Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i>
Type I fimbriae are the main adhesive organelles of uropathogenic <i>Escherichia coli</i> (UPEC), consisting of four different subunits. Their component with the most important role in establishing bacterial infections is the FimH adhesin located at the fimbrial tip. This two-domain prot...
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/3/1018 |
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| author | Georgia I. Nasi Konstantina I. Georgakopoulou Marilena K. Theodoropoulou Nikos C. Papandreou Evangelia D. Chrysina Paraskevi L. Tsiolaki Vassiliki A. Iconomidou |
| author_facet | Georgia I. Nasi Konstantina I. Georgakopoulou Marilena K. Theodoropoulou Nikos C. Papandreou Evangelia D. Chrysina Paraskevi L. Tsiolaki Vassiliki A. Iconomidou |
| author_sort | Georgia I. Nasi |
| collection | DOAJ |
| description | Type I fimbriae are the main adhesive organelles of uropathogenic <i>Escherichia coli</i> (UPEC), consisting of four different subunits. Their component with the most important role in establishing bacterial infections is the FimH adhesin located at the fimbrial tip. This two-domain protein mediates adhesion to host epithelial cells through interaction with terminal mannoses on epithelial glycoproteins. Here, we propose that the amyloidogenic potential of FimH can be exploited for the development of therapeutic agents against Urinary Tract Infections (UTIs). Aggregation-prone regions (APRs) were identified via computational methods, and peptide-analogues corresponding to FimH lectin domain APRs were chemically synthesized and studied with the aid of both biophysical experimental techniques and molecular dynamic simulations. Our findings indicate that these peptide-analogues offer a promising set of antimicrobial candidate molecules since they can either interfere with the folding process of FimH or compete for the mannose-binding pocket. |
| first_indexed | 2024-03-11T06:01:00Z |
| format | Article |
| id | doaj.art-36b98c881e124e52bb0e1d7aea8cdc6b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:01:00Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-36b98c881e124e52bb0e1d7aea8cdc6b2023-11-17T13:17:38ZengMDPI AGPharmaceutics1999-49232023-03-01153101810.3390/pharmaceutics15031018Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i>Georgia I. Nasi0Konstantina I. Georgakopoulou1Marilena K. Theodoropoulou2Nikos C. Papandreou3Evangelia D. Chrysina4Paraskevi L. Tsiolaki5Vassiliki A. Iconomidou6Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, GreeceType I fimbriae are the main adhesive organelles of uropathogenic <i>Escherichia coli</i> (UPEC), consisting of four different subunits. Their component with the most important role in establishing bacterial infections is the FimH adhesin located at the fimbrial tip. This two-domain protein mediates adhesion to host epithelial cells through interaction with terminal mannoses on epithelial glycoproteins. Here, we propose that the amyloidogenic potential of FimH can be exploited for the development of therapeutic agents against Urinary Tract Infections (UTIs). Aggregation-prone regions (APRs) were identified via computational methods, and peptide-analogues corresponding to FimH lectin domain APRs were chemically synthesized and studied with the aid of both biophysical experimental techniques and molecular dynamic simulations. Our findings indicate that these peptide-analogues offer a promising set of antimicrobial candidate molecules since they can either interfere with the folding process of FimH or compete for the mannose-binding pocket.https://www.mdpi.com/1999-4923/15/3/1018FimHlectintype I fimbriaeaggregation-prone regionspredictionUTIs |
| spellingShingle | Georgia I. Nasi Konstantina I. Georgakopoulou Marilena K. Theodoropoulou Nikos C. Papandreou Evangelia D. Chrysina Paraskevi L. Tsiolaki Vassiliki A. Iconomidou Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i> Pharmaceutics FimH lectin type I fimbriae aggregation-prone regions prediction UTIs |
| title | Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i> |
| title_full | Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i> |
| title_fullStr | Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i> |
| title_full_unstemmed | Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i> |
| title_short | Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i> |
| title_sort | bacterial lectin fimh and its aggregation hot spots an alternative strategy against uropathogenic i escherichia coli i |
| topic | FimH lectin type I fimbriae aggregation-prone regions prediction UTIs |
| url | https://www.mdpi.com/1999-4923/15/3/1018 |
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