ArticleProceedings of the National Academy of Sciences of the United States of America2009
Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 186 citations in OpenAlex.
- Prevalence of bovine endometritis, virulence mechanisms ofVirulence · 2026Pooled it
- Effect of human urinary microenvironment and fluid flow on antibiotic and phage therapy efficacy against uropathogenic Escherichia coli.Nature communications · 2026Article
- RstAB activates type 1 fimbriae to promote uropathogeniciScience · 2026Article
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- Lineage-specific type 1 fimbriae in hypervirulent ST23 Klebsiella pneumoniae target α3β1 integrin to promote intestinal epithelial invasion.BMC microbiology · 2026Article
- Carbapenem-resistantbioRxiv : the preprint server for biology · 2026Article
- An mRNA-based FimH nanoparticle vaccine against uropathogenicFrontiers in immunology · 2026Article
- Parallel within-host evolution alters virulence factors in an opportunistic Klebsiella pneumoniae during a hospital outbreak.Nature communications · 2025Article
- Uropathogenic Escherichia coli niche occupancy determines the effects of mucosal vaccine against FimH.Cell reports · 2025Article
- Monoclonal antibodies targeting the FimH adhesin protect against uropathogenicScience advances · 2025Article
- Bacterial adhesion strategies and countermeasures in urinary tract infection.Nature microbiology · 2025Review
- Comparison of phenotypic and genetic traits of ESBL-producing UPEC strains causing recurrent or single episode UTI in postmenopausal women.Annals of clinical microbiology and antimicrobials · 2025Article
- Involvement of adhesins (EcpD, FdeC, FimH) expressed in mammary pathogenic Escherichia coli on adhesion to bovine mammary epithelial cells.Antonie van Leeuwenhoek · 2024Article
- RFGR: Repeat Finder for Complete and Assembled Whole Genomes and NGS Reads.Biochemical genetics · 2024Article
- Conformational ensembles inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Genome-wide identification of genes critical forVirulence · 2023Article
- A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals.Science advances · 2023Article
- Nature of the Interaction of Alpha-D-Mannose and Escherichia coli Bacteria, and Implications for its Regulatory Classification. A Delphi Panel European Consensus Based on Chemistry and Legal Evidence.Therapeutic innovation & regulatory science · 2023Article
- Urinary Tract Infections Caused by UropathogenicInternational journal of molecular sciences · 2023Review
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
FimH, the type 1 pilus adhesin of uropathogenic Escherichia coli (UPEC), contains a receptor-binding domain with an acidic binding pocket specific for mannose. The fim operon, and thus type 1 pilus production, is under transcriptional control via phase variation of an invertible promoter element. FimH is critical during urinary tract infection for mediating colonization and invasion of the bladder epithelium and establishment of intracellular bacterial communities (IBCs). In silico analysis of FimH gene sequences from 279 E. coli strains identified specific amino acids evolving under positive selection outside of its mannose-binding pocket. Mutating two of these residues (A27V/V163A) had no effect on phase variation, pilus assembly, or mannose binding in vitro. However, compared to wild-type, this double mutant strain exhibited a 10,000-fold reduction in mouse bladder colonization 24 h after inoculation and was unable to form IBCs even though it bound normally to mannosylated receptors in the urothelium. In contrast, the single A62S mutation altered phase variation, reducing the proportion of piliated cells, reduced mannose binding 8-fold, and decreased bladder colonization 30-fold in vivo compared to wild-type. A phase-locked ON A62S mutant restored virulence to wild-type levels even though in vitro mannose binding remained impaired. Thus, positive selection analysis of FimH has separated mannose binding from in vivo fitness, suggesting that IBC formation is critical for successful infection of the mammalian bladder, providing support for more general use of in silico positive selection analysis to define the molecular underpinnings of bacterial pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.