؜⁨مراجعات PREreview لIn Vivo Dual RNA-Seq Analysis Reveals the Basis for Differential Tissue Tropism of Clinical Isolates of Streptococcus pneumoniae⁩

الانتقال إلى تفاصيل المسودة البحثية الأولية الانتقال إلى مراجعات PREreview

In Vivo Dual RNA-Seq Analysis Reveals the Basis for Differential Tissue Tropism of Clinical Isolates of Streptococcus pneumoniae

Vikrant Minhas وRieza Aprianto وLauren J. McAllister وHui Wang وShannon C. David وKimberley T. McLean وIain Comerford وShaun R. McColl وJames C. Paton وJan-Willem Veening وClaudia Trappetti

تاريخ النشر: 3 ديسمبر 2019
الخادم: bioRxiv
DOI: 10.1101/862755

الملخص

Streptococcus pneumoniae is a genetically diverse human-adapted pathogen commonly carried asymptomatically in the nasopharynx. We have recently shown that a single nucleotide polymorphism (SNP) in the raffinose pathway regulatory gene rafR accounts for a significant difference in the capacity of clonally-related strains to cause localised versus systemic infection. Here we have used dual RNA-seq to show that this SNP extensively impacts both bacterial and host transcriptomes in infected lungs. It affects expression of bacterial genes encoding multiple sugar transporters, and fine-tunes carbohydrate metabolism, along with extensive rewiring of host transcriptional responses to infection, particularly expression of genes encoding cytokine and chemokine ligands and receptors. The dual RNA-seq data predicted a crucial role for differential neutrophil recruitment in the distinct virulence profiles of the infecting strains and single cell analysis revealed that while reduced expression of the RafR regulon driven by a single rafR SNP provides a clear advantage for pneumococci to colonize the ear, in the lung it leads to massive recruitment of neutrophils and bacterial clearance. 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. Thus, dual RNA-seq provides a powerful tool for understanding complex host-pathogen interactions and revealed how a single bacterial SNP can drive differential disease outcomes.

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مراجعة PREreview بواسطة Craig McCormick

من تأليف Craig McCormick

We, the students of MICI5029/5049, a _Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint:

Vikrant Minhas, Rieza Aprianto, Lauren J. McAllister, Hui Wang, Shannon C. David, Kimberley…

اقرأ مراجعة PREreview التي أجراها Craig McCormick