Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and Mice

J. P. Garcia, V. Adams, J. Beingesser, M. L. Hughes, R. Poon, D. Lyras, Ashley E Hill, B. A. McClane, J. I. Rood, Francisco A Uzal

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)2405-2414
Number of pages10
JournalInfection and Immunity
Volume81
Issue number7
DOIs
StatePublished - Jul 2013

Fingerprint

Clostridium perfringens
Goats
Virulence
Sheep
Infection
Sheep Diseases
Brain Edema
Ruminants
Acute Disease
Pulmonary Edema
Colitis
Bacteria
Lung
Mutation

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and Mice. / Garcia, J. P.; Adams, V.; Beingesser, J.; Hughes, M. L.; Poon, R.; Lyras, D.; Hill, Ashley E; McClane, B. A.; Rood, J. I.; Uzal, Francisco A.

In: Infection and Immunity, Vol. 81, No. 7, 07.2013, p. 2405-2414.

Research output: Contribution to journalArticle

Garcia, JP, Adams, V, Beingesser, J, Hughes, ML, Poon, R, Lyras, D, Hill, AE, McClane, BA, Rood, JI & Uzal, FA 2013, 'Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and Mice', Infection and Immunity, vol. 81, no. 7, pp. 2405-2414. https://doi.org/10.1128/IAI.00238-13
Garcia, J. P. ; Adams, V. ; Beingesser, J. ; Hughes, M. L. ; Poon, R. ; Lyras, D. ; Hill, Ashley E ; McClane, B. A. ; Rood, J. I. ; Uzal, Francisco A. / Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and Mice. In: Infection and Immunity. 2013 ; Vol. 81, No. 7. pp. 2405-2414.
@article{4d0323e8f7d440cfa2e7bf4cf520473d,
title = "Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and Mice",
abstract = "Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis.",
author = "Garcia, {J. P.} and V. Adams and J. Beingesser and Hughes, {M. L.} and R. Poon and D. Lyras and Hill, {Ashley E} and McClane, {B. A.} and Rood, {J. I.} and Uzal, {Francisco A}",
year = "2013",
month = "7",
doi = "10.1128/IAI.00238-13",
language = "English (US)",
volume = "81",
pages = "2405--2414",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and Mice

AU - Garcia, J. P.

AU - Adams, V.

AU - Beingesser, J.

AU - Hughes, M. L.

AU - Poon, R.

AU - Lyras, D.

AU - Hill, Ashley E

AU - McClane, B. A.

AU - Rood, J. I.

AU - Uzal, Francisco A

PY - 2013/7

Y1 - 2013/7

N2 - Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis.

AB - Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84879458553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879458553&partnerID=8YFLogxK

U2 - 10.1128/IAI.00238-13

DO - 10.1128/IAI.00238-13

M3 - Article

C2 - 23630957

AN - SCOPUS:84879458553

VL - 81

SP - 2405

EP - 2414

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 7

ER -