Lessons from an LPS-deficient Neisseria meningitidis mutant.
In the pathogen Neisseria meningitidis, a completely LPS-deficient but viable mutant can be obtained by insertional inactivation of the lpxA gene, encoding UDP-GlcNAc acyltransferase required for the first step of lipid A biosynthesis. The expression and assembly of integral outer membrane proteins in the absence of LPS is largely unaffected. However, the expression of iron limitation-inducible, cell surface-exposed lipoproteins is greatly reduced. Major changes were seen in the phospholipid composition, with a shift towards PE and PG species containing mostly shorter chain, saturated fatty acids. The presence of the capsular polysaccharide turned out to be essential for viability without LPS. The immunogenicity of outer membrane proteins in mice was greatly reduced for the LPS-deficient mutant, showing the importance of LPS as an internal adjuvant in such vaccines. Stimulation of MM6 cells and peripheral blood mononuclear cells showed that induction of TNF-alpha by whole meningococci was greatly reduced for the LPS-deficient mutant. However, even without LPS the mutant strain could still induce a significant inflammatory response.
van der Ley
Peter
P
Laboratory of Vaccine Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Steeghs
Liana
L
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional / Q000379:methods; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics* / Q000378:metabolism; D030781:Organisms, Genetically Modified; D010743:Phospholipids / Q000378:metabolism; D014169:Transformation, Bacterial; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D008563:Membrane Lipids; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha