Concurrent host-pathogen transcriptional responses in a clostridium perfringens murine myonecrosis infection

Lee-Yean Low, Paul F. Harrison, Jodee Gould, David R. Powell, Jocelyn M. Choo, Samuel C. Forster, Ross Chapman, Linden J. Gearing, Jackie K. Cheung, Paul Hertzog, Julian I. Rood

Research output: Contribution to journalArticleResearchpeer-review

Abstract

To obtain an insight into host-pathogen interactions in clostridial myonecrosis, we carried out comparative transcriptome analysis of both the bacterium and the host in a murine Clostridium perfringens infection model, which is the first time that such an investigation has been conducted. Analysis of the host transcriptome from infected muscle tissues indicated that many genes were upregulated compared to the results seen with mock-infected mice. These genes were enriched for host defense pathways, including Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling components. Real-time PCR confirmed that host TLR2 and NLRP3 inflammasome genes were induced in response to C. perfringens infection. Comparison of the transcriptome of C. perfringens cells from the infected tissues with that from broth cultures showed that host selective pressure induced a global change in C. perfringens gene expression. A total of 33% (923) of C. perfringens genes were differentially regulated, including 10 potential virulence genes that were upregulated relative to their expression in vitro. These genes encoded putative proteins that may be involved in the synthesis of cell wall-associated macromolecules, in adhesion to host cells, or in protection from host cationic antimicrobial peptides. This report presents the first successful expression profiling of coregulated transcriptomes of bacterial and host genes during a clostridial myonecrosis infection and provides new insights into disease pathogenesis and host-pathogen interactions. IMPORTANCE Clostridium perfringens is the causative agent of traumatic clostridial myonecrosis, or gas gangrene. In this study, we carried out transcriptional analysis of both the host and the bacterial pathogen in a mouse myonecrosis infection. The results showed that in comparison to mock-infected control tissues, muscle tissues from C. perfringens-infected mice had a significantly altered gene expression profile. In particular, the expression of many genes involved in the innate immune system was upregulated. Comparison of the expression profiles of C. perfringens cells isolated from the infected tissues with those from equivalent broth cultures identified many potential virulence genes that were significantly upregulated in vivo. These studies have provided a new understanding of the range of factors involved in hostpathogen interactions in a myonecrosis infection.

Original languageEnglish
Article numbere00473-18
Number of pages15
JournalmBio
Volume9
Issue number2
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Clostridial myonecrosis
  • Clostridium perfringens
  • Gas gangrene
  • Host-pathogen interactions
  • Inflammasome
  • Innate immunity
  • RNA-seq
  • Transcriptomics

Cite this

@article{d4839e350980472286984dc57fd26945,
title = "Concurrent host-pathogen transcriptional responses in a clostridium perfringens murine myonecrosis infection",
abstract = "To obtain an insight into host-pathogen interactions in clostridial myonecrosis, we carried out comparative transcriptome analysis of both the bacterium and the host in a murine Clostridium perfringens infection model, which is the first time that such an investigation has been conducted. Analysis of the host transcriptome from infected muscle tissues indicated that many genes were upregulated compared to the results seen with mock-infected mice. These genes were enriched for host defense pathways, including Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling components. Real-time PCR confirmed that host TLR2 and NLRP3 inflammasome genes were induced in response to C. perfringens infection. Comparison of the transcriptome of C. perfringens cells from the infected tissues with that from broth cultures showed that host selective pressure induced a global change in C. perfringens gene expression. A total of 33{\%} (923) of C. perfringens genes were differentially regulated, including 10 potential virulence genes that were upregulated relative to their expression in vitro. These genes encoded putative proteins that may be involved in the synthesis of cell wall-associated macromolecules, in adhesion to host cells, or in protection from host cationic antimicrobial peptides. This report presents the first successful expression profiling of coregulated transcriptomes of bacterial and host genes during a clostridial myonecrosis infection and provides new insights into disease pathogenesis and host-pathogen interactions. IMPORTANCE Clostridium perfringens is the causative agent of traumatic clostridial myonecrosis, or gas gangrene. In this study, we carried out transcriptional analysis of both the host and the bacterial pathogen in a mouse myonecrosis infection. The results showed that in comparison to mock-infected control tissues, muscle tissues from C. perfringens-infected mice had a significantly altered gene expression profile. In particular, the expression of many genes involved in the innate immune system was upregulated. Comparison of the expression profiles of C. perfringens cells isolated from the infected tissues with those from equivalent broth cultures identified many potential virulence genes that were significantly upregulated in vivo. These studies have provided a new understanding of the range of factors involved in hostpathogen interactions in a myonecrosis infection.",
keywords = "Clostridial myonecrosis, Clostridium perfringens, Gas gangrene, Host-pathogen interactions, Inflammasome, Innate immunity, RNA-seq, Transcriptomics",
author = "Lee-Yean Low and Harrison, {Paul F.} and Jodee Gould and Powell, {David R.} and Choo, {Jocelyn M.} and Forster, {Samuel C.} and Ross Chapman and Gearing, {Linden J.} and Cheung, {Jackie K.} and Paul Hertzog and Rood, {Julian I.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1128/mBio.00473-18",
language = "English",
volume = "9",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
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Concurrent host-pathogen transcriptional responses in a clostridium perfringens murine myonecrosis infection. / Low, Lee-Yean; Harrison, Paul F.; Gould, Jodee; Powell, David R.; Choo, Jocelyn M.; Forster, Samuel C.; Chapman, Ross; Gearing, Linden J.; Cheung, Jackie K.; Hertzog, Paul; Rood, Julian I.

In: mBio, Vol. 9, No. 2, e00473-18, 01.03.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Concurrent host-pathogen transcriptional responses in a clostridium perfringens murine myonecrosis infection

AU - Low, Lee-Yean

AU - Harrison, Paul F.

AU - Gould, Jodee

AU - Powell, David R.

AU - Choo, Jocelyn M.

AU - Forster, Samuel C.

AU - Chapman, Ross

AU - Gearing, Linden J.

AU - Cheung, Jackie K.

AU - Hertzog, Paul

AU - Rood, Julian I.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - To obtain an insight into host-pathogen interactions in clostridial myonecrosis, we carried out comparative transcriptome analysis of both the bacterium and the host in a murine Clostridium perfringens infection model, which is the first time that such an investigation has been conducted. Analysis of the host transcriptome from infected muscle tissues indicated that many genes were upregulated compared to the results seen with mock-infected mice. These genes were enriched for host defense pathways, including Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling components. Real-time PCR confirmed that host TLR2 and NLRP3 inflammasome genes were induced in response to C. perfringens infection. Comparison of the transcriptome of C. perfringens cells from the infected tissues with that from broth cultures showed that host selective pressure induced a global change in C. perfringens gene expression. A total of 33% (923) of C. perfringens genes were differentially regulated, including 10 potential virulence genes that were upregulated relative to their expression in vitro. These genes encoded putative proteins that may be involved in the synthesis of cell wall-associated macromolecules, in adhesion to host cells, or in protection from host cationic antimicrobial peptides. This report presents the first successful expression profiling of coregulated transcriptomes of bacterial and host genes during a clostridial myonecrosis infection and provides new insights into disease pathogenesis and host-pathogen interactions. IMPORTANCE Clostridium perfringens is the causative agent of traumatic clostridial myonecrosis, or gas gangrene. In this study, we carried out transcriptional analysis of both the host and the bacterial pathogen in a mouse myonecrosis infection. The results showed that in comparison to mock-infected control tissues, muscle tissues from C. perfringens-infected mice had a significantly altered gene expression profile. In particular, the expression of many genes involved in the innate immune system was upregulated. Comparison of the expression profiles of C. perfringens cells isolated from the infected tissues with those from equivalent broth cultures identified many potential virulence genes that were significantly upregulated in vivo. These studies have provided a new understanding of the range of factors involved in hostpathogen interactions in a myonecrosis infection.

AB - To obtain an insight into host-pathogen interactions in clostridial myonecrosis, we carried out comparative transcriptome analysis of both the bacterium and the host in a murine Clostridium perfringens infection model, which is the first time that such an investigation has been conducted. Analysis of the host transcriptome from infected muscle tissues indicated that many genes were upregulated compared to the results seen with mock-infected mice. These genes were enriched for host defense pathways, including Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling components. Real-time PCR confirmed that host TLR2 and NLRP3 inflammasome genes were induced in response to C. perfringens infection. Comparison of the transcriptome of C. perfringens cells from the infected tissues with that from broth cultures showed that host selective pressure induced a global change in C. perfringens gene expression. A total of 33% (923) of C. perfringens genes were differentially regulated, including 10 potential virulence genes that were upregulated relative to their expression in vitro. These genes encoded putative proteins that may be involved in the synthesis of cell wall-associated macromolecules, in adhesion to host cells, or in protection from host cationic antimicrobial peptides. This report presents the first successful expression profiling of coregulated transcriptomes of bacterial and host genes during a clostridial myonecrosis infection and provides new insights into disease pathogenesis and host-pathogen interactions. IMPORTANCE Clostridium perfringens is the causative agent of traumatic clostridial myonecrosis, or gas gangrene. In this study, we carried out transcriptional analysis of both the host and the bacterial pathogen in a mouse myonecrosis infection. The results showed that in comparison to mock-infected control tissues, muscle tissues from C. perfringens-infected mice had a significantly altered gene expression profile. In particular, the expression of many genes involved in the innate immune system was upregulated. Comparison of the expression profiles of C. perfringens cells isolated from the infected tissues with those from equivalent broth cultures identified many potential virulence genes that were significantly upregulated in vivo. These studies have provided a new understanding of the range of factors involved in hostpathogen interactions in a myonecrosis infection.

KW - Clostridial myonecrosis

KW - Clostridium perfringens

KW - Gas gangrene

KW - Host-pathogen interactions

KW - Inflammasome

KW - Innate immunity

KW - RNA-seq

KW - Transcriptomics

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U2 - 10.1128/mBio.00473-18

DO - 10.1128/mBio.00473-18

M3 - Article

VL - 9

JO - mBio

JF - mBio

SN - 2161-2129

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M1 - e00473-18

ER -