Exploitation of physiology and metabolomics to identify pneumococcal vaccine candidates

Abstract

Streptococcus pneumoniae (the pneumococcus) is the etiologic agent of community-acquired pneumonia and invasive pneumococcal diseases such as septicemia and bacterial meningitis. The increasing antibiotic resistance and the suboptimal efficacy or limited serotype coverage of currently available vaccines urgently requires novel approaches in exploring new antimicrobials, therapeutic intervention strategies and vaccines. The current vaccine development strategies rely on the hypothesis that surface-exposed proteins, which are essential for pneumococcal virulence, are the most suitable candidates for future protein-based vaccines. Since virulence is closely linked with bacterial fitness, the potential of a pathogen to colonize and infect the host depends further on its physiology. This review summarizes the application of genome-wide techniques and their exploitation to decipher fundamental insights into bacterial factors associated with fitness, metabolism and virulence, leading to the discovery of vaccine candidates or antimicrobials.

Keywords::

• ABC transporter
• enzymes
• metabolome
• regulator proteins
• Streptococcus pneumoniae
• vaccine

Acknowledgments

Our apologies in advance to the authors of primary articles whom we have failed to cite owing to space restrictions.

Financial & competing interests disclosure

Research in the laboratory is supported by grants from the Deutsche Forschungsgemeinschaft (HA 3125/2-1; Priority program SPP1316: Host-adapted Metabolism of Bacterial Pathogens project HA 3125/3-2; HA 3125/4-2; and CRC TRR34 project C10) and the Federal Ministry of Education and Research (BMBF, Medical Infection Genomics, FKZ 0315828A). 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Low-cost vaccine for developing countries and vaccine campaigns to reduce carriage and transmission.

• • Induction of herd immunization.

• • Development of protein-based conjugate vaccines covering all serotypes.

• • Preventing development and spread of antibiotic-resistant pneumococci.

Notes