Streptococcus pneumoniae (the pneumococcus) is a commensal of the human nasopharynx during childhood, but also causes a variety of infections, such as otitis media (OM), pneumonia, bacteremia, and meningitis, mainly affecting infants, the elderly and immunocompromised patients. Pneumococcal pneumonia alone produces more child deaths, every year, than any other bacterial disease worldwide.

To date, more than 90 distinct capsular serotypes have been identified. Current pneumococcal conjugate vaccines (PCV) protect against 7, 10 or 13 different pneumococcal types. These vaccines have decreased the burden of pneumococcal disease produced by vaccine types but provide poor protection against non-vaccine serotypes. Additionally, the increasing prevalence of multi-drug resistant S. pneumoniae strains results in more challenge for treatment of pneumococcal infections. Therefore, it is imperative to continue investigating the molecular pathogenesis of the pneumococcus.

There are currently a variety of key virulence determinants known to be involved in pathogenesis of pneumococcal disease. Virulence factors and host immune defense are major players during pathogen - host interactions. Some metabolic pathways have also been shown to play a role in pneumococcal pathogenesis. These metabolic pathways include proteins involved in copper efflux, arginine metabolism, and zinc homeostasis. From the human host side, new host factors have been found to play essential roles in clearance of S. pneumoniae during infection, such as microRNA-155. Moreover, biofilm-like structures may alter both pneumococcal phenotypes and the host immunity during nasopharyngeal carriage and/or during disease. Understanding the interaction between pneumococcus and its human host is a key to combat pneumococcal infections.

It has been well known for several years that pneumococcal pneumonia is worsened during poly-microbial infection. During the past few years, rapid progress has been made in this area. For example, it was recently shown that influenza A virus increases pneumococcal nasal colonization and it is a risk factor for pneumococcal pneumonia. Other important respiratory viruses and bacterial pathogens, such as Moraxella catarrhalis and Haemophilus influenzae, appear to increase the risk of pneumococcal colonization and disease. A better understanding of the molecular mechanism leading to these pathogenic synergisms will provide a fundamental basis for prevention and treatment of secondary pneumococcal infection.

The elderly population is generally more susceptible to pneumococcal infections. In addition to their declined immunity, alteration of the microbiome seen in the elderly may play a role for the susceptibility of infection. Research with the elderly or using elderly animal infection models will largely enhance our knowledge and significantly reduce the morbidity and mortality caused by pneumococcal infections.