Abstract
Streptococcus pneumoniae (the pneumococcus) causes a range of life-threatening diseases including pneumonia, sepsis and meningitis. Despite widespread vaccine deployment, pneumococcal disease remains a leading cause of global mortality. The human nasopharynx is its principal ecological niche, and all pneumococcal disease originates from this reservoir of organisms. Acute infections are, however, an evolutionary dead-end for the pneumococcus. What sustains the pneumococcus within human populations are cycles of colonisation and transmission. To persist within the nasopharynx, it must overcome the physical and immunological barriers established by the host while acquiring sufficient nutrients to proliferate in the face of competing airway microbes. Here, we outline the metabolic, microbial, and immunological challenges of colonisation, and the often-competing demands of transmission, which together have shaped the pneumococcus into one of the most formidable human pathogens.