Lauren McAllister, Australia

The University of Adelaide Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science

Poster Author Of 1 e-Poster

Online Abstracts Basic Sciences - Immunology, Pathogenesis, and Host-pathogen Interactions A1 Immunology, Pathogenesis, and Host-pathogen Interactions

Author Of 1 Presentation

IN VIVO DUAL RNA-SEQ ANALYSIS REVEALS THE BASIS FOR DIFFERENTIAL TISSUE TROPISM OF CLINICAL ISOLATES OF STREPTOCOCCUS PNEUMONIAE (ID 208)

Abstract

Background

Recently we showed that a single nucleotide polymorphism (SNP) in the raffinose pathway regulatory gene rafR accounts for differences in the capacity of clonally-related pneumococcal strains to cause localised versus systemic infection. However, the underlying mechanism for these differences remain unclear.

Methods

6h post intranasal infection, a time-point were the wildtype and rafR-swapped strains are present in the lungs at similar levels, RNA was isolated from murine lungs. Host and pathogen transcriptomes were then simulatenously sequenced.

Results

The Dual RNA-seq data highlighted that this SNP extensively impacts both bacterial and host transcriptomes in infected lungs, affecting bacterial carbohydrate utilization and host inflammatory responses. A crucial role was predicted for differential neutrophil recruitment in the distinct virulence profiles of the infecting strains. Single cell analysis revealed that reduced expression of the RafR regulon, driven by the single rafR SNP, leads to massive recruitment of neutrophils and bacterial clearance in the lungs. Importantly, the observed disease outcomes were confirmed by in vivo neutrophil depletion showing that early detection of bacteria by the host in the lung environment is crucial for effective clearance.

Conclusions

Dual RNA-seq provides a powerful tool for understanding complex host-pathogen interactions, revealing how a single pneumococcal SNP drives differential disease outcomes.

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