ArticleProceedings of the National Academy of Sciences of the United States of America2013
Positively selected FimH residues enhance virulence during urinary tract infection by altering FimH conformation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Prevalence of bovine endometritis, virulence mechanisms ofVirulence · 2026Pooled it
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- Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.BMC microbiology · 2021Trial
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- Biofilm-Forming Capacity andAntibiotics (Basel, Switzerland) · 2026Article
- Molecular characterization of extended-spectrum β-lactamases-producing Escherichia coli isolated from patients with bacteremia.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026Article
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- An update on Escalating Drug Resistance among Uropathogenic Bacteria: Challenges in Treatment and Scope for Maneuver.Current microbiology · 2026Review
- Mast cell specific receptor Mrgprb2/X2 regulates bladder immunity during urinary tract infections.Research square · 2026Article
- TheInternational journal of molecular sciences · 2026Review
- Succinate-driven virulence enhancement in hypervirulentMicrobiology spectrum · 2026Article
- Structural and Functional Characterization of Protein Adhesins and Pili in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Article
- An mRNA-based FimH nanoparticle vaccine against uropathogenicFrontiers in immunology · 2026Article
- Article
- "Super Sandwich" Assay Using Phenylboronic Acid for the Detection ofMicroorganisms · 2025Article
- Prevalence, antimicrobial susceptibility, and virulence profiles of fluoroquinolone-resistant Escherichia coli isolated from companion animals in Sapporo, Japan.The Journal of veterinary medical science · 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
- Distribution of Fimbrial Genes and Their Association with Virulence and Levofloxacin Resistance/Extended-Spectrum Beta-Lactamase Production in UropathogenicAntibiotics (Basel, Switzerland) · 2025Article
- Pathogenesis and Immunomodulation of Urinary Tract Infections Caused by UropathogenicMicroorganisms · 2025Review
26 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
7 authors at 1 institution in 1 country.
Funding
Abstract
Chaperone-usher pathway pili are a widespread family of extracellular, Gram-negative bacterial fibers with important roles in bacterial pathogenesis. Type 1 pili are important virulence factors in uropathogenic Escherichia coli (UPEC), which cause the majority of urinary tract infections (UTI). FimH, the type 1 adhesin, binds mannosylated glycoproteins on the surface of human and murine bladder cells, facilitating bacterial colonization, invasion, and formation of biofilm-like intracellular bacterial communities. The mannose-binding pocket of FimH is invariant among UPEC. We discovered that pathoadaptive alleles of FimH with variant residues outside the binding pocket affect FimH-mediated acute and chronic pathogenesis of two commonly studied UPEC strains, UTI89 and CFT073. In vitro binding studies revealed that, whereas all pathoadaptive variants tested displayed the same high affinity for mannose when bound by the chaperone FimC, affinities varied when FimH was incorporated into pilus tip-like, FimCGH complexes. Structural studies have shown that FimH adopts an elongated conformation when complexed with FimC, but, when incorporated into the pilus tip, FimH can adopt a compact conformation. We hypothesize that the propensity of FimH to adopt the elongated conformation in the tip corresponds to its mannose binding affinity. Interestingly, FimH variants, which maintain a high-affinity conformation in the FimCGH tip-like structure, were attenuated during chronic bladder infection, implying that FimH's ability to switch between conformations is important in pathogenesis. Our studies argue that positively selected residues modulate fitness during UTI by affecting FimH conformation and function, providing an example of evolutionary tuning of structural dynamics impacting in vivo survival.
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Registered trials
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.