title: Metabolism and virulence in Neisseria meningitidis.
abstract: A longstanding question in infection biology addresses the genetic basis for invasive behavior in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.
authors.affiliation: Institute for Hygiene and Microbiology, University of Würzburg Würzburg, Germany ; Research Center for Infectious Diseases (ZINF), University of Würzburg Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schoen
authors.affiliation: Institute for Hygiene and Microbiology, University of Würzburg Würzburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Kischkies
authors.affiliation: Institute for Hygiene and Microbiology, University of Würzburg Würzburg, Germany ; National Reference Centre for Meningococci and Haemophilus influenzae (NRZMHi), University of Würzburg Würzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Elias
authors.affiliation: Institute for Hygiene and Microbiology, University of Würzburg Würzburg, Germany.
authors.forename: Biju Joseph
authors.initials: BJ
authors.lastname: Ampattu
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism; D002353:Carrier State; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D016680:Genome, Bacterial; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008585:Meningitis, Meningococcal / Q000382:microbiology*; D055442:Metabolome; D055432:Metabolomics; D009305:Nasopharynx / Q000382:microbiology; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D018384:Oxidative Stress; D059467:Transcriptome; D014774:Virulence
chemical_list: D045222:Electron Transport Chain Complex Proteins; D018698:Glutamic Acid; D002244:Carbon
keywords: Neisseria meningitidis; glutamate dehydrogenase; glutathione; nitrite respiration; oxidative stress; pathometabolism; virulence; γ-glutamyl cycle