MARTX Toxin-Stimulated Interplay between Human Cells and Vibrio vulnificus

To understand toxin-stimulated host-pathogen interactions, we per -formed 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 multi...

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Veröffentlicht in:mSphere 2020-08, Vol.5 (4), Article 00659
Hauptverfasser: Kim, Byoung Sik, Kim, Jong-Hwan, Choi, Sanghyeon, Park, Shinhye, Lee, Eun-Young, Koh, Serry, Ryu, Choong-Min, Kim, Seon-Young, Kim, Myung Hee
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container_title mSphere
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creator Kim, Byoung Sik
Kim, Jong-Hwan
Choi, Sanghyeon
Park, Shinhye
Lee, Eun-Young
Koh, Serry
Ryu, Choong-Min
Kim, Seon-Young
Kim, Myung Hee
description To understand toxin-stimulated host-pathogen interactions, we per -formed 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 re-sponses in gut epithelial cells but accelerates inflammation and nuclear factor kappa B (NF-kappa B) signaling in immune cells. With respect to the pathogen, siderophore biosynthe-sis 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 re-sponse to this, host cells mount a counterattack against the invaders by upregulat-ing 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.
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F.</contributor><creatorcontrib>Kim, Byoung Sik ; Kim, Jong-Hwan ; Choi, Sanghyeon ; Park, Shinhye ; Lee, Eun-Young ; Koh, Serry ; Ryu, Choong-Min ; Kim, Seon-Young ; Kim, Myung Hee ; D'Orazio, Sarah E. F.</creatorcontrib><description>To understand toxin-stimulated host-pathogen interactions, we per -formed 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 re-sponses in gut epithelial cells but accelerates inflammation and nuclear factor kappa B (NF-kappa B) signaling in immune cells. With respect to the pathogen, siderophore biosynthe-sis 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 re-sponse to this, host cells mount a counterattack against the invaders by upregulat-ing 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.</description><identifier>ISSN: 2379-5042</identifier><identifier>EISSN: 2379-5042</identifier><identifier>DOI: 10.1128/mSphere.00659-20</identifier><identifier>PMID: 32817457</identifier><language>eng</language><publisher>WASHINGTON: Amer Soc Microbiology</publisher><subject>dual-RNA sequencing ; Host-Microbe Biology ; iron limitation ; Life Sciences &amp; Biomedicine ; MARTX toxin ; Microbiology ; Research Article ; Science &amp; Technology ; siderophore ; Vibrio vulnificus</subject><ispartof>mSphere, 2020-08, Vol.5 (4), Article 00659</ispartof><rights>Copyright © 2020 Kim et al.</rights><rights>Copyright © 2020 Kim et al. 2020 Kim et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>8</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000568744900006</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-a518t-62e977844eb3a39f4c278c68e3125a52822ff8762871b3bd8c691d5a709267343</citedby><cites>FETCH-LOGICAL-a518t-62e977844eb3a39f4c278c68e3125a52822ff8762871b3bd8c691d5a709267343</cites><orcidid>0000-0002-7276-1189 ; 0000-0003-2856-9066</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.asm.org/doi/pdf/10.1128/msphere.00659-20$$EPDF$$P50$$Gasm2$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.asm.org/doi/full/10.1128/msphere.00659-20$$EHTML$$P50$$Gasm2$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,3189,27929,27930,28253,52756,52757,52758,53796,53798</link.rule.ids></links><search><contributor>D'Orazio, Sarah E. F.</contributor><creatorcontrib>Kim, Byoung Sik</creatorcontrib><creatorcontrib>Kim, Jong-Hwan</creatorcontrib><creatorcontrib>Choi, Sanghyeon</creatorcontrib><creatorcontrib>Park, Shinhye</creatorcontrib><creatorcontrib>Lee, Eun-Young</creatorcontrib><creatorcontrib>Koh, Serry</creatorcontrib><creatorcontrib>Ryu, Choong-Min</creatorcontrib><creatorcontrib>Kim, Seon-Young</creatorcontrib><creatorcontrib>Kim, Myung Hee</creatorcontrib><title>MARTX Toxin-Stimulated Interplay between Human Cells and Vibrio vulnificus</title><title>mSphere</title><addtitle>MSPHERE</addtitle><addtitle>mSphere</addtitle><description>To understand toxin-stimulated host-pathogen interactions, we per -formed 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). 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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 re-sponse to this, host cells mount a counterattack against the invaders by upregulat-ing 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. 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F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MARTX Toxin-Stimulated Interplay between Human Cells and Vibrio vulnificus</atitle><jtitle>mSphere</jtitle><stitle>MSPHERE</stitle><stitle>mSphere</stitle><date>2020-08-12</date><risdate>2020</risdate><volume>5</volume><issue>4</issue><artnum>00659</artnum><issn>2379-5042</issn><eissn>2379-5042</eissn><abstract>To understand toxin-stimulated host-pathogen interactions, we per -formed 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 re-sponses in gut epithelial cells but accelerates inflammation and nuclear factor kappa B (NF-kappa B) signaling in immune cells. With respect to the pathogen, siderophore biosynthe-sis 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 re-sponse to this, host cells mount a counterattack against the invaders by upregulat-ing 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.</abstract><cop>WASHINGTON</cop><pub>Amer Soc Microbiology</pub><pmid>32817457</pmid><doi>10.1128/mSphere.00659-20</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-7276-1189</orcidid><orcidid>https://orcid.org/0000-0003-2856-9066</orcidid><oa>free_for_read</oa></addata></record>
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subjects dual-RNA sequencing
Host-Microbe Biology
iron limitation
Life Sciences & Biomedicine
MARTX toxin
Microbiology
Research Article
Science & Technology
siderophore
Vibrio vulnificus
title MARTX Toxin-Stimulated Interplay between Human Cells and Vibrio vulnificus
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