The DOI matches its Crossref record; 247 of the 247 references it cites were found in a registry or an index.
Stress, drugs, and evolution: the role of cellular signaling in fungal drug resistance.
Open accessAbstract
The survival of all organisms depends critically upon interactions with the environment, mediated largely through the action of small molecules.Small molecules can provide the nutrients to support life (195), mediate communication between organisms (25,76, 238), or exert toxicity that threatens viability (86, 183).The discovery of small molecules with exquisite potency and selective toxicity to microbes revolutionized modern medicine, as exemplified by the archetypal antibiotic penicillin, the first broad-spectrum antibiotic and the most famous fungal secondary metabolite (14, 211).There are relatively few antimicrobial structural scaffolds that are purely synthetic in origin, and humans rely heavily upon many natural products and their derivatives as agrochemicals, antimicrobials, immunosuppressants, and antineoplastic agents (24,73,97).Given that small molecules can have profound effects on cellular signaling and are a ubiquitous presence in the environment, it is not surprising that microbes have evolved diverse mechanisms to survive the challenges of exposure to antimicrobial drugs.Antimicrobials represent one of the many stresses that a microbial pathogen must sense and respond to in order to thrive in harsh environmental conditions.Antimicrobial drug resistance mechanisms that span the kingdoms can largely be classified into two broad categories.The first category includes mechanisms to bypass the effects of the antimicrobial on the cell.Such mechanisms include alterations in the drug target that block drug binding (6,99, 165, 227) or increased production of multidrug transporters that simply remove the drug from the cell (72,74, 175, 200, 214).The second category includes mechanisms that allow the cell to cope with druginduced stress.Such mechanisms include metabolic alterations that minimize the toxicity of the drug, as well as the activation of chaperones and signal transduction cascades dedicated to sensing and responding to various stresses (26,32).Alterations in resistance can reflect physiological adaptation to a drug, epigenetic changes, or stable genetic alterations, depending on the nature of the drug, the duration of exposure, and the organism.Drug resistance is of particular importance in fungi as they
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“The 1,3-β-D-glucan synthases are encoded by FKS1, FKS2, and FKS3 in S. cerevisiae, C. glabrata, and C. albicans, and require a regulatory subunit encoded by RHO1 for activity [3], [20], [32], [33].”
From Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata (2012) · cites this paper as [32]
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“The echinocandins are the only novel class of antifungal drugs approved for clinical use in decades and target the biosynthesis of the key fungal cell wall component, 1,3-β-D-glucan [3], [20], [32].”
From Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata (2012) · cites this paper as [32]
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Fungal secondary metabolism — from biochemistry to genomics
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Multidrug-resistance efflux pumps ? not just for resistance
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Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance
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Research works printed but not linked: 1
- Warris, A., C. M. Weemaes, and P. E. Verweij. 2002. Multidrug resistance in Aspergillus fumigatus. N. Engl. J. Med.347:2173-2174.
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Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond
Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00199 · Cited by 801
Self-citationMechanisms of Antifungal Drug Resistance
Cowen, L. E., Sanglard, D., Howard, S. J., Rogers, P. D., & Perlin, D. S. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019752 · Cited by 647
Self-citationEfflux-Mediated Antifungal Drug Resistance
Cannon, R. D., Lamping, E., Holmes, A. R., Niimi, K., Baret, P. V., Keniya, M. V., Tanabe, K., Niimi, M., Goffeau, A., & Monk, B. C. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00051-08 · Cited by 608
Regulatory circuitry governing fungal development, drug resistance, and disease.
Shapiro, R. S., Robbins, N., & Cowen, L. E. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00045-10 · Cited by 576
Self-citationSionov, E., Lee, H., Chang, Y. C., & Kwon-Chung, K. J. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000848 · Cited by 479
Metadata
- Authors
- Cowen, L. E., & Steinbach, W. J.
- Affiliations
- Duke University (US)
- Corresponding author
- Cowen, Leah E.
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2008-05
- Volume
- 7
- Issue
- 5
- Pages
- 747-764
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC2394973
- OpenAlex
- W2156217754
- Cited by
- 285
- References
- 247
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 12 · 2023: 9 · 2022: 14 · 2021: 19 · 2020: 20 · 2019: 10 · 2018: 19 · 2017: 16 · 2016: 14 · 2015: 17 · 2014: 18 · 2013: 22 · 2012: 18
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- Children's Miracle Network Hospitals
- National Institutes of Health
- U.S. Public Health Service (K08 A1061149)
- Canadian Institutes of Health Research (MOP-86452)
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
- Keywords
- fungal drug resistance, antimicrobial resistance, signal transduction, stress response, drug target alterations, multidrug transporter, molecular chaperones, epigenetic modifications, natural products, secondary metabolites, resistance evolution
- MeSH terms
- Antifungal Agents, Aspergillus fumigatus, Candida albicans, Cell Membrane, Cell Wall, Cryptococcus neoformans, Humans, Mycoses, Signal Transduction, Evolution, Molecular, Drug Resistance, Fungal
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