Cargando…

Diaryl Urea Derivative Molecule Inhibits Cariogenic Streptococcus mutans by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism

Different small molecules have been developed to target cariogenic bacteria Streptococcus mutans. Based on target-based designing and in silico screening, a novel diaryl urea derivative, 1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea (BPU), has previously been found effective in inhibiting the growth o...

Descripción completa

Detalles Bibliográficos
Autores principales: Liao, Ying, Zhang, Mengyun, Lin, Xingnan, Yan, Fuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127343/
https://www.ncbi.nlm.nih.gov/pubmed/35619645
http://dx.doi.org/10.3389/fcimb.2022.904488
_version_ 1784712331050090496
author Liao, Ying
Zhang, Mengyun
Lin, Xingnan
Yan, Fuhua
author_facet Liao, Ying
Zhang, Mengyun
Lin, Xingnan
Yan, Fuhua
author_sort Liao, Ying
collection PubMed
description Different small molecules have been developed to target cariogenic bacteria Streptococcus mutans. Based on target-based designing and in silico screening, a novel diaryl urea derivative, 1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea (BPU), has previously been found effective in inhibiting the growth of S. mutans. However, the exact mechanism remains unclear. This current study aimed to explore the antimicrobial and antibiofilm effects of BPU on S. mutans and locate key enzymes and biological processes affected by the molecule via in silico molecular docking analysis and transcriptomic profile. Our in vitro results confirmed that BPU was capable of inhibiting planktonic growth as well as biofilm formation of S. mutans. The virtual binding analysis predicted that the molecule had strong binding potentials with vital enzymes (3AIC and 2ZID) involved in extracellular exopolysaccharide (EPS) synthesis. The predicted inhibitive binding was further confirmed by in vitro quantification of EPS, which found a decreased amount of EPS in the biofilms. The transcriptomic profile also found differential expression of genes involved in EPS synthesis. Moreover, the transcriptomic profile implied alterations in stress response and nitrogen metabolism in S. mutans treated with BPU. Examination of differentially expressed genes involved in these biological processes revealed that altered gene expression could contribute to impaired growth, biofilm formation, and competitiveness of S. mutans. In conclusion, the novel diaryl urea derivative BPU can inhibit the virulence of S. mutans by affecting different biological processes and serves as a potent anti-caries agent.
format Online
Article
Text
id pubmed-9127343
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-91273432022-05-25 Diaryl Urea Derivative Molecule Inhibits Cariogenic Streptococcus mutans by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism Liao, Ying Zhang, Mengyun Lin, Xingnan Yan, Fuhua Front Cell Infect Microbiol Cellular and Infection Microbiology Different small molecules have been developed to target cariogenic bacteria Streptococcus mutans. Based on target-based designing and in silico screening, a novel diaryl urea derivative, 1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea (BPU), has previously been found effective in inhibiting the growth of S. mutans. However, the exact mechanism remains unclear. This current study aimed to explore the antimicrobial and antibiofilm effects of BPU on S. mutans and locate key enzymes and biological processes affected by the molecule via in silico molecular docking analysis and transcriptomic profile. Our in vitro results confirmed that BPU was capable of inhibiting planktonic growth as well as biofilm formation of S. mutans. The virtual binding analysis predicted that the molecule had strong binding potentials with vital enzymes (3AIC and 2ZID) involved in extracellular exopolysaccharide (EPS) synthesis. The predicted inhibitive binding was further confirmed by in vitro quantification of EPS, which found a decreased amount of EPS in the biofilms. The transcriptomic profile also found differential expression of genes involved in EPS synthesis. Moreover, the transcriptomic profile implied alterations in stress response and nitrogen metabolism in S. mutans treated with BPU. Examination of differentially expressed genes involved in these biological processes revealed that altered gene expression could contribute to impaired growth, biofilm formation, and competitiveness of S. mutans. In conclusion, the novel diaryl urea derivative BPU can inhibit the virulence of S. mutans by affecting different biological processes and serves as a potent anti-caries agent. Frontiers Media S.A. 2022-05-10 /pmc/articles/PMC9127343/ /pubmed/35619645 http://dx.doi.org/10.3389/fcimb.2022.904488 Text en Copyright © 2022 Liao, Zhang, Lin and Yan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Liao, Ying
Zhang, Mengyun
Lin, Xingnan
Yan, Fuhua
Diaryl Urea Derivative Molecule Inhibits Cariogenic Streptococcus mutans by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism
title Diaryl Urea Derivative Molecule Inhibits Cariogenic Streptococcus mutans by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism
title_full Diaryl Urea Derivative Molecule Inhibits Cariogenic Streptococcus mutans by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism
title_fullStr Diaryl Urea Derivative Molecule Inhibits Cariogenic Streptococcus mutans by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism
title_full_unstemmed Diaryl Urea Derivative Molecule Inhibits Cariogenic Streptococcus mutans by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism
title_short Diaryl Urea Derivative Molecule Inhibits Cariogenic Streptococcus mutans by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism
title_sort diaryl urea derivative molecule inhibits cariogenic streptococcus mutans by affecting exopolysaccharide synthesis, stress response, and nitrogen metabolism
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127343/
https://www.ncbi.nlm.nih.gov/pubmed/35619645
http://dx.doi.org/10.3389/fcimb.2022.904488
work_keys_str_mv AT liaoying diarylureaderivativemoleculeinhibitscariogenicstreptococcusmutansbyaffectingexopolysaccharidesynthesisstressresponseandnitrogenmetabolism
AT zhangmengyun diarylureaderivativemoleculeinhibitscariogenicstreptococcusmutansbyaffectingexopolysaccharidesynthesisstressresponseandnitrogenmetabolism
AT linxingnan diarylureaderivativemoleculeinhibitscariogenicstreptococcusmutansbyaffectingexopolysaccharidesynthesisstressresponseandnitrogenmetabolism
AT yanfuhua diarylureaderivativemoleculeinhibitscariogenicstreptococcusmutansbyaffectingexopolysaccharidesynthesisstressresponseandnitrogenmetabolism