Macro-recombination in Streptococcus pneumoniae

Streptococcus pneumoniae is a gram positive bacterium that colonizes humans, but that may also cause a wide spectrum of diseases including pneumonia and invasive diseases, posing a threat to the public health worldwide. Antibiotic resistant and vaccine escape variants in Streptococcus pneumoniae often arise by multiple large gene replacements, termed macro-recombinations. However, no laboratory model reproducing streptococcal macro-recombination events have been developed. In this study we propose to combine a mouse model of S. pneumoniae colonization and last generation DNA sequencing to investigate the mechanisms behind large gene replacements in pneumococci. The model is well established, and will include up to 1250 mice. To reduce the number of animals used we have designed a staged study, including an initial exploratory phase. The colonization model uses procedures that should not promote major distresses to the mice. The mice will be kept in Cages that are environmentally enriched With impellers and paper nest building, and will be given standard feed and tap water ad libidum. We expect that the study will provide novel mechanistic insights into how recombination of large DNA fragments occurs in streptococci, and reveal important targets to improve prevention and treatment of S. pneumoniae infections.