Summary A fundamental aspect of the success of Streptococcus pneumoniae as a human pathogen is the ability to successfully transmit and infect new hosts. The mechanisms underlying transmission are complex, with both bacterial and host factors playing important roles. It would be expected the capacity is sense and response to the dynamic environment of the mammalian host is critical for transmission, however the regulation underscoring this process remains poorly understood. We hypothesize transmission is controlled via a specific, uncharacterized two- component regulatory system (TCS11). This TCS has atypical operon structure for pneumococcal TCSs, whereby two small hypothetical proteins and a putative transporter are in the same operon and co-transcribed with TCS11. Preliminary data suggests is this operon is in fact a TCS coupled to a bacteriocin secretion system that facilitates transmission via targeting the resident bacterial flora, enabling pneumococcal transmission. We hypothesize that TCS11 mediates pneumococcal transmission via coordination of transmission factor gene expression coupled with bacteriocin production to effectively compete against the respiratory microbiota at the initial stages of epithelial colonization.