Pneumococcal 6-Phospho-β-Glucosidase (BglA3) Is Involved in Virulence and Nutrient Metabolism

For the generation of energy, the important human pathogen Streptococcus pneumoniae relies on host-derived sugars, including beta-glucoside analogs. The catabolism of these nutrients involves the action of 6-phospho-beta-glucosidase to convert them into usable monosaccharaides. In this study, we characterized a 6-phospho-beta-glucosidase (BglA3) encoded by SPD_0247. We found that this enzyme has a cell membrane localization and is active only against a phosphorylated substrate. A mutated pneumococcal Delta SPD0247 strain had reduced 6-phospho-glucosidase activity and was attenuated in growth on cellobiose and hyaluronic acid compared to the growth of wild-type D39. Delta SPD0247-infected mice survived significantly longer than the wild-type-infected cohort, and the colony counts of the mutant were lower than those of the wild type in the lungs. The expression of SPD_0247 in S. pneumoniae harvested from infected tissues was significantly increased relative to its expression in vitro on glucose. Additionally, Delta SPD0247 is severely impaired in its attachment to an abiotic surface. These results indicate the importance of beta-glucoside metabolism in pneumococcal survival and virulence.