Molecular basis of resistance to azole antifungals.

Lupetti, A

doi:10.1016/s1471-4914(02)02280-3

Cited by 449Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

Molecular basis of resistance to azole antifungals.

Lupetti, A·2002·Trends in Molecular Medicine

DOI 10.1016/s1471-4914(02)02280-3

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Abstract

The increased incidence of invasive mycoses and the emerging problem of antifungal drug resistance has prompted investigations of the underlying molecular mechanisms, particularly for the azole compounds central to current therapy. The target site for the azoles is the ERG11 gene product, the cytochrome P450 lanosterol 14alpha-demethylase, which is part of the ergosterol biosynthetic pathway. The resulting ergosterol depletion renders fungal cells vulnerable to further membrane damage. Development of azole resistance in fungi may occur through increased levels of the cellular target, upregulation of genes controlling drug efflux, alterations in sterol synthesis and decreased affinity of azoles for the cellular target. Here, we review the adaptative changes in fungi, in particular Candida albicans, in response to inhibitors of ergosterol biosynthesis. The molecular mechanisms of azole resistance might help in devising more effective antifungal therapies.

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Terbinafine targets squalene epoxidase ERG1, upstream of ERG11, while amorolfine targets ERG2 and ERG24 downstream of ERG11.
“Different from azoles, TERB targets squalene epoxidase ERG1 (NCU08280), an enzyme upstream of sterol 14α-demethylase ERG11, while AMOR targets two enzymes downstream of ERG11 in the ergosterol biosynthetic pathway, sterol C8-C7 isomerase ERG2 and C-14 sterol reductase ERG24 (Lupetti et al., 2002) (Figure 1).”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Lupetti et al., 2002

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Authors: Lupetti, A.
Affiliations: University of Pisa (IT)
Corresponding author: Lupetti, A
ORCID: Lupetti, A
Venue: Trends in Molecular Medicine
Publisher: Elsevier BV
Published: 2002-02-01
Volume: 8
Issue: 2
Pages: 76-81
ISSN: 1471-4914 (ISSN-L)
DOI: 10.1016/s1471-4914(02)02280-3
OpenAlex: W2051903523
Cited by: 449
References: 58
Citations by year: 2026: 7 · 2025: 10 · 2024: 24 · 2023: 16 · 2022: 11 · 2021: 12 · 2020: 23 · 2019: 21 · 2018: 18 · 2017: 28 · 2016: 25 · 2015: 31 · 2014: 25 · 2013: 29 · 2012: 17
FWCI: 9.90
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Molecular Medicine (publishedVersion)
PubMed (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
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 › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords: azole resistance, ERG11, ergosterol biosynthesis, Candida albicans, drug efflux pumps, sterol biosynthesis, invasive fungal infections
MeSH terms: Adaptation, Physiological, Antifungal Agents, Azoles, Candida albicans, Ergosterol, Humans, Mycoses, Polyenes, Drug Resistance, Fungal

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Molecular basis of resistance to azole antifungals.

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