Active Infection & Immunity

Disrupting oral biofilm formation & maturation: Covalently inhibiting glucan sucrases from Streptococci

In plain English

AI plain-English summary

A chemical glue designed to permanently jam the enzymes that build dental plaque could stop oral biofilms from forming in the first place. Oral biofilms—sticky communities of bacteria that coat teeth and gums—are the root cause of tooth decay and contribute to wider oral disease. Their structural backbone is a sugary substance called glucan, which is assembled by enzymes known as glucan sucrases. Current treatments mostly scrape biofilms away after they form, or kill bacteria indiscriminately. This project targets the construction process itself: it will design small molecules that slip into the enzyme’s active site and form a permanent covalent bond, disabling it for good. The team will synthesise these inhibitors, then test them in bacterial cultures and in vitro models to see whether they block biofilm maturation without harming the rest of the oral microbiome. If the strategy works, it could lead to a new class of preventive treatments—perhaps a mouthwash or toothpaste additive—that stops plaque from building up in the first place. That would shift oral care from mechanical removal to chemical prevention, reducing caries and gum disease without relying on broad-spectrum antimicrobials. The project is fundamental science at the interface of chemistry and microbiology, but the same covalent-inhibition approach has already succeeded against other disease-relevant enzymes, making a practical outcome plausible.

View original technical description
This project is supported by the National Biofilms Innovation Centre, involving research at the interface between chemistry and microbiology. Oral biofilm is implicated not only in caries but also in wider oral health and pathology. The formation and maturation of oral biofilm are considered to be affected by some key enzymes. These enzymes are involved in the biosynthesis of glucans, other carbohydrates, and proteins. Glucans provide the base material of biofilms that create favourable environments for pathogens to grow and proliferate, leading to pathogenesis. The reaction mechanism of the enzymes making glucans and other carbohydrates has been intensively studied and will be utilised to design inhibitors. In this project, inhibitors that will make a covalent bond, thus permanently disable the enzyme will be developed in an attempt to control the activities of these enzymes. Bacterial and in vitro models will be built and tested with synthesised compounds, which will provide valuable insight into the microbiome of the oral cavity. This highly multidisciplinary project combines a wide variety of expertise including carbohydrate chemistry, enzymology, molecular biology, and microbiology, pioneering a novel chemical strategy to control the formation and maturation of biofilm in the oral microbiome using small molecules, thereby cracking the code of oral biofilm's impact on the oral health.

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