Deciphering Proteoglycans and Glycosaminoglycans Metabolism in Bacterial Opportunism – OPPORTUNITY

Enterococcus faecalis is a commensal bacterium that colonizes the human gastrointestinal tract at an early stage, accounting for 1% of its total flora. However, it can also become opportunistic, causing 10% of hospital-acquired infections in France, including endocarditis, intra-abdominal infections and septicemia. The OPPORTUNITY project aims to understand this transition from commensalism to opportunism. Due to their location close to the gastric epithelium, enterococci are in contact with mucus, the extracellular matrix and other bacteria, which are made up of or possess glycosaminoglycans (GAGs) and proteoglycans (PGs) on their surface. PGs and GAGs have 2 potential roles: they represent a source of carbon and energy, but they also enable bacteria to adhere and internalize, to initiate infection and colonization processes. This project aims to understand the importance of PG and GAG metabolism in the commensalism-opportunism transition of E. faecalis.
This work will therefore involve the characterization of enzymes selected for their glycoside hydrolase and polysaccharide lyase activity: (i) at the metabolic level, by identifying their substrate and physiological role, (ii) at the virulence level, by determining their involvement in biofilm formation and translocation across the intestinal barrier in vitro and in vivo, (iii) at the regulatory level, their expression condition being indicative of their membership of one or more virulence-related regulons. The importance of metabolism in infection mechanisms is a largely neglected aspect in the pathogenic bacteria characterization: this study will therefore enable to understand the commensalism-opportunism transition of enterococci, with a view to identifying new strategies to fight infections.