Inflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection

Abstract

SUMMARY Uropathogenic E. coli (UPEC) is the dominant cause of urinary tract infections, clinically described as cystitis. UPEC express CUP pili, which are extracellular fibers tipped with adhesins that bind mucosal surfaces of the urinary tract. Here we identify the role of the F9/Yde/Fml pilus for UPEC persistence in the inflamed urothelium. The Fml adhesin FmlH binds galactose β1-3 N-acetylgalactosamine found in core-1 and -2 O-glycans. Deletion of fmlH had no effect on UPEC virulence in an acute mouse model of cystitis. However, FmlH provided a fitness advantage during chronic cystitis, which is manifested as persistent bacteriuria, high bladder bacterial burdens and chronic inflammation. In situ binding confirmed that FmlH bound avidly to the inflamed, but not the naïve bladder. In accordance with its pathogenic profile, vaccination with FmlH significantly protected mice from chronic cystitis. Thus, UPEC employ separate CUP pili to adapt to the rapidly changing niche during bladder infection.

A randomized, double-blind, placebo-controlled pilot study to assess bacterial anti-adhesive activity in human urine following consumption of a cranberry supplement

“…10 P-fimbriated UPEC plays an important role in the pathogenesis of ascending UTIs and pyelonephritis 11 and UPEC expressing F9 fimbriae are associated with binding to chronic and inflamed bladder epithelium. 12 Extensive research has been conducted to investigate bioactive components in cranberries that are responsible for the anti-adhesion activity. Previous studies have shown that cranberry polyphenolic compounds such as proanthocyanidins, 13,14 flavonols and their glycosides (e.g.…”

Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection

“…A homolog of the type 1 pilus, the F9 pilus, is one of the most common CUP pili in the E. coli pan genome and an important urovirulence factor employed by UPEC for the maintenance of UTI ( 21 , 33 ). Our recent work has demonstrated that UPEC up-regulates the expression of F9 pili in response to bladder inflammation and epithelial remodeling induced upon UPEC infection ( 34 ). These pili display the FimH-like adhesin FmlH, which is capable of binding terminal galactose (Gal), N -acetylgalactosamine (GalNAc), or Thomsen-Friedenreich antigen (TF) [Gal(β1-3)GalNAc(α)].…”

Oligosaccharides and Complex Carbohydrates: A New Paradigm for Cranberry Bioactivity

“…These include both human red blood cell (HRBC) agglutination and epithelial cell binding assays and have primarily focused on the use of uropathogenic P-fimbriated and Type 1 fimbriated E. coli strains (e.g., CFT073, MG1655), though additional E. coli strains have also been used. In vivo, bacteria such as E. coli may express multiple and diverse adhesion phenotypes that provide fitness advantages in specific environments [199,206]. Bacterial-epithelial cell adhesion assays are therefore more representative of the complexity of bacteria-host interactions within in vivo systems than those that depend on specific receptor binding such as bacterial-HRBC anti-agglutination assays [198,199,207].…”