Abstract
ABSTRACTPathogen 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.
Highlights
Pathogen attachment to host tissue is critical in the progress of many infections
We show that the biomechanical microenvironment of host tissues strongly regulates the adhesion behavior of bacteria to their target cells, indicating that this process cannot be solely reduced to adhesin-receptor interactions
To systematically probe bacterial adhesion to host cells without relying on virulence factors, we engineered an exogenous adhesin in a nonflagellated E. coli and cognate receptor in HeLa cells (Fig. 1A)
Summary
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 target host cells, they decorate themselves with adhesins, proteins that bind to mammalian cell surface receptors. 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. 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. The dynamics of attachment of single bacteria to host cells can dramatically influence the outcome of infection or regulate host-microbiota homeostasis [4]. The physical and biological complexity of biotic surfaces remains overlooked when making the analogy between living and inert materials. In contrast with abiotic adhesion, bacterial attachment to host cell involves specific molecular interactions [3]. As a result, drawing analogies between biotic and abiotic adhesion can be informative but may overlook critical physical and biological regulators
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