TY - JOUR
T1 - Inhibition of Streptococcus mutans Biofilms by the Natural Stilbene Piceatannol Through the Inhibition of Glucosyltransferases
AU - Nijampatnam, Bhavitavya
AU - Zhang, Hua
AU - Cai, Xia
AU - Michalek, Suzanne M.
AU - Wu, Hui
AU - Velu, Sadanandan E.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/7/31
Y1 - 2018/7/31
N2 - Removal of oral biofilms involves the use of broad-spectrum antimicrobials, which eradicate both pathogenic and protective oral commensal species. Ideal therapeutics for dental caries should be able to selectively inhibit pathogenic biofilms caused by Streptococcus mutans. S. mutans extracellular glucosyltransferases (Gtfs), particularly GtfB and GtfC, synthesize predominantly water-insoluble glucans, which contribute to the structural scaffold of biofilms. The lead stilbene identified through our docking study against the catalytic domain of GtfC is a natural product known as piceatannol, which inhibited S. mutans biofilm formation in a dose-dependent manner, with considerable selectivity over growth inhibition of S. mutans and commensal streptococci. Binding kinetic analysis of piceatannol was performed using Octet RED against both GtfB and GtfC, which produced low micromolar KD values. Piceatannol inhibited S. mutans colonization in an in vivo drosophila model and a rat model of dental caries.
AB - Removal of oral biofilms involves the use of broad-spectrum antimicrobials, which eradicate both pathogenic and protective oral commensal species. Ideal therapeutics for dental caries should be able to selectively inhibit pathogenic biofilms caused by Streptococcus mutans. S. mutans extracellular glucosyltransferases (Gtfs), particularly GtfB and GtfC, synthesize predominantly water-insoluble glucans, which contribute to the structural scaffold of biofilms. The lead stilbene identified through our docking study against the catalytic domain of GtfC is a natural product known as piceatannol, which inhibited S. mutans biofilm formation in a dose-dependent manner, with considerable selectivity over growth inhibition of S. mutans and commensal streptococci. Binding kinetic analysis of piceatannol was performed using Octet RED against both GtfB and GtfC, which produced low micromolar KD values. Piceatannol inhibited S. mutans colonization in an in vivo drosophila model and a rat model of dental caries.
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U2 - 10.1021/acsomega.8b00367
DO - 10.1021/acsomega.8b00367
M3 - Article
AN - SCOPUS:85050940601
SN - 2470-1343
VL - 3
SP - 8378
EP - 8385
JO - ACS Omega
JF - ACS Omega
IS - 7
ER -