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, Chayanika; Chen, Sharon C.-A.; Halliday, C; Kennedy, Karina; Playford, Elliott Geoffrey; Marriott, D.J.; Slavin, Monica; Sorrell, Tania; Sintchenko, Vitali
Description
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...[Show more]
dc.contributor.author | Biswas, Chayanika | |
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dc.contributor.author | Chen, Sharon C.-A. | |
dc.contributor.author | Halliday, C | |
dc.contributor.author | Kennedy, Karina | |
dc.contributor.author | Playford, Elliott Geoffrey | |
dc.contributor.author | Marriott, D.J. | |
dc.contributor.author | Slavin, Monica | |
dc.contributor.author | Sorrell, Tania | |
dc.contributor.author | Sintchenko, Vitali | |
dc.date.accessioned | 2022-06-15T01:39:20Z | |
dc.identifier.issn | 1198-743X | |
dc.identifier.uri | http://hdl.handle.net/1885/267286 | |
dc.description.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 | |
dc.description.sponsorship | This work was supported by the Centre for Infectious Diseases and MicrobiologydPublic Health | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en_AU | |
dc.publisher | Elsevier | |
dc.source | Clinical Microbiology and Infection | |
dc.subject | Antifungal resistance | |
dc.subject | Candida glabrata | |
dc.subject | Next-generation sequencing | |
dc.subject | Echinocandins | |
dc.subject | Azoles | |
dc.subject | Single nucleotide polymorphisms | |
dc.title | Identification of genetic markers of resistance to echinocandins, azoles and 5-fluorocytosine in Candida glabrata by next-generation sequencing: A feasibility study | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 23 | |
dc.date.issued | 2017 | |
local.identifier.absfor | 110801 - Medical Bacteriology | |
local.identifier.ariespublication | a383154xPUB5880 | |
local.publisher.url | © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. | |
local.type.status | Published Version | |
local.contributor.affiliation | Biswas, Chayanika, Westmead Hospital, Centre for Infectious Diseases and Microbiology | |
local.contributor.affiliation | Chen, Sharon C.-A., Westmead Hospital | |
local.contributor.affiliation | Halliday, C, Westmead Hospital | |
local.contributor.affiliation | Kennedy, Karina, College of Health and Medicine, ANU | |
local.contributor.affiliation | Playford, Elliott Geoffrey, Princess Alexandra Hospital Brisbane, Infection Management Services | |
local.contributor.affiliation | Marriott, D.J., St Vincent's Hospital | |
local.contributor.affiliation | Slavin, Monica, Peter MacCallum Cancer Institute | |
local.contributor.affiliation | Sorrell, Tania, Westmead Hospital | |
local.contributor.affiliation | Sintchenko, Vitali, The University of Sydney | |
local.description.embargo | 2099-12-31 | |
local.bibliographicCitation.issue | 9 | |
local.bibliographicCitation.startpage | 676.e7 | |
local.bibliographicCitation.lastpage | 676.e10 | |
local.identifier.doi | 10.1016/j.cmi.2017.03.014 | |
dc.date.updated | 2021-02-14T07:21:04Z | |
local.identifier.scopusID | 2-s2.0-85018751780 | |
local.identifier.thomsonID | 000407933400022 | |
Collections | ANU Research Publications |
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