Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Associated disease: infection due to Streptococcus agalactiae [ICD11:
XN0KC 
]
The structure was elucidated in this paperNCBI PubMed ID: 35180210Publication DOI: 10.1371/journal.pbio.3001555Journal NLM ID: 101183755Publisher: San Francisco, CA: Public Library of Science
Correspondence: K.S. Doran <Kelly.Doran
CUAnschutz.edu>; K.L. PalmerI <Kelli.Palmer
UTDallas.edu>; Z. Guan <Ziqiang.Guan
Duke.edu>
Institutions: Department of Biological Sciences, The University of Texas at Dallas, Richardson, Texas, United States of America, Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America, Rio de Janeiro State University, Roberto Alcantara Gomes Biology Institute, Rio de Janeiro, Rio de Janeiro, Brazil, Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America
Bacterial membrane lipids are critical for membrane bilayer formation, cell division, protein localization, stress responses, and pathogenesis. Despite their critical roles, membrane lipids have not been fully elucidated for many pathogens. Here, we report the discovery of a novel cationic glycolipid, lysyl-glucosyl-diacylglycerol (Lys-Glc-DAG), which is synthesized in high abundance by the bacterium Streptococcus agalactiae (Group B Streptococcus, GBS). To our knowledge, Lys-Glc-DAG is more positively charged than any other known lipids. Lys-Glc-DAG carries 2 positive net charges per molecule, distinct from the widely described lysylated phospholipid lysyl-phosphatidylglycerol (Lys-PG) that carries one positive net charge due to the presence of a negatively charged phosphate moiety. We use normal phase liquid chromatography (NPLC) coupled with electrospray ionization (ESI) high-resolution tandem mass spectrometry (HRMS/MS) and genetic approaches to determine that Lys-Glc-DAG is synthesized by the enzyme MprF in GBS, which covalently modifies the neutral glycolipid Glc-DAG with the cationic amino acid lysine. GBS is a leading cause of neonatal meningitis, which requires traversal of the endothelial blood-brain barrier (BBB). We demonstrate that GBS strains lacking mprF exhibit a significant decrease in the ability to invade BBB endothelial cells. Further, mice challenged with a GBS?mprF mutant developed bacteremia comparably to wild-type (WT) infected mice yet had less recovered bacteria from brain tissue and a lower incidence of meningitis. Thus, our data suggest that Lys-Glc-DAG may contribute to bacterial uptake into host cells and disease progression. Importantly, our discovery provides a platform for further study of cationic lipids at the host-pathogen interface.
group B Streptococcus, mass spectrometry, Streptococcus agalactiae, lipids, cationic glycolipid
Structure type: monomer ; 884.670
C
49H
92N
2O
11Location inside paper: Fig. 1F, Lys-Glc-DAG
Compound class: glycolipid
Contained glycoepitopes: IEDB_136017,IEDB_141181,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_983931,SB_192
Methods: PCR, DNA techniques, ELISA, MS/MS, radiolabeling, genetic methods, HPLC, LC-ESI-MS, molecular biology techniques, extractions, TIC, hCMEC cell adherence assays, animal experiments, histology
Enzymes that release or process the structure: MprF
Comments, role: Streptococcus agalactiae (Group B Streptococcus, GBS); proposed structure of the lipid
NCBI Taxonomy refs (TaxIDs): 205921,
1427374,
1311
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
report error