Meningitis caused by a lipopolysaccharide deficient Neisseria meningitidis

Summary 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...

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Bibliographic Details
Published in:The Journal of infection 2014-10, Vol.69 (4), p.352-357
Main Authors: Piet, Jurgen R, Zariri, Afshin, Fransen, Floris, Schipper, Kim, van der Ley, Peter, van de Beek, Diederik, van der Ende, Arie
Format: Article
Language:English
Subjects:
Adult
Bacterial diseases
Bacterial diseases of the nervous system. Bacterial myositis
Biological and medical sciences
General aspects
Genes, Bacterial
Human bacterial diseases
Humans
Infectious Disease
Infectious diseases
Interleukin-6 - blood
Lipopolysaccharide
Lipopolysaccharides - deficiency
Lipopolysaccharides - genetics
Lipopolysaccharides - metabolism
Male
Medical sciences
Meningitis
Meningitis, Meningococcal - immunology
Meningitis, Meningococcal - microbiology
Mutation
Neisseria meningitidis
Neisseria meningitidis - genetics
Neisseria meningitidis - isolation & purification
Neisseria meningitidis - metabolism
Thunderclap headache
Whole genome sequencing
Young Adult
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Summary:Summary 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.
ISSN:0163-4453
1532-2742
DOI:10.1016/j.jinf.2014.06.005