A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans

Hélène Martin-Yken (Corresponding Author), Tina Bedekovic, Alexandra C. Brand, Mathias L. Richard, Sadri Znaidi, Christophe d'Enfert, Etienne Dague

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Abstract

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.
Original languageEnglish
Pages (from-to)10-19
Number of pages10
JournalThe Cell Surface
Volume4
Early online date29 Oct 2018
DOIs
Publication statusPublished - Dec 2018

Bibliographical note

Dr. Jean-Luc Parrou (LISBP, Toulouse) for vector YEplac195 PGK/CYC1 and Gregory Da Costa (INRA, Jouy-en-Josas) for technical help.

SZ is an Institut Pasteur International Network Affiliate Program Fellow (Institut Pasteur de Tunis, Institut Pasteur, Paris) and has also been supported by grants from the European commission (FinSysB PITN-GA-2008-214004), the Agence Nationale de la Recherche (KANJI, ANR-08-MIE- 033-01) and the French Government’s Investissement d’Avenir program (Institut de Recherche Technologique BIOASTER, ANR-10-AIRT-03) to Chd’E.

HMY acknowledges the FEBS society and the organizers of the Human Fungal Pathogen Schools 2015 and 2017 for a great introduction to C. albicans and other human fungal pathogens, as well as Formation permanente of the Centre INRA Toulouse Occitanie for financing her attendance to these researcher schools.

HMY is forever grateful to Frans M. Klis for his kindness throughout the years and his great advice to “Start working on C. albicans”.

Keywords

  • Fungal Cell Wall
  • Adhesion
  • Caspofungin
  • Atomic Force Microscopy
  • Candida albicans

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