Haemophilus Influenzae Gene Expression and Bacterial Invasion

Abstract

The pathogenesis of bacterial meningitis involves several sequential events: acquisition of the causative organism by a susceptible individual, nasopharyngeal colonisation, invasion of the respiratory epithelium resulting in bacteraemia, haematogenous dissemination, invasion of the blood-brain barrier, and the occurrence of inflammatory changes in the sub-arachnoid space followed by bacterial replication within the central nervous system. The molecular basis of the bacterial invasiveness of Haemophilus influenzae, a major cause of meningitis in infants and young children, has been investigated through the application of genetic techniques and the use of a biologically relevant experimental rat model of meningitis. Genes for capsular polysaccharide and lipopolysaccharide are important determinants of Haemophilus influenzae virulence and contribute to the invasive potential of the organism by enhancing intravascular survival. The genes for the type b capsule confer greater efficiency in evading host clearance mechanisms than do the genes for the other capsular polysaccharides. This enhanced survival has at least two important potential pathophysiological consequences, since there is a direct relationship between the magnitude of bacteraemia and the probability of meningitis, and since increased blood-brain barrier permeability is directly related to the number of bacteria in the cerebrospinal fluid.