Bacterial and host factors affecting acquisition of <i>Streptococcus pneumoniae</i> in a murine model

Initial acquisition is a critical step in the establishment of colonization that in turn enables transmission to new hosts and potentially leads to invasive disease. Here, we studied host and bacterial factors affecting acquisition, as distinct from those affecting colonization density, using <i>Streptococcus pneumoniae</i> (Spn) in a mouse model. Acquisition was quantified using nasal inocula of limiting size to determine the proportion of hosts infected, as well as the median infectious dose. Infant mice (<7 days of age) were highly susceptible to acquisition (ID₅₀<30 CFU) compared with adults (>6 weeks of age), with rates declining with increasing host age. Prior influenza A infection greatly increased acquisition in adults. Expression of Spn capsule was also an important factor influencing acquisition in adults, with less of a role for the highly susceptible infants. Prior Spn colonization with a heterologous or homologous strain effectively blocked acquisition in infants by completely occupying the upper respiratory tract niche. Immunity due to prior colonization and nasal microbiota were not found to be factors limiting acquisition. Together, our findings show how high carriage rates of encapsulated Spn during early life and in the setting of recent viral infection could be explained by effects on acquisition. Our study describes an approach for studying factors that specifically affect the step of acquisition.