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Cited by 11Antifungal resistance and susceptibilityFungal and yeast genetics researchBacterial biofilms and quorum sensing

Transcription Factors of CAT1, EFG1, and BCR1 Are Effective in Persister Cells of Candida albicans-Associated HIV-Positive and Chemotherapy Patients

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Aboualigalehdari, Elham, Tahmasebi Birgani, Maryam, Fatahinia, Mahnaz, Hosseinzadeh, Mehran·2021·Frontiers in Microbiology
DOI 10.3389/fmicb.2021.651221PMC PMC8425484
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Abstract

Background: Biofilm is an accumulation of cells, which are formed on mucosal surfaces of the host as well as on medical devices. The inherent resistance of Candida strains producing biofilms to antimicrobial agents is an important and key feature for biofilm growth, which can lead to treatment failure. This resistance is due to the regulatory increase of the output pumps, the presence of extracellular matrix, and the existence of persister cells. Persister cells are phenotypic variants that have MICs similar to antibiotic-sensitive populations and are able to tolerate high doses of antibiotics. The current study investigated the possible role of EFG1, BCR1, and CAT1 in the establishment or maintenance of persister cells in Candida albicans strains that produce biofilms. Methods: After identifying Candida isolates by molecular methods, C. albicans isolates were confirmed by sequencing. Isolation of persister cells and determination of their MIC were performed by microdilution method. Then, RNA extraction and cDNA synthesis were performed from 60 C. albicans isolates under promoting and inducing conditions. Afterward, the mean expression of BCR1, EFG1, and CAT1 genes in both persister and non-persister groups was calculated using real-time qPCR. Phylogeny tree of persister and non-persister group isolates was drawn using ITS fragment. Results: A total of 77 persister isolates were taken from the oral cavity of HIV patients as well as from patients undergoing chemotherapy. Biofilm intensity in persister isolates separated from HIV-infected patients was different from the non-persister group. The mean fold change of BCR1 (10.73), CAT1 (15.34), and EFG1 (2.41) genes in persister isolates was significantly higher than these genes in isolates without persister. Conclusion: It can be concluded that the most important factor in the production of persister cells is biofilm binding and production, not biofilm development or mature biofilm production, which was found in the expression of BCR1 gene without change in the expression of EFG1 gene in the persister group. Also, catalase plays an essential role in the production of persister in C. albicans biofilm producers with ROS detoxification.

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  • BCR1 exhibits significantly higher expression in persistent C. albicans populations compared to non-persistent groups, both with and without AmB induction.

    “Further, BCR1, a gene that promotes biofilm formation by regulating adhesion through the major surface adhesins Hwp1 and Als3, exhibits significantly higher expression in persistent C. albicans populations compared to non-persistent groups, both with and without AmB induction.”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [81]

    The Results (Inducing Condition, Table 5) report significantly higher BCR1 expression in persister isolates under inducing conditions (p = 0.008). Under promoting conditions, expression was higher but not significant (p = 0.08), so the claim of significance in both conditions is unsupported. The Methods define these conditions by biofilm formation, not by the presence or absence of AmB induction; page numbers are unavailable in our copy. (LLM, conf=0.92)

    Experimental — accuracy not yet measured

  • EFG1 has no significant difference between the two groups.

    “Meanwhile, EFG1, a gene regulates biofilm development and cell morphology, has no significant difference between the two groups [81].”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [81]

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Cited by

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Authors
Aboualigalehdari, E., Tahmasebi Birgani, M., Fatahinia, M., & Hosseinzadeh, M.
Affiliations
Ahvaz Jundishapur University of Medical Sciences (IR)
Corresponding author
Fatahinia, Mahnaz
ORCID
Venue
Frontiers in Microbiology
Publisher
Frontiers Media SA
Published
2021-08-24
Volume
12
Pages
651221-651221
ISSN
1664-302X (ISSN-L)
DOI
10.3389/fmicb.2021.651221
PMC
PMC8425484
OpenAlex
W3196239099
Cited by
11
References
7
Citations by year
2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1
FWCI
0.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Microbiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ahvaz Jundishapur University of Medical Sciences
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords
Candida albicans, persister cells, biofilm, transcription factors, BCR1, EFG1, CAT1, catalase, gene expression, HIV, chemotherapy patients, oral candidiasis, biofilm-associated infections, antifungal resistance, reactive oxygen species scavenging

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