Things are always better when we work together - and the same can be said even for microscopic organisms. Our featured structure for January 2021 discusses these tiny communities, and the proteins that help bring them together.
A microscopic community
When many people think of bacteria, they likely think of a single cell, perhaps moving around under a microscope. However, most bacteria do not live as individual cells, they instead form microscopic communities that grow together and support each other. These communities are called biofilms, and you probably encounter these often without realising it. A build-up of plaque on your teeth is a biofilm that, if not treated, can lead to tooth decay or gum disease. A pebble picked up from a stream will likely have a slimy coating of biofilm, as bacteria are often quick to colonise surfaces in water. But why do these communities of microorganisms exist, and why are they so widespread?
Greater than the sum of their parts
Bacteria have adapted over time to form communities in order to improve their survival through shared resources, much like humans have done. These bacterial communities can often be diverse, with exchange of substrates, removal of toxins, and even ‘communication� between the bacterial cells, allowing each species to support each other. Biofilms can also contribute to antibiotic resistance, as bacteria can exist in a low activity state, providing 10�1000 times higher antibiotic resistance than non-biofilm cells. This can be particularly problematic in patients with medical implants, as these non-biological surfaces provide an environment for biofilm formation, causing significant post-surgical complications. Biofilms form after attachment of bacteria to a surface, where the cells then excrete an extracellular matrix, the ‘slime� that encloses the colonies of bacteria. This extracellular matrix can be extremely varied, however is generally composed of polysaccharides, nucleic acids and proteins. Here, we will discuss more about the role of proteins in biofilm formation.
Proteins bringing cells together
Proteins have various roles in biofilm formation, including in surface attachment, cell adhesion, extracellular matrix structure, and enzymatic activity. Surface colonisation is supported by cell surface proteins, pili and flagella, which are involved in the attachment and migration of cells along surfaces. Proteins in the matrix itself contribute to the structure and stability of the biofilm, while others include enzymatic properties, such as polysaccharide and DNA degradation, thought to be required in reorganisation or break down of the biofilm matrix. There are many different extracellular matrix proteins that have a structural role in biofilms, however here we will focus on one specific example.
This image displays scanning electron microscopy (SEM) images of B. subtilis biofilm samples displayed at A) 2000x and B) 5000x magnifications, highlighting the intricate network of bacterial cells that form the biofilm. Image adapted from
TasA - tying things together
TasA is a protein from Bacillus subtilis, initially identified as having a role in antimicrobial activity in B. subtilis spores. It has since been identified as a major component of the biofilm extracellular matrix and found to form amyloid-type fibres. These fibres are required for effective biofilm formation, by giving structural integrity to the extracellular matrix. A related protein, TapA, has been suggested to function as a cell wall anchor for TasA, helping mesh together the bacterial cells in the biofilm.
TasA - both structure and flexibility
The structure of individual monomeric components of TasA from B. subtilis has been solved by X-ray crystallography to 1.56 Ångström resolution. Most amyloid forming proteins are predominantly unstructured in their monomeric form, however by expressing TasA without a C-terminal unstructured region, the authors were able to isolate and crystallise a predominantly globular monomeric protein. The structure is predominantly rigid and well-structured, however there are a number of loops which show significant flexibility.
This image shows the TasA protein structure (5of1) displayed in putty representation, with the thickness and colour related to the B factors of each amino acid. Increasing B-factor is highlighted by increasing thickness and a colour change from blue to red. Higher B-factors suggest increased conformational variability, which can be seen in the external loop regions of the protein. Loop 117-125 is unobserved in the structure due to significant conformational variability and is shown at the top of the image with split putty, linked by a dashed tube. View the structure at PDBe.org/5of1/3d.
The authors hypothesise that these loop regions may drive the formation of TasA fibres, particularly at low pH. This is supported by NMR experiments that indicate significant changes to the environment around loop 117-125 at low pH, suggesting a conformational change in this region that could drive fibre formation. The example of TasA highlights the importance of using multiple techniques to fully understand the structural conformations of proteins and that sometimes a lack of clear structure can be just as important as a high resolution structure for understanding protein function.
The artwork
The artwork, inspired by biofilm proteins, was created by Hannah Simon from in Cambridge, UK. This digital artwork incorporates copies of overlaid, hand-drawn proteins to represent the web of proteins in the extracellular matrix. Hannah aimed to produce a ‘complex and interesting pattern alluding to the idea of community� with the protein images making ‘a product greater than the sum of its parts.� View the artwork in the .
David Armstrong
