Infectious and parasitic diseases of the al.imentary

tract

Enteropathogenic co[ibaci[[osis

Enteropathogenic

E. coli

(EPEC) are those that cause direct dam-

age to the mucosa, through a

characteristic mechanism of attachment to, and

effacement of, epithelium.These

attaching-effacing

E. coli

(AEEC) are

more common in humans than in animals, where they are most

important in pigs, dogs, and rabbits, though they have also been iso-

lated from cats. Control of attaching-effacing activity resides in the

locus

for enterocyte effacement

(LEE), a chromosomal patho-

genicity island. EPEC have a complicated and sequential relationship

with host cells. Long polar fimbriae may mediate initial bacterial

interaction with the enterocyte. Secretion of bacterial proteins ensues,

including intimin, which is an adhesin. A second protein, the

translocated intimin receptor,

is transported via a type III secre-

tion system into the enterocyte cytoplasm, emerging on the cell

membrane as the intimin receptor. In response to translocated EPEC

proteins, the cell's cytoskeleton is reorganized, resulting in formation

of cupped

pedestal-like structures

beneath the attached bacteria, and the

subsequent loss of microvilli (Figs 1.119, 1.120, 1.131, and 1.132).

Paracellular permeability increases as tight junctions between entero-

cytes loosen, and neutrophils migrate between cells into the lumen.

In animals and humans, some strains of AEEC are pathogenic

despite failure to secrete enterotoxins or cytotoxins.A heavy layer of

plump coccobacilli may be found over the luminal aspect of entero-

cytes on villi throughout the small intestine, and on the surface of

the large intestine.

The degree of diarrhea seems related to the extent of

bacterial colonization, which is most consistent in lower small intestine and

large bowel.

Enterocytes to which bacteria are adherent round up or

contract, and exfoliate from the mucosa singly or in clumps, result-

ing in mild to severe atrophy of villi in the small bowel, and attenu-

ation of surface cells, or microerosions, in the large intestine. Fusion

of villi may occur in small intestine, and goblet-cell numbers are

depleted in both large and small bowel. There is moderate mucosal

congestion, and local infiltration by neutrophils.

Diarrhea is presumably related to maldigestion and malabsorp-

tion of nutrients and electrolytes in small intestine, perhaps with the

additive effect of increased mucosal permeability, overloading the

colon, the absorptive ability of which is also compromised by damage

to surface cells.

Microscopic diagnosis is based on recognition of bacteria on

the mucosal su~ace.

In pigs, EPEC belonging to serogroups 045 and O 103, infecting

small and large intestine, are responsible for some cases of postwean-

ing diarrhea. In dogs, and occasionally in cats, EPEC have been asso-

ciated with diarrhea, often as a component of co-infections with

viral or protozoal agents. Microscopic lesions characteristic of AEEC

are typically found in the jejunum and ileum, less commonly in the

colon, and, in dogs, sometimes in the stomach.

A distinct subset of EPEC is the

Shiga toxin-producing

E. coli

(STEC), also known as enterohemorrhagic

E. coli

(EHEC). In

addition to their ability to attach and efface, these strains produce

cytotoxic Shiga toxins (Stxl, and its homologue Stx2 with its vari-

ants, c, d, e, f). Shigatoxin 1 is structurally identical to the Shiga toxin

produced by

Shigella dysenteriae,

which has a profound cytopathic

effect. Due to their effect onVero cells in culture, these

E. coli

are also

referred to as verotoxin-producing

E. coli

(VTEC). Shiga toxins,

encoded in the genome of bacteriophages, are composed of an A

subunit that has enzymatic activity and a B subunit that binds the

toxin to the glycolipid receptor globotriaosylceramide (Gb3) on the

Figure 1.131

Scanning etectron micrograph of the colon of a calf with

enterohemorrhagic

Escherichio coli

infection.

Lower: note irregutarity of

microvitti on cetts infected by attaching-effacing E.

colt,

in comparison with

microvitti on uninfected cetts in background. Outtine indicates fietd ittustrated in

upper photo.Adherent bacteria are on pedestats projecting from the surface of

enterocytes. Occasiona[ bacteria have been [ost artifactuatty, exposing under-

tying "mushroom-tike" pedestats. (Courtesy of M Schoonderwoerd, R Oarke.)

Figure 1.132

Transmission etectron micrograph of enterocytes in the coton

of a catf infected with enterohemorrhagic

E. colL

Enterocyte attaching-

effacing

E. colt

are on pedestals projecting from surface of infected celts.

Microvi[[i are irregular and effaced on infected cetts. Normal celt ([eft).

(Reprinted with permission from Schoonderwoerd M, et aL Can J Vet Res

1988;52:484-487.)