NEW STRUCTURAL FEATURES REVEAL HOW BACTERIA STICK TO HOST SURFACES
Authors: Paxman Jason John , Lo Alvin , Panjikar Santosh , Kuiper Mike , Luan Chi‐Hao , Schembri Mark , Heras Begoña 
Published: June 2021

The process of adhesion is fundamental for bacteria to colonise the host and cause infection. Bacterial adhesion is achieved by bacterial surface proteins termed adhesins that include large ~1 μm fimbrial adhesion complexes along with the vast majority of smaller (~10 nm) single non‐fimbrial adhesins. Most non‐fimbrial adhesins are autotransporter proteins which represent the largest group of outer membrane and secreted proteins in Gram negative bacteria. Due to the importance and prevalence of these autotransporters, they are a rapidly emerging field of research as we currently know little about the structure or the mechanism of action for most autotransporter proteins, and almost nothing for non‐fimbrial autotransporter adhesins which facilitate intimate adherence to host surfaces.

We reveal the first structure and mode of action for an autotransporter adhesin that binds host cell surfaces. UpaB is required for bladder colonisation by Uropathogenic E. coli. Our crystal structure of UpaB shows an unprecedented re‐shaping from the common long autotransporter right‐handed β‐helix fold to include a large groove along its axis. Our work provides evidence to show that this groove interacts with cell surface glycosaminoglycans, an entirely new function for an autotransporter. Furthermore, on the opposite face of the UpaB structure we located a second cell surface binding site for interacting with host fibronectin. UpaB was found to form a completely new type of interaction with human fibronectin. This is very significant considering that most of the 100 bacterial fibronectin binding proteins follow a single and very different type of interaction with fibronectin. These findings show that the autotransporter β‐helix can function as another type of multi‐functional protein‐binding domain, rather than just as a structural scaffold as previously thought. Together, the glycosaminoglycan and fibronectin binding sites allow UpaB on the Uropathogenic E. coli cell surface to promote colonisation of the urinary tract.

This first mechanism of how a non‐fimbrial adhesin binds to host cell surfaces which may be common to many adhesins widespread across bacteria, and so form an overall fundamental principle as to how bacteria intimately colonise their hosts. These findings will have important implications for the development of anti‐microbials that can block these adhesin‐host surface interactions. The further comprehension of how bacterial proteins bind to host surfaces, could be used to re‐engineer these adhesins for use in diagnostics or for tissue specific targeted therapies.

Support or Funding Information

Australian Research Council (ARC) project grant (DP150102287), La Trobe University Research Focus Area Understanding Disease Express Grant, Victorian Life Sciences Computation Initiative grant (LTU0011.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.