The DOI matches its Crossref record; 237 of the 237 references it cites were found in a registry or an index.
Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond
Open accessAbstract
Fungal infections are a major contributor to infectious disease-related deaths across the globe. Candida species are among the most common causes of invasive mycotic disease, with Candida albicans reigning as the leading cause of invasive candidiasis. Given that fungi are eukaryotes like their human host, the number of unique molecular targets that can be exploited for antifungal development remains limited. Currently, there are only three major classes of drugs approved for the treatment of invasive mycoses, and the efficacy of these agents is compromised by the development of drug resistance in pathogen populations. Notably, the emergence of additional drug-resistant species, such as Candida auris and Candida glabrata, further threatens the limited armamentarium of antifungals available to treat these serious infections. Here, we describe our current arsenal of antifungals and elaborate on the resistance mechanisms Candida species possess that render them recalcitrant to therapeutic intervention. Finally, we highlight some of the most promising therapeutic strategies that may help combat antifungal resistance, including combination therapy, targeting fungal-virulence traits, and modulating host immunity. Overall, a thorough understanding of the mechanistic principles governing antifungal drug resistance is fundamental for the development of novel therapeutics to combat current and emerging fungal threats.
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“In addition, large-scale genomic alterations, including aneuploidy, loss-of-heterozygosity (LOH), and chromosomal rearrangements, can affect the expression of drug targets, efflux pumps, and other resistance factors (7).”
From Potential role of lysine acetylation in the stepwise adaptation of Candida albicans to fluconazole (2025) · cites this paper as [7]
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“These mutations lead to either the overexpression of the enzyme itself (14) or alterations in its activity that can lower fluconazole’s binding strength, leading to reduced drug effectiveness (15).”
From Candida albicans enhances iron uptake to maintain fluconazole resistance (2025) · cites this paper as [15]
In the citing paper
“the only new class of antifungal drugs developed in decades, the echinocandins, displays negligible antifungal activity against Cryptococcus spp.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [2]
In the citing paper
“Treatment options for invasive cryptococcal infection are limited, given that Cryptococcus spp. are intrinsically resistant to echinocandins and that they employ an arsenal of defences that enable resistance to azoles2,8.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [2]
In the citing paper
“the polyene amphotericin B has been the primary treatment for cryptococcal infection for more than half a century, despite the fact that it causes substantial toxicity and that its availability is limited by economic and logistical constraints2,4”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [2]
In the citing paper
“current antifungal drug treatments for invasive fungal infections are limited to polyenes, azoles and echinocandins2”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [2]
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“Combination therapy has the potential to confer enhanced efficacy and fungal selectivity while reducing vulnerability to the evolution of resistance2.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [2]
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Cites
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The Genetic Landscape of a Cell
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Worldwide emergence of resistance to antifungal drugs challenges human health and food security
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Flagged first, then by citations
Research works printed but not linked: 1
- Besterman, J.; Nguyen, D. T.; Ste-Croix, H. MGCD290, an Oral Fungal Hos2 Inhibitor, Enhances the Antifungal Properties of Fluconazole Following Multiple-or Single-Dose Oral Administration in Pre-and Post-Infection Settings. In Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) ; MethylGene, Inc.: San Francisco, CA, 2012; Vol. Poster M-1711.
Cited by
Sorted by citations
Treatment strategies for cryptococcal infection: challenges, advances and future outlook
Iyer, K. R., Revie, N. M., Fu, C., Robbins, N., & Cowen, L. E. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00511-0 · Cited by 363
Self-citationAntifungal drug-resistance mechanisms in Candida biofilms
Kaur, J., & Nobile, C. J. (2022) · Current Opinion in Microbiology · doi:10.1016/j.mib.2022.102237 · Cited by 279
Geng, C., He, S., Yu, S., Johnson, H. M., Shi, H., Chen, Y., Chan, Y. K., He, W., Qin, M., Li, X., et al. (2024) · Advanced Materials · doi:10.1002/adma.202310599 · Cited by 252
The importance of antimicrobial resistance in medical mycology
Gow, N. A. R., Johnson, C., Berman, J. G., Coste, A. T., Cuomo, C. A., Perlin, D. S., Bicanic, T. A., Harrison, T. S., Wiederhold, N. P., Bromley, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32249-5 · Cited by 232
Mechanisms of Antifungal Properties of Metal Nanoparticles
Slavin, Y. N., & Bach, H. (2022) · Nanomaterials · doi:10.3390/nano12244470 · Cited by 222
Metadata
- Authors
- Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Cowen, Leah E.
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-05-22
- Volume
- 121
- Issue
- 6
- Pages
- 3390-3411
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- PMC
- PMC8519031
- OpenAlex
- W3026958586
- Cited by
- 801
- References
- 237
- Citations by year
- 2026: 109 · 2025: 192 · 2024: 168 · 2023: 133 · 2022: 132 · 2021: 63 · 2020: 4
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Chemical Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research (FDN-154288)
- National Institute of Allergy and Infectious Diseases (1R01AI127375-01)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- antifungal resistance, Candida albicans, Candida auris, Candida glabrata, invasive candidiasis, antifungal agents, molecular mechanisms of resistance, combination antifungal therapy, fungal virulence factors, emerging fungal pathogens
- MeSH terms
- Drug Development, Animals, Antifungal Agents, Candida, Candida albicans, Drug Therapy, Combination, Humans, Mycoses, Virulence, Molecular Structure, Signal Transduction, Drug Resistance, Fungal, Candida glabrata
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