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Updated: Apr 28, 2026

Induction of Leptomeningeal Cells Modification Via Intracisternal Injection
Published on: May 7, 2020
Meningitis caused by a lipopolysaccharide deficient Neisseria meningitidis
Jurgen R Piet1, Afshin Zariri2, Floris Fransen2
1Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, PO Box 22660, The Netherlands; Department of Medical Microbiology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, PO Box 22660, The Netherlands.
Objective:
Lipopolysaccharide (LPS) is a major component of the Neisseria meningitidis outer membrane. Here we report a patient with meningococcal meningitis of which the causative isolate lacked LPS. Thus far, no naturally occurring LPS-deficient meningococcal isolate has been known to cause clinical disease.
Methods:
We used SDS-PAGE, silver staining and LPS-specific antibodies in whole cell ELISA to determine LPS presence in the causative isolate. Meningococcal whole genome sequencing was performed using Roche 454-sequencing. The N. meningitidis strain MC58 was used to compare all LPS biosynthesis associated genes. We compared growth characteristics of Escherichia coli transformed with a plasmid containing 2 lpxH types.
Results:
The patient presented with isolated thunderclap headache. Analysis of the causative N. meningitidis showed no LPS. Whole genome sequencing revealed a mutation located in lpxH explaining LPS-deficiency. Expression of this lpxH variant in E. coli resulted in growth impairment compared to E. coli expressing the meningococcal wild type lpxH variant. In addition, inactivating lpxH in N. meningitidis H44/76 by insertional inactivation with a kanamycin cassette resulted in a LPS-deficient phenotype.
Conclusions:
We describe invasive meningococcal disease caused by a naturally occurring LPS-deficient meningococcal isolate.
Insights
A rare case of meningococcal meningitis was caused by a lipopolysaccharide (LPS)-deficient Neisseria meningitidis strain. This LPS-deficient strain, identified through whole genome sequencing, highlights a novel cause of invasive meningococcal disease.
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- Lipopolysaccharide (LPS) is a critical outer membrane component of Neisseria meningitidis.
- Naturally occurring LPS-deficient meningococcal isolates causing clinical disease have not been previously documented.
Observation:
- A patient presented with thunderclap headache, and the causative Neisseria meningitidis isolate was found to be LPS-deficient.
- Whole genome sequencing identified a mutation in the lpxH gene as the cause of LPS deficiency.
Findings:
- The identified lpxH variant impaired growth in E. coli compared to the wild-type.
- Insertional inactivation of lpxH in N. meningitidis H44/76 also resulted in an LPS-deficient phenotype.
Implications:
- This study describes the first known case of invasive meningococcal disease caused by a naturally LPS-deficient meningococcal isolate.
- The findings expand our understanding of meningococcal pathogenesis and the potential for LPS-deficient strains to cause disease.
Related Concept Videos
Bacterial Meningitis II: Pathophysiology
Bacterial Meningitis I: Introduction
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Formation of Lipopolysaccharides
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