A team from the Institute of Molecular Biology of Barcelona (IBMB-CSIC), based in the Barcelona Science Park, has discovered an unprecedented attack and defence mechanism in one of the bacteria which causes periodontitis, Tannerella forsythia, which could serve in the investigation of new strategies against the disease. The work, led by researcher F. Xavier Gomis-Rüth, is published in Chemical Science, the flagship journal of the prestigious English Royal Society of Chemistry.

Periodontitis, an inflammatory gum disease, has a major impact on public health and quality of life. It is estimated to affect 10% of the world’s population, according to the World Health Organization. In Spain, some 8 million people are affected. Periodontitis has negative effects on other pathologies and, in the most serious cases, it can lead to the loss of the bone that supports the teeth, and the teeth themselves.

Periodontitis is caused by the presence of pathogenic bacteria in the oral microbiome. Now, a team from the IBMB-CSIC has discovered that one of the main bacteria causing periodontitis, Tannerella forsythia, has a never-before-seen attack and defence mechanism: it secretes proteins which inhibit its own virulence factors.

The virulence factors are molecules with which pathogenic bacteria attack other cells. In its case, T. forsythia secretes six proteases, which, during the development of periodontitis, break down the proteins of the cellular tissue of the gums. The six proteases, which were already known, have an identical amino acid sequence in the last five positions (K–L–I–K–K) of their genetic sequence, so they are therefore known as “KLIKK proteases”.

What researchers at the IBMB-CSIC have now seen is that, in the bacterium’s genome, the genes of each of these proteases are preceded by a DNA sequence, which had not been identified until now. “We investigated their function and mechanism of action by genetic, phylogenetic, biochemical, structural, functional, and in vivo analysis,” say the researchers of the work. The results reveal “an unprecedented network of virulence and competence regulation on the cell surface of the Tannerella forsythia bacterium.”

As they explain in the article published in Chemical Science, whose first authors are Mirosław Książek, Theodoros Goulas and Danuta Mizgalska, these six novel DNA sequences encode six proteins, named “potempins”, which have turned out to be specific inhibitors of the KLIKK proteases.

“It may seem like a contradiction that the bacterium has molecules to counteract its own attack ‘weapons”, notes F. Xavier Gomis Rüth. However, the interpretation suggests that “the bacterium has inhibitors of its own virulence factors, to prevent it from harming its own membrane.”

These inhibiting molecules can provide clues to develop new strategies against periodontitis and can be used to inhibit the virulence factors of the pathogenic bacteria. From a practical point of view, Gomis-Rüth explains that they could be incorporated, for example, into oral hygiene products to inhibit the action of the virulence factors of pathogenic bacteria.

Among the proteins discovered, the scientists highlight that one of them, potempin A, is a potent and selective inhibitor of the MMP12 (acronym for matrix metalloprotease 12) molecule, which is found in the macrophages of the human immune system and which forms part of the human organism’s defensive arsenal. It also plays an important causative role in the development and progression of chronic pulmonary obstruction caused by tobacco smoke and its severe pathological variant, pulmonary emphysema. Potempin A is, therefore, “the first specific inhibitor of the MMP protein-type described since the discovery of the classic TIMP, tissue inhibitors of metalloproteases, decades ago; and it could be used in novel therapies against these lung diseases,” they conclude.

» Reference article: Mirosław Książek et al. “A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen Tannerella forsythia”. Chem. Sci., 2023, https://doi.org/10.1039/D2SC04166A