A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans
Drug resistance and cellular adhesion are two key elements of both dissemination and prevalence of the human fungal pathogen Candida albicans. Smi1 belongs to a family of hub proteins conserved among the fungal kingdom whose functions in cellular signaling affect morphogenesis, cell wall synthesis a...
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doaj-71e695beb51b4a88b808dc02f25082582020-11-25T01:43:52ZengElsevierThe Cell Surface2468-23302018-12-0141019A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicansHélène Martin-Yken0Tina Bedekovic1Alexandra C. Brand2Mathias L. Richard3Sadri Znaidi4Christophe d'Enfert5Etienne Dague6LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France; LAAS CNRS UPR 8001, Université de Toulouse, Toulouse, France; Corresponding author at: Institut Louis Malardé, BP30, 98713 Papeete, Tahiti, French Polynesia.MRC Centre for Medical Mycology, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, United KingdomMRC Centre for Medical Mycology, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, United KingdomINRA, UMR1319 Micalis, AgroParisTech, Jouy-en-Josas, FranceInstitut Pasteur de Tunis, Laboratoire de Microbiologie Moléculaire, Vaccinologie et Développement Biotechnologique, 13 Place Pasteur, Tunis-Belvédère, Tunisia; Institut Pasteur, INRA USC2019, Unité Biologie et Pathogénicité Fongiques, 25 rue du Docteur Roux, Paris, FranceInstitut Pasteur, INRA USC2019, Unité Biologie et Pathogénicité Fongiques, 25 rue du Docteur Roux, Paris, FranceLAAS CNRS UPR 8001, Université de Toulouse, Toulouse, FranceDrug resistance and cellular adhesion are two key elements of both dissemination and prevalence of the human fungal pathogen Candida albicans. Smi1 belongs to a family of hub proteins conserved among the fungal kingdom whose functions in cellular signaling affect morphogenesis, cell wall synthesis and stress resistance. The data presented here indicate that C. albicans SMI1 is a functional homolog of Saccharomyces cerevisiae KNR4 and is involved in the regulation of cell wall synthesis. Expression of SMI1 in S. cerevisiae knr4Δ null mutants rescued their sensitivity to caspofungin and to heat stress. Deletion of SMI1 in C. albicans resulted in sensitivity to the cell-wall-perturbing compounds Calcofluor White and Caspofungin. Analysis of wild-type and mutant cells by Atomic Force Microscopy showed that the Young’s Modulus (stiffness) of the cell wall was reduced by 85% upon deletion of SMI1, while cell surface adhesion measured by Force Spectroscopy showed that the surface expression of adhesive molecules was also reduced in the mutant. Over-expression of SMI1, on the contrary, increased cell surface adhesion by 6-fold vs the control strain. Finally, Smi1-GFP localized as cytoplasmic patches and concentrated spots at the sites of new cell wall synthesis including the tips of growing hyphae, consistent with a role in cell wall regulation. Thus, Smi1 function appears to be conserved across fungi, including the yeast S. cerevisiae, the yeast and hyphal forms of C. albicans and the filamentous fungus Neurospora crassa. Keywords: Fungal cell wall, Adhesion, Caspofungin, Candida albicans, Atomic Force Microscopyhttp://www.sciencedirect.com/science/article/pii/S2468233018300239 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hélène Martin-Yken Tina Bedekovic Alexandra C. Brand Mathias L. Richard Sadri Znaidi Christophe d'Enfert Etienne Dague |
spellingShingle |
Hélène Martin-Yken Tina Bedekovic Alexandra C. Brand Mathias L. Richard Sadri Znaidi Christophe d'Enfert Etienne Dague A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans The Cell Surface |
author_facet |
Hélène Martin-Yken Tina Bedekovic Alexandra C. Brand Mathias L. Richard Sadri Znaidi Christophe d'Enfert Etienne Dague |
author_sort |
Hélène Martin-Yken |
title |
A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans |
title_short |
A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans |
title_full |
A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans |
title_fullStr |
A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans |
title_full_unstemmed |
A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans |
title_sort |
conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen candida albicans |
publisher |
Elsevier |
series |
The Cell Surface |
issn |
2468-2330 |
publishDate |
2018-12-01 |
description |
Drug resistance and cellular adhesion are two key elements of both dissemination and prevalence of the human fungal pathogen Candida albicans. Smi1 belongs to a family of hub proteins conserved among the fungal kingdom whose functions in cellular signaling affect morphogenesis, cell wall synthesis and stress resistance. The data presented here indicate that C. albicans SMI1 is a functional homolog of Saccharomyces cerevisiae KNR4 and is involved in the regulation of cell wall synthesis. Expression of SMI1 in S. cerevisiae knr4Δ null mutants rescued their sensitivity to caspofungin and to heat stress. Deletion of SMI1 in C. albicans resulted in sensitivity to the cell-wall-perturbing compounds Calcofluor White and Caspofungin. Analysis of wild-type and mutant cells by Atomic Force Microscopy showed that the Young’s Modulus (stiffness) of the cell wall was reduced by 85% upon deletion of SMI1, while cell surface adhesion measured by Force Spectroscopy showed that the surface expression of adhesive molecules was also reduced in the mutant. Over-expression of SMI1, on the contrary, increased cell surface adhesion by 6-fold vs the control strain. Finally, Smi1-GFP localized as cytoplasmic patches and concentrated spots at the sites of new cell wall synthesis including the tips of growing hyphae, consistent with a role in cell wall regulation. Thus, Smi1 function appears to be conserved across fungi, including the yeast S. cerevisiae, the yeast and hyphal forms of C. albicans and the filamentous fungus Neurospora crassa. Keywords: Fungal cell wall, Adhesion, Caspofungin, Candida albicans, Atomic Force Microscopy |
url |
http://www.sciencedirect.com/science/article/pii/S2468233018300239 |
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