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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Bibliographic Details
Published in:International journal of molecular sciences 2021-01, Vol.22 (1), p.377
Main Authors: Rivera-Quiroga, Raúl E., Cardona, Néstor, Padilla, Leonardo, Rivera, Wbeimar, Rocha-Roa, Cristian, Diaz De Rienzo, Mayri A., Morales, Sandra M., Martinez, María C.
Format: Article
Language:English
Subjects:
Adhesins
Adhesion
Antigens
Antimicrobial agents
Bacteria
Bacterial proteins
Binding sites
Biofilms
Crystal structure
Cytotoxicity
Dental caries
Dental plaque
Dynamic stability
Fluorides
Microbiota
Molecular dynamics
Oral hygiene
Pathogens
Pellicle
Polystyrene resins
Probiotics
Scanning electron microscopy
Streptococcus infections
Streptococcus mutans
Sucrose
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22010377