Urinary tract infections (UTIs) are one of the most common bacterial infections in humans [4]. Treatments for these infections are becoming scarcer due to the increasing bacterial antibiotic resistance [6]. Therefore, new approaches to tackle UTIs are urgently required. The main cause of UTIs is Uropathogenic Escherichia coli (UPEC), a pathogen that encodes multiple virulence factors, which play a key role in the establishment and persistence of the infection [3, 4, 5]. The biggest family of secreted virulent proteins in E. coli is the Autotransporter proteins (ATs) family, which contains an important group known as the AIDA-I-type adhesins [1, 2, 8]. These surface proteins promote multiple phenotypes including bacterial aggregation and biofilm formation [2, 6, 8]. This study is focused on the most prevalent E. coli AT adhesin, Antigen 43 (Ag43) [7]. Specifically, this research aims at analysing structure-function relationships, processing and mechanism of action of Ag43, in order to develop an approach to block its function. The functional domain of Ag43b from the UPEC strain CFT073 was purified and the structure was characterised by X-ray crystallography.
The identification of molecules that block the function of Ag43 has been attempted using single-domain antibodies derived from the variable region (vNAR) of a shark antibody known as the IgNAR. Screening of a vNAR phage-displayed library resulted in the identification of two binders that specifically recognise Ag43 homologues. Ongoing work with these vNARs will establish their ability to halt the aggregative ability of Ag43.
The outcomes of this project will provide essential data for future studies on the function and inhibition of this key AT to allow the future development of alternative therapeutic approaches to tackle UTIs.