Intervening in Symbiotic Cross-Kingdom Biofilm Interactions: a Binding Mechanism-Based Nonmicrobicidal Approach

Area of Science:

• Microbiology and Oral Health
• Biofilm Research
• Enzyme Therapeutics

Background:

• Early childhood caries involves synergistic interactions between *Candida albicans* and *Streptococcus mutans*, forming resilient, acidic biofilms.
• These biofilms exacerbate tooth decay, with *Candida albicans* cell wall mannans mediating interactions with bacterial glucosyltransferases (GtfB).

Purpose of the Study:

• To investigate an enzymatic strategy targeting GtfB-mannan interactions in *Candida albicans* and *Streptococcus mutans* biofilms.
• To evaluate the efficacy of mannan-degrading enzymes in disrupting biofilm structure and virulence factors.

Main Methods:

• Application of mannan-degrading exo- and endo-enzymes to disrupt GtfB-mannan binding.
• Assessment of biofilm biomass, pH, mechanical stability, and enamel demineralization.
• Biophysical analysis using single-molecule atomic force microscopy and surface topography studies.

Main Results:

• Enzyme treatment significantly reduced GtfB binding to *Candida albicans* (approximately 15-fold decrease).
• Reduced biofilm biomass and alleviated acidic pH production without microbial killing.
• Disrupted biofilm mechanical stability and significantly decreased enamel demineralization, with no cytotoxicity to human gingival keratinocytes.

Conclusions:

• Mannan-degrading enzymes offer a promising non-biocidal therapeutic approach for early childhood caries.
• Targeting interkingdom receptor-ligand interactions provides a novel strategy against pathogenic bacterial-fungal biofilms.
• This enzymatic intervention shows potential for preventing dental caries by disrupting crucial microbial interactions.