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FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens

1
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Laboratory affiliated to Institute Pasteur Italia- Cenci Bolognetti Foundation, 00185 Rome, Italy
2
Research Laboratories, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
3
Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran 1316943551, Iran
4
Department of Microbiology, College of Basic Sciences, Shahr-e-Qods Branch, Islamic Azad University, Tehran 37541-374, Iran
5
IRCCS San Raffaele Pisana, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy
6
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
7
Dani Di Giò Foundation-Onlus, 00193 Rome, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Antibiotics 2020, 9(7), 397; https://doi.org/10.3390/antibiotics9070397
Received: 30 June 2020 / Revised: 6 July 2020 / Accepted: 8 July 2020 / Published: 10 July 2020
(This article belongs to the Special Issue Pathogenic Escherichia coli: Infections and Therapies)
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. View Full-Text
Keywords: FimH; adhesins; uropathogenic Escherichia coli; uropathogenic Klebsiella pneumoniae; uropathogenic Proteus mirabilis; urinary tract infection; antagonists; mannose-binding lectin; affinity FimH; adhesins; uropathogenic Escherichia coli; uropathogenic Klebsiella pneumoniae; uropathogenic Proteus mirabilis; urinary tract infection; antagonists; mannose-binding lectin; affinity
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Sarshar, M.; Behzadi, P.; Ambrosi, C.; Zagaglia, C.; Palamara, A.T.; Scribano, D. FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens. Antibiotics 2020, 9, 397.

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