Streptococcus pneumoniae proteomics: determinants of pathogenesis and vaccine development

Abstract

Streptococcus pneumoniae is a major pathogen that is responsible for a variety of invasive diseases. The bacteria gain entry initially by establishing a carriage state in the nasopharynx from where they migrate to other sites in the body. The worldwide distribution of the bacteria and the severity of the diseases have led to a significant level of interest in the development of vaccines against the bacteria. Current vaccines, based on the bacterial polysaccharide, have a number of limitations including poor immunogenicity and limited effectiveness against all pneumococcal serotypes. There are many challenges in developing vaccines that will be effective against the diverse range of isolates and serotypes for this highly variable bacterial pathogen. This review considers how proteomic technologies have extended our understanding of the pathogenic mechanisms of nasopharyngeal colonization and disease development as well as the critical areas in developing protein-based vaccines.

KEYWORDS:

• Cell wall proteins
• pathogenesis
• proteome
• Streptococcus pneumoniae
• vaccines

Key issues

• Streptococcus pneumoniae is a significant human pathogen causing life-threatening infections of both the young and old worldwide. Although vaccines are available, they have limitations due to restricted serotype specificity and immunogenicity.

• The development of protein-based vaccines holds great promise for the future and can help overcome some of the existing vaccine limitations.

• S. pneumoniae exists as >90 distinct serotypes and individual isolates, even within a serotype, can exhibit a high degree of variation making this a challenging bacterial pathogen to study.

• Differences in the S. pneumoniae proteome during nasopharyngeal colonization and invasive disease present a challenge for future control measures at each of these stages of infection.

• Comprehensive genomic sequences are available for different serotypes and clinical isolates of S. pneumoniae and information from proteomic analyses complement these genomic data to improve our understanding of bacterial pathogenesis and vaccine development.

• Studies on the global proteome of S. pneumoniae are limited but extensive information has been collected on the bacterial surface proteome, a major source for identifying vaccine targets.

• A number of potential vaccine candidates have been identified but many still have to be confirmed as being able to induce protective immune responses in humans.

Financial & competing interests disclosure

M Bittaye is supported by a PhD studentship awarded by the MRC, The Gambia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.