Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

Whaley, Sarah G.; Berkow, Elizabeth L.; Rybak, Jeffrey M.; Nishimoto, Andrew T.; Barker, Katherine S.; Rogers, P. David

doi:10.3389/fmicb.2016.02173

Cited by 900Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal and yeast genetics research

Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

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Whaley, Sarah G., Berkow, Elizabeth L., Rybak, Jeffrey M., Nishimoto, Andrew T., Barker, Katherine S., Rogers, P. David·2017·Frontiers in Microbiology

DOI 10.3389/fmicb.2016.02173PMC PMC5226953

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Abstract

Within the limited antifungal armamentarium, the azole antifungals are the most frequent class used to treat Candida infections. Azole antifungals such as fluconazole are often preferred treatment for many Candida infections as they are inexpensive, exhibit limited toxicity, and are available for oral administration. There is, however, extensive documentation of intrinsic and developed resistance to azole antifungals among several Candida species. As the frequency of azole resistant Candida isolates in the clinical setting increases, it is essential to elucidate the mechanisms of such resistance in order to both preserve and improve upon the azole class of antifungals for the treatment of Candida infections. This review examines azole resistance in infections caused by C. albicans as well as the emerging non-albicans Candida species C. parapsilosis, C. tropicalis, C. krusei, and C. glabrata and, in particular, describes the current understanding of molecular basis of azole resistance in these fungal species.

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C. krusei is highly resistant to fluconazole associated with an increased incidence of invasive candidiasis, candidemia, and mortality.
“(iii) C. krusei is highly resistant to fluconazole associated with an increased incidence of invasive candidiasis, candidemia, and mortality.4,40”
From Aggregation and adhesion ability of various probiotic strains and Candida species: An in vitro study (2024) · cites this paper as [40]
The Candida krusei section states that C. krusei is intrinsically resistant to fluconazole. The Introduction reports that its involvement in invasive candidiasis and candidemia has increased over time. Our copy does not link that increase causally to fluconazole resistance or report increased mortality from C. krusei; the Azole resistance in Candida infections section says the role of fluconazole exposure in its increased infection rate is controversial. (LLM, conf=0.88)
Experimental — accuracy not yet measured
C. glabrata has the highest prevalence of NAC species isolated from oral candidiasis.
“(ii) C. glabrata has the highest prevalence of NAC species isolated from oral candidiasis”
From Aggregation and adhesion ability of various probiotic strains and Candida species: An in vitro study (2024) · cites this paper as [40]
The Introduction (page unavailable) identifies C. glabrata as a species that can cause oral infections and says it is the most commonly isolated NAC species in candidemia in several regions, vulvovaginal candidiasis, and candiduria. It does not say C. glabrata has the highest prevalence among NAC species isolated from oral candidiasis; the cited ranking concerns other infection sites. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Altered drug uptake or efflux and changes in ergosterol biosynthesis are the major known mechanisms of azole resistance.
“Altered drug uptake or efflux and changes in ergosterol biosynthesis (the target for azole drugs) 8 are the major known mechanisms of azole resistance.”
From Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia (2018) · cites this paper as [8]
C. albicans is the most common cause of Candida infection.
“This is particularly significant given that (i) C. albicans is the most common cause of Candida infection”
From Aggregation and adhesion ability of various probiotic strains and Candida species: An in vitro study (2024) · cites this paper as [40]
Candida resistance is mediated by amplification of transcription factors such as UPC2, TAC1, MRR1, or CgPdr1, causing ERG11 overexpression or drug efflux transporter overexpression; ERG11 point mutations can alter LDM structure.
“Resistance in Candida species is mediated by the amplification of zinc cluster transcription factors such as UPC2, TAC1, MRR1, or CgPdr1 (particularly in C. glabrata). UPC2 upregulation causes the overexpression of the LDM gene ERG11, while mutations in TAC1, MRR1, and CgPdr1 overexpress drug efflux transporters. Additionally, resistance can occur via altered LDM structure from point mutations in”
From Investigational Agents for the Treatment of Resistant Yeasts and Molds (2021) · cites this paper as [9]

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Authors: Whaley, S. G., Berkow, E. L., Rybak, J. M., Nishimoto, A. T., Barker, K. S., & Rogers, P. D.
Affiliations: University of Tennessee Health Science Center (US)
Corresponding author: Rogers, P. David
ORCID: Whaley, Sarah G.
Berkow, Elizabeth L.
Rybak, Jeffrey M.
Nishimoto, Andrew T.
Barker, Katherine S.
Rogers, P. David
Venue: Frontiers in Microbiology
Publisher: Frontiers Media SA
Published: 2017-01-12
Volume: 7
Pages: 2173-2173
ISSN: 1664-302X (ISSN-L)
DOI: 10.3389/fmicb.2016.02173
PMC: PMC5226953
OpenAlex: W2574417950
Cited by: 900
References: 145
Citations by year: 2026: 77 · 2025: 107 · 2024: 95 · 2023: 109 · 2022: 115 · 2021: 124 · 2020: 99 · 2019: 92 · 2018: 60 · 2017: 21
FWCI: 11.47
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Microbiology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institutes of Health (R01 AI058145)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: azole resistance, Candida albicans, non-albicans Candida, Candida parapsilosis, Candida tropicalis, Candida krusei, Candida glabrata, fluconazole, resistance mechanisms, molecular basis of resistance, candidiasis

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Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

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