Identification of genetic markers of resistance to echinocandins, azoles and 5-fluorocytosine in Candida glabrata by next-generation sequencing: a feasibility study.

Biswas, C.; Chen, S.C.-A.; Halliday, C.; Kennedy, K.; Playford, E.G.; Marriott, D.J.; Slavin, M.A.; Sorrell, T.C.; Sintchenko, V.

doi:10.1016/j.cmi.2017.03.014

Cited by 36Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

Identification of genetic markers of resistance to echinocandins, azoles and 5-fluorocytosine in Candida glabrata by next-generation sequencing: a feasibility study.

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Biswas, C., Chen, S.C.-A., Halliday, C., Kennedy, K., Playford, E.G., Marriott, D.J., Slavin, M.A., Sorrell, T.C. +1 more·2017·Clinical Microbiology and Infection

DOI 10.1016/j.cmi.2017.03.014

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Abstract

Objectives Multi-antifungal drug resistance in Candida glabrata is increasing. We examined the feasibility of next-generation sequencing (NGS) to investigate the presence of antifungal drug resistance markers in C. glabrata.Methods The antifungal susceptibility of 12 clinical isolates and one ATCC strain of C. glabrata was determined using the Sensititre YeastOne® YO10 assay. These included three isolate pairs where the second isolate of each pair had developed a rise in drug MICs. Single nucleotide polymorphisms (SNPs) in genes known to be linked to echinocandin, azole and 5-fluorocytosine resistance were analysed in all isolates through NGS.Results High-quality non-synonymous SNPs in antifungal resistance genes such as FKS1, FKS2, CgCDR1, CgPDR1 and FCY2 were identified. For two of three isolate pairs, there was a >60-fold rise in MICs to all echinocandins in the second isolate from each pair; one echinocandin-resistant isolate harboured a mutation in FKS1 (S629P) and the other in FKS2 (S663P). Of the third pair, both the 5-fluorocytosine-susceptible, and resistant isolates had a mutation in FCY2 (A237T). SNPs in CgPDR1 were found in pan-azole-resistant isolates. SNPs in other genes linked to azole resistance (CgCDR1, ERG9 and CgFLR1) were present in both azole-susceptible and azole-resistant isolates. SNPs were also identified in Candida adhesin genes EPA1, EPA6, PWP2 and PWP5 but their presence was not associated with higher drug MICs.Conclusions Genome-wide analysis of antifungal resistance markers was feasible and simultaneously revealed mutation patterns of genes implicated in resistance to different antifungal drug classes.

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The original comparison of the two echinocandin resistant strains CMRL2 and CMRL4 with their susceptible paired strains reported mutations in FKS1 (S629P) and FKS2 (S663P), respectively.
“The original comparison of the two echinocandin resistant strains, CMRL2 and CMRL4, with their susceptible paired strains, reported mutations in FKS1 (S629P) and FKS2 (S663P), respectively (Biswas et al., 2017).”
From Genome Comparisons of Candida glabrata Serial Clinical Isolates Reveal Patterns of Genetic Variation in Infecting Clonal Populations (2019) · cites this paper as Biswas et al., 2017
Most recent analyses of C. glabrata isolates obtained from the same patient revealed very little genetic variation, supporting the idea that a single clonal population colonizes different body sites and jointly contributes to infection.
“Most of these analyses revealed very little genetic variation, supporting the idea that a single clonal population colonizes different body sites and jointly contributes to infection.”
From Genome Comparisons of Candida glabrata Serial Clinical Isolates Reveal Patterns of Genetic Variation in Infecting Clonal Populations (2019) · cites this paper as Biswas et al., 2017
DSY565, CMRL6, NRZ-2016-057, and NRZ-2016-058 were shown to be azole resistant.
“DSY565, CMRL6, NRZ-2016-057, and NRZ-2016-058 were shown to be azole resistant; and CMRL2, CMRL4, and NRZ-2016-058 were shown to be echinocandin resistant (Biswas et al., 2017; Vale-Silva et al., 2017; Barber et al., 2018).”
From Genome Comparisons of Candida glabrata Serial Clinical Isolates Reveal Patterns of Genetic Variation in Infecting Clonal Populations (2019) · cites this paper as Biswas et al., 2017
CMRL2, CMRL4, and NRZ-2016-058 were shown to be echinocandin resistant.
“DSY565, CMRL6, NRZ-2016-057, and NRZ-2016-058 were shown to be azole resistant; and CMRL2, CMRL4, and NRZ-2016-058 were shown to be echinocandin resistant (Biswas et al., 2017; Vale-Silva et al., 2017; Barber et al., 2018).”
From Genome Comparisons of Candida glabrata Serial Clinical Isolates Reveal Patterns of Genetic Variation in Infecting Clonal Populations (2019) · cites this paper as Biswas et al., 2017
Most strains within a pair showed a very low density of SNPs (0.037-0.047 SNPs/Kb), confirming their clonal nature.
“Similarly, most strains within a pair showed a very low density of SNPs (0.037–0.047 SNPs/Kb), confirming their clonal nature (Biswas et al., 2017; Vale-Silva et al., 2017; Carreté et al., 2018).”
From Genome Comparisons of Candida glabrata Serial Clinical Isolates Reveal Patterns of Genetic Variation in Infecting Clonal Populations (2019) · cites this paper as Biswas et al., 2017

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Authors: Biswas, C., Chen, S. C.-A., Halliday, C., Kennedy, K., Playford, E. G., Marriott, D. J., Slavin, M. A., Sorrell, T. C., & Sintchenko, V.
Affiliations: Westmead Hospital (AU)
The University of Sydney (AU)
Australian National University (AU)
Princess Alexandra Hospital (AU)
St Vincent's Hospital Sydney (AU)
Peter MacCallum Cancer Centre (AU)
Corresponding author: Biswas, C.
ORCID: Halliday, C.
Slavin, M.A.
Sorrell, T.C.
Sintchenko, V.
Venue: Clinical Microbiology and Infection
Publisher: Elsevier BV
Published: 2017-09
Volume: 23
Issue: 9
Pages: 676.e7-676.e10
ISSN: 1198-743X (ISSN-L)
DOI: 10.1016/j.cmi.2017.03.014
OpenAlex: W2603290438
Cited by: 36
References: 21
Citations by year: 2025: 5 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 5
FWCI: 3.79
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
Locations: Clinical Microbiology and Infection (publishedVersion)
PubMed (publishedVersion)
ANU Open Research (Australian National University) (submittedVersion)
Griffith Research Online (submittedVersion, other-oa)
Funders: Centre for Infectious Diseases and Microbiology—Public Health
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords: Candida glabrata, antifungal resistance, echinocandin resistance, azole resistance, 5-fluorocytosine resistance, genetic markers, single nucleotide polymorphisms, FKS1, FKS2, minimum inhibitory concentration, multidrug resistance
MeSH terms: Antifungal Agents, Azoles, Candidiasis, Feasibility Studies, Flucytosine, Genetic Markers, Humans, Microbiological Techniques, Polymorphism, Single Nucleotide, Drug Resistance, Fungal, Candida glabrata, Echinocandins, High-Throughput Nucleotide Sequencing

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Identification of genetic markers of resistance to echinocandins, azoles and 5-fluorocytosine in Candida glabrata by next-generation sequencing: a feasibility study.

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