Abstract
Uropathogenic Escherichia coli (UPEC) is the leading causative agent of urinary tract infections (UTI) in the developed world. Among the major virulence factors of UPEC, surface expressed adhesins mediate attachment and tissue tropism. UPEC strains typically possess a range of adhesins, with type 1 fimbriae and P fimbriae of the chaperone-usher class the best characterised. We previously identified and characterised F9 as a new chaperone-usher fimbrial type that mediates biofilm formation. However, the regulation and specific role of F9 fimbriae remained to be determined in the context of wild-type clinical UPEC strains. In this study we have assessed the distribution and genetic context of the f9 operon among diverse E. coli lineages and pathotypes and demonstrated that f9 genes are significantly more conserved in a UPEC strain collection in comparison to the well-defined E. coli reference (ECOR) collection. In the prototypic UPEC strain CFT073, the global regulator protein H-NS was identified as a transcriptional repressor of f9 gene expression at 37°C through its ability to bind directly to the f9 promoter region. F9 fimbriae expression was demonstrated at 20°C, representing the first evidence of functional F9 fimbriae expression by wild-type E. coli. Finally, glycan array analysis demonstrated that F9 fimbriae recognise and bind to terminal Galβ1-3GlcNAc structures.
Highlights
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity
To evaluate the conservation and evolutionary history of F9 fimbriae among E. coli phylogroups, a phylogenetic tree based on multi-locus sequence typing (MLST) of 7 concatenated housekeeping genes (,9 kb) was constructed and combined with f9 genomic context alignments (Figure 1)
The intact f9 operon was highly prevalent in intestinal pathogenic E. coli, including adherent-invasive E. coli (AIEC; 3/3), enteroaggregative E. coli (EAEC; 2/2), enteropathogenic E. coli (EPEC; 3/3) and enterohemorrhagic E. coli (EHEC; 7/8), but not in enterotoxigenic E. coli (ETEC; 0/2) (Table 2)
Summary
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity. In the USA, UTI account for approximately $1.6 billion in medical expenditures each year [1]. It is estimated that 40–50% of adult healthy women will experience at least one UTI episode in their lifetime. The recurrence rate of UTI is high and often the infections tend to become chronic with many subsequent episodes. UTIs usually start as cystitis but often evolve to encompass the kidneys and can result in dissemination into the bloodstream and/or renal failure. Catheter-associated UTIs are very common and account for 40% of all nosocomial infections. Most patients with an indwelling urinary catheter for thirty days or more develop bacteriuria [2]
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