An Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion

ABSTRACT 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 cell...

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Autores principales:	Vida Ho, Philippe Herman-Bausier, Christopher Shaw, Karen A. Conrad, Melissa C. Garcia-Sherman, Jeremy Draghi, Yves F. Dufrene, Peter N. Lipke, Jason M. Rauceo
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	functional amyloid adhesion cell wall nanodomain β-aggregation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/417fa0c7130d4adc9535ba8c456b7443
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spelling	oai:doaj.org-article:417fa0c7130d4adc9535ba8c456b74432021-11-15T15:59:41ZAn Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion10.1128/mBio.01766-192150-7511https://doaj.org/article/417fa0c7130d4adc9535ba8c456b74432019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01766-19https://doaj.org/toc/2150-7511ABSTRACT 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 (Als1pWT) and Als1p with the V326N mutation (Als1pV326N) were expressed at similar levels in a Saccharomyces cerevisiae surface display model. Als1pV326N cells adhered to bovine serum albumin (BSA)-coated beads similarly to Als1pWT cells. However, cells displaying Als1pV326N 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 Als1pWT cells but was absent in Als1pV326N 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. IMPORTANCE Microbial cell surface adhesins control essential processes such as adhesion, colonization, and biofilm formation. In the opportunistic fungal pathogen Candida albicans, the agglutinin-like sequence (ALS) gene family encodes eight cell surface glycoproteins that mediate adherence to biotic and abiotic surfaces and cell-cell aggregation. Als proteins are critical for commensalism and virulence. Their activities include attachment and invasion of endothelial and epithelial cells, morphogenesis, and formation of biofilms on host tissue and indwelling medical catheters. At the molecular level, Als5p-mediated cell-cell aggregation is dependent on the formation of amyloid-like nanodomains between Als5p-expressing cells. A single-site mutation to valine 326 abolishes cellular aggregation and amyloid formation. Our results show that the binding characteristics of Als1p follow a mechanistic model similar to Als5p, despite its differential expression and biological roles.Vida HoPhilippe Herman-BausierChristopher ShawKaren A. ConradMelissa C. Garcia-ShermanJeremy DraghiYves F. DufrenePeter N. LipkeJason M. RauceoAmerican Society for Microbiologyarticlefunctional amyloidadhesioncell wallnanodomainβ-aggregationadhesionMicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	functional amyloid adhesion cell wall nanodomain β-aggregation adhesion Microbiology QR1-502
spellingShingle	functional amyloid adhesion cell wall nanodomain β-aggregation adhesion Microbiology QR1-502 Vida Ho Philippe Herman-Bausier Christopher Shaw Karen A. Conrad Melissa C. Garcia-Sherman Jeremy Draghi Yves F. Dufrene Peter N. Lipke Jason M. Rauceo An Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion
description	ABSTRACT 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 (Als1pWT) and Als1p with the V326N mutation (Als1pV326N) were expressed at similar levels in a Saccharomyces cerevisiae surface display model. Als1pV326N cells adhered to bovine serum albumin (BSA)-coated beads similarly to Als1pWT cells. However, cells displaying Als1pV326N 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 Als1pWT cells but was absent in Als1pV326N 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. IMPORTANCE Microbial cell surface adhesins control essential processes such as adhesion, colonization, and biofilm formation. In the opportunistic fungal pathogen Candida albicans, the agglutinin-like sequence (ALS) gene family encodes eight cell surface glycoproteins that mediate adherence to biotic and abiotic surfaces and cell-cell aggregation. Als proteins are critical for commensalism and virulence. Their activities include attachment and invasion of endothelial and epithelial cells, morphogenesis, and formation of biofilms on host tissue and indwelling medical catheters. At the molecular level, Als5p-mediated cell-cell aggregation is dependent on the formation of amyloid-like nanodomains between Als5p-expressing cells. A single-site mutation to valine 326 abolishes cellular aggregation and amyloid formation. Our results show that the binding characteristics of Als1p follow a mechanistic model similar to Als5p, despite its differential expression and biological roles.
format	article
author	Vida Ho Philippe Herman-Bausier Christopher Shaw Karen A. Conrad Melissa C. Garcia-Sherman Jeremy Draghi Yves F. Dufrene Peter N. Lipke Jason M. Rauceo
author_facet	Vida Ho Philippe Herman-Bausier Christopher Shaw Karen A. Conrad Melissa C. Garcia-Sherman Jeremy Draghi Yves F. Dufrene Peter N. Lipke Jason M. Rauceo
author_sort	Vida Ho
title	An Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion
title_short	An Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion
title_full	An Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion
title_fullStr	An Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion
title_full_unstemmed	An Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion
title_sort	amyloid core sequence in the major <named-content content-type="genus-species">candida albicans</named-content> adhesin als1p mediates cell-cell adhesion
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/417fa0c7130d4adc9535ba8c456b7443
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An Amyloid Core Sequence in the Major <named-content content-type="genus-species">Candida albicans</named-content> Adhesin Als1p Mediates Cell-Cell Adhesion

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