The development of invasive pneumococcal disease is frequently preceded by the establishment of the “carrier state”, this is, the colonization of the human nasopharynx by Streptococcus pneumoniae (pneumococcus). Pneumococcal carriage takes place through the establishment of a still largely unknown, host-pathogen interplay as well as by interactions with other bacteria colonizing the same habitat, such as non-typeable pneumococci, other streptococci of the mitis group, or pathogens like Haemophilus influenzae. Most of these interactions involve bacterial surface proteins on one hand, and cellular receptors and host defense mechanisms on the other. The surface-located, chain-dispersing S. pneumoniae enzyme LytB is involved in pathogenesis. LytB is needed both for attachment/colonization as well as for complement evasion but the structural requirements are essentially unknown. Another relevant example of surface protein is the main pneumococcal autolysin (LytA) that is also required for biofilm formation and that is thought to play an important role in pathogenesis by releasing cell wall fragments that are markedly pro-inflammatory. Moreover, autolysis allows the liberation of the toxin pneumolysin (Ply), which is partially responsible for immune response evasion. The role(s) in colonization of LytA and pneumolysin will be studied using biofilms (either mono or multispecies), cell cultures, and a mouse model of nasopharyngeal colonization.