MARTX toxin-stimulated interplay between human cells and Vibrio vulnificus

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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 RyuSeon-Young KimMyung Hee Kim
Bibliographic Citation
mSphere, vol. 5, no. 4, pp. e00659-20-e00659-20
Publication Year
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 κB (NF-κB) 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.
dual-RNA sequencingiron limitationsiderophoreMARTX toxinVibrio vulnificus
Amer Soc Microb
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Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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