Loss of an Intimin-Like Protein Encoded on a Uropathogenic E. coli Pathogenicity Island Reduces Inflammation and Affects Interactions with the Urothelium

• Published in: Infection and immunity 2022-02, Vol.90 (2), p.e0027521-e0027521
• Main Authors: Shea, Allyson E, Stocki, Jolie A, Himpsl, Stephanie D, Smith, Sara N, Mobley, Harry L T
• Format: Article
• Language: English
• Subjects: Adhesins, Bacterial - genetics; Adhesins, Bacterial - metabolism; Animals; Bacteriology; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions; Escherichia coli Infections - genetics; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Female; Genomic Islands - genetics; Humans; Inflammation - genetics; Male; Mice; Urinary Tract Infections - genetics; Uropathogenic Escherichia coli; Urothelium
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.00275-21

Uropathogenic Escherichia coli (UPEC) causes the majority of uncomplicated urinary tract infections (UTI), which affect nearly half of women worldwide. Many UPEC strains carry an annotated intimin-like adhesin ( ) locus in their genome related to a well-characterized virulence factor in diarrheagenic E. coli pathotypes. Its role in UPEC uropathogenesis, however, remains unknown. In prototype UPEC strain CFT073, there is an locus that contains three predicted intimin-like genes, , , and . We used approaches to determine the phylogeny and genomic distribution of this locus among uropathogens. We found that the currently annotated intimin locus-encoded proteins in CFT073 are more closely related to invasin proteins found in Salmonella. Deletion of the individual , , and genes did not result in measurable effects on growth, biofilm formation, or motility . On average, was more highly expressed in clinical strains during active human UTI than in human urine . Unexpectedly, we found that strains lacking this locus had increased adherence to bladder cells , coupled with a decrease in bladder cell invasion and death. The mutant displayed a significant fitness defect in the murine model of ascending UTI, including reduced inflammation in the bladder. These data confirmed an inhibitory role in bladder cell adherence to facilitate invasion and inflammation; therefore, the locus should be termed invasin-like rather than intimin-like. Collectively, our data suggest that loss of this locus mediates measurable interactions with bladder cells and contributes to fitness during UTI.