Quick Detection of
            <i>FKS1</i>
            Mutations Responsible for Clinical Echinocandin Resistance in Candida albicans

Dudiuk, Catiana; Gamarra, Soledad; Jiménez‐Ortigosa, Cristina; Leonardelli, Florencia; Macedo, Daiana; Perlin, David S.; García‐Effrón, Guillermo

doi:10.1128/jcm.00398-15

Cited by 18 publications

(12 citation statements)

References 33 publications

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“…All mutations were detected in GSC1 HS 1 or its immediate vicinity. The mutations observed were S645P [18], which was detected three times, F641C, F641S [7, 35], P649H [36–38] and M696V. For the isolates Ca13 and Ca16 the mutations F641C and S645P, respectively, are shown as heterozygous.…”

Section: Resultsmentioning

confidence: 99%

Analysis of antifungal resistance genes in Candida albicans and Candida glabrata using next generation sequencing

et al. 2019

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Introduction/ObjectivesAn increase in antifungal resistant Candida strains has been reported in recent years. The aim of this study was to detect mutations in resistance genes of azole-resistant, echinocandin-resistant or multi-resistant strains using next generation sequencing technology, which allows the analysis of multiple resistance mechanisms in a high throughput setting.MethodsForty clinical Candida isolates (16 C. albicans and 24 C. glabrata strains) with MICs for azoles and echinocandins above the clinical EUCAST breakpoint were examined. The genes ERG11, ERG3, TAC1 and GSC1 (FKS1) in C. albicans, as well as ERG11, CgPDR1, FKS1 and FKS2 in C. glabrata were sequenced.ResultsFifty-four different missense mutations were identified, 13 of which have not been reported before. All nine echinocandin-resistant Candida isolates showed mutations in the hot spot (HS) regions of FKS1, FKS2 or GSC1. In ERG3 two homozygous premature stop codons were identified in two highly azole-resistant and moderately echinocandin-resistant C. albicans strains. Seven point mutations in ERG11 were determined in azole-resistant C. albicans whereas in azole-resistant C. glabrata, no ERG11 mutations were detected. In 10 out of 13 azole-resistant C. glabrata, 12 different potential gain-of-function mutations in the transcription factor CgPDR1 were verified, which are associated with an overexpression of the efflux pumps CDR1/2.ConclusionThis study showed that next generation sequencing allows the thorough investigation of a large number of isolates more cost efficient and faster than conventional Sanger sequencing. Targeting different resistance genes and a large sample size of highly resistant strains allows a better determination of the relevance of the different mutations, and to differentiate between causal mutations and polymorphisms.

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Section: Resultsmentioning

confidence: 99%

Analysis of antifungal resistance genes in Candida albicans and Candida glabrata using next generation sequencing

et al. 2019

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“…The current methods for the rapid detection of resistance include molecular-based analyses [ 49 , 50 ], flow cytometry [ 51 ] or porous aluminum oxide (PAO)-based cultures [ 52 , 53 ], which deliver results within a few hours. Furthermore, the improvement of the conventional methods by the direct inoculation of standard tests with positive blood cultures [ 54 ] or shortening the time to result by automated approaches such as as the Vitek 2 yeast panel [ 55 , 56 , 57 ] have been investigated.…”

Section: Discussionmentioning

confidence: 99%

Rapid Antifungal Susceptibility Testing of Yeasts and Molds by MALDI-TOF MS: A Systematic Review and Meta-Analysis

Knoll

Ulmer

Lass‐Flörl

2021

JoF

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Due to the growing burden of fungal infections and a recent rise in antifungal resistance, antifungal susceptibility testing (AFST) is of increasing importance. The common methods of AFST have turnaround times of 24 to 48 h, and the available rapid methods are limited by applicability, cost-efficiency or accuracy. Given the urgency of adequate antifungal treatment in invasive mycoses, the need for the rapid and reliable detection of resistance is evident. In this systematic review and meta-analysis, we evaluated the diagnostic accuracy of AFST based on matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Twelve studies were reviewed, and data for the comparative analysis of their accuracy and methodology were systematically extracted. Compared to broth dilution as the gold standard, MALDI-TOF MS-based AFST reached a pooled sensitivity and specificity of 91% (95% Confidence Interval [CI], 84% to 96%) and 95% (95% CI, 90% to 98%), respectively. A comparative analysis showed that the sensitivity was higher for the semi-quantitative matrix-assisted laser desorption ionization Biotyper antibiotic susceptibility test rapid assay (MBT ASTRA) technique (96%) than for the correlate composite index (CCI) approach (85%), which is based on spectrum changes. Turnaround times below eight hours reached better diagnostic values than longer incubation periods, qualifying MALDI-TOF MS-based AFST as a rapid and accurate method for the detection of antifungal resistance.

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“…echinocandin resistance in Candida species and azole resistance in Aspergillus fumigatus ) are also currently available and will further enhance early targeted antifungal therapy [63, 64]. …”

Section: Molecular Fungal Toolsmentioning

confidence: 99%

“…Several PCR based methods for the detection of fungal pathogens including mutations conferring resistance to specific antifungals (e.g. echinocandin resistance in Candida species and azole resistance in Aspergillus fumigatus ) are also currently available and will further enhance early targeted antifungal therapy [ 63 , 64 ].…”

Section: Molecular Fungal Toolsmentioning

confidence: 99%

Progress in the Diagnosis of Invasive Fungal Disease in Children

Warris

Lehrnbecher

2017

Curr Fungal Infect Rep

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Purpose of ReviewThis review summarizes the fungal diagnostic measures currently available for use in paediatric patients at high risk for developing invasive fungal disease (IFD) and those suspected of having an IFD. The clinical utility of each test is described based on reported performances of individual tests in specific paediatric populations.Recent FindingsAvailable studies in the paediatric population are scarce and are characterized by a huge heterogeneity in underlying diseases (e.g. different risk for IFD), different study objectives and management strategies (screening versus diagnostic) used.SummaryA final valuation of paediatric studies on fungal diagnostic tools is limited. While the galactomannan and fungal PCR assays are useful to exclude the presence of IFD, it is unclear if mannan, mannan antibodies and β-D-glucan are of benefit due to a lack of studies or validation of the cut-off, respectively. Well-designed multicentre paediatric studies are urgently needed to improve the outcome of IFD.

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Quick Detection of FKS1 Mutations Responsible for Clinical Echinocandin Resistance in Candida albicans

Cited by 18 publications

References 33 publications

Analysis of antifungal resistance genes in Candida albicans and Candida glabrata using next generation sequencing

Analysis of antifungal resistance genes in Candida albicans and Candida glabrata using next generation sequencing

Rapid Antifungal Susceptibility Testing of Yeasts and Molds by MALDI-TOF MS: A Systematic Review and Meta-Analysis

Progress in the Diagnosis of Invasive Fungal Disease in Children

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