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 interactionsoccurring at the cerebral level and to analyze the pathogenetic mechanisms behind this life-threateningdisease. In this study, we have developed a mouse model of meningococcal meningitis based on the intracisternalinoculation of bacteria. Experiments were performed with mouse-passaged serogroup C Neisseriameningitidis. Survival and clinical parameters of infected mice and microbiological and histological analysis ofthe brain demonstrated the establishment of meningitis with features comparable to those of the disease inhumans. When using low bacterial inocula, meningococcal replication in the brain was very efficient, with a1,000-fold increase of viable counts in 18 h. Meningococci were also found in the blood, spleens, and livers ofinfected mice, and bacterial loads in different organs were dependent on the infectious dose. As glutamateuptake from the host has been implicated in meningococcal virulence, mice were infected intracisternally withan isogenic strain deficient in the ABC-type L-glutamate transporter GltT. Noticeably, the mutant was attenuatedin virulence in mixed infections, indicating that wild-type bacteria outcompeted the GltT-deficientmeningococci. The data show that the GltT transporter plays a role in meningitis and concomitant systemicinfection, suggesting that meningococci may use L-glutamate as a nutrient source and as a precursor tosynthesize the antioxidant glutathione.