MARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>

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...

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Autores principales:	Byoung Sik Kim, Jong-Hwan Kim, Sanghyeon Choi, Shinhye Park, Eun-Young Lee, Serry Koh, Choong-Min Ryu, Seon-Young Kim, Myung Hee Kim
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	siderophore MARTX toxin Vibrio vulnificus dual-RNA sequencing iron limitation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7979ad30bca240669143209de5b99e24
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spelling	oai:doaj.org-article:7979ad30bca240669143209de5b99e242021-11-15T15:30:51ZMARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>10.1128/mSphere.00659-202379-5042https://doaj.org/article/7979ad30bca240669143209de5b99e242020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00659-20https://doaj.org/toc/2379-5042ABSTRACT 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. IMPORTANCE V. vulnificus is an opportunistic human pathogen that can cause life-threatening sepsis in immunocompromised patients via seafood poisoning or wound infection. Among the toxic substances produced by this pathogen, the MARTX toxin greatly contributes to disease progression by promoting the dysfunction and death of host cells, which allows the bacteria to disseminate and colonize the host. In response to this, host cells mount a counterattack against the invaders by upregulating various defense genes. In this study, the gene expression profiles of both host cells and V. vulnificus were analyzed by RNA sequencing to gain a comprehensive understanding of host-pathogen interactions. Our results suggest that V. vulnificus uses the MARTX toxin to subvert host cell immune responses as well as to oppose host counterattacks such as iron limitation.Byoung Sik KimJong-Hwan KimSanghyeon ChoiShinhye ParkEun-Young LeeSerry KohChoong-Min RyuSeon-Young KimMyung Hee KimAmerican Society for MicrobiologyarticlesiderophoreMARTX toxinVibrio vulnificusdual-RNA sequencingiron limitationMicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	siderophore MARTX toxin Vibrio vulnificus dual-RNA sequencing iron limitation Microbiology QR1-502
spellingShingle	siderophore MARTX toxin Vibrio vulnificus dual-RNA sequencing iron limitation Microbiology QR1-502 Byoung Sik Kim Jong-Hwan Kim Sanghyeon Choi Shinhye Park Eun-Young Lee Serry Koh Choong-Min Ryu Seon-Young Kim Myung Hee Kim MARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>
description	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 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. IMPORTANCE V. vulnificus is an opportunistic human pathogen that can cause life-threatening sepsis in immunocompromised patients via seafood poisoning or wound infection. Among the toxic substances produced by this pathogen, the MARTX toxin greatly contributes to disease progression by promoting the dysfunction and death of host cells, which allows the bacteria to disseminate and colonize the host. In response to this, host cells mount a counterattack against the invaders by upregulating various defense genes. In this study, the gene expression profiles of both host cells and V. vulnificus were analyzed by RNA sequencing to gain a comprehensive understanding of host-pathogen interactions. Our results suggest that V. vulnificus uses the MARTX toxin to subvert host cell immune responses as well as to oppose host counterattacks such as iron limitation.
format	article
author	Byoung Sik Kim Jong-Hwan Kim Sanghyeon Choi Shinhye Park Eun-Young Lee Serry Koh Choong-Min Ryu Seon-Young Kim Myung Hee Kim
author_facet	Byoung Sik Kim Jong-Hwan Kim Sanghyeon Choi Shinhye Park Eun-Young Lee Serry Koh Choong-Min Ryu Seon-Young Kim Myung Hee Kim
author_sort	Byoung Sik Kim
title	MARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_short	MARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_full	MARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_fullStr	MARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_full_unstemmed	MARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_sort	martx toxin-stimulated interplay between human cells and <named-content content-type="genus-species">vibrio vulnificus</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/7979ad30bca240669143209de5b99e24
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MARTX Toxin-Stimulated Interplay between Human Cells and <named-content content-type="genus-species">Vibrio vulnificus</named-content>

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