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Infection and Immunity, September 2009, p. 3578-3587, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.01424-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
The Meningococcal ABC-Type L-Glutamate Transporter GltT Is Necessary for the Development of Experimental Meningitis in Mice
,
Roberta Colicchio,1
Susanna Ricci,2
Florentia Lamberti,3
Caterina Pagliarulo,4
Chiara Pagliuca,3
Velia Braione,2
Tiziana Braccini,2
Adelfia Talà,5
Donatella Montanaro,6
Sergio Tripodi,7
Marcella Cintorino,7
Giancarlo Troncone,6,8
Cecilia Bucci,5
Gianni Pozzi,2
Carmelo B. Bruni,3,10
Pietro Alifano,5* and
Paola Salvatore3,9*
IRCCS Fondazione SDN, 80143 Naples,1 Dipartimento di Biologia Molecolare, LA.M.M.B., Università di Siena, 53100 Siena,2 D.B.P.C.M. "L. Califano," Università di Napoli "Federico II," 80131 Naples,3 D.S.B.A., Università del Sannio, 82100 Benevento,4 Di.S.Te.B.A., Università del Salento, 73100 Lecce,5 Unità di Patologia Comparativa, Ceinge s.c.ar.l. Biotecnologie Avanzate, 80145 Naples,6 Dipartimento di Patologia Umana e Oncologia, Università di Siena, 53100 Siena,7 Dipartimento di Scienze Biomorfologiche e Funzionali, Università di Napoli "Federico II," 80131 Naples,8 Facoltà di Scienze Biotecnologiche, Università di Napoli "Federico II," 80131 Naples,9 Ceinge s.c.ar.l. Biotecnologie Avanzate, 80145 Naples, Italy,10
Received 20 November 2008/ Returned for modification 21 January 2009/ Accepted 5 June 2009
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.
* Corresponding author. Mailing address for Paola Salvatore: D.B.P.C.M. "L. Califano," Università di Napoli "Federico II," 80131 Naples, Italy. Phone: (39) 081 7462058. Fax: (39) 081 7703285. E-mail: psalvato{at}unina.it. Mailing address for Pietro Alifano: Di.S.Te.B.A., Università del Salento, 73100 Lecce, Italy. Phone: (39) 0832 298856. Fax: (39) 0832 298626. E-mail: alifano{at}ilenic.unile.it
Published ahead of print on 15 June 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Infection and Immunity, September 2009, p. 3578-3587, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.01424-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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