Triggering pneumococcal competence:Memoirs of an escape artist

Streptococcus pneumoniae (the pneumococcus) is a bacterium that commonly resides in the upper respiratory tract of healthy individuals. However, when the pneumococcus spreads to other parts of the human body, it can cause potentially lethal infections, leading to over a million deaths each year. Both vaccination programs and antibiotic treatment have proven effective in preventing pneumococcus-related deaths. However, the long-term efficacy of these approaches is undermined by the pneumococcus’ ability to take up and integrate DNA from its surroundings. The state in which pneumococci are able to do so is called competence, which may accelerate the spread of antibiotic resistance and hamper recognition of the bacterium by the human immune system (i.e. vaccine escape). In this thesis, the genetic code of the pneumococcus was analyzed with an unprecedented level of detail. The resulting information was shared in a publicly accessible database called PneumoBrowse. Furthermore, the responses of the pneumococcus to a wide range of infection-relevant conditions were determined and presented in a second database, PneumoExpress. Both databases were used to refine our knowledge of the aforementioned competence system and which genes and proteins are affected by it. Finally, we identified two distinct mechanisms by which certain antibiotics induce the activation of the competence system. These findings help to understand which triggers are responsible for the activation of competence and thereby contribute to the spread of antibiotic resistance and vaccine escape