The meningococcal ABC-Type L-glutamate transporter GltT is necessary for the development of experimental meningitis in mice.
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.
Colicchio
Roberta
R
IRCCS Fondazione SDN, 80143 Naples, Italy.
Ricci
Susanna
S
Lamberti
Florentia
F
Pagliarulo
Caterina
C
Pagliuca
Chiara
C
Braione
Velia
V
Braccini
Tiziana
T
Talà
Adelfia
A
Montanaro
Donatella
D
Tripodi
Sergio
S
Cintorino
Marcella
M
Troncone
Giancarlo
G
Bucci
Cecilia
C
Pozzi
Gianni
G
Bruni
Carmelo B
CB
Alifano
Pietro
P
Salvatore
Paola
P
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
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D001426:Bacterial Proteins; D018698:Glutamic Acid