Streptococcus agalactiae MprF synthesizes a novel cationic glycolipid and plays a role in brain entry and meningitis

Abstract Multiple peptide resistance factor (MprF) is highly conserved in bacterial pathogens and is an attractive target for novel antimicrobials due to its important roles in bacterial virulence. We uncovered novel biochemical and pathophysiological functions of MprF in Streptococcus agalactiae (Group B Streptococcus; GBS), which is a common cause of meningitis and severe infection in newborns. Uniquely, GBS MprF catalyzes the synthesis of lysyl-glucosyl-diacylglyerol (Lys-Glc-DAG), a novel cationic glycolipid, and to a lesser extent, lysyl-phosphatidylglycerol (Lys-PG). We show that GBS MprF significantly lowers the GBS surface negative charge and increases GBS acid tolerance. Further, we demonstrate that GBS MprF promotes brain entry and meningeal inflammation, using a mouse model of GBS meningitis. These results expand our knowledge of MprF functions, and the pathogenesis of meningitis caused by GBS.