The polysaccharide-encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae (Hi) and Streptococcus pneumoniae are leading causes of serious bacterial infections. Beta lactams are the first line antibiotics in the treatment. These bacteria share the same ecological niche with possible DNA exchanges and also present similarity of the mechanisms of resistance to beta lactams. We aim to use an integrative approach to address the issue of resistance to beta lactams. The methodology combines genomic approaches, structure-function analysis and in vivo validation using relevant animal models. A major force of the project is its use of large collections of clinical isolates from diseased subjects and not a laboratory established strains. It also brings together complementary expertise of two collaborating teams in the fields of molecular epidemiology, pathogenesis and structure-function analysis.