Streptococcus pneumoniae and the host cell

PhD ceremony: Mr. P.H. Gradstedt, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Streptococcus pneumoniae and the host cell

Promotor(s): prof. J.M. van Dijl

Faculty: Medical Sciences

Streptococcus pneumoniae is a bacterium that colonizes the human nasopharynx. It occasionally switches niche and spreads through the body as an invasive pathogen, causing pneumonia, sepsis, meningitis, and other morbidities. The risk groups include children, elderly and the immunocompromised. In general, little is known about how this switch from colonizer to invasive pathogen occurs, but we do know it involves traversing cell barriers. This thesis focusses on the ability of S. pneumoniae to invade host cells as a first step towards invasive disease progression. To develop an overall view of the factors involved in this process, the studies ranged from basic bacterial physiology, to how the host cell responds to invading S. pneumoniae. Several bacterial factors involved in the adhesion to, invasion of, and survival inside host cells were identified. Additionally, a previously unknown bacterial factor influencing the amount of capsule (S. pneumoniae‘s main virulence factor) was discovered. Furthermore, it was shown that S. pneumoniae invades the host cell by using the host cells normal uptake mechanisms. Once inside the cells, most of the bacteria are killed and some of the pathways involved were uncovered. This reinforces the idea that, when it comes to modeling S. pneumoniae infection, bacterial and host cell factors should not be viewed as separate entities, but require cellular microbiology studies, which is the combination of microbiology and cellular biology. Indeed, this line of research is of paramount importance for understanding how S. pneumoniae and other opportunistic bacterial pathogens switch from colonizer to invasive pathogens.