## 4 Discussion  
Biofilm production by _S. mutans_ is critical in the pathogenesis of dental plague associated oral diseases [38,39]. Several natural products have been evaluated for their anti-plaque properties in an effort to attenuate oral bacteria biofilm formation [28,38,39]. However, most of them have shown detrimental effects on the oral microbiome. Numerous studies have shown that inhibiting glucansucrase synthesis will affect the ability of _S. mutans_ to produce extracellular polysaccharide-like glucans implicated in the pathogenicity of dental plaque [16,40]. Glucansucrase provides the binding elements that create the enabling environment for biofilm formation. In the present study, we report the inhibitory potentials of mangiferin, a naturally synthesized product from _Mangifera indica_, on glucansucrase's glucan synthesis. Using a computational approach, we demonstrated a significant binding interaction of mangiferin with glucansucrase at domains A and B amino acid sequence. Documented evidence indicates that these domains harbor the enzyme's catalytic sites [41,42]. The binding interactions as revealed by docking analysis in this study occurred at 8 regions of the amino acid components of glucansucrase. Interestingly, ARG 475, ASP 588, and ASP 593, which were involved in this binding interaction, are considered as the enzyme's catalytic active sites [43,44]. ARG 475 was identified as a key stabilizer of the biofilm structure, whereas ASP 593 is reported by [PERSON] et al. [43] to have a critical influence on transglycosylation. This phenomenon is responsible for the production of either soluble or insoluble glucan. Therefore, the binding interaction of mangiferin with glucansucrase provided the impetus to explore its potential to inhibit biofilm formation. Abundant evidence shows that the production of glucan by glucansucrase secreted by _S. mutans_ is the main pathogenic feature implicated in dental biofilm formation [45]. Hence, suppressing the ability of glucansucrase to synthesize glucan will in turn reduce the generation of polysaccharide production and disrupt bacteria dental plaque formation. [PERSON] et al. [45] reported that a glucan synthesized polysaccharide matrix enhances early phase bacteria adherence to tooth surfaces. It also acts as a crucial carbohydrate reserve, shielding the microbes from antibacterial action [46]. The present study indicates that mangiferin inhibited glucansucrase activity in a concentration-dependent manner by 75%. However, the observation, that all concentrations of mangiferin did not affect the growth of planktonic _S. mutans_ is contrary to earlier reports by [PERSON] et al., [26] and [PERSON] et al., [47], who documented antibacterial activity of extracts of _Mangifera indica_ leaves. A number of molecules of natural origins are reported to inhibit _S. mutans_ activity, particularly, essential oils as documented by [PERSON] et al. [48] and [PERSON] et al. [49]. This attribute places essential oils as a likely alternative to antimicrobials, particularly with the emergence of multi drug resistance. It could also, reduce their ability to be pathogenic [49]. [PERSON] et al. [50], reported antibiofilm activity of _Mentha piperita_ essential oils against _S. mutans_. The present work showed a mangiferin-induced suppressing effect on the biofilm formation in concentration-dependent fashion. This effect is consequent to the inhibition of glucansucrase as aforementioned. Colony-forming units (CFU) were reduced as well, indicating that mangiferin could be a potential candidate in the control of dental plaque formation. Our findings are in agreement with the work of [PERSON] et al. [26]. The inability of _S. mutans_ to form colonies in the presence of mangiferin decreased the bacteria's propensity to form biofilm in the absence of adherent glucan. This affected the ability of _S. mutans_ to create an enabling microbial environment that is appropriate for colonization and subsequently plaque formation [12].