Identification of antigen Ag43 in uropathogenic Escherichia coli Dr+ strains and defining its role in the pathogenesis of urinary tract infections

Abstract

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are amongst the most common bacterial infectious diseases in the developed world. The urovirulence of UPEC is mainly associated with the surface-exposed fimbrial adhesins and adhesins of the autotransporter (AT) family. The best studied of these proteins is antigen Ag43 mediating cell aggregation, adhesion and biofilm development as the causes of chronic UTIs. The E. coli IH11128 Dr + (dra + ) strain of the Dr/Afa + family of adhesins possesses two major surfaceexposed virulence factors: Dr fimbrial polyadhesin and DraD protein (fimbrial tip subunit or protein component of the adhesive sheath). Here, we identified for the first time, to our knowledge, the agn43 gene encoding Ag43 in the WT clinical isolate of UPEC Dr + as a new virulence factor not yet tested. We also found that Dr fimbrial expression, which like Ag43 is under the control of a phase-variable mechanism, did not exclude Ag43 surface presentation. However, the presence of Dr fimbriae supported by other structures on the cell surface caused a physical neutralization of Ag43-mediated autoaggregation during in vitro growth. The fimbrial bundling further increased the distance between the adjacent Ag43 + cells, thus preventing head-to-tail association between surface-exposed Ag43 subunits and their interactions with the host cells. The investigations showed that Ag43 did not act as a specific adhesin and invasin, conversely to the major virulence factors of E. coli Dr + , but played significant roles in the viability and metabolic activity of bacterial cells forming biofilm, and in the survival of bacteria within invaded epithelial cells.

Intranasal Immunization of Mice with Multiepitope Chimeric Vaccine Candidate Based on Conserved Autotransporters SigA, Pic and Sap, Confers Protection against Shigella flexneri

“…The autotransporters that were chosen for the vaccine construction are well conserved in Shigella spp. and other Enterobacteriaceae that affect the human being [5,35,36].…”

Bacterial autoaggregation

“…Nonetheless, internalized UPEC IH11128 Dr + Ag43 + cells were viable after 72 h post infection, whereas only 7% of UPEC IH11128 Dr + Ag43 − survived the first 24 hours post infection, and no viable cells could be detected after 48 hours post infection. Thus, Ag43 is believed to enhance intracellular survival and virulence due to the formation of intracellular aggregates [117].…”

Nanoparticles as Potential Novel Therapies for Urinary Tract Infections

“…In other research, authors investigated the capacity of ZnO NPs to reduce both biofilm formation and antigen 43 (Ag43) expressions in UPEC CFT073. Ag43 is an important surface adhesin encoded by the E. coli-flu gene (Zalewska-Pia Tek et al, 2015). E. coli surface also presents the Ag43 receptor, which mediates bacteria-bacteria adherence, favoring their auto-aggregation, essential for the biofilm formation (Ulett et al, 2007).…”