Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris

Jenull, Sabrina; Shivarathri, Raju; Tsymala, Irina; Penninger, Philipp; Trinh, Phan-Canh; Nogueira, Filomena; Chauhan, Manju; Singh, Ashutosh; Petryshyn, Andriy; Stoiber, Anton; Chowdhary, Anuradha; Chauhan, Neeraj; Kuchler, Karl

doi:10.1128/mbio.00799-22

Cited by 11 publications

(21 citation statements)

References 99 publications

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“…The abilities of Candida auris to acquire resistance to different antifungal drugs have been demonstrated using comparative genomes, and in vitro , and in vivo approaches [ 29 , 32 , 36 , 37 , 38 ]. The molecular mechanisms involve activation of efflux pumps due to mutations in transcription factors or upregulation of one of several genes involved in ergosterol synthesis [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs

Abid¹,

Salah²,

Sundararaju³

et al. 2023

Clinical Microbiology and Infection

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs

Abid¹,

Salah²,

Sundararaju³

et al. 2023

Clinical Microbiology and Infection

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“…Transcriptomics of multidrug-resistant (MDR) versus drug-sensitive C. auris clinical isolates revealed numerous genes of carboxylic acid metabolism, mitochondrial function, translation, as well as membrane transporters as critical indicators of antifungal resistance in C. auris [19][20][21] . Hence, we integrated transcriptomics datasets with proteomics data from the same strains to identify major genes/pathways implicated in C. auris MDR traits.…”

Section: Integrated Omics Reveals Multidrug-resistant Mechanisms In C...mentioning

confidence: 99%

“…Cells were quantified using the CASY Cell Counter. Next, 2×10 6 cells were washed twice with FACS buffer and pelleted for cell wall carbohydrate staining as described before 11 . Exposed mannan was stained by incubating cells for 45 min at 30 °C in 1 ml FACS buffer containing 25 μg/ml Concanavalin-TexasRed (Invitrogen).…”

Section: Supplementary Information (Si)mentioning

confidence: 99%

“…All staining was conducted in the dark. Raw data were analyzed with the FlowJo v10.8 software using the same gating strategy described before 11 .…”

Section: Supplementary Information (Si)mentioning

confidence: 99%

“…RNA-seq bioinformatics data analysis used a workflow established before 19 with some minor modification (https://github.com/kakulab/CSP2024). Briefly, quality of raw RNA-seq data was assessed by fastQC v0.11.9 77 .…”

Section: Rna Isolation Qpcr and Rna-sequencingmentioning

confidence: 99%

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Carbon Dioxide Controls Fungal Fitness and Skin Tropism ofCandida auris

Phan-Canh,

Penninger,

Seiser

et al. 2024

Preprint

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The pronounced skin tropism and pan-antifungal resistance traits of the fungal pathogenCandida aurisstand out as a serious health threat. Here, we show that a carbonic sensing pathway (CSP) promotes development of resistance to amphotericin B through a reactive oxygen species (ROS) response, as well as ectopic cell wall and membrane lipid homeostasis. Mechanistically, the transcription factor Rca1 acts in cooperation with Efg1 to control the expression and activity of the carbonic anhydrase Nce103 as a key effector component. The conversion of carbon dioxide to bicarbonate provides a direct link to energy metabolism, facilitating colonization and growth on skin tissues. Native mouse and human skin models unequivocally show that the CSP is essential for maintaining skin tropism as well as fungal fitness. Curiously, upon ablation of Rca1 and Efg1,C. aurisdebilitates efficient growth on native skin. Collectively, our findings highlight critical roles of the CSP inC. aurisskin tropism and antifungal drug resistance. The work suggests therapeutic options for disrupting skin colonization and thus preventing infections.

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Candida auris Resistance Mechanisms to Amphotericin B Alternative Treatments Development

Fenton,

John

2024

Curr Clin Micro Rpt

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Purpose of Review Systemic fungal infections caused by Candida auris have been identified since 2009, with mortality rates and drug resistance being noticeably higher than other forms of fungal or nosocomial infections. This review article will be a timely addition to the growing body of literature on how alternative or dual-action treatments may become mainstream or required outside the initial trio of antifungal drug classes, including C. auris. Recent Findings Amphotericin B of the polyene class of antifungals has been used in infections caused by this organism but has also been associated with adverse events and patient toxicity. The use of this drug has been demonstrated in dual-action treatments and clinical investigations and confers a greater degree of infection clearance. Summary A greater understanding of fungal yeast infections has also shown the ability for cell-mediated apoptosis in response to Amphotericin B damaging the fungal cell. This supports treatment methods that can still cause cell death with lower dosages being required, though this drug’s specific mechanism of cell membrane binding is not entirely understood. This demonstrates that alternative or dual action treatments may become mainstream or required outside the initial trio of antifungal drug classes.

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Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris

Cited by 11 publications

References 99 publications

Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs

Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs

Carbon Dioxide Controls Fungal Fitness and Skin Tropism ofCandida auris

Candida auris Resistance Mechanisms to Amphotericin B Alternative Treatments Development

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