Cardiopulmonary Lesions in Sheep Produced by Experimental Acute Clostridium Perfringens Type D Enterotoxemia

Abstract

Enterotoxemia caused by Clostridium perfringens type D is one of the most prevalent clostridial diseases of sheep. The lesions of the acute form of this disease, particularly the cerebral lesions, are well characterized; however, detailed descriptions of the cardiac and pulmonary lesions are lacking. Here we describe cardiopulmonary lesions in experimental acute type D enterotoxemia in sheep and determine the role of epsilon toxin (ETX) in the development of these lesions. Four groups of 6 sheep were intraduodenally inoculated with either a wild-type C. perfringens type D strain; its etx knockout mutant, which is unable to produce ETX; the etx mutant complemented with the wild-type etx gene, which regains the ETX toxigenic ability; or sterile culture medium as a control. All sheep were subjected to postmortem examination within 24 hours of inoculation. Lesion scores were compared between groups for pulmonary edema; hydrothorax; ascites; hydropericardium; endocardial, myocardial and epicardial hemorrhages; microscopic lesions of acute myocardial degeneration and necrosis; and myocardial, endocardial, and epicardial edema, hemorrhage, and inflammation. Only sheep inoculated with the wild-type and complemented ETX-toxigenic bacterial strains developed cardiopulmonary lesions, which were present in varying degrees of severity and proportions. These lesions were not present in sheep inoculated with the etx mutant or in the negative control. We conclude that severe acute cardiopulmonary lesions in sheep with experimental enterotoxemia are associated with the capacity of the strains to produce ETX. These changes are likely contributors to the clinical signs and even death of affected animals.

Pathology and Pathogenesis of Brain Lesions Produced by Clostridium perfringens Type D Epsilon Toxin

“…These fine structural changes are also found in ETX-exposed pulmonary, hepatic, renal and retinal microvessels [ 43 , 57 , 58 , 59 , 60 ]. Brain microvessel endothelial damage results in the accumulation of perivascular and intramural lakes of albumin-rich, plasma protein-derived fluid ( Figure 3 ), which is typical of type D disease, and a diffusely distributed parenchymal vasogenic edema [ 15 , 61 , 62 ].…”

“…However, since this gross appearance probably reflects accelerated autolysis, its diagnostic importance should not be overestimated, especially if the autopsy is delayed. There is usually scant evidence of enteritis, but segments of small intestine are sometimes distended with gas and the mucosa is hyperemic [ 16 , 22 , 23 , 42 , 43 ]. Gross findings are similar in goats and cattle.…”

“…It has recently been confirmed [ 43 ] that only ETX-producing strains of Clostridium perfringens cause acute cardiopulmonary lesions, of varying severity, in sheep. Death can occur very rapidly when these lesions are severe and, in addition to brain damage, cardiac dysfunction caused by ETX is a potential cause of mortality.…”

Yellow Lamb Disease (Clostridium perfringens Type A Enterotoxemia of Sheep): A Review

“…However, in that case, pulmonary edema was striking and there was also red-tinged subcutaneous edema and accumulation of pink serous fluid in the thoracic cavity [ 7 ]. It was speculated that such lesions could be mediated by the action of ETX on the vascular endothelium resulting in increased vascular permeability [ 20 ]. That case also had moderate enlargement of the spleen [ 7 ].…”

Reevaluation of whether a Functional Agr-like Quorum-Sensing System Is Necessary for Production of Wild-Type Levels of Epsilon-Toxin by Clostridium perfringens Type D Strains

“…In laboratory animal models and natural disease hosts, epsilon-toxin (ETX) plays a critical role in the virulence of Clostridium perfringens type D strains and, likely, type B strains ( 1 – 4 ). Our 2011 mBio paper ( 5 ) reported that an agrB null mutant of type D strain CN3718 grew similarly in tryptone-glucose-yeast extract (TGY) broth to its wild-type parent, but produced less ETX, and that this effect was partially reversible by complementation.…”