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.

Bacterial peptide transporters: Messengers of nutrition to virulence

“…This may slow down the growth but does not affect survival and therefore leave little scope for the development of resistance. Metabolism associated genes of pathogens have been consistently linked with virulence of major pathogens, [1][2][3][4][5][6][7][8][9] such as, role of carbon metabolism related pathways like glycolysis 10 and TCA cycle 11 in virulence of Salmonella Typhimurium and requirement of metabolism associated pathways for protection of Mycobacterium tuberculosis from host immune system. 9 Salmonella is even known to modulate host to exploit the limited supply of nutrients.…”

Significance of Meningococcal Hyperinvasive Clonal Complexes and Their Influence on Vaccines Development

“…They are called hyperinvasive clonal complexes and are responsible for the majority of meningococcal infection in the world. Despite their deep analysis including genome sequencing in comparison to carriage strains, the reasons of their superiority and predominance are still not fully understood (Schoen et al, 2014) The most common hyperinvasive clonal complexes responsible for IMD -historical background and the present status Some hyperinvasive CCs have been persistent for many decades, other emerged recently or were prevalent in the past and nowadays are observed very rarely. In spite of this variability, among all hyperinvasive CCs the most frequently mentioned in the literature and overrepresented among meningococci are those belonging to ST-5CC, ST-32CC, ST-41/44CC and ST-11CC.…”

HexR Controls Glucose-Responsive Genes and Central Carbon Metabolism in Neisseria meningitidis

“…In contrast, NADPH-specific gdhA was upregulated by glucose. High-level expression of gdhA is dependent on ammonia assimilation from the TCA cycle intermediate 2-oxoglutarate and may result in growth advantages when the glucose concentration is higher than that of lactate (55), such as in human whole blood, where gdhA has been found to be upregulated (21).…”