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Cited by 30Antifungal resistance and susceptibilityYeasts and Rust Fungi StudiesFungal and yeast genetics research

Molecular epidemiology, antifungal susceptibility, and ERG11 gene mutation of Candida species isolated from vulvovaginal candidiasis: Comparison between recurrent and non-recurrent infections

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Esfahani, Aida, Omran, Ayatollah Nasrollahi, Salehi, Zahra, Shams-Ghahfarokhi, Masoomeh, Ghane, Masood, Eybpoosh, Sana, Razzaghi-Abyaneh, Mehdi·2022·Microbial Pathogenesis
DOI 10.1016/j.micpath.2022.105696
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Abstract

Vulvovaginal candidiasis (VVC) is a prevalent infection of the genitourinary tract affecting millions of women worldwide. In the present study, the importance of virulence factors, ERG11 gene mutations, ERG11 gene expression, and plasma membrane ergosterol content for fluconazole resistance in Candida species was investigated in 200 women suspected of vulvovaginitis. Isolated Candida species were identified using the ITS-restriction fragment length polymorphism (ITS-RFLP) technique. Antifungal susceptibility testing was performed according to the CLSI document. ERG11 gene expression was analyzed using real-time PCR. ERG11 gene mutation analysis was performed using sequencing methods, and the ergosterol content of the cell membrane was determined in fluconazole-resistant isolates. Furthermore, the production of phospholipase and proteinase enzymes was evaluated in recurrent and non-recurrent infections. VVC was diagnosed in 101 (50.5%) of the 200 clinical cases, of which 21 (20.8%) were confirmed as RVVC. Candida albicans was the most prevalent species, followed by C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, and C. guilliermondii. Ketoconazole and fluconazole were the most effective drugs against C. albicans among five tested antifungals with MIC ranges between 0.06 and 16 μg/mL and 0.25-64 μg/mL. Substitutions of A114S, Y257H, T123I and A114V were detected in fluconazole-resistant C. albicans. The ergosterol content of the fungal cell membrane and the mean levels of ERG11 gene expression transcript were higher in fluconazole-resistant C. albicans isolates obtained from RVVC than in those obtained from VVC cases. Phospholipase and proteinase were produced in different amounts in all Candida species isolated from VVC and RVVC cases. In this review, our results demonstrated that several molecular mechanisms, including ERG11 gene expression, changes in the cell membrane ergosterol content, and mutations in ERG11 gene alone or simultaneously involved in fluconazole resistance of C. albicans species and the recurrence of VVC.

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Authors
Esfahani, A., Omran, A. N., Salehi, Z., Shams-Ghahfarokhi, M., Ghane, M., Eybpoosh, S., & Razzaghi-Abyaneh, M.
Affiliations
  • Islamic Azad University Tonekabon (IR)
  • Pasteur Institute of Iran (IR)
Corresponding author
Omran, Ayatollah Nasrollahi
ORCID
Venue
Microbial Pathogenesis
Publisher
Elsevier BV
Published
2022-09
Volume
170
Pages
105696
ISSN
0882-4010 (ISSN-L)
DOI
10.1016/j.micpath.2022.105696
OpenAlex
W4289079912
Cited by
30
References
45
Citations by year
2026: 7 · 2025: 10 · 2024: 7 · 2023: 6
FWCI
2.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Microbial Pathogenesis (acceptedVersion)
  • PubMed (publishedVersion)
Funders
National Institute for Medical Research Development
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
vaginal candidiasis, recurrent vulvovaginal candidiasis, Candida albicans, ERG11, fluconazole resistance, antifungal susceptibility, ergosterol, virulence factors, phospholipase, proteolytic enzymes, Candida glabrata, Candida tropicalis, Candida krusei, Candida parapsilosis, Candida guilliermondii, ketoconazole, molecular epidemiology
MeSH terms
Candida parapsilosis, Antifungal Agents, Candida, Candida albicans, Candidiasis, Vulvovaginal, Ergosterol, Female, Fungal Proteins, Humans, Microbial Sensitivity Tests, Mutation, Peptide Hydrolases, Phospholipases, Fluconazole, Molecular Epidemiology, Drug Resistance, Fungal, Candida tropicalis, Candida glabrata

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