Mechanisms of Meningeal Invasion by Septicemic Extracellular Pathogens: The Examples ofNeisseria meningitidis,Streptococcus agalactiaeandEscherichia coli

Abstract

Bacterial meningitis is a leading cause of central nervous system infections. It is an infl ammatory process that results from bacterial entry into the subarachnoidal space s ( SAS ). Bacterial meningitis can be due to the dissemination of contiguous infections such as sinusitis or mastoiditis of the meningeal membranes, but most cases are caused by blood -borne pathogens. Unlike other peripheral organs, the central nervous system ( CNS ) is protected from blood -borne insults by specialized structures that separate the nervous parenchyma and the cerebrospinal fl uid from the blood. These blood -brain barrier s ( BBB ) effectively protect the CNS from most circulating bacteria, restricting the etiology of bacterial meningitis to a few and predominantly extracellular pathogens: Escherichia coli K1 and Streptococcus agalactiae (Group B Streptococcus) in the newborn, Neisseria meningitidis , Haemophilus infl uenzae type b and Streptococcus pneumoniae in children and adults [1 -3] . It has been estimated that 63 and 9% of bacteremia due to N. meningitidis and S. pneumoniae, respectively, are associated with meningitis [4] , demonstrating that the ability of these bacteria to enter the subarachnoidal spaces varies. Paradoxically, these bacteria are commensal in the nasopharynx ( N. meningtidis , S. pneumoniae and H. infl uenzae ) and digestive tract ( E. coli , S. agalactiae ) [5] .The pathophysiology of bacterial meningitis is thus a multi -step process that refl ects the ability of bacterial pathogens to cross the oropharyngeal or digestive mucosal barrier, to survive and to multiply in bloodstream and fi nally, to cross the blood -brain barrier [5 -7] . As stated above, the number of bacteria capable of invading the meninges is limited, suggesting that specifi c virulence factors are required for bacteria to enter the subarachnoidal space. Indeed it has been demonstrated that these extracellular pathogens express various virulence factors which allow them to survive in the extracellular fl uids and eventually to interact directly with the components of the blood -brain barrier. The main virulence factor expressed Bacterial Virulence: Basic Principles, Models and Global Approaches. Edited by Philippe Sansonetti