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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 52; pp. 33507 - 33518
• Main Authors: D’Mello, Adonis, Riegler, Ashleigh N., Martínez, Eriel, Beno, Sarah M., Ricketts, Tiffany D., Foxman, Ellen F., Orihuela, Carlos J., Tettelin, Hervé
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 29.12.2020
• Subjects: Animals; Biological Sciences; Colony Count, Microbial; Female; Gene Expression Regulation, Bacterial; Genes, Bacterial; Host-Pathogen Interactions - genetics; Interferons - metabolism; Male; Mice, Inbred C57BL; Mutation - genetics; Phylogeny; Pneumococcal Infections - genetics; Pneumococcal Infections - microbiology; Principal Component Analysis; Signal Transduction; Streptococcus pneumoniae - growth & development; Streptococcus pneumoniae - physiology; Transcriptome - genetics; dual species RNA-seq; in vivo transcriptomics; host–pathogen interactions; mouse models of colonization and invasive disease; Streptococcus pneumoniae
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/PNAS.2010428117

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 organspecific 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.