title: Glutamate utilization promotes meningococcal survival in vivo through avoidance of the neutrophil oxidative burst.
abstract: Polymorphonuclear neutrophil leucocytes (PMNs) are a critical part of innate immune defence against bacterial pathogens, and only a limited subset of microbes can escape killing by these phagocytic cells. Here we show that Neisseria meningitidis, a leading cause of septicaemia and meningitis, can avoid killing by PMNs and this is dependent on the ability of the bacterium to acquire L-glutamate through its GltT uptake system. We demonstrate that the uptake of available L-glutamate promotes N. meningitidis evasion of PMN reactive oxygen species produced by the oxidative burst. In the meningococcus, L-glutamate is converted to glutathione, a key molecule for maintaining intracellular redox potential, which protects the bacterium from reactive oxygen species such as hydrogen peroxide. We show that this mechanism contributes to the ability of N. meningitidis to cause bacteraemia, a critical step in the disease process during infections caused by this important human pathogen.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Provinciale Monteroni, 73100 Lecce, Italy.
authors.forename: Adelfia
authors.initials: A
authors.lastname: Talà
authors.forename: Caterina
authors.initials: C
authors.lastname: Monaco
authors.forename: Krzysztofa
authors.initials: K
authors.lastname: Nagorska
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Exley
authors.forename: Anne
authors.initials: A
authors.lastname: Corbett
authors.forename: Arturo
authors.initials: A
authors.lastname: Zychlinsky
authors.forename: Pietro
authors.initials: P
authors.lastname: Alifano
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Tang
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism; D000818:Animals; D016470:Bacteremia / Q000473:pathology; D001426:Bacterial Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008589:Meningococcal Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009345:Neisseria meningitidis / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D018384:Oxidative Stress / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D001426:Bacterial Proteins; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D005978:Glutathione