Investigating the role of Rgg1518 transcriptional regulator in Streptococcus pneumoniae biology

Rggs are a group of transcriptional regulators found commonly in multiple homologous in a given species of streptococci, and they play diverse roles in metabolism and virulence. Here we studied Rgg1518’s (SPD_1518) role in sugar metabolism, and in vivo survival and virulence of Streptococcus pneumoniae. In vitro analysis showed that Rgg1518 is highly induced by galactose and mannose, and its isogenic mutant is attenuated in growth on these sugars compared to the wild type. The regulon information obtained by microarray analysis showed that Rgg1518 has by far the largest regulon on galactose compared to the other Rggs and controls the expression of functionally diverse set of genes involved in galactose uptake and catabolism, capsule biosynthesis, protein translation as well as those involved in other metabolic functions. We showed that Rgg1518 is the repressor of capsule biosynthesis, and identified Rgg1518 binding motif in the regulatory region of capsule locus. We demonstrated an interregulatory interactions among Rggs. Furthermore, the rgg1518 mutant was found to be attenuated in colonization and virulence in a mouse model of colonisation and pneumonia. One condition design comparision of two strains including a dye swap