FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens
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 f...
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doaj-aa049fdf4f2a4a188f354c15bae203dc2020-11-25T03:42:14ZengMDPI AGAntibiotics2079-63822020-07-01939739710.3390/antibiotics9070397FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against UropathogensMeysam Sarshar0Payam Behzadi1Cecilia Ambrosi2Carlo Zagaglia3Anna Teresa Palamara4Daniela Scribano5Department of Public Health and Infectious Diseases, Sapienza University of Rome, Laboratory affiliated to Institute Pasteur Italia- Cenci Bolognetti Foundation, 00185 Rome, ItalyDepartment of Microbiology, College of Basic Sciences, Shahr-e-Qods Branch, Islamic Azad University, Tehran 37541-374, IranIRCCS San Raffaele Pisana, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Laboratory affiliated to Institute Pasteur Italia- Cenci Bolognetti Foundation, 00185 Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, ItalyChaperone-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 <i>Escherichia coli</i> (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 <span style="font-variant: small-caps;">d</span>-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.https://www.mdpi.com/2079-6382/9/7/397FimHadhesinsuropathogenic <i>Escherichia coli</i>uropathogenic <i>Klebsiella pneumoniae</i>uropathogenic <i>Proteus mirabilis</i>urinary tract infection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meysam Sarshar Payam Behzadi Cecilia Ambrosi Carlo Zagaglia Anna Teresa Palamara Daniela Scribano |
spellingShingle |
Meysam Sarshar Payam Behzadi Cecilia Ambrosi Carlo Zagaglia Anna Teresa Palamara Daniela Scribano FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens Antibiotics FimH adhesins uropathogenic <i>Escherichia coli</i> uropathogenic <i>Klebsiella pneumoniae</i> uropathogenic <i>Proteus mirabilis</i> urinary tract infection |
author_facet |
Meysam Sarshar Payam Behzadi Cecilia Ambrosi Carlo Zagaglia Anna Teresa Palamara Daniela Scribano |
author_sort |
Meysam Sarshar |
title |
FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens |
title_short |
FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens |
title_full |
FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens |
title_fullStr |
FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens |
title_full_unstemmed |
FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens |
title_sort |
fimh and anti-adhesive therapeutics: a disarming strategy against uropathogens |
publisher |
MDPI AG |
series |
Antibiotics |
issn |
2079-6382 |
publishDate |
2020-07-01 |
description |
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 <i>Escherichia coli</i> (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 <span style="font-variant: small-caps;">d</span>-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. |
topic |
FimH adhesins uropathogenic <i>Escherichia coli</i> uropathogenic <i>Klebsiella pneumoniae</i> uropathogenic <i>Proteus mirabilis</i> urinary tract infection |
url |
https://www.mdpi.com/2079-6382/9/7/397 |
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