Description
The colonization of the upper respiratory tract by Streptococcus pneumoniae (pneumococcus) and the eventual development of diseases as pneumonia, sepsis and/or meningitis, take place through the establishment of a complex interplay between the pathogen and the human host. Most of those interactions involve bacterial surface proteins on one hand, and cellular receptors and host defense mechanims on the other. We will intend to study the genes responsible of biofilm formation and the biochemical composition of the intercellular matrix that is much needed for the structural integrity of biofilm and the onset of nasopharyngeal colonization. Moreover, the interactions between the pneumococcal cell wall hydrolases and cellular receptors as well as the role of those hydrolases on immunity evasion will be also examined. S. pneumoniae mutants deficient in one or more cell wall hydrolases will be tested using model systems (like biofilms, cell cultures, and opsonophagocytic assays) and animal models of infection (colonization, pneumonia, sepsis, and meningitis). Finally, the therapeutic potential of some cell wall hydrolases, either from the bacterium or from its phages, will be tested using biofilms as well as animal models of pneumococcal infection.