Assembly and Inhibition of the Porphyromonas Protein Secretion System
Project acronym: TOOTHPASTE
Topics: tooth infections, gingipains, Porphyromonas, protein T9SS
Concerned disciplinary fields: chemistry, microbiology, biology, biochemistry, infectious diseases
Summary: Periodontitis and gum diseases are considered as major public health concerns as roughly 36% of the world population (20% in industrialized countries) suffer of serious tooth tissue damages and tooth decay. The main microorganism responsible for periodontitis and gingivitis is the oral pathogenic bacterium Porphyromonas gingivalis. Infection by this Gram-negative bacterium causes severe lesions in periodontal tissues such as gingiva or the alveolar bone by disrupting the tooth-supporting structure. These damages are induced by a cocktail of specialized toxin proteins secreted by Porphyromonas, called gingipains. While the risks of gum diseases are diminished with preventive care, no efficient treatment is currently available to fight and eradicate Porphyromonas or to interfere with the activities of the gingipains. P. gingivalis being a strictly anaerobe pathogen, medical treatments consist to inject hydrogen peroxide in the gum or the tooth tissues. However, this approach has a very limited impact. The most obvious solution is to identify molecules that will interfere with a mechanism shared by all gingipains such as those that specifically inhibit the function of the protein complex called the Type IX secretion system (T9SS) and/or specifically target the gingipain secretion signal and interfere with its recruitment to the secretion apparatus. There is therefore a need to gain insights into the composition, assembly and mode of action of the T9SS. The present proposal wishes to tackle these questions.
Project duration : 04/01/2018 – 03/31/2021
Call for application : Interdisciplinarité 2016