Cited by 290Fungal and yeast genetics researchAntifungal resistance and susceptibilityMicrobial Natural Products and Biosynthesis

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Stress, drugs, and evolution: the role of cellular signaling in fungal drug resistance.

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Cowen, Leah E., Steinbach, William J.·2008·Eukaryotic Cell

DOI 10.1128/ec.00041-08PMC PMC2394973

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Abstract

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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Authors: Cowen, L. E., & Steinbach, W. J.
Affiliations: Duke University (US)
Corresponding author: Cowen, Leah E.
ORCID: Cowen, Leah E.
Steinbach, William J.
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
DOI: 10.1128/ec.00041-08
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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Stress, drugs, and evolution: the role of cellular signaling in fungal drug resistance.

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