Cargando…

The VirS/VirR Two-Component System Regulates the Anaerobic Cytotoxicity, Intestinal Pathogenicity, and Enterotoxemic Lethality of Clostridium perfringens Type C Isolate CN3685

Clostridium perfringens vegetative cells cause both histotoxic infections (e.g., gas gangrene) and diseases originating in the intestines (e.g., hemorrhagic necrotizing enteritis or lethal enterotoxemia). Despite their medical and veterinary importance, the molecular pathogenicity of C. perfringens...

Descripción completa

Detalles Bibliográficos
Autores principales: Ma, Menglin, Vidal, Jorge, Saputo, Juliann, McClane, Bruce A., Uzal, Francisco
Formato: Texto
Lenguaje:English
Publicado: American Society of Microbiology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025664/
https://www.ncbi.nlm.nih.gov/pubmed/21264065
http://dx.doi.org/10.1128/mBio.00338-10
_version_ 1782196935155777536
author Ma, Menglin
Vidal, Jorge
Saputo, Juliann
McClane, Bruce A.
Uzal, Francisco
author_facet Ma, Menglin
Vidal, Jorge
Saputo, Juliann
McClane, Bruce A.
Uzal, Francisco
author_sort Ma, Menglin
collection PubMed
description Clostridium perfringens vegetative cells cause both histotoxic infections (e.g., gas gangrene) and diseases originating in the intestines (e.g., hemorrhagic necrotizing enteritis or lethal enterotoxemia). Despite their medical and veterinary importance, the molecular pathogenicity of C. perfringens vegetative cells causing diseases of intestinal origin remains poorly understood. However, C. perfringens beta toxin (CPB) was recently shown to be important when vegetative cells of C. perfringens type C strain CN3685 induce hemorrhagic necrotizing enteritis and lethal enterotoxemia. Additionally, the VirS/VirR two-component regulatory system was found to control CPB production by CN3685 vegetative cells during aerobic infection of cultured enterocyte-like Caco-2 cells. Using an isogenic virR null mutant, the current study now reports that the VirS/VirR system also regulates CN3685 cytotoxicity during infection of Caco-2 cells under anaerobic conditions, as found in the intestines. More importantly, the virR mutant lost the ability to cause hemorrhagic necrotic enteritis in rabbit small intestinal loops. Western blot analyses demonstrated that the VirS/VirR system mediates necrotizing enteritis, at least in part, by controlling in vivo CPB production. In addition, vegetative cells of the isogenic virR null mutant were, relative to wild-type vegetative cells, strongly attenuated in their lethality in a mouse enterotoxemia model. Collectively, these results identify the first regulator of in vivo pathogenicity for C. perfringens vegetative cells causing disease originating in the complex intestinal environment. Since VirS/VirR also mediates histotoxic infections, this two-component regulatory system now assumes a global role in regulating a spectrum of infections caused by C. perfringens vegetative cells.
format Text
id pubmed-3025664
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher American Society of Microbiology
record_format MEDLINE/PubMed
spelling pubmed-30256642011-01-25 The VirS/VirR Two-Component System Regulates the Anaerobic Cytotoxicity, Intestinal Pathogenicity, and Enterotoxemic Lethality of Clostridium perfringens Type C Isolate CN3685 Ma, Menglin Vidal, Jorge Saputo, Juliann McClane, Bruce A. Uzal, Francisco mBio Research Article Clostridium perfringens vegetative cells cause both histotoxic infections (e.g., gas gangrene) and diseases originating in the intestines (e.g., hemorrhagic necrotizing enteritis or lethal enterotoxemia). Despite their medical and veterinary importance, the molecular pathogenicity of C. perfringens vegetative cells causing diseases of intestinal origin remains poorly understood. However, C. perfringens beta toxin (CPB) was recently shown to be important when vegetative cells of C. perfringens type C strain CN3685 induce hemorrhagic necrotizing enteritis and lethal enterotoxemia. Additionally, the VirS/VirR two-component regulatory system was found to control CPB production by CN3685 vegetative cells during aerobic infection of cultured enterocyte-like Caco-2 cells. Using an isogenic virR null mutant, the current study now reports that the VirS/VirR system also regulates CN3685 cytotoxicity during infection of Caco-2 cells under anaerobic conditions, as found in the intestines. More importantly, the virR mutant lost the ability to cause hemorrhagic necrotic enteritis in rabbit small intestinal loops. Western blot analyses demonstrated that the VirS/VirR system mediates necrotizing enteritis, at least in part, by controlling in vivo CPB production. In addition, vegetative cells of the isogenic virR null mutant were, relative to wild-type vegetative cells, strongly attenuated in their lethality in a mouse enterotoxemia model. Collectively, these results identify the first regulator of in vivo pathogenicity for C. perfringens vegetative cells causing disease originating in the complex intestinal environment. Since VirS/VirR also mediates histotoxic infections, this two-component regulatory system now assumes a global role in regulating a spectrum of infections caused by C. perfringens vegetative cells. American Society of Microbiology 2011-01-25 /pmc/articles/PMC3025664/ /pubmed/21264065 http://dx.doi.org/10.1128/mBio.00338-10 Text en Copyright © 2011 Ma et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ma, Menglin
Vidal, Jorge
Saputo, Juliann
McClane, Bruce A.
Uzal, Francisco
The VirS/VirR Two-Component System Regulates the Anaerobic Cytotoxicity, Intestinal Pathogenicity, and Enterotoxemic Lethality of Clostridium perfringens Type C Isolate CN3685
title The VirS/VirR Two-Component System Regulates the Anaerobic Cytotoxicity, Intestinal Pathogenicity, and Enterotoxemic Lethality of Clostridium perfringens Type C Isolate CN3685
title_full The VirS/VirR Two-Component System Regulates the Anaerobic Cytotoxicity, Intestinal Pathogenicity, and Enterotoxemic Lethality of Clostridium perfringens Type C Isolate CN3685
title_fullStr The VirS/VirR Two-Component System Regulates the Anaerobic Cytotoxicity, Intestinal Pathogenicity, and Enterotoxemic Lethality of Clostridium perfringens Type C Isolate CN3685
title_full_unstemmed The VirS/VirR Two-Component System Regulates the Anaerobic Cytotoxicity, Intestinal Pathogenicity, and Enterotoxemic Lethality of Clostridium perfringens Type C Isolate CN3685
title_short The VirS/VirR Two-Component System Regulates the Anaerobic Cytotoxicity, Intestinal Pathogenicity, and Enterotoxemic Lethality of Clostridium perfringens Type C Isolate CN3685
title_sort virs/virr two-component system regulates the anaerobic cytotoxicity, intestinal pathogenicity, and enterotoxemic lethality of clostridium perfringens type c isolate cn3685
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025664/
https://www.ncbi.nlm.nih.gov/pubmed/21264065
http://dx.doi.org/10.1128/mBio.00338-10
work_keys_str_mv AT mamenglin thevirsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT vidaljorge thevirsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT saputojuliann thevirsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT mcclanebrucea thevirsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT uzalfrancisco thevirsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT mamenglin virsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT vidaljorge virsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT saputojuliann virsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT mcclanebrucea virsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685
AT uzalfrancisco virsvirrtwocomponentsystemregulatestheanaerobiccytotoxicityintestinalpathogenicityandenterotoxemiclethalityofclostridiumperfringenstypecisolatecn3685