Association of chronic meningococcemia with infection by meningococci with underacylated lipopolysaccharide

J Infect. 2011 Jun;62(6):479-83. doi: 10.1016/j.jinf.2011.03.010. Epub 2011 Mar 31.

Abstract

Objectives: Chronic meningococcemia is an uncommon manifestation of meningococcal disease. Our objective was to asses whether a bacterial factor, a mutation in the lpxL1 gene resulting in underacylated lipopolysaccharide, might be important in chronic meningococcemia.

Methods: We identified 15 patients with chronic meningococcemia over a 50-year period. Chronic meningococcemia episodes were defined by a febrile episode of at least one week and presence of meningococci in blood and/or cerebrospinal fluid (CSF). Meningococcal isolates from these patients were characterised by serogrouping, multi-locus sequence typing, and in vitro interleukin 6 inducing capacity. lpxL1 gene mutations were determined by direct sequencing.

Results: The median age was 21 years (range, 2-62) and median duration of symptoms before diagnosis was four weeks (range, 1-12). Of the 15 isolates, seven (47%) strains had a reduced interleukin 6 inducing capacity and were found to have a mutation in lpxL1 resulting in penta-acylated lipid A. This frequency is higher than previously reported among adult patients with meningococcal meningitis (7%; p < 0.0001) and invasive meningococcal disease (9%; p = 0.001).

Conclusions: We conclude that chronic meningococcemia patients are often infected with meningococci with a mutation in lpxL1 resulting in underacylated lipid A. The lpxL1 mutations may well explain the protracted and benign clinical course in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Acyltransferases / deficiency
  • Acyltransferases / genetics
  • Adolescent
  • Adult
  • Bacteremia / microbiology*
  • Bacteremia / pathology*
  • Bacterial Proteins / genetics
  • Bacterial Typing Techniques
  • Blood / microbiology
  • Cerebrospinal Fluid / microbiology
  • Child
  • Child, Preschool
  • Chronic Disease
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Endotoxins / chemistry
  • Endotoxins / metabolism*
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / metabolism*
  • Male
  • Meningococcal Infections / microbiology*
  • Meningococcal Infections / pathology*
  • Middle Aged
  • Multilocus Sequence Typing
  • Mutation
  • Neisseria meningitidis / enzymology
  • Neisseria meningitidis / immunology
  • Neisseria meningitidis / isolation & purification*
  • Neisseria meningitidis / metabolism
  • Sequence Analysis, DNA
  • Serotyping
  • Young Adult

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • Endotoxins
  • Interleukin-6
  • Lipopolysaccharides
  • Acyltransferases
  • LpxL protein, bacteria