Comparative Genomics for the Elucidation of Multidrug Resistance in Candida lusitaniae
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Abstract
Antifungal resistance is an inevitable phenomenon when fungal pathogens are exposed to antifungal drugs. These drugs can be grouped in four distinct classes (azoles, candins, polyenes, and pyrimidine analogs) and are used in different clinical settings. Failures in therapy implicate the sequential or combined use of these different drug classes, which can result in some cases in the development of multidrug resistance (MDR). MDR is particularly challenging in the clinic since it drastically reduces possible treatment alternatives. In this study, we report the rapid development of MDR in Candida lusitaniae in a patient, which became resistant to all known antifungal agents used until now in medicine. To understand how MDR developed in C. lusitaniae , whole-genome sequencing followed by comparative genome analysis was undertaken in sequential MDR isolates. This helped to detect all specific mutations linked to drug resistance and explained the different MDR patterns exhibited by the clinical isolates.
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“…of MFS7 , a multidrug transporter protein that mediated azole-5-FC cross-resistance in Clavispora lusitaniae (formerly Candida lusitaniae ) [94] Billmyre et al. found that deletion of the mismatch repair gene, MSH2 , in C. deuterogattii also led to an elevated rate of 5-FC resistance [95].”
- Authors
- Kannan, A., Asner, S. A., Trachsel, E., Kelly, S., Parker, J., & Sanglard, D.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Swansea University (GB)
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2019-12-24
- Volume
- 10
- Issue
- 6
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC6935856
- OpenAlex
- W2998321296
- Cited by
- 63
- References
- 65
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 10 · 2023: 8 · 2022: 12 · 2021: 8 · 2020: 3
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-02-11)
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IRIS (submittedVersion, cc-by)
- SERVAL (Université de Lausanne) (submittedVersion, cc-by)
- Funders
- Swiss National Science Foundation (31003A_172958)
- 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 lusitaniae, multidrug resistance, antifungal resistance, comparative genomics, drug resistance mutations, azoles, polyenes, echinocandin resistance, pyrimidine analogues, clinical isolates, whole genome sequencing
- MeSH terms
- Azoles, Candida, Flucytosine, Fungal Proteins, Polymorphism, Single Nucleotide, Drug Resistance, Fungal, Comparative Genomic Hybridization
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