Streptococcus mutans (the bad bacteria in our mouths) is the principal causative agent of human tooth decay, an oral disease which affects the majority of the world’s population. The bacteria breaks down tooth enamel and left untreated tooth decay can lead to pain, infection and tooth loss.
The knowledge of pathogenicity and the survival mechanisms of S. mutans is still incomplete as many of the proteins encoded by its genome have not been characterized. Moreover, almost every species of Streptococcus contains plasmids (short pieces of circular DNA) which encode proteins that mediate the bacterium’s resistance to antibiotics and its pathogenesis. Some of these proteins could constitute novel targets that could be exploited to develop novel drugs to fight human tooth decay.
However, isolation and experimental characterization of these proteins would be a time-consuming and expensive process. In this context, bioinformatics tools represent an alternative route for identifying and selecting promising drug targets. In the paper by researcher Silvia Caprari and co-workers published in the journal Bio-Algorithms and Med-Systems, bioinformatics protein structure and function prediction tools were employed to characterize a set of nine S. mutans plasmidic proteins.
This approach allowed the researchers to identify two promising targets: a toxin-antitoxin systems and a conjugation protein which are responsible for conferring important pathogenic features to S. mutans. In particular, the toxin-antitoxin interaction inhibits the toxin action and increases the fitness of bacteria containing the plasmid.
Drugs targeting the antitoxin can thus be developed to inhibit its association with the toxin which in the free state would exert its toxic activity on the bacterium. The conjugation protein is essential for the transfer of plasmidic genes from one S. mutans strain to the other and to other Streptococcus species, thus contributing to spread pathogenicity features among bacterial microorganisms.
Thus, these two protein systems can be considered potential pharmacological targets and the structural and functional information obtained in this study could be exploited for molecular docking studies aimed at identifying compounds able to inhibit their activity.
The structural information obtained on Streptococcus mutans plasmidic proteins can be used to select novel targets for the design of innovative therapeutic agents for human tooth decay.
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