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Mechanical force-induced morphology changes in a human fungal pathogen

BACKGROUND: The initial step of a number of human or plant fungal infections requires active penetration of host tissue. For example, active penetration of intestinal epithelia by Candida albicans is critical for dissemination from the gut into the bloodstream. However, little is known about how thi...

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Autores principales: Puerner, Charles, Kukhaleishvili, Nino, Thomson, Darren, Schaub, Sebastien, Noblin, Xavier, Seminara, Agnese, Bassilana, Martine, Arkowitz, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488538/
https://www.ncbi.nlm.nih.gov/pubmed/32912212
http://dx.doi.org/10.1186/s12915-020-00833-0
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author Puerner, Charles
Kukhaleishvili, Nino
Thomson, Darren
Schaub, Sebastien
Noblin, Xavier
Seminara, Agnese
Bassilana, Martine
Arkowitz, Robert A.
author_facet Puerner, Charles
Kukhaleishvili, Nino
Thomson, Darren
Schaub, Sebastien
Noblin, Xavier
Seminara, Agnese
Bassilana, Martine
Arkowitz, Robert A.
author_sort Puerner, Charles
collection PubMed
description BACKGROUND: The initial step of a number of human or plant fungal infections requires active penetration of host tissue. For example, active penetration of intestinal epithelia by Candida albicans is critical for dissemination from the gut into the bloodstream. However, little is known about how this fungal pathogen copes with resistive forces upon host cell invasion. RESULTS: In the present study, we have used PDMS micro-fabrication to probe the ability of filamentous C. albicans cells to penetrate and grow invasively in substrates of different stiffness. We show that there is a threshold for penetration that corresponds to a stiffness of ~ 200 kPa and that invasive growth within a stiff substrate is characterized by dramatic filament buckling, along with a stiffness-dependent decrease in extension rate. We observed a striking alteration in cell morphology, i.e., reduced cell compartment length and increased diameter during invasive growth, that is not due to depolarization of active Cdc42, but rather occurs at a substantial distance from the site of growth as a result of mechanical compression. CONCLUSIONS: Our data reveal that in response to this compression, active Cdc42 levels are increased at the apex, whereas active Rho1 becomes depolarized, similar to that observed in membrane protrusions. Our results show that cell growth and morphology are altered during invasive growth, suggesting stiffness dictates the host cells that C. albicans can penetrate.
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spelling pubmed-74885382020-09-16 Mechanical force-induced morphology changes in a human fungal pathogen Puerner, Charles Kukhaleishvili, Nino Thomson, Darren Schaub, Sebastien Noblin, Xavier Seminara, Agnese Bassilana, Martine Arkowitz, Robert A. BMC Biol Research Article BACKGROUND: The initial step of a number of human or plant fungal infections requires active penetration of host tissue. For example, active penetration of intestinal epithelia by Candida albicans is critical for dissemination from the gut into the bloodstream. However, little is known about how this fungal pathogen copes with resistive forces upon host cell invasion. RESULTS: In the present study, we have used PDMS micro-fabrication to probe the ability of filamentous C. albicans cells to penetrate and grow invasively in substrates of different stiffness. We show that there is a threshold for penetration that corresponds to a stiffness of ~ 200 kPa and that invasive growth within a stiff substrate is characterized by dramatic filament buckling, along with a stiffness-dependent decrease in extension rate. We observed a striking alteration in cell morphology, i.e., reduced cell compartment length and increased diameter during invasive growth, that is not due to depolarization of active Cdc42, but rather occurs at a substantial distance from the site of growth as a result of mechanical compression. CONCLUSIONS: Our data reveal that in response to this compression, active Cdc42 levels are increased at the apex, whereas active Rho1 becomes depolarized, similar to that observed in membrane protrusions. Our results show that cell growth and morphology are altered during invasive growth, suggesting stiffness dictates the host cells that C. albicans can penetrate. BioMed Central 2020-09-11 /pmc/articles/PMC7488538/ /pubmed/32912212 http://dx.doi.org/10.1186/s12915-020-00833-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Puerner, Charles
Kukhaleishvili, Nino
Thomson, Darren
Schaub, Sebastien
Noblin, Xavier
Seminara, Agnese
Bassilana, Martine
Arkowitz, Robert A.
Mechanical force-induced morphology changes in a human fungal pathogen
title Mechanical force-induced morphology changes in a human fungal pathogen
title_full Mechanical force-induced morphology changes in a human fungal pathogen
title_fullStr Mechanical force-induced morphology changes in a human fungal pathogen
title_full_unstemmed Mechanical force-induced morphology changes in a human fungal pathogen
title_short Mechanical force-induced morphology changes in a human fungal pathogen
title_sort mechanical force-induced morphology changes in a human fungal pathogen
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488538/
https://www.ncbi.nlm.nih.gov/pubmed/32912212
http://dx.doi.org/10.1186/s12915-020-00833-0
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