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Infection and Immunity, December 2001, p. 7318-7325, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7318-7325.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Streptococcus pneumoniae Causes Experimental Meningitis following Intranasal and Otitis Media Infections via a Nonhematogenous Route

Andrea Marra* and Daniel Brighamdagger

Protein Design Labs, Inc., Fremont, California 94555

Received 20 July 2001/Returned for modification 28 August 2001/Accepted 5 September 2001

Using two different animal models of Streptococcus pneumoniae infection, we have demonstrated that this organism is able to spread to the central nervous system and cause meningitis by bypassing the bloodstream. Following respiratory tract infection induced via intranasal inoculation, bacteria were rapidly found in the bloodstream and brains in the majority of infected mice. A similar pattern of dissemination occurred following otitis media infection via transbullar injection of gerbils. However, a small percentage of animals infected by either route showed no bacteria in the blood and yet did have significant numbers of bacteria in brain tissue. Subsequent experiments using a galU mutant of S. pneumoniae, which is impaired in its ability to disseminate to the bloodstream following infection, showed that this organism is able to spread to the brain and cerebrospinal fluid. These results demonstrate that, unlike many bacterial pathogens that cause meningitis, S. pneumoniae is able to do so independent of bloodstream involvement upon different routes of infection. This may address the difficulty in treating human infections caused by this organism.


* Corresponding author. Present address: Antibacterials, Discovery, MS 8118W-249, Pfizer Global Research and Development, Eastern Point Rd., Groton, CT 06340. E-mail: andrea_marra{at}groton.pfizer.com.

dagger Present address: Genencor International, Inc., Palo Alto, CA 94304.


Infection and Immunity, December 2001, p. 7318-7325, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7318-7325.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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