New strategies against resistant pneumococcus
Diseases caused by Streptococcus pneumoniae are a global public health issue with children, elderly people and immuno-compromised individuals being the high-risk targets. Despite the availability of antibiotics, mortality and morbidity due to S. pneumoniae infections remain very high. This is exacerbated by the fact that the current vaccine is only effective against a limited number of S. pneumoniae serotypes, often forcing serotype switching. To address these issues, the EU-funded CAREPNEUMO (Combating antibiotics resistant Pneumococci by novel strategies based on in vivo and in vitro host – pathogen interactions) initiative performed a large epidemiological analysis of 3 000 clinical isolates collected from different regions across the globe. Scientists observed that diverse serotypes were prevalent in different geographical regions while vaccination combined with antibiotic resistance increased the emergence of non-vaccine serotypes. In addition, they isolated for the first time, the serotype 6D from invasive pneumococcal disease in Europe. Considerable effort went towards the elucidation of adherence, invasion and multidrug tolerance mechanisms. Scientists observed that the adherence of the bacterium to endothelial cells stimulated the release of cytokines, while interaction of pneumococcal phosphoglyceric acid with plasminogen was identified as a new tissue invasion mechanism. The consortium established a murine model for pneumococcal infections that was used to determine the virulence potential of different clinical isolates. Interestingly, the behaviour of the different S. pneumoniae strains in this mouse model reflected the severity of infection in humans. From a therapeutic perspective, researchers identified new pneumococcal targets for the development of a new generation of antimicrobials against resistant pneumococci. With respect to meningitis caused by antibiotic-resistant pneumococci, scientists found that an improved host defence in the brain can be achieved through stimulation of microglia. Furthermore, novel vaccines were generated and demonstrated full protection in the mouse model of pneumococcal infection. Collectively, the findings of the project provide a solid basis for the development of new combat strategies for resistant pneumococci and underscore the importance of a universal vaccine.
Keywords
Streptococcus pneumoniae, vaccine, CAREPNEUMO, meningitis, microglia
