Molecular and Cellular Biology of Pneumococcal Infection

THE THREE MAJOR INVASIVE pathogens of children, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, are carried in the nasopharynx by a significant proportion of healthy individuals. For the pneumococcus, an asymptomatic carrier state persists for several weeks at a time in as many as 40% of the general population. During a small fraction of these encounters, pneumococci spread and gain access to the ear, lung, or blood stream but do not necessarily evoke symptoms. In only a few does symptomatic otitis media, pneumonia, bacteremia, or meningitis develop. These epidemiological observations imply that there exists three levels of encounter between the human host and this pathogen. In the first, recognition of and attachment to human nasopharyngeal cells, all pneumococci appear to be able to establish a carrier state because the human is the only known host. Some variability in the efficiency of this property may exist because some strains are found more frequently than others. The second level of encounter where pneumococi move to another body site may arise from a less widely distributed set of capabilities because most disease is limited to 20 of the 90 serotypes. Finally, still other events often derived from the host contribute to development of symptoms referrable to the infected site. This review evaluates current understanding of the molecular events contributing to targetting pneumococci to various sites of infection and then examines additional steps that promote development of symptomatic pneumococcal disease. This information has been assembled by first identifying the receptors for pneumococci on various human cells and then searching libraries of mutants for nonadherent clones indicative of potential bacterial adhesins. Similarly for the dissection of disease, the pneumococcal components responsible for initiating inflammation have been identified by a systematic analysis of the bioactivities of several classes of surface molecules.