title: The meningococcal ABC-Type L-glutamate transporter GltT is necessary for the development of experimental meningitis in mice.
abstract: Experimental animal models of bacterial meningitis are useful to study the host-pathogen interactions occurring at the cerebral level and to analyze the pathogenetic mechanisms behind this life-threatening disease. In this study, we have developed a mouse model of meningococcal meningitis based on the intracisternal inoculation of bacteria. Experiments were performed with mouse-passaged serogroup C Neisseria meningitidis. Survival and clinical parameters of infected mice and microbiological and histological analysis of the brain demonstrated the establishment of meningitis with features comparable to those of the disease in humans. When using low bacterial inocula, meningococcal replication in the brain was very efficient, with a 1,000-fold increase of viable counts in 18 h. Meningococci were also found in the blood, spleens, and livers of infected mice, and bacterial loads in different organs were dependent on the infectious dose. As glutamate uptake from the host has been implicated in meningococcal virulence, mice were infected intracisternally with an isogenic strain deficient in the ABC-type L-glutamate transporter GltT. Noticeably, the mutant was attenuated in virulence in mixed infections, indicating that wild-type bacteria outcompeted the GltT-deficient meningococci. The data show that the GltT transporter plays a role in meningitis and concomitant systemic infection, suggesting that meningococci may use L-glutamate as a nutrient source and as a precursor to synthesize the antioxidant glutathione.
authors.affiliation: IRCCS Fondazione SDN, 80143 Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Colicchio
authors.forename: Susanna
authors.initials: S
authors.lastname: Ricci
authors.forename: Florentia
authors.initials: F
authors.lastname: Lamberti
authors.forename: Caterina
authors.initials: C
authors.lastname: Pagliarulo
authors.forename: Chiara
authors.initials: C
authors.lastname: Pagliuca
authors.forename: Velia
authors.initials: V
authors.lastname: Braione
authors.forename: Tiziana
authors.initials: T
authors.lastname: Braccini
authors.forename: Adelfia
authors.initials: A
authors.lastname: Talà
authors.forename: Donatella
authors.initials: D
authors.lastname: Montanaro
authors.forename: Sergio
authors.initials: S
authors.lastname: Tripodi
authors.forename: Marcella
authors.initials: M
authors.lastname: Cintorino
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Troncone
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bucci
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
authors.forename: Carmelo B
authors.initials: CB
authors.lastname: Bruni
authors.forename: Pietro
authors.initials: P
authors.lastname: Alifano
authors.forename: Paola
authors.initials: P
authors.lastname: Salvatore
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D027322:Amino Acid Transport System X-AG / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008585:Meningitis, Meningococcal / Q000209:etiology* / Q000473:pathology; D051379:Mice; D009345:Neisseria meningitidis / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D001426:Bacterial Proteins; D018698:Glutamic Acid