Synergy of the antibiotic colistin with echinocandin antifungals in Candida species

Zeidler, U.; Bougnoux, M.-E.; Lupan, A.; Helynck, O.; Doyen, A.; Garcia, Z.; Sertour, N.; Clavaud, C.; Munier-Lehmann, H.; Saveanu, C.; d'Enfert, C.

doi:10.1093/jac/dks538

Cited by 58Antifungal resistance and susceptibilityFungal and yeast genetics researchAntimicrobial Peptides and Activities

Synergy of the antibiotic colistin with echinocandin antifungals in Candida species

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Zeidler, U., Bougnoux, M.-E., Lupan, A., Helynck, O., Doyen, A., Garcia, Z., Sertour, N., Clavaud, C. +3 more·2013·Journal of Antimicrobial Chemotherapy

DOI 10.1093/jac/dks538

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Abstract

OBJECTIVES: Candida albicans is the most prevalent fungal pathogen of humans, causing a wide range of infections from harmless superficial to severe systemic infections. Improvement of the antifungal arsenal is needed since existing antifungals can be associated with limited efficacy, toxicity and antifungal resistance. Here we aimed to identify compounds that act synergistically with echinocandin antifungals and that could contribute to a faster reduction of the fungal burden. METHODS: A total of 38 758 compounds were tested for their ability to act synergistically with aminocandin, a β-1,3-glucan synthase inhibitor of the echinocandin family of antifungals. The synergy between echinocandins and an identified hit was studied with chemogenomic screens and testing of individual Saccharomyces cerevisiae and C. albicans mutant strains. RESULTS: We found that colistin, an antibiotic that targets membranes in Gram-negative bacteria, is synergistic with drugs of the echinocandin family against all Candida species tested. The combination of colistin and aminocandin led to faster and increased permeabilization of C. albicans cells than either colistin or aminocandin alone. Echinocandin susceptibility was a prerequisite to be able to observe the synergy. A large-scale screen for genes involved in natural resistance of yeast cells to low doses of the drugs, alone or in combination, identified efficient sphingolipid and chitin biosynthesis as necessary to protect S. cerevisiae and C. albicans cells against the antifungal combination. CONCLUSIONS: These results suggest that echinocandin-mediated weakening of the cell wall facilitates colistin targeting of fungal membranes, which in turn reinforces the antifungal activity of echinocandins.

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Screens of chemical libraries have identified compounds that disrupt formation and/or maintenance of biofilms.
“Screens of chemical libraries have identified compounds that disrupt formation and/or maintenance of biofilms (25, 101, 185, 210).”
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Relative Frequency of Paradoxical Growth and Trailing Effect with Caspofungin, Micafungin, Anidulafungin, and the Novel Echinocandin Rezafungin against Candida Species
Tóth, Z., Forgács, L., Kardos, T., Kovács, R., Locke, J. B., Kardos, G., Nagy, F., Borman, A. M., Adnan, A., & Majoros, L. (2020) · Journal of Fungi · doi:10.3390/jof6030136 · Cited by 20 · see citing works

Authors: Zeidler, U., Bougnoux, M.-E., Lupan, A., Helynck, O., Doyen, A., Garcia, Z., Sertour, N., Clavaud, C., Munier-Lehmann, H., Saveanu, C., & d'Enfert, C.
Affiliations: Institut Pasteur (FR)
Hôpital Necker-Enfants Malades (FR)
Centre National de la Recherche Scientifique (FR)
ORCID: Bougnoux, M.-E.
Garcia, Z.
Clavaud, C.
Saveanu, C.
Venue: Journal of Antimicrobial Chemotherapy
Publisher: Oxford University Press (OUP)
Published: 2013-02-01
Volume: 68
Issue: 6
Pages: 1285-1296
ISSN: 0305-7453 (ISSN-L)
1460-2091
DOI: 10.1093/jac/dks538
OpenAlex: W2128824216
Cited by: 58
References: 72
Citations by year: 2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 6 · 2018: 2 · 2017: 6 · 2016: 5 · 2015: 3 · 2014: 1 · 2013: 4
FWCI: 3.15
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Antimicrobial Chemotherapy (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, cc-by-nc-sa)
HighWire Press Open Archive (submittedVersion)
Funders: Jawaharlal Nehru University
University of Aberdeen
Agence Nationale de la Recherche (ANR-08-JCJC-0019)
Centre Hospitalier Universitaire Vaudois
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 › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
Keywords: colistin, echinocandins, Candida albicans, Candida species, drug synergy, combination antifungal therapy, cell wall integrity, sphingolipid biosynthesis, chitin synthesis, antifungal resistance, Saccharomyces cerevisiae
MeSH terms: Animals, Antifungal Agents, Candida, Candidiasis, Cell Membrane Permeability, Cell Wall, Chitin, Colistin, Drug Synergism, Coloring Agents, Genotype, Indicator Dilution Techniques, Mice, Inbred BALB C, Microbial Sensitivity Tests, Mutation, Propidium, Saccharomyces cerevisiae, Sphingolipids, Gene Library, Mice, Echinocandins, Lipopeptides, Genetic Fitness

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Synergy of the antibiotic colistin with echinocandin antifungals in Candida species

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