title: Peptidoglycan fragment release from Neisseria meningitidis.
abstract: Neisseria meningitidis (meningococcus) is a symbiont of the human nasopharynx. On occasion, meningococci disseminate from the nasopharynx to cause invasive disease. Previous work showed that purified meningococcal peptidoglycan (PG) stimulates human Nod1, which leads to activation of NF-κB and production of inflammatory cytokines. No studies have determined if meningococci release PG or activate Nod1 during infection. The closely related pathogen Neisseria gonorrhoeae releases PG fragments during normal growth. These fragments induce inflammatory cytokine production and ciliated cell death in human fallopian tubes. We determined that meningococci also release PG fragments during growth, including fragments known to induce inflammation. We found that N. meningitidis recycles PG fragments via the selective permease AmpG and that meningococcal PG recycling is more efficient than gonococcal PG recycling. Comparison of PG fragment release from N. meningitidis and N. gonorrhoeae showed that meningococci release less of the proinflammatory PG monomers than gonococci and degrade PG to smaller fragments. The decreased release of PG monomers by N. meningitidis relative to N. gonorrhoeae is partly due to ampG, since replacement of gonococcal ampG with the meningococcal allele reduced PG monomer release. Released PG fragments in meningococcal supernatants induced significantly less Nod1-dependent NF-κB activity than released fragments in gonococcal supernatants and tended to induce less interleukin-8 (IL-8) secretion in primary human fallopian tube explants. These results support a model in which efficient PG recycling and extensive degradation of PG fragments lessen inflammatory responses and may be advantageous for maintaining meningococcal carriage in the nasopharynx.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Katelynn L
authors.initials: KL
authors.lastname: Woodhams
authors.forename: Jia Mun
authors.initials: JM
authors.lastname: Chan
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Lenz
authors.forename: Kathleen T
authors.initials: KT
authors.lastname: Hackett
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Dillard
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D005187:Fallopian Tubes / Q000378:metabolism / Q000382:microbiology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D016209:Interleukin-8 / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008585:Meningitis, Meningococcal / Q000378:metabolism / Q000382:microbiology*; D016328:NF-kappa B / Q000378:metabolism; D009305:Nasopharynx / Q000378:metabolism / Q000382:microbiology*; D009344:Neisseria gonorrhoeae / Q000378:metabolism; D009345:Neisseria meningitidis / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism*
chemical_list: C084284:AmpG protein, Bacteria; D001426:Bacterial Proteins; D016209:Interleukin-8; D026901:Membrane Transport Proteins; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D010457:Peptidoglycan