Gram-negative pathogens are equipped with specialized hair-like appendages that play a crucial role in the onset and persistence of bacterial infections. These pili mediate bacterial attachment and determine tissue and host tropism. The majority of adhesive pili are assembled by the chaperone-usher (CU) pathway, like the type 1 and P pili, long known to be implicated in urinary tract infections. More recently, genomic data have shown that pathogenic and commensal E. coli strains carry at least 10 different fimbrial gene clusters in their genomes. The structures and functions of the proteins encoded by these genes are mostly unknown. However, given a number of clusters are positively selected in specific E. coli pathotypes, it can be expected these take a role in pathotype-related disease processes.
In this work we explore the possible role of pilus – glycan recognition in the observed population responses of E. coli to physiological changes in the host such as tissue inflammation and/or transformation. We describe a novel E. coli pilus that binds specifically core 2 O-glycans. Our structural data show the binding epitope for the F9 pilus adhesin FmlD is formed by the Thomsen-Friedenreich antigen (Galβ1-3GalNAcα1), a well-described cancer antigen. Under native conditions, F9 pili are expected to allow bacterial adherence to the mucus layer lining the gastrointestinal tract. We further investigate the possibility that F9 pili drive the increased association of E. coli with inflamed or transformed tissues, conditions that lead to exposure of the TF antigen.
