Escherichia Coli Enteric Infections

The Pathogen

E. coli is a small catalase-positive, oxidase-negative, gram-negative bacillus in the family Enterobacteriaceae. E. coli is the predominant member of the Gammaproteobacteria in the intestinal tract of humans and other mammals, although it is greatly outnumbered by members of other bacterial phyla, which largely consist of strict anaerobes.

E. coli possess a complex envelope that consists of a plasma membrane, a peptidoglycan cell wall, and an outer membrane. The microorganism’s outer membrane confers mechanical properties of stiffness and strength. The lipopolysaccharide cell wall of E. coli contains immunostimulatory lipid A attached to a core oligosaccharide chain. Most E. coli have immunogenic carbohydrate chains, known as O antigens, attached to this core glycolipid to produce over 170 O serogroups. E. coli also have at least 56 distinct flagellar (H) antigens based on variable domains of the flagellin gene. Some 80 variably heat-labile capsular (K) antigens have also been described.

E. coli are major components of the normal gut microbiota, but diarrheagenic E. coli differ from these commensals in their specific abilities to cause clinically meaningful infection in the gut. These pathogens seldom spread systemically, but they share virulence traits with extraintestinal pathogenic E. coli and uropathogenic E. coli , although these latter organisms are typically hybrid strains as opposed to classic diarrheagenic strains. Numerous adherence, enterotoxic, cytotoxic, and invasiveness factors may be gained or lost by a particular serotype because they are characteristically encoded on transmissible genetic elements such as plasmids or bacteriophages. These factors convey the pathotype of disease because they allow colonization and perturbation of host intestinal physiology. Molecular analysis shows that commensal and pathogenic E. coli cluster into phylogenetic groups that are independent of O:H serotype. Moreover, the E. coli taxon now also includes Shigella , based on genomic identity, although the latter can still be distinguished biochemically. Nevertheless, relatively few O serogroups tend to predominate in the normal human colon (O groups 1, 2, 4, 6, 7, 8, 18, 25, 45, 75, and 81), whereas others tend to be associated with specific virulence traits and thus different types of pathogenesis in the intestine.

Enteropathogenic and Enterotoxigenic Strains

A human reservoir is probably required for most recognized types of enteropathogenic E. coli and enterotoxigenic E. coli , but domestic dogs and cats can also harbor human pathogenic strains. The infectious dose of enterotoxigenic E. coli in volunteers is 10 ⁶ to 10 ¹⁰ organisms, thereby indicating that the organism usually must multiply in contaminated food or water for its effective transmission and that spread directly from person to person is unusual, except in rare outbreaks in newborn nurseries. Heavy contamination with enterotoxigenic E. coli has been documented in foods prepared in homes, restaurants, and by street vendors, as well as in drinking water in many tropical areas. Contaminated water and food represent the major sources of human enterotoxigenic E. coli infection, primarily in warm or wet seasons.

As with most diarrheal illnesses, the highest age-specific attack rates of enterotoxigenic E. coli are found in young children, in whom enterotoxigenic E. coli account for anywhere from 3 to 39% (average, 13%) of acute diarrheal illnesses. As for immunologically inexperienced young children, a traveler visiting tropical areas has a 30 to 50% chance of acquiring traveler’s diarrhea ( Chapters 262 and 265 ) during a 2- to 3-week stay unless they avoid untreated water or ice and uncooked foods such as salads. The most commonly identified pathogen associated with diarrhea in most studies of travelers to tropical areas of the world is enterotoxigenic E. coli . A close second is enteroaggregative E. coli .

Typical enteropathogenic E. coli strains have been recognized primarily in poor urban areas. “Atypical” enteropathogenic E. coli strains, which possess the locus of enterocyte effacement but not the bundle-forming pilus gene, predominate in developed areas but can be found in developing areas as well. Enteropathogenic strains remain a common pathogen, and “typical” enteropathogenic E. coli are still generally associated with diarrhea rather than asymptomatic colonization.

Enteroaggregative Strains

The natural reservoir of enteroaggregative E. coli is not known, but outbreaks have been traced to contaminated food, and live organisms can be found in drinking water, table salsa, and other consumable items in endemic tropical areas. A high infectious dose is required for acquisition, but person-to-person transmission can occur among men who have sex with men. In addition to its role in traveler’s diarrhea, enteroaggregative E. coli is an important cause of both acute and persistent diarrhea, as well as malnutrition ( Chapter 197 ), especially in children in tropical areas and in patients with HIV/AIDS ( Chapter 358 ). It also is a major cause of sporadic diarrhea in the United States, Europe, China, and other developed areas.

Diffusely Adherent Strains

Diffusely adherent E. coli remain the least well-understood pathotype and have not consistently been found more often in patients with diarrhea than in controls, except for acute diarrhea in children in developing areas. Part of the difficulty is the heterogeneity of strains, some of which express different types of adhesins and different groups of virulence traits, thereby leading to inconsistent pathogenicity.

Enterohemorrhagic Strains

Enterohemorrhagic E. coli frequently colonize commercial livestock but do not infect them. Enterohemorrhagic E. coli (O157:H7 and others) infections can be caused by undercooked hamburgers, but large outbreaks have also been associated with contamination of the domestic water supply, unpasteurized apple juice, spinach, seed sprouts, flour, and other vegetable items such as lettuce and tomatoes. ^,

Unlike enterotoxigenic strains, transmission requires only a low infectious dose of enterohemorrhagic E. coli O157:H7, so person-to-person spread can lead to secondary cases. Secondary cases of shigatoxigenic/enteroaggregative E. coli O104:H4 may have occured but appear to be very rare. Enterohemorrhagic E. coli and shigatoxigenic E. coli infections are especially alarming because of the risk of hemolytic-uremic syndrome ( Chapter 158 ).

Enteroinvasive Strains

Limited data on enteroinvasive E. coli suggest that infectious doses are relatively high, but adequate numbers of organisms can readily be spread in food with high attack rates in outbreak situations. This characteristic distinguishes enteroinvasive E. coli epidemiologically from Shigella ( Chapter 285 ), which is easily spread person-to-person as well as by contaminated food and water.

Enteropathogenic E. coli

Typical enteropathogenic E. coli strains express plasmid-encoded genes that confer localized adherence to epithelial cells (through specialized bundle-forming pili) and chromosomal genes that mediate attachment and effacement of microvilli. The latter is characterized by the formation of cellular pedestals that hold the bacteria intimately to the cell surface. These changes in the host epithelia are mediated by protein effectors injected directly into host cells by a specialized type III secretion system encoded on the chromosomal locus of enterocyte effacement. These secreted effectors cause cellular changes that lead to villous atrophy, mucosal thinning, inflammation in the lamina propria, and variable hyperplasia of crypt cells. These morphologic changes are associated with a reduction in mucosal brush border enzymes and may contribute to the impaired absorptive function and diarrhea. Atypical enteropathogenic E. coli strains are generally defined as strains that express the locus of enterocyte effacement but not the bundle-forming pili; they maintain the ability to attach/efface and cause epithelial injury.