E. coli Gastroenteritis Pathotypes

Here we will learn about five pathotypes of Escherichia coli that cause gastroenteritis, with a focus on their virulence factors and the symptoms they produce. A general overview of E. coli is presented elsewhere. Watery diarrhea and vomiting. Occurs most often in toddlers and infants in developing countries. Adhesion and effacing lesions formed on the epithelial cells of the small intestine. The lesions destroy the microvillus brush border, which is where the final stages of carbohydrate and protein digestion and absorption take place. Bundle-forming pili (BFP) mediate initial attachment to host and bacterial cells and form microcolonies. BFP genes are found on the EPEC adherence factor plasmid in typical strains. Interactions between intimin and the translocated intimin receptor (Tir) mediate more intimate attachment; their genes are found on the Locus of Enterocyte Effacement (LEE) pathogenicity island. The Type 3 Secretion System (T3SS) translocates Tir and various cytotoxic effectors into the host cell cytoplasm; EPEC cytotoxic effectors are encoded by pathogenicity islands and phages. Watery diarrhea with vomiting, fever, and abdominal cramps. Travelers and infants in developing countries. Attaches to epithelial cells of the small intestine via colonization factor antigens I-III; the genes for CFAs are carried on plasmids. Flagellar adhesions and outer membrane proteins Tia and TibA also promote adherence; these traits are carried on pathogenicity islands. Heat-stable and heat-labile enterotoxins cause water and ion loss by altering activity in the cells of the small intestine; as a result, water and ions are flushed out of the body in diarrhea. The genes for both enterotoxins are on plasmids. Heat-stable enterotoxin (STa) increases cGMP in host cells; As a result, sodium absorption decreases and water secretion increases. Heat-labile enterotoxin increases cAMP; as a result, chloride secretion increases and sodium and chloride absorption decreases. Watery diarrhea with inflammatory cell infiltration, vomiting, and dehydration. Causes gastroenteritis in travelers and infants; in some children, it can lead to chronic diarrhea and growth retardation. Characterized by aggregative adherence to each other and the epithelial cells of the small and large intestines; this results in a "stacked brick" aggregation pattern Attachment is mediated via aggregative adherence fimbriae; the genes for AAF are carried on a plasmid. AAF also trigger mononuclear cell infiltration and inflammation. Cytotoxins damage the intestinal mucosa. The specific cytotoxins vary by strain. Plasma-encoded toxin (Pet), which is coded for by plasmid genes, and induces exfoliation. Be aware that some isolates produce Shigella enterotoxin 1 and EAST1. Watery diarrhea that can progress to hemorrhagic colitis with severe abdominal cramping; some patients develop hemolytic uremic syndrome. Children younger than 5 years old are most commonly infected by STEC. Enterohemorragic E. coli (EHEC) is generally considered to be a subset of STEC, and there is phenotypic variation even within EHEC isolates. Animals, particularly cattle, are key reservoirs for STEC. Humans are infected upon ingestion of foods, especially undercooked meat and raw fruits and vegetables; water is also a source of infection. Undercooked hamburger was once the main cause of STEC infection in the U.S.; increased awareness of proper handling has reduced the rate of hamburger-associated infections. Because STEC has a low infectious dose, person-to-person transmission is also possible. Some strains produce adhesion and effacing lesions that damage microvilli brush border; as in EPEC strains, this is mediated by intimin and Tir; Hemorrhagic coli pilus is a type IV pilus. Cytotoxins cause necrosis and cell death; Shiga toxins damage the microvasculature; the genes for these toxins are on phages. In some cases of severe infection, Shiga toxins destroy red blood cells resulting in hemolytic uremia syndrome, aka, HUS. HUS is characterized by microvascular thrombi, thrombocytopenia, hemolytic anemia and renal damage that leads to renal failure. Antibiotics increase the risk of HUS complications, and should NOT be given to patients with STEC infections; it is thought that antibiotics cause phage lysis and increase toxin release. Watery, then bloody, diarrhea and abdominal cramps. Fever helps to distinguish EIEC from STEC. EIEC infection is rare, and the bacteria are closely related to Shigella. In fact, many authors consider them to be members of the same species, and much of what we know about EIEC comes from research on Shigella. Unlike most other strains of E. coli, EIEC are non-motile, and do not ferment lactose. EIEC bacteria are intracellular pathogens that invade cells of the colon. Genes for the following invasion virulence factors are on the Invasion plasmid (InvP): – The type 3 secretion system and IpaC effector protein promote bacterial entry into cells – IpgD, IpaA, and VirA effectors facilitate bacterial invasion of phagosomes – IpaB, IpaC, and IpaD effectors facilitate phagosome escape – OpsB, OpsF, and OpsG effectors inhibit host immune responses Intra- and intercellular movement is facilitated by VirG, which promotes actin polymerization; these actin tails push the bacteria within and between host cells. Severe infection can lead to Shigellosis, aka, bacillary dysentery, which is characterized by colon epithelium destruction and inflammation. However, the EIEC-associated form is rare. Overview of E. coli