Meningitis caused by a lipopolysaccharide deficient Neisseria meningitidis

Jurgen R. Piet, Afshin Zariri, Floris Fransen, Kim Schipper, Peter van der Ley, Diederik van de Beek, Arie van der Ende

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

Abstract

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. 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. 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. We describe invasive meningococcal disease caused by a naturally occurring LPS-deficient meningococcal isolate
Original languageEnglish
Pages (from-to)352-357
JournalJournal of Infection
Volume69
Issue number4
DOIs
Publication statusPublished - 2014

Cite this