasaki, Yoji
AU - Kordalewska, Milena
AU - Press, Ellen G.
AU - Shields, Ryan K.
AU - Nguyen, M. Hong
AU - Clancy, Cornelius J.
AU - Perlin, David S.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84994508552&partnerID=8YFLogxK
U2 - 10.1128/AAC.01574-16
DO - 10.1128/AAC.01574-16
M3 - Article
VL - 60
SP - 6573
EP - 6577
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 11
ER -