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

Biswas, Chayanika; Chen, S.C.-A.; Halliday, Catriona; Kennedy, Karina; Playford, E. Geoffrey; Marriott, Debbie; Slavin, Monica A; Sorrell, Tania C.; Sintchenko, Vitali

doi:10.1016/j.cmi.2017.03.014

Cited by 28 publications

(39 citation statements)

References 21 publications

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“…The exception may be in C. glabrata where azole resistance is associated with mutations in the transcription factor pdr1 (Ferrari et al, 2009), or if targeted DNA sequencing is performed for a mutation already known to confer resistance. Resistance mutations are broadly distributed throughout the genome and as such, NGS approaches have been studied for the detection of mutations in genes associated with azole resistance including in ERG11, ERG3, TAC1, and CgPDR1 (Garnaud et al, 2015;Biswas et al, 2017;Castanheira et al, 2017). NGS further has potential to detect novel mutations implicated in phenotypic resistance that may otherwise be missed by targeted DNA sequencing.…”

Section: Molecular Methods To Detect Azole Resistance In Candida Speciesmentioning

confidence: 99%

Section: Molecular Methods To Detectmentioning

confidence: 99%

“…Finally, NGS is suited to detecting a large number of mutations in multiple FKS genes in clinical isolates of C. glabrata with high MICs to the echinocandins (Garnaud et al, 2015;Biswas et al, 2017). Biswas et al (2017) used NGS to retrospectively study three strain pairs of C. glabrata from three patients where antifungal resistance developed during treatment. Two of three isolate pairs developed a > 60-fold increase in the MICs to all echinocandins and NGS detected mutations in either the FKS1 (S629P) or FKS2 (S663P) genes of the resistant isolates (Biswas et al, 2017).…”

Section: Molecular Methods To Detectmentioning

confidence: 99%

“…Biswas et al (2017) used NGS to retrospectively study three strain pairs of C. glabrata from three patients where antifungal resistance developed during treatment. Two of three isolate pairs developed a > 60-fold increase in the MICs to all echinocandins and NGS detected mutations in either the FKS1 (S629P) or FKS2 (S663P) genes of the resistant isolates (Biswas et al, 2017).…”

Section: Molecular Methods To Detectmentioning

confidence: 99%

See 3 more Smart Citations

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

et al. 2020

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Section: Molecular Methods To Detect Azole Resistance In Candida Speciesmentioning

confidence: 99%

Section: Molecular Methods To Detectmentioning

confidence: 99%

Section: Molecular Methods To Detectmentioning

confidence: 99%

Section: Molecular Methods To Detectmentioning

confidence: 99%

See 2 more Smart Citations

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

et al. 2020

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“…Additionally, changes in the FKS2 gene were associated with the highest increase in echinocandin resistance and a considerable cost in fitness. Finally, another study in C. glabrata used a whole genome sequencing approach, but only searched for mutations in genes suggested to play a role in resistance [ 146 ]. More specifically FKS1 and FKS2 in echinocandin resistance; FCY1 , FCY2 , FUR1 , FPS1 , and FPS2 in luorocytosine resistance; and ERG9 , ERG11 , CDR1 , PDR1 , FLR1 , and SNQ2 in azole resistance.…”

Section: Whole Genome Sequencing Of Serial Isolates To Track the Ementioning

confidence: 99%

Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens

Ksiezopolska

Gabaldón

2018

Genes

193

124

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Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates.

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The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges

et al. 2020

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Fungal disease is an increasingly recognised global clinical challenge associated with high mortality. Early diagnosis of fungal infection remains problematic due to the poor sensitivity and specificity of current diagnostic modalities. Advances in sequencing technologies hold promise in addressing these shortcomings and for improved fungal detection and identification. To translate such emerging approaches into mainstream clinical care will require refinement of current sequencing and analytical platforms, ensuring standardisation and consistency through robust clinical benchmarking and its validation across a range of patient populations. In this stateof-the-art review, we discuss current diagnostic and therapeutic challenges associated with fungal disease and provide key examples where the application of sequencing technologies has potential diagnostic application in assessing the human 'mycobiome'. We assess how ready access to fungal sequencing may be exploited in broadening our insight into hostfungal interaction, providing scope for clinical diagnostics and the translation of emerging mycobiome research into clinical practice.

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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

Abstract: Genome-wide analysis of antifungal resistance markers was feasible and simultaneously revealed mutation patterns of genes implicated in resistance to different antifungal drug classes.

Cited by 28 publications

References 21 publications

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens

The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges

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