Signs and Their Pathogenesis

EPEC strains carry the eaeA gene on their chromosome (E. coli attaching effacing), which is located in a “pathogenicity island” referred to as LEE (locus of enterocyte effacement). The eaeA gene encodes a 94-kDa protein, intimin, which allows the organism to adhere intimately to intestinal epithelial cells. This leads to local effacement of the microvilli and formation of numerous, actin-rich pedestals on which the bacteria reside (Figure 46-1).⁵ The bacteria secrete their own receptor, the Tir receptor, and Tir-intimin interactions are involved in pedestal formation. The pedestals may help the bacteria to remain extracellular, and thus escape immune recognition by the host. The resulting characteristic histopathologic lesions on enterocytes have been referred to as “attaching and effacing lesions.” Subsequent signal transduction events induced by EPEC may be associated with loss of tight junction integrity and altered electrolyte transport, with associated watery diarrhea. The EPEC pathovar does not produce Shiga toxin, Shiga-like toxin, or verotoxins. EPEC serotypes that have been associated with diarrhea in humans have been identified in dogs and cats.^6,7

ETEC are a major cause of diarrhea in human infants in developing countries and are the agents most frequently responsive for traveler’s diarrhea. ETEC pathovars have been associated with up to 31% of cases of canine diarrhea, particularly in young dogs.8–10 Most of the canine ETEC strains express ST enterotoxin, whereas ETEC strains that produce LT enterotoxin are rarely found. The bacteria adhere to the proximal small intestinal mucosa and produce plasmid-encoded LT and ST enterotoxins. LT is related to cholera toxin and is taken up by enterocytes. Once within intestinal epithelial cells, it activates adenylate cyclase, which leads to increased concentrations of intracellular cyclic AMP with resultant secretion of electrolytes and water that lead to diarrhea, hypovolemia, and metabolic acidosis. LT may also downregulate innate host immune responses and promote ETEC adherence. In contrast, ST binds to the extracellular domain of guanylyl cyclase C, which leads to accumulation of intracellular cyclic GMP and ultimately secretion of chloride and decreased absorption of NaCl, with resultant osmotic diarrhea. Two different ST enterotoxins have been identified, STa and STb. ST-producing ETEC have been detected in young dogs with diarrhea.^8–10

In addition to producing attaching and effacing lesions similar to those created by EPEC, EHEC (Shiga-toxin–producing E. coli, or STEC) produce Shiga-like toxins (also known as verotoxins). They cause diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS) (e.g., E. coli strain O157:H7). Shiga-like toxins are absorbed from the intestinal lumen and cause vascular endothelial damage, which may lead to a multiorgan thrombotic process in the absence of bacteremia. EHEC can also produce other toxins that contribute to the pathogenesis of the disease. HUS in humans is characterized by renal failure, widespread microthrombotic damage to a variety of organs, hemolytic anemia, and sometimes diarrhea. Similar syndromes have been described in dogs, but an associated E. coli infection was not demonstrated.11,12 HUS has been reproduced experimentally in dogs with a non-O157:H7 E. coli serotype.¹³ Based on the similarity of renal lesions to those described in HUS, and the practice of feeding predominantly raw meat diets to greyhounds, it has been hypothesized that cutaneous and renal glomerular vasculopathy of greyhounds (also known as “Alabama rot” or “Greenetrack disease”) may result from infection with EHEC strains such as O157:H7.¹⁴ A similar condition was described in a great Dane from Germany.¹⁵ Some dogs develop cutaneous lesions in the absence of renal failure; other dogs develop renal failure before the onset of cutaneous lesions.

NTEC produce two toxins: CNF and cytolethal distending toxin. Multiple CNF types have been identified (CNF1, CNF2, and CNF3). NTEC have been associated with diarrhea, bacteremia, and urinary tract infections in human patients, as well as with diarrhea in dogs.¹⁶

EIEC actively invade colonic epithelial cells. This, together with the associated inflammatory response, leads to hemorrhagic, large bowel diarrhea. In human patients, the EIEC pathovar is uncommonly detected compared with EPEC and ETEC. AIEC, which lack the virulence genes that identify EIEC, have been associated with granulomatous colitis in boxer dogs and infrequently in the French bulldog and Border collie. This infection typically affects young adult boxer dogs that show signs of severe colitis, with colonic thickening and ulceration, and weight loss that is often marked.4,17 It has been suggested that a heritable anomaly in boxer dogs predisposes them to the infection, given the marked breed predisposition for the disease.¹⁸

The EAEC pathovar is considered an emerging pathogen in human patients. It adheres to epithelial cells of the terminal ileum and colon using fimbriae in a characteristic “stacked brick” pattern. Expression of these fimbriae is encoded by a plasmid gene known as aggR. Bacterial aggregation is followed by damage and a subsequent inflammatory response, which leads to development of persistent watery diarrhea. Occasionally, EAEC strains also produce toxins, such as verocytotoxin.¹⁹ Their role in dogs and cats requires further investigation.

Physical Examination Findings

Physical examination may reveal dehydration and abdominal pain in puppies with E. coli diarrhea. Dogs with HUS have had cutaneous erythema and well-demarcated, multifocal cutaneous ulcers of the limbs. Fever and peripheral edema have also been described. Boxer dogs with granulomatous colitis may have poor body condition. A thickened and irregular rectal wall may be detected on rectal palpation, and the feces may contain fresh blood and mucus.

Laboratory Abnormalities