Evidence map›Paper›PMID 35180210›Full record

ArticlePLoS biology2022

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

Luke R Joyce, Haider S Manzer, Jéssica da C Mendonça, Ricardo Villarreal, Prescilla E Nagao, Kelly S Doran, Kelli L Palmer, Ziqiang Guan

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
0.4field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
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  5. Article
  6. Article
  7. Evidence of a novel sublineage ofMicrobial genomics · 2025
    Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Identification of glyoxalase A in group BInfection and immunity · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Identification of Glyoxalase A in Group BbioRxiv : the preprint server for biology · 2024
    Article
  17. Article
  18. Group BJournal of bacteriology · 2024
    Article
  19. Science advances · 2024
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Luke R JoyceDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, Texas, United States of America.ORCID 0000-0002-9346-671X
Haider S ManzerDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.ORCID 0000-0002-2864-6212
Jéssica da C MendonçaDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.ORCID 0000-0002-2555-4582
Ricardo VillarrealDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.ORCID 0000-0001-7641-4136
Prescilla E NagaoRio de Janeiro State University, Roberto Alcântara Gomes Biology Institute, Rio de Janeiro, Rio de Janeiro, Brazil.ORCID 0000-0001-6007-0033
Kelly S DoranDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.ORCID 0000-0003-4232-6837
Kelli L PalmerDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, Texas, United States of America.ORCID 0000-0002-7343-9271
Ziqiang GuanDepartment of Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America.ORCID 0000-0002-8082-3423
The University of Texas at Dallas · USUniversidade do Estado do Rio de Janeiro · BRUniversity of Colorado Denver · USDuke Medical Center · US

Funding

STEROL LIPIDSU54GM069338 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DENNIS, EDWARD A · 2003 to 2013
$72.2M
Host and bacterial mechanisms governing Group B streptococcal persistence in the female genital tractR01AI153332 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DORAN, KELLY S · 2021 to 2025
$2.9M
Molecular Pathogenesis of Infectious DiseasesT32AI052066 · NIAID · UNIVERSITY OF COLORADO DENVER · PI VAN DYK, LINDA F. · 2002 to 2022
$2.3M
Modulation of Blood-Brain Barrier Defense and Dysfunction during Bacterial MeningitisR01NS116716 · NINDS · UNIVERSITY OF COLORADO DENVER · PI DORAN, KELLY S · 2020 to 2024
$1.9M
Adaptive Alterations of Lipids in Streptococcus MitisR56AI139105 · NIAID · UNIVERSITY OF TEXAS DALLAS · PI GUAN, ZIQIANG, PALMER, KELLI LEA · 2019 to 2019
$479k
Genetic basis for virulence in Streptococcus mitis and S. oralisR21AI130666 · NIAID · UNIVERSITY OF TEXAS DALLAS · PI PALMER, KELLI LEA · 2018 to 2019
$440k
Characterizing the Contribution of the Group B Streptococcal Surface Adhesin BspC Interaction with Host Vimentin to Disease and ColonizationF31AI164674 · NIAID · UNIVERSITY OF COLORADO DENVER · PI MANZER, HAIDER SYED · 2021 to 2022
$69k
NIAID NIH HHS F31 AI164674NIAID NIH HHS R01 AI153332NIAID NIH HHS R21 AI130666NIAID NIH HHS R56 AI139105NIAID NIH HHS T32 AI052066NIGMS NIH HHS U54 GM069338NINDS NIH HHS R01 NS116716
6 · The paper itself

Abstract

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.

Indexed as

AminoacyltransferasesAnimalsBacterial ProteinsBiological TransportBlood-Brain BarrierBrainCationsChromatography, LiquidGlycolipidsHumansMaleMeningitisMiceMutationSpectrometry, Mass, Electrospray IonizationStreptococcus agalactiaeAminoacyltransferasesBacterial ProteinsCationsGlycolipids

Identifiers

PMID35180210
PMCPMC8893666
OpenAlexW3108193717

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.