Abstract
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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