Mechanisms of uropathogenic E. coli mucosal association in the gastrointestinal tract

Sci Adv. 2025 Jan 31;11(5):eadp7066. doi: 10.1126/sciadv.adp7066. Epub 2025 Jan 31.

Abstract

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic Escherichia coli (UPEC) strains that can be found in patient intestines. Seeding of the urinary tract from this intestinal reservoir likely contributes to UTI recurrence (rUTI) rates. Thus, understanding the factors that promote UPEC intestinal colonization is of critical importance to designing therapeutics to reduce rUTI incidence. Although E. coli is found in high abundance in large intestine mucus, little is known about how it is able to maintain residence in this continuously secreted hydrogel. We discovered that the FimH adhesin of type 1 pili (T1P) bound throughout the secreted mucus layers of the colon and to epithelial cells in mouse and human samples. Disruption of T1P led to reduced association with colon mucus. Notably, this mutant up-regulated flagellar production and infiltrated the protective inner mucus layer of the colon. This could explain how UPEC resists being washed off by the continuously secreted mucus layers of the colon.

MeSH terms

  • Adhesins, Escherichia coli / genetics
  • Adhesins, Escherichia coli / metabolism
  • Animals
  • Bacterial Adhesion
  • Escherichia coli Infections* / microbiology
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism
  • Gastrointestinal Tract* / microbiology
  • Humans
  • Intestinal Mucosa* / metabolism
  • Intestinal Mucosa* / microbiology
  • Mice
  • Urinary Tract Infections* / microbiology
  • Uropathogenic Escherichia coli* / metabolism
  • Uropathogenic Escherichia coli* / pathogenicity
  • Uropathogenic Escherichia coli* / physiology

Substances

  • Adhesins, Escherichia coli
  • Fimbriae Proteins
  • fimH protein, E coli