Streptococcus pneumoniae is a common resident of the human nasorpharynx thatcan cause severe illness, including bacterial meningitis and pneumonia. Ruminococcusgnavus is a commensal resident of the human gastrointestinal tract, present in the vastmajority and overrepresented in those with inflammatory bowel disease. Both bacteriaexploit very different niches, however both make use of sialidases, a class of enzymesthat releases terminal sialic acids from sialoglycoconjugates by hydrolysing the α-glycosidic linkage. There are three pneumococcal sialidases: SpNanA, a hydrolyticsialdiase; SpNanB, an intra-molecular trans-sialidase; and SpNanC. The primary reactionproduct of SpNanC is Neu5Ac2en (2-deoxy-2,3-didehydro-N-acetylneuraminicacid, also known as DANA), a potent inhibitor of hydrolytic bacterial and viral sialidases.The crystal structure of SpNanC in complex with Neu5Ac2en has been solvedand a reaction mechanism for its formation proposed. R. gnavus can grow on sialylatedsubstrates however it does not grow on sialic acid. The crystal structure ofRgNanH has also been solved, confirming that it is an intra-molecular trans-sialidase,like SpNanB, that produces 2,7-anhydro-Neu5Ac, a sialic acid derivative with an intra-molecular linkage. This suggests a method of partitioning an important carbonsource in a competitive environment. These works highlight the importance of thoroughstructural characterisation of sialidases, because although they may appearsuperficially very similar, they have significant diversity in their reaction mechanismsand their responses to inhibitors.
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