Molecular mechanism of azoles resistant Candida albicans in a patient with chronic mucocutaneous candidiasis
Open accessAbstract
Background: More and more azole-resistant strains emerged through the development of acquired resistance and an epidemiological shift towards inherently less susceptible species. The mechanisms of azoles resistance of Candida albicans is very complicated. In this study, we aim to investigate the mechanism of azole-resistant C. albicans isolated from the oral cavity of a patient with chronic mucocutaneous candidiasis (CMC). Case presentation: CMC diagnosis was given based on clinical manifestations, laboratory test findings and gene sequencing technique. Minimum inhibitory concentration (MIC) of the fungal isolate, obtained from oral cavity termed as CA-R, was obtained by in vitro anti-fungal drugs susceptibility test. To further investigate the resistant mechanisms, we verified the mutations of drug target genes (i.e. ERG11 and ERG3) by Sanger sequencing, and verified the over-expression of ERG11 and drug efflux genes (i.e. CDR1 and CDR2) by RT-PCR. A heterozygous mutation of c.1162A > G resulting in p.K388E was detected in STAT1 of the patient. The expression of CDR1 and CDR2 in CA-R was 4.28-fold and 5.25-fold higher than that of type strain SC5314, respectively. Conclusions: Up-regulation of CDR1 and CDR2 was mainly responsible for the resistance of CA-R. For CMC or other immunodeficiency patients, drug resistance monitoring is necessary.
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The obtained results are consistent with recent studies, which noticed that due to the wide usage of azole drugs and prolonged antifungal therapy, the number of azole-resistant Candida isolates is still increasing.
“The obtained results are consistent with recent studies, which noticed that due to the wide usage of azole drugs and prolonged antifungal therapy, the number of azole-resistant Candida isolates is still increasing (Bhattacharya et al. 2020; Zhang et al. 2020; Tan et al. 2021).”
From In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans (2021) · cites this paper as Zhang et al. 2020
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- Authors
- Zhang, M.-R., Zhao, F., Wang, S., Lv, S., Mou, Y., Yao, C.-L., Zhou, Y., & Li, F.-Q.
- Affiliations
- Chinese Center For Disease Control and Prevention (CN)
- Jilin University (CN)
- Venue
- BMC Infectious Diseases
- Published
- 2020-02-11
- Volume
- 20
- Issue
- 1
- Pages
- 126-126
- ISSN
- 1471-2334 (ISSN-L)
- PMC
- PMC7014776
- OpenAlex
- W3007075185
- Cited by
- 26
- References
- 32
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 4
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Infectious Diseases (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- Peking University First Hospital
- Peking University
- 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 albicans, azole resistance, chronic mucocutaneous candidiasis, CDR1, CDR2, drug efflux pumps, ERG11, ERG3, STAT1 mutation, oral candidiasis, antifungal resistance, immunocompromised patients
- MeSH terms
- Adolescent, Antifungal Agents, Azoles, Candida albicans, Candidiasis, Chronic Mucocutaneous, Fungal Proteins, Humans, Male, Microbial Sensitivity Tests, Mouth, Mutation, Gene Expression Regulation, Fungal, Drug Resistance, Fungal, Membrane Transport Proteins
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