Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity
[EN]Fission yeast contains three essential β(1,3)-D-glucan synthases (GSs), Bgs1, Bgs3, and Bgs4, with non-overlapping roles in cell integrity and morphogenesis. Only the bgs4+ mutants pbr1-8 and pbr1-6 exhibit resistance to GS inhibitors, even in the presence of the wild-type (WT) sequences of bgs1...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/166729 |
| Acceso en línea: | http://hdl.handle.net/10366/166729 https://doi.org/10.3390/ph14121332 |
| Access Level: | acceso abierto |
| Palabra clave: | fungi invasive fungal infections fission yeast cell wall β(1,3)-D-glucan synthase antifungal drugs echinocandin drugs Fks resistance hot spots Cytokinesis Septation Cell separation Cell integrity 2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica 2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica |
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Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell IntegrityYagüe, NataliaGómez-Delgado, LauraCurto, M. ÁngelesCarvalho, Vanessa da Silva Dutra deMoreno, M. BelénPérez, PilarRibas Elcorobarrutia, Juan CarlosGarcía Cortés, Juan Carlosfungiinvasive fungal infectionsfission yeastcell wallβ(1,3)-D-glucan synthaseantifungal drugsechinocandin drugsFks resistance hot spotsCytokinesisSeptationCell separationCell integrity2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica2414 Microbiología2407 Biología Celular2302.21 Biología Molecular2302 Bioquímica[EN]Fission yeast contains three essential β(1,3)-D-glucan synthases (GSs), Bgs1, Bgs3, and Bgs4, with non-overlapping roles in cell integrity and morphogenesis. Only the bgs4+ mutants pbr1-8 and pbr1-6 exhibit resistance to GS inhibitors, even in the presence of the wild-type (WT) sequences of bgs1+ and bgs3+. Thus, Bgs1 and Bgs3 functions seem to be unaffected by those GS inhibitors. To learn more about echinocandins’ mechanism of action and resistance, cytokinesis progression and cell death were examined by time-lapse fluorescence microscopy in WT and pbr1-8 cells at the start of treatment with sublethal and lethal concentrations of anidulafungin, caspofungin, and micafungin. In WT, sublethal concentrations of the three drugs caused abundant cell death that was either suppressed (anidulafungin and micafungin) or greatly reduced (caspofungin) in pbr1-8 cells. Interestingly, the lethal concentrations induced differential phenotypes depending on the echinocandin used. Anidulafungin and caspofungin were mostly fungistatic, heavily impairing cytokinesis progression in both WT and pbr1-8. As with sublethal concentrations, lethal concentrations of micafungin were primarily fungicidal in WT cells, causing cell lysis without impairing cytokinesis. The lytic phenotype was suppressed again in pbr1-8 cells. Our results suggest that micafungin always exerts its fungicidal effect by solely inhibiting Bgs4. In contrast, lethal concentrations of anidulafungin and caspofungin cause an early cytokinesis arrest, probably by the combined inhibition of several GSs.202520252021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/166729https://doi.org/10.3390/ph14121332reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésPGC2018-098924-B-I00CSI150P20CLU-2017-03Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1667292026-06-07T06:28:51Z |
| dc.title.none.fl_str_mv |
Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity |
| title |
Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity |
| spellingShingle |
Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity Yagüe, Natalia fungi invasive fungal infections fission yeast cell wall β(1,3)-D-glucan synthase antifungal drugs echinocandin drugs Fks resistance hot spots Cytokinesis Septation Cell separation Cell integrity 2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica 2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica |
| title_short |
Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity |
| title_full |
Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity |
| title_fullStr |
Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity |
| title_full_unstemmed |
Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity |
| title_sort |
Echinocandin Drugs Induce Differential Effects in Cytokinesis Progression and Cell Integrity |
| dc.creator.none.fl_str_mv |
Yagüe, Natalia Gómez-Delgado, Laura Curto, M. Ángeles Carvalho, Vanessa da Silva Dutra de Moreno, M. Belén Pérez, Pilar Ribas Elcorobarrutia, Juan Carlos García Cortés, Juan Carlos |
| author |
Yagüe, Natalia |
| author_facet |
Yagüe, Natalia Gómez-Delgado, Laura Curto, M. Ángeles Carvalho, Vanessa da Silva Dutra de Moreno, M. Belén Pérez, Pilar Ribas Elcorobarrutia, Juan Carlos García Cortés, Juan Carlos |
| author_role |
author |
| author2 |
Gómez-Delgado, Laura Curto, M. Ángeles Carvalho, Vanessa da Silva Dutra de Moreno, M. Belén Pérez, Pilar Ribas Elcorobarrutia, Juan Carlos García Cortés, Juan Carlos |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
fungi invasive fungal infections fission yeast cell wall β(1,3)-D-glucan synthase antifungal drugs echinocandin drugs Fks resistance hot spots Cytokinesis Septation Cell separation Cell integrity 2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica 2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica |
| topic |
fungi invasive fungal infections fission yeast cell wall β(1,3)-D-glucan synthase antifungal drugs echinocandin drugs Fks resistance hot spots Cytokinesis Septation Cell separation Cell integrity 2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica 2414 Microbiología 2407 Biología Celular 2302.21 Biología Molecular 2302 Bioquímica |
| description |
[EN]Fission yeast contains three essential β(1,3)-D-glucan synthases (GSs), Bgs1, Bgs3, and Bgs4, with non-overlapping roles in cell integrity and morphogenesis. Only the bgs4+ mutants pbr1-8 and pbr1-6 exhibit resistance to GS inhibitors, even in the presence of the wild-type (WT) sequences of bgs1+ and bgs3+. Thus, Bgs1 and Bgs3 functions seem to be unaffected by those GS inhibitors. To learn more about echinocandins’ mechanism of action and resistance, cytokinesis progression and cell death were examined by time-lapse fluorescence microscopy in WT and pbr1-8 cells at the start of treatment with sublethal and lethal concentrations of anidulafungin, caspofungin, and micafungin. In WT, sublethal concentrations of the three drugs caused abundant cell death that was either suppressed (anidulafungin and micafungin) or greatly reduced (caspofungin) in pbr1-8 cells. Interestingly, the lethal concentrations induced differential phenotypes depending on the echinocandin used. Anidulafungin and caspofungin were mostly fungistatic, heavily impairing cytokinesis progression in both WT and pbr1-8. As with sublethal concentrations, lethal concentrations of micafungin were primarily fungicidal in WT cells, causing cell lysis without impairing cytokinesis. The lytic phenotype was suppressed again in pbr1-8 cells. Our results suggest that micafungin always exerts its fungicidal effect by solely inhibiting Bgs4. In contrast, lethal concentrations of anidulafungin and caspofungin cause an early cytokinesis arrest, probably by the combined inhibition of several GSs. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10366/166729 https://doi.org/10.3390/ph14121332 |
| url |
http://hdl.handle.net/10366/166729 https://doi.org/10.3390/ph14121332 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
PGC2018-098924-B-I00 CSI150P20 CLU-2017-03 |
| dc.rights.none.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
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reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca instname:Universidad de Salamanca (USAL) |
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Universidad de Salamanca (USAL) |
| reponame_str |
GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| collection |
GREDOS. Repositorio Institucional de la Universidad de Salamanca |
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1869407441762910208 |
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15.811543 |