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An Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion

The human fungal commensal Candida albicans can become a serious opportunistic pathogen in immunocompromised hosts. The C. albicans cell adhesion protein Als1p is a highly expressed member of a large family of paralogous adhesins. Als1p can mediate binding to epithelial and endothelial cells, is upr...

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Autores principales: Ho, Vida, Herman-Bausier, Philippe, Shaw, Christopher, Conrad, Karen A., Garcia-Sherman, Melissa C., Draghi, Jeremy, Dufrene, Yves F., Lipke, Peter N., Rauceo, Jason M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786869/
https://www.ncbi.nlm.nih.gov/pubmed/31594814
http://dx.doi.org/10.1128/mBio.01766-19
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author Ho, Vida
Herman-Bausier, Philippe
Shaw, Christopher
Conrad, Karen A.
Garcia-Sherman, Melissa C.
Draghi, Jeremy
Dufrene, Yves F.
Lipke, Peter N.
Rauceo, Jason M.
author_facet Ho, Vida
Herman-Bausier, Philippe
Shaw, Christopher
Conrad, Karen A.
Garcia-Sherman, Melissa C.
Draghi, Jeremy
Dufrene, Yves F.
Lipke, Peter N.
Rauceo, Jason M.
author_sort Ho, Vida
collection PubMed
description The human fungal commensal Candida albicans can become a serious opportunistic pathogen in immunocompromised hosts. The C. albicans cell adhesion protein Als1p is a highly expressed member of a large family of paralogous adhesins. Als1p can mediate binding to epithelial and endothelial cells, is upregulated in infections, and is important for biofilm formation. Als1p includes an amyloid-forming sequence at amino acids 325 to 331, identical to the sequence in the paralogs Als5p and Als3p. Therefore, we mutated Val326 to test whether this sequence is important for activity. Wild-type Als1p (Als1p(WT)) and Als1p with the V326N mutation (Als1p(V326N)) were expressed at similar levels in a Saccharomyces cerevisiae surface display model. Als1p(V326N) cells adhered to bovine serum albumin (BSA)-coated beads similarly to Als1p(WT) cells. However, cells displaying Als1p(V326N) showed visibly smaller aggregates and did not fluoresce in the presence of the amyloid-binding dye Thioflavin-T. A new analysis tool for single-molecule force spectroscopy-derived surface mapping showed that statistically significant force-dependent Als1p clustering occurred in Als1p(WT) cells but was absent in Als1p(V326N) cells. In single-cell force spectroscopy experiments, strong cell-cell adhesion was dependent on an intact amyloid core sequence on both interacting cells. Thus, the major adhesin Als1p interacts through amyloid-like β-aggregation to cluster adhesin molecules in cis on the cell surface as well as in trans to form cell-cell bonds.
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spelling pubmed-67868692019-10-15 An Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion Ho, Vida Herman-Bausier, Philippe Shaw, Christopher Conrad, Karen A. Garcia-Sherman, Melissa C. Draghi, Jeremy Dufrene, Yves F. Lipke, Peter N. Rauceo, Jason M. mBio Research Article The human fungal commensal Candida albicans can become a serious opportunistic pathogen in immunocompromised hosts. The C. albicans cell adhesion protein Als1p is a highly expressed member of a large family of paralogous adhesins. Als1p can mediate binding to epithelial and endothelial cells, is upregulated in infections, and is important for biofilm formation. Als1p includes an amyloid-forming sequence at amino acids 325 to 331, identical to the sequence in the paralogs Als5p and Als3p. Therefore, we mutated Val326 to test whether this sequence is important for activity. Wild-type Als1p (Als1p(WT)) and Als1p with the V326N mutation (Als1p(V326N)) were expressed at similar levels in a Saccharomyces cerevisiae surface display model. Als1p(V326N) cells adhered to bovine serum albumin (BSA)-coated beads similarly to Als1p(WT) cells. However, cells displaying Als1p(V326N) showed visibly smaller aggregates and did not fluoresce in the presence of the amyloid-binding dye Thioflavin-T. A new analysis tool for single-molecule force spectroscopy-derived surface mapping showed that statistically significant force-dependent Als1p clustering occurred in Als1p(WT) cells but was absent in Als1p(V326N) cells. In single-cell force spectroscopy experiments, strong cell-cell adhesion was dependent on an intact amyloid core sequence on both interacting cells. Thus, the major adhesin Als1p interacts through amyloid-like β-aggregation to cluster adhesin molecules in cis on the cell surface as well as in trans to form cell-cell bonds. American Society for Microbiology 2019-10-08 /pmc/articles/PMC6786869/ /pubmed/31594814 http://dx.doi.org/10.1128/mBio.01766-19 Text en Copyright © 2019 Ho et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Ho, Vida
Herman-Bausier, Philippe
Shaw, Christopher
Conrad, Karen A.
Garcia-Sherman, Melissa C.
Draghi, Jeremy
Dufrene, Yves F.
Lipke, Peter N.
Rauceo, Jason M.
An Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion
title An Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion
title_full An Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion
title_fullStr An Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion
title_full_unstemmed An Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion
title_short An Amyloid Core Sequence in the Major Candida albicans Adhesin Als1p Mediates Cell-Cell Adhesion
title_sort amyloid core sequence in the major candida albicans adhesin als1p mediates cell-cell adhesion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786869/
https://www.ncbi.nlm.nih.gov/pubmed/31594814
http://dx.doi.org/10.1128/mBio.01766-19
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