Researchers have identified how bacteria are able to colonize the gut and resist shear forces and stay attached to the cells of the intestine. Before the bacteria can proliferate, they must attach to the cells of the intestine, but the molecular mechanisms involved were not well understood. Bacteria in the gut are essential to human health, so knowledge of how they bind to the cells of the intestine is important for improving understanding of the gut microbiome.
Through simulations using single-molecule force spectroscopy (SMFS), single-molecule FRET (smFRET), and molecular dynamics (MD), the researchers identified the molecular mechanism behind an ultrastable protein complex that allows the bacterium, R. champanellensis (Rc) to bind to the cells of the gut wall and resist hydrodynamic forces that would otherwise expel them out of the body.
The cellulosome network used by the bacteria to bind to the intestine consists of a scaffold of proteins and enzymes on the outer cell wall which attach to and partially degrade the insoluble cellulose fibers in the gut.
Cellulosome networks are held together by families of interacting proteins. One of the interactions between proteins is the cohesin-dockerin interaction, which is responsible for binding the cellulosome network to the cell wall and resisting hydrodynamic forces. Further investigation of the cohesin-dockerin interaction revealed how the complex is able to resist external forces.
The researchers identified two different binding modes that are used to attach to cellulose fibers in the human gut under shear flow. The dual binding mode of the cellulosome network sees protein families bind in two different ways, each of which has distinct properties. Cohesin-dockerin bonds are possible in two different ways, with a 180-degree rotation possible to achieve a different bond confirmation with different properties.
One of these formations breaks at low forces of around 200 piconewtons, while the other is much stronger, capable of resisting forces up to 600 piconewtons. The latter is a catch bond, one where the protein interaction becomes stronger in response to increasing force. This catch bond is believed to be used by bacteria to bind to cells under shear force and release when the forces reduce, allowing the bacteria to explore new environments.
“We clearly observe the dual binding modes, but can only speculate on their biological significance. We think the bacteria might control the binding mode preference by modifying the proteins. This would allow switching from a low to high adhesion state depending on the environment,” said Michael Nash, PhD.
The binding mechanism acts as a kind of bacterial superglue. Further research could lead to the development of artificial molecular mechanisms for adhesion, which could be used on therapeutic nanoparticles to allow them to bind to disease targets.
You can read more about the study in the paper – High force catch bond mechanism of bacterial adhesion in the human gut – which was recently published in Nature Communications. DOI: 10.1038/s41467-020-18063-x