Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 52, Pages 33507-33518Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2010428117
Keywords
dual species RNA-seq; in vivo transcriptomics; Streptococcus pneumoniae; mouse models of colonization and invasive disease; host-pathogen interactions
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Funding
- Merck, Sharpe, and Dohme, under the Merck Investigator Studies Program [57329Pneumovax]
- NIH, National Institute of Allergy and Infectious Diseases [R01AI114800]
- Hartwell Foundation
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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.
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