Interaction of Uropathogenic Escherichia Coli Strains Carrying Type 6 Secretion System (T6ss) with Renal and Gut Epithelial Cells

Abstract

We previously identified the presence of a type 6 secretion system (T6SS) in a group of translocating Escherichia coli strains isolated from blood and mesenteric lymph nodes of laboratory animals and human and showed its expression upon interacting with the gut epithelial cells. Here we investigated the prevalence of T6SS in a collection of uropathogenic E. coli (UPEC) isolated from female patients with community-acquired urinary tract infections (UTI). We further tested interaction of these strains with the renal and the gut epithelial cells. The presence T6SS was confirmed using vgrG and clpV genes associated with T6SS. Previous typing of the strains using a combination of PhPlate and RAPD-PCR, grouped the strains into 19 common types (CTs) with group sizes ranging from 2 to 22 strains per CT and 3 single types (STs). A representative strain from each CT (n=19) and all STs were tested for their interaction with A498 renal epithelial cells and Caco2:HT29-MTX intestinal epithelial cells. All tested UPEC strains colonised both cell types, however T6SS-positive strains exhibited significantly greater adhesion, invasion, and translocation abilities compared to T6SS-negative strains (p<0.001 for all parameters). CTs with highest number of strains (i.e. CT9 with 22 strains) showed the highest rate of translocation through A498 renal epithelial cells. In contrast, strains belonging to CT4 (10 strains) showed the highest rate of translocation across the Caco-2:HT29-MTX cells. These findings underscore the critical role of T6SS in the pathogenesis of UPEC by facilitating their adhesion, invasion, and translocation through epithelial barriers. These data also suggest that while certain clonal types of UPEC have a better ability to translocate into blood stream via upper urinary tract, some others may translocate via gut epithelium to cause a gut-associated septicaemia.

Note:
Funding declaration: We would like to thank USC for the financial support provided for this project via PhD scholarship to Miss B. Asgari (scholarship no. 210105-000332) and the financial support for Honours students involved in this project.

Conflict of Interests: No conflict of interest declared.

Keywords: Uropathogenic Escherichia coli, urinary tract infection, Type 6 Secretion System, adhesion, invasion, translocation