Dual transcriptomics of host-pathogen interaction of cystic fibrosis isolate Pseudomonas aeruginosa PASS1 with zebrafish

Sheemal S. Kumar, Julia I. Tandberg, Anahit Penesyan, Liam D. H. Elbourne, Nadia Suarez-Bosche, Emily Don, Eline Skadberg, Federico Fenaroli, Nicholas Cole, Hanne Cecilie Winther-Larsen, Ian T. Paulsen

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Abstract

Pseudomonas aeruginosa is a significant cause of mortality in patients with cystic fibrosis (CF). To explore the interaction of the CF isolate P. aeruginosa PASS1 with the innate immune response, we have used Danio rerio (zebrafish) as an infection model. Confocal laser scanning microscopy (CLSM) enabled visualization of direct interactions between zebrafish macrophages and P. aeruginosa PASS1. Dual RNA-sequencing of host-pathogen was undertaken to profile RNA expression simultaneously in the pathogen and the host during P. aeruginosa infection. Following establishment of infection in zebrafish embryos with PASS1, 3 days post infection (dpi), there were 6739 genes found to be significantly differentially expressed in zebrafish and 176 genes in PASS1. A range of virulence genes were upregulated in PASS1, including genes encoding pyoverdine biosynthesis, flagellin, non-hemolytic phospholipase C, proteases, superoxide dismutase and fimbrial subunits. Additionally, iron and phosphate acquisition genes were upregulated in PASS1 cells in the zebrafish. Transcriptional changes in the host immune response genes highlighted phagocytosis as a key response mechanism to PASS1 infection. Transcriptional regulators of neutrophil and macrophage phagocytosis were upregulated alongside transcriptional regulators governing response to tissue injury, infection, and inflammation. The zebrafish host showed significant downregulation of the ribosomal RNAs and other genes involved in translation, suggesting that protein translation in the host is affected by PASS1 infection.

Original languageEnglish
Article number406
Pages (from-to)1-15
Number of pages15
JournalFrontiers in cellular and infection microbiology
Volume8
DOIs
Publication statusPublished - 22 Nov 2018

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Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • RNA-Seq
  • host-pathogen interactions
  • virulence
  • Pseudomonas aeruginosa
  • zebrafish
  • innate immunity

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