Characterization of a phospholipid-regulated β-galactosidase from Akkermansia muciniphila involved in mucin degradation.

The gut microbe Akkermansia muciniphila is important for the human health as the occurrence of the organism is inversely correlated with different metabolic disorders. The metabolism of the organism includes the degradation of intestinal mucins. Thus, the gut health-promoting properties are not immediately obvious and mechanisms of bacteria-host interactions are mostly unclear. In this study, we characterized a novel extracellular β-galactosidase (Amuc_1686) with a preference for linkages from the type Galβ1-3GalNAc. Additionally, Amuc_1686 possesses a discoidin-like domain, which enables the interaction with anionic phospholipids. We detected a strong inhibition by phosphatidylserine, phosphatidylglycerol, phosphatidic acid, and lysophosphatidic acid while phosphatidylcholine and phosphatidylethanolamine had no influence. Amuc_1686 is the first example of a prokaryotic hydrolase that is strongly inhibited by certain phospholipids. These inhibiting phospholipids have important signal functions in immune response and cell clearance processes. Hence, Amuc_1686 might be regulated based on the health status of the large intestine and could therefore contribute to the mutualistic relationship between the microbe and the host on a molecular level. In this sense, Amuc_1686 could act as an altruistic enzyme that does not attack the mucin layer of apoptotic epithelial cells to ensure tissue regeneration, for example, in areas with inflammatory damages.