Ashleigh N. Riegler, United States of America

University of Alabama at Birmingham Microbiology

Author Of 1 Presentation

STREPTOCOCCUS PNEUMONIAE ANATOMICAL SITE GENE EXPRESSION ATLAS: DISSECTION OF HOST-PATHOGEN INTERACTIONS USING LARGE-SCALE DUAL TRANSCRIPTOMICS OF THREE STREPTOCOCCUS PNEUMONIAE ISOLATES IN VIVO (ID 571)

Abstract

Background

Streptococcus pneumoniae (Spn) colonizes the nasopharynx asymptomatically but is also a leading cause of community-acquired pneumonia, otitis media, bacteremia, sepsis, and meningitis. Spn pathogenesis studies have largely focused on the middle ear, airway, bloodstream, and central nervous system. Yet, increasing evidence indicates that during severe infections, Spn gains access to other vital organs.

Methods

Using dual species RNA-seq transcriptomics and mouse models of asymptomatic colonization and invasive disease, we characterized the pneumococcal (3 strains) and host transcriptomes during colonization and disease. This included the nasopharynx, lungs, and blood. Bacterial and host regulated pathways were validated using a panel of knock-out Spn strains and/or treatment of mice with relevant molecules.

Results

Spn differentially regulates genes in vivo in a site-specific manner, including upregulation of diverse scavenger pathways within the nasopharynx. Core genes highly expressed at all disease sites, and therefore targets for intervention, were identified, including pspA. Novel insights include that pneumococcal infection induces a Type I interferon response during pneumonia and invasive disease, but not colonization.

Conclusions

The pneumococcal transcriptome varies in anatomical site-specific manner and is vastly different during asymptomatic colonization versus disease. Host transcriptomes during invasive disease provide novel insights about potential therapeutic targets.

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