An in vivo atlas of host–pathogen transcriptomes during Streptococcus pneumoniae colonization and disease

Autor: Adonis D'Mello, Carlos J. Orihuela, Hervé Tettelin, Sarah M. Beno, Ashleigh N. Riegler, Eriel Martínez, Tiffany Davia Ricketts, Ellen F. Foxman
Rok vydání: 2020
Předmět:
Zdroj: Proceedings of the National Academy of Sciences. 117:33507-33518
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.2010428117
Popis: Streptococcus pneumoniae (Spn) colonizes the nasopharynx and can cause pneumonia. From the lungs it spreads to the bloodstream and causes organ damage. We characterized the in vivo Spn and mouse transcriptomes within the nasopharynx, lungs, blood, heart, and kidneys using three Spn strains. We identified Spn 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 Spn and host gene-expression profiles were observed during colonization and disease states, revealing specific genes/operons whereby Spn adapts to and influences host sites in vivo. We identified and experimentally verified host-defense pathways induced by Spn during invasive disease, including proinflammatory responses and the interferon response. These results shed light on the pathogenesis of Spn and identify therapeutic targets.
Databáze: OpenAIRE