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In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II

Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation...

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Autores principales: Rivera-Quiroga, Raúl E., Cardona, Néstor, Padilla, Leonardo, Rivera, Wbeimar, Rocha-Roa, Cristian, Diaz De Rienzo, Mayri A., Morales, Sandra M., Martinez, María C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795114/
https://www.ncbi.nlm.nih.gov/pubmed/33396525
http://dx.doi.org/10.3390/ijms22010377
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author Rivera-Quiroga, Raúl E.
Cardona, Néstor
Padilla, Leonardo
Rivera, Wbeimar
Rocha-Roa, Cristian
Diaz De Rienzo, Mayri A.
Morales, Sandra M.
Martinez, María C.
author_facet Rivera-Quiroga, Raúl E.
Cardona, Néstor
Padilla, Leonardo
Rivera, Wbeimar
Rocha-Roa, Cristian
Diaz De Rienzo, Mayri A.
Morales, Sandra M.
Martinez, María C.
author_sort Rivera-Quiroga, Raúl E.
collection PubMed
description Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates.
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spelling pubmed-77951142021-01-10 In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II Rivera-Quiroga, Raúl E. Cardona, Néstor Padilla, Leonardo Rivera, Wbeimar Rocha-Roa, Cristian Diaz De Rienzo, Mayri A. Morales, Sandra M. Martinez, María C. Int J Mol Sci Article Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates. MDPI 2020-12-31 /pmc/articles/PMC7795114/ /pubmed/33396525 http://dx.doi.org/10.3390/ijms22010377 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rivera-Quiroga, Raúl E.
Cardona, Néstor
Padilla, Leonardo
Rivera, Wbeimar
Rocha-Roa, Cristian
Diaz De Rienzo, Mayri A.
Morales, Sandra M.
Martinez, María C.
In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II
title In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II
title_full In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II
title_fullStr In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II
title_full_unstemmed In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II
title_short In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II
title_sort in silico selection and in vitro evaluation of new molecules that inhibit the adhesion of streptococcus mutans through antigen i/ii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795114/
https://www.ncbi.nlm.nih.gov/pubmed/33396525
http://dx.doi.org/10.3390/ijms22010377
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