title: Meningitis caused by a lipopolysaccharide deficient Neisseria meningitidis.
abstract: 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.
authors.affiliation: Department 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.
authors.forename: Jurgen R
authors.initials: JR
authors.lastname: Piet
authors.affiliation: Institute for Translational Vaccinology (InTraVacc), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands; Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands.
authors.forename: Afshin
authors.initials: A
authors.lastname: Zariri
authors.affiliation: Institute for Translational Vaccinology (InTraVacc), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands; Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Fransen
authors.affiliation: Department of Medical Microbiology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, PO Box 22660, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Schipper
authors.affiliation: Institute for Translational Vaccinology (InTraVacc), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.affiliation: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, PO Box 22660, The Netherlands.
authors.forename: Diederik
authors.initials: D
authors.lastname: van de Beek
authors.affiliation: Department of Medical Microbiology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, PO Box 22660, The Netherlands; The Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center, Amsterdam, PO Box 22660, The Netherlands. Electronic address: A.vanderende@amc.uva.nl.
authors.forename: Arie
authors.initials: A
authors.lastname: van der Ende
mesh_terms: D000328:Adult; D005798:Genes, Bacterial; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000382:microbiology*; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides
keywords: Lipopolysaccharide; Meningitis; Neisseria meningitidis; Thunderclap headache; Whole genome sequencing