All ETDs from UAB

Advisory Committee Chair

David E Briles

Advisory Committee Members

Scott Barnum

Michael Niederweis

Alexander Szalai

Kurt Zinn

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Streptococcus pneumoniae (pneumococcus) is one of the leading causes of bacterial meningitis world-wide. The classic paradigm in the establishment of bacterial meningitis is that in the absence of physical trauma, infection in the peripheral blood is needed to cause invasion of the central nervous system (CNS). Our previous studies have shown that pneumococci, a frequent colonizer of the nasopharynx, can cause bacterial meningitis through a nonhematogenous route by which bacteria appear to travel along the olfactory nerves, through the cribriform plate to the olfactory bulbs and into the rest of the CNS. However, with the frequency of nasopharyngeal colonization and the infrequent reports of nonhematogenous meningitis, there have been no studies that have identified any molecular or environmental factors that promote this type of infection. The purpose of this study was to determine whether free sialic acid, a naturally occurring terminal carbohydrate ubiquitously expressed in the nasopharynx and on most cells in the human body, can stimulate nonhematogenous meningitis. To accomplish this goal we incorporated sialic acid into our intranasal infection model and analyzed bacterial load from the nasopharynx to tissues leading into the CNS. We also determined whether sialic acid had any immunological effect that would contribute to bacterial dissemination. While we were able to show that sialic acid could be used as a molecular pneumococcal stimulant for invasion into the CNS and for immunologic effects accompanying CNS infection, we were unable to identify the exact mechanism by which sialic acid contributes to pneumococcal invasion of the CNS. Here we present an animal model that can be used to study nonhematogenous meningitis and the factors associated with its establishment.

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