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Updated: Sep 22, 2025
Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
E-site drug specificity of the human pathogen Candida albicans ribosome
Yury Zgadzay1,2, Olga Kolosova1, Artem Stetsenko3
1Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, University of Strasbourg, Illkirch, France.
Abstract:
Candida albicans is a widespread commensal fungus with substantial pathogenic potential and steadily increasing resistance to current antifungal drugs. It is known to be resistant to cycloheximide (CHX) that binds to the E-transfer RNA binding site of the ribosome. Because of lack of structural information, it is neither possible to understand the nature of the resistance nor to develop novel inhibitors. To overcome this issue, we determined the structure of the vacant C. albicans 80S ribosome at 2.3 angstroms and its complexes with bound inhibitors at resolutions better than 2.9 angstroms using cryo-electron microscopy. Our structures reveal how a change in a conserved amino acid in ribosomal protein eL42 explains CHX resistance in C. albicans and forms a basis for further antifungal drug development.
Insights
Candida albicans resistance to cycloheximide (CHX) was structurally uncharacterized. New cryo-electron microscopy structures reveal a conserved amino acid change in ribosomal protein eL42 as the cause, enabling new antifungal drug development.
Area of Science:
- Structural Biology
- Mycology
- Biochemistry
Background:
- * *Candida albicans* is a fungus that can cause serious infections and is increasingly resistant to antifungal drugs.
- * Cycloheximide (CHX) is an antifungal drug that *C. albicans* is resistant to, due to its binding to the ribosome's E-transfer RNA site.
- * Lack of structural data has hindered understanding of CHX resistance and development of new drugs.
Purpose of the Study:
- * To determine the structure of the *C. albicans* 80S ribosome.
- * To elucidate the structural basis of CHX resistance in *C. albicans*.
- * To provide a foundation for developing novel antifungal inhibitors.
Main Methods:
- * Cryo-electron microscopy (cryo-EM) was used to determine high-resolution structures.
- * Structures of the vacant *C. albicans* 80S ribosome were obtained at 2.3 angstroms.
- * Complexes with bound inhibitors were resolved at resolutions better than 2.9 angstroms.
Main Results:
- * The study determined the structure of the vacant *C. albicans* 80S ribosome.
- * Structures of ribosome-inhibitor complexes were also resolved.
- * A change in a conserved amino acid in ribosomal protein eL42 was identified as the cause of CHX resistance.
Conclusions:
- * The structural findings explain CHX resistance in *C. albicans*.
- * This research provides a basis for the rational design of new antifungal drugs targeting the ribosome.
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