FimH and anti-adhesive therapeutics: A disarming strategy against uropathogens

Meysam Sarshar, Payam Behzadi, Cecilia Ambrosi, Carlo Zagaglia, Anna Teresa Palamara, Daniela Scribano

Research output: Contribution to journalReview articlepeer-review

Abstract

Chaperone-usher fimbrial adhesins are powerful weapons against the uropathogens that allow the establishment of urinary tract infections (UTIs). As the antibiotic therapeutic strategy has become less effective in the treatment of uropathogen-related UTIs, the anti-adhesive molecules active against fimbrial adhesins, key determinants of urovirulence, are attractive alternatives. The best-characterized bacterial adhesin is FimH, produced by uropathogenic Escherichia coli (UPEC). Hence, a number of high-affinity mono-and polyvalent mannose-based FimH antagonists, characterized by different bioavailabilities, have been reported. Given that antagonist affinities are firmly associated with the functional heterogeneities of different FimH variants, several FimH inhibitors have been developed using ligand-drug discovery strategies to generate high-affinity molecules for successful anti-adhesion therapy. As clinical trials have shown d-mannose’s efficacy in UTIs prevention, it is supposed that mannosides could be a first-in-class strategy not only for UTIs, but also to combat other Gram-negative bacterial infections. Therefore, the current review discusses valuable and effective FimH anti-adhesive molecules active against UTIs, from design and synthesis to in vitro and in vivo evaluations.

Original languageEnglish
Article number397
Pages (from-to)1-16
Number of pages16
JournalAntibiotics
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Adhesins
  • Affinity
  • Antagonists
  • FimH
  • Mannose-binding lectin
  • Urinary tract infection
  • Uropathogenic Escherichia coli
  • Uropathogenic Klebsiella pneumoniae
  • Uropathogenic Proteus mirabilis

ASJC Scopus subject areas

  • Microbiology
  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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