The Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells

ABSTRACT Pathogen attachment to host tissue is critical in the progress of many infections. Bacteria use adhesion in vivo to stabilize colonization and subsequently regulate the deployment of contact-dependent virulence traits. To specifically target host cells, they decorate themselves with adhesin...

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Autores principales:	Xavier Pierrat, Jeremy P. H. Wong, Zainebe Al-Mayyah, Alexandre Persat
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	adhesins autotransporter proteins cell adhesion cell membranes cytoskeleton microfluidics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/456deff8fd854f9a98b3ee707d026b6b
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spelling	oai:doaj.org-article:456deff8fd854f9a98b3ee707d026b6b2021-11-10T18:37:51ZThe Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells10.1128/mBio.01392-212150-7511https://doaj.org/article/456deff8fd854f9a98b3ee707d026b6b2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01392-21https://doaj.org/toc/2150-7511ABSTRACT Pathogen attachment to host tissue is critical in the progress of many infections. Bacteria use adhesion in vivo to stabilize colonization and subsequently regulate the deployment of contact-dependent virulence traits. To specifically target host cells, they decorate themselves with adhesins, proteins that bind to mammalian cell surface receptors. One common assumption is that adhesin-receptor interactions entirely govern bacterial attachment. However, how adhesins engage with their receptors in an in vivo-like context remains unclear, in particular under the influence of a heterogeneous mechanical microenvironment. We here investigate the biophysical processes governing bacterial adhesion to host cells using a tunable adhesin-receptor system. By dynamically visualizing attachment, we found that bacterial adhesion to host cell surface, unlike adhesion to inert surfaces, involves two consecutive steps. Bacteria initially attach to their host without engaging adhesins. This step lasts about 1 min, during which bacteria can easily detach. We found that at this stage, the glycocalyx, a layer of glycosylated proteins and lipids, shields the host cell by keeping adhesins away from their receptor ligand. In a second step, adhesins engage with their target receptors to strengthen attachment for minutes to hours. The active properties of the membrane, endowed by the actin cytoskeleton, strengthen specific adhesion. Altogether, our results demonstrate that adhesin-ligand binding is not the sole regulator of bacterial adhesion. In fact, the host cell’s surface mechanical microenvironment mediates the physical interactions between host and bacteria, thereby playing an essential role in the onset of infection. IMPORTANCE Microbial adhesion to host cells is the initial step toward many infections. Despite playing a pivotal role in the onset of disease, we still know little about how bacteria attach in an in vivo-like context. By employing a biophysical approach where we investigated host-microbe physical interactions at the single-cell level, we unexpectedly discovered that bacteria attach to mammalian cell membranes in two successive steps. We found that mechanical factors of the cell microenvironment regulate each of these steps, and even dominate biochemical factors, thereby challenging preconceptions on how pathogens interact with their hosts.Xavier PierratJeremy P. H. WongZainebe Al-MayyahAlexandre PersatAmerican Society for Microbiologyarticleadhesinsautotransporter proteinscell adhesioncell membranescytoskeletonmicrofluidicsMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adhesins autotransporter proteins cell adhesion cell membranes cytoskeleton microfluidics Microbiology QR1-502
spellingShingle	adhesins autotransporter proteins cell adhesion cell membranes cytoskeleton microfluidics Microbiology QR1-502 Xavier Pierrat Jeremy P. H. Wong Zainebe Al-Mayyah Alexandre Persat The Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells
description	ABSTRACT Pathogen attachment to host tissue is critical in the progress of many infections. Bacteria use adhesion in vivo to stabilize colonization and subsequently regulate the deployment of contact-dependent virulence traits. To specifically target host cells, they decorate themselves with adhesins, proteins that bind to mammalian cell surface receptors. One common assumption is that adhesin-receptor interactions entirely govern bacterial attachment. However, how adhesins engage with their receptors in an in vivo-like context remains unclear, in particular under the influence of a heterogeneous mechanical microenvironment. We here investigate the biophysical processes governing bacterial adhesion to host cells using a tunable adhesin-receptor system. By dynamically visualizing attachment, we found that bacterial adhesion to host cell surface, unlike adhesion to inert surfaces, involves two consecutive steps. Bacteria initially attach to their host without engaging adhesins. This step lasts about 1 min, during which bacteria can easily detach. We found that at this stage, the glycocalyx, a layer of glycosylated proteins and lipids, shields the host cell by keeping adhesins away from their receptor ligand. In a second step, adhesins engage with their target receptors to strengthen attachment for minutes to hours. The active properties of the membrane, endowed by the actin cytoskeleton, strengthen specific adhesion. Altogether, our results demonstrate that adhesin-ligand binding is not the sole regulator of bacterial adhesion. In fact, the host cell’s surface mechanical microenvironment mediates the physical interactions between host and bacteria, thereby playing an essential role in the onset of infection. IMPORTANCE Microbial adhesion to host cells is the initial step toward many infections. Despite playing a pivotal role in the onset of disease, we still know little about how bacteria attach in an in vivo-like context. By employing a biophysical approach where we investigated host-microbe physical interactions at the single-cell level, we unexpectedly discovered that bacteria attach to mammalian cell membranes in two successive steps. We found that mechanical factors of the cell microenvironment regulate each of these steps, and even dominate biochemical factors, thereby challenging preconceptions on how pathogens interact with their hosts.
format	article
author	Xavier Pierrat Jeremy P. H. Wong Zainebe Al-Mayyah Alexandre Persat
author_facet	Xavier Pierrat Jeremy P. H. Wong Zainebe Al-Mayyah Alexandre Persat
author_sort	Xavier Pierrat
title	The Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells
title_short	The Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells
title_full	The Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells
title_fullStr	The Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells
title_full_unstemmed	The Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells
title_sort	mammalian membrane microenvironment regulates the sequential attachment of bacteria to host cells
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/456deff8fd854f9a98b3ee707d026b6b
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The Mammalian Membrane Microenvironment Regulates the Sequential Attachment of Bacteria to Host Cells

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