MARTX Toxin-stimulated interplay between human cells and Vibrio vulnificus

Byoung Sik Kim, Jong Hwan Kim, Sanghyeon Choi, Shinhye Park, Eun Young Lee, Serry Koh, Choong Min Ryu, Seon Young Kim, Myung Hee Kima

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

To understand toxin-stimulated host-pathogen interactions, we performed dual-transcriptome sequencing experiments using human epithelial (HT-29) and differentiated THP-1 (dTHP-1) immune cells infected with the sepsis-causing pathogen Vibrio vulnificus (either the wild-type [WT] pathogen or a multifunctional-autoprocessing repeats-in-toxin [MARTX] toxin-deficient strain). Gene set enrichment analyses revealed MARTX toxin-dependent responses, including negative regulation of extracellular related kinase 1 (ERK1) and ERK2 (ERK1/2) signaling and cell cycle regulation in HT-29 and dTHP-1 cells, respectively. Further analysis of the expression of immune-related genes suggested that the MARTX toxin dampens immune responses in gut epithelial cells but accelerates inflammation and nuclear factor B (NF-kB) signaling in immune cells. With respect to the pathogen, siderophore biosynthesis genes were significantly more highly expressed in WT V. vulnificus than in the MARTX toxin-deficient mutant upon infection of dTHP-1 cells. Consistent with these results, iron homeostasis genes that limit iron levels for invading pathogens were overexpressed in WT V. vulnificus-infected dTHP-1 cells. Taken together, these results suggest that MARTX toxin regulates host inflammatory responses during V. vulnificus infection while also countering host defense mechanisms such as iron limitation.

Original languageEnglish
Article numbere00659
JournalmSphere
Volume5
Issue number4
DOIs
StatePublished - 2020

Keywords

  • Dual-RNA sequencing
  • Iron limitation
  • MARTX toxin
  • Siderophore
  • Vibrio vulnificus

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