Researchers have elucidated the molecular mechanism by which bacteria attach to cellulose fibers in the intestine. By binding to the fibers in two different ways, they can withstand the shear forces in the human body. The research team published their results in the journal "Nature Communications".
Cellulose is a main component of plant cell walls. It consists of molecules that are connected to form solid fibers. Cellulose is indigestible to humans, and the majority of intestinal bacteria also lack the enzymes necessary for its breakdown.
Recently, however, genetic material from the cellulose- degrading bacterium R. champanellensis has been detected in human intestinal samples. Bacterial colonization of the gut is fundamental to human physiology, and knowing how gut bacteria attach to cellulose broadens our understanding of the microbiome and its role in human health.
In order to adhere to and break down cellulose fibers, the examined bacterium uses a complex network of scaffold proteins and enzymes on the outer cell wall, which is known as the cellulosome. The cellulosomes are held together by interacting proteins from specific families.
Of particular interest is the Cohesin-Dockerin interaction, which ensures that the cellulosomes are anchored to the cell wall. It has to withstand the shear forces in the body so that the bacterium can adhere to the fibers. It was this property, which is vital for the bacterium, that motivated the researchers to investigate how exactly the anchorage reacts to mechanical forces.
The team used a combination of single-molecule atomic force microscopy, single-molecule fluorescence and molecular dynamics simulations to clarify how the protein complex resists external forces.
The researchers observed that the protein complex exhibited a rare behavior called a dual mode of binding. The proteins form a complex in two different ways. Further analyzes showed that the two binding modes have very different mechanical properties, with one breaking at low forces of around 200 piconewtons and the other having a much higher stability and withstanding a force of 600 piconewtons.
In addition, they demonstrated what is known as a “catch bond” in the protein complex - a bond that does not become weaker, but stronger when the proteins are pulled quickly. The researchers suspect that this dynamic enables the bacteria, on the one hand, to adhere stably to cellulose and, on the other hand, to release the complex in response to new substrates or to explore a new environment.
“We can only speculate about the biological significance of the dual modes of attachment. We suspect that the bacteria can control the preference of the binding mode by modifying the proteins. This would make it possible to switch from a low to a high state of adhesion depending on the environment, ”explains the senior author.
The new findings on this complex natural adhesion mechanism are fundamental for the development of artificial molecular mechanisms that show a similar behavior but, for example, bind to disease-relevant target molecules. Such materials could be used in bio-based medical superglues in the future or help therapeutic nanoparticles to bind better in the body despite shear forces. “For now, we're excited to return to the laboratory and see what sticks,” says the author.
How bacteria cling to fibers in the intestine
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