biostudies-literatureJoyce LRNIAID NIH HHSNINDS NIH HHSeadn7848https://www.ebi.ac.uk/biostudies/studies/S-EPMC11135403biostudies-literatureUnknown10(22)<i>Streptococcus agalactiae</i> [group B <i>Streptococcus</i> (GBS)] is a leading cause of neonatal meningitis, with late-onset disease (LOD) occurring after gastrointestinal tract colonization in infants. Bacterial membrane lipids are essential for host-pathogen interactions, and the functions of glycolipids are yet to be fully elucidated. GBS synthesizes three major glycolipids: glucosyl-diacylglycerol (Glc-DAG), diglucosyl-DAG (Glc<sub>2</sub>-DAG), and lysyl-Glc-DAG (Lys-Glc-DAG). Here, we identify the enzyme, IagB, as responsible for biosynthesis of Glc-DAG, the precursor for the two other glycolipids in GBS. To examine the collective role of glycolipids to GBS virulence, we adapted a murine model of neonatal meningitis to simulate LOD. The GBS∆<i>iagB</i> mutant traversed the gut-epiScience advances<i>Streptococcus agalactiae</i> glycolipids promote virulence by thwarting immune cell clearance.PMC11135403R01 AI153332R01 AI178692R01 NS116716R01 NS098273R01 AI148366Kim SDoran KSGuan ZChristensen PMJoyce LRSpencer BLPalmer KLSiegenthaler JAfalse<i>Streptococcus agalactiae</i> glycolipids promote virulence by thwarting immune cell clearance.<i>Streptococcus agalactiae</i> [group B <i>Streptococcus</i> (GBS)] is a leading cause of neonatal meningitis, with late-onset disease (LOD) occurring after gastrointestinal tract colonization in infants. Bacterial membrane lipids are essential for host-pathogen interactions, and the functions of glycolipids are yet to be fully elucidated. GBS synthesizes three major glycolipids: glucosyl-diacylglycerol (Glc-DAG), diglucosyl-DAG (Glc<sub>2</sub>-DAG), and lysyl-Glc-DAG (Lys-Glc-DAG). Here, we identify the enzyme, IagB, as responsible for biosynthesis of Glc-DAG, the precursor for the two other glycolipids in GBS. To examine the collective role of glycolipids to GBS virulence, we adapted a murine model of neonatal meningitis to simulate LOD. The GBS∆<i>iagB</i> mutant traversed the gut-epi2024-01-01T00:00:00Z2024 May2026-03-11T00:06:06.503Z2025-08-13T03:04:16.446ZS-EPMC111354033880998910.1126/sciadv.adn7848