Journal
JOURNAL OF DENTAL RESEARCH
Volume 98, Issue 3, Pages 322-330Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0022034518818480
Keywords
biofilms; dental caries; extracellular polymeric substance matrix; anti-infective agents; drug resistance; streptococcus
Categories
Funding
- Johnson Johnson
- China Scholarship Council (CSC)
- National Natural Science Foundation of China [81371135]
- National Key Technologies R&D Program of China during the 12th Five-Year Plan Period [2012BAI07B03]
- CAPES [88881.119452/2016-01]
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Biofilm formation is a key virulence factor responsible for a wide range of infectious diseases, including dental caries. Cariogenic biofilms are structured microbial communities embedded in an extracellular matrix that affords bacterial adhesion-cohesion and drug tolerance, making them difficult to treat using conventional antimicrobial monotherapy. Here, we investigated a multitargeted approach combining exopolysaccharide (EPS) matrix-degrading glucanohydrolases with a clinically used essential oils-based antimicrobial to potentiate antibiofilm efficacy. Our data showed that dextranase and mutanase can synergistically break down the EPS glucan matrix in preformed cariogenic biofilms, markedly enhancing bacterial killing by the antimicrobial agent (3-log increase versus antimicrobial alone). Further analyses revealed that an EPS-degrading/antimicrobial (EDA) approach disassembles the matrix scaffold, exposing the bacterial cells for efficient killing while concurrently causing cellular dispersion and physical collapse of the bacterial clusters. Unexpectedly, we found that the EDA approach can also selectively target the EPS-producing cariogenic bacteria Streptococcus mutans with higher killing specificity (versus other species) within mixed biofilms, disrupting their accumulation and promoting dominance of commensal bacteria. Together, these results demonstrate a dual-targeting approach that can enhance antibiofilm efficacy and precision by dismantling the EPS matrix and its protective microenvironment, amplifying the killing of pathogenic bacteria within.
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