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Identification of a novel cationic glycolipid in Streptococcus agalactiae that contributes to brain entry and meningitis.

Publication ,  Journal Article
Joyce, LR; Manzer, HS; da C Mendonça, J; Villarreal, R; Nagao, PE; Doran, KS; Palmer, KL; Guan, Z
Published in: PLoS Biol
February 2022

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 GBSΔmprF 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.

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Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

February 2022

Volume

20

Issue

2

Start / End Page

e3001555

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • Streptococcus agalactiae
  • Spectrometry, Mass, Electrospray Ionization
  • Mutation
  • Mice
  • Meningitis
  • Male
  • Humans
  • Glycolipids
  • Developmental Biology
 

Citation

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Joyce, L. R., Manzer, H. S., da C Mendonça, J., Villarreal, R., Nagao, P. E., Doran, K. S., … Guan, Z. (2022). Identification of a novel cationic glycolipid in Streptococcus agalactiae that contributes to brain entry and meningitis. PLoS Biol, 20(2), e3001555. https://doi.org/10.1371/journal.pbio.3001555
Joyce, Luke R., Haider S. Manzer, Jéssica da C Mendonça, Ricardo Villarreal, Prescilla E. Nagao, Kelly S. Doran, Kelli L. Palmer, and Ziqiang Guan. “Identification of a novel cationic glycolipid in Streptococcus agalactiae that contributes to brain entry and meningitis.PLoS Biol 20, no. 2 (February 2022): e3001555. https://doi.org/10.1371/journal.pbio.3001555.
Joyce LR, Manzer HS, da C Mendonça J, Villarreal R, Nagao PE, Doran KS, et al. Identification of a novel cationic glycolipid in Streptococcus agalactiae that contributes to brain entry and meningitis. PLoS Biol. 2022 Feb;20(2):e3001555.
Joyce, Luke R., et al. “Identification of a novel cationic glycolipid in Streptococcus agalactiae that contributes to brain entry and meningitis.PLoS Biol, vol. 20, no. 2, Feb. 2022, p. e3001555. Pubmed, doi:10.1371/journal.pbio.3001555.
Joyce LR, Manzer HS, da C Mendonça J, Villarreal R, Nagao PE, Doran KS, Palmer KL, Guan Z. Identification of a novel cationic glycolipid in Streptococcus agalactiae that contributes to brain entry and meningitis. PLoS Biol. 2022 Feb;20(2):e3001555.
Journal cover image

Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

February 2022

Volume

20

Issue

2

Start / End Page

e3001555

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • Streptococcus agalactiae
  • Spectrometry, Mass, Electrospray Ionization
  • Mutation
  • Mice
  • Meningitis
  • Male
  • Humans
  • Glycolipids
  • Developmental Biology