Streptococcus pneumoniae adaptation to nutrient deprivation and immune modulation drives upper respiratory tract colonization.

Streptococcus pneumoniae is a successful colonizer of the human upper respiratory tract, however the mechanisms that enable its persistence in this nutrient-limited environment, with numerous immune mechanisms in place, remain enigmatic. Here, we examined how pneumococci adapt to upper respiratory tract conditions and how this affects host interactions. We measured intranasal metal ion and monosaccharide concentrations to create an in vivo-mimicking medium for studying pneumococcal adaptation. Growth in this medium was reduced compared to glucose-rich chemically defined media (CDM). Proteome analysis revealed a shift to galactose as the major carbohydrate source, and decreased levels of fatty acid biosynthesis proteins and pneumolysin, compared to other CDMs. Glycerophosphocholine accumulated extracellularly leading to decreased CRP and IgM binding to pneumococci. Pneumococci grown in in vivo-mimicking medium, compared to glucose-rich media, were more capable colonizers of primary epithelium and induced less epithelial cytokine release. Together this shows how pneumococci adapt to the nutrient-limited respiratory environment, modulate epithelial cells and evade humoral responses to facilitate persistent colonization.