In Silico Approach for the Identification of Potential Targets and Specific Antimicrobials for Streptococcus mutans

Tooth decay affects most of the population in developed countries. The multifactorial etiology of the disease includes multiple bacterial species, S. mutans is the main pathogen associated with the disease. This bacterium adheres to the tooth surface and allows the colonization of other microorganisms resulting in dental biofilm. Several therapeutic agents are available to treat or prevent tooth decay, but none, with the exception of fluoride, has significantly influenced the disease’s global burden. Moreover, the probable development of resistance of microorganisms to existing antibacterial agents and the scarcity of good antimicrobial agents motivates this effort for innovation. The detailed knowledge obtained in recent years on the S. mutans allowed the identification of potential targets in this microorganism, enabling the development of specific drugs to combat tooth decay. Thus, the identification of potential targets in these pathogens is the first step in the discovery process of new therapeutic agents. Currently, the experimental assays used for this purpose are expensive and time consuming. In contrast, bioinformatics methods to predict drug targets are cheap, quick and workaday in the biotechnology. This article will review the potential drug targets in S. mutans, as well as the bioinformatics methods used to identify these targets and effective drugs for specific pharmacological treatment of dental caries.

Targeted Antimicrobial Therapy Against Streptococcus mutans Establishes Protective Non-cariogenic Oral Biofilms and Reduces Subsequent Infection

Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization. Methodology Controlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides （STAMPs） against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization. Results S. mutans colonization was considerably reduced （9 ± 0.4 fold reduction, P=0.01） when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization （5 minutes treatment： 38 ± 13 fold reduction P=0.01; 16 hours treatment： 96 ± 28 fold reduction P=0.07）. Conclusion S. mutans infection is reduced by the pre- sence of existing biofilms. Thus maintaining a healthy or ＂normal＂ biofilm through targeted antimicrobial therapy （such as the STAMPs） could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression.