An in vivo atlas of host-pathogen transcriptomes during <i>Streptococcus pneumoniae</i> colonization and disease.

Abstract

<i>Streptococcus pneumoniae</i> (<i>Spn</i>) colonizes the nasopharynx and can cause pneumonia. From the lungs it spreads to the bloodstream and causes organ damage. We characterized the in vivo <i>Spn</i> and mouse transcriptomes within the nasopharynx, lungs, blood, heart, and kidneys using three <i>Spn</i> strains. We identified <i>Spn</i> genes highly expressed at all anatomical sites and in an organ-specific manner; highly expressed genes were shown to have vital roles with knockout mutants. The in vivo bacterial transcriptome during colonization/disease was distinct from previously reported in vitro transcriptomes. Distinct <i>Spn</i> and host gene-expression profiles were observed during colonization and disease states, revealing specific genes/operons whereby <i>Spn</i> adapts to and influences host sites in vivo. We identified and experimentally verified host-defense pathways induced by <i>Spn</i> during invasive disease, including proinflammatory responses and the interferon response. These results shed light on the pathogenesis of <i>Spn</i> and identify therapeutic targets.