Pathogenic Escherichia coli

Escherichia coli is a gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms. Most E.coli strains are harmless, but pathogenic varieties cause serious food poisoning, septic shock, meningitis, or urinary tract infections in humans. Unlike normal flora E.coli, the pathogenic varieties produce toxins and other virulence factors that enable them to reside in parts of the body normally not inhabited by E.coli, and to damage host cells. These pathogenic traits are encoded by virulence genes carried only by the pathogens.

Introduction

E. coli and related bacteria constitute about 0.1% of gut flora, and fecal–oral transmission is the major route through which pathogenic strains of the bacterium cause disease. Cells are able to survive outside the body for only a limited amount of time, which makes them ideal indicator organisms to test environmental samples for fecal contamination. The bacterium can also be grown easily and inexpensively in a laboratory setting, and has been intensively investigated for over 60 years. E. coli is the most widely studied prokaryotic model organism, and an important species in the fields of biotechnology and microbiology, where it has served as the host organism for the majority of work with recombinant DNA.
German paediatrician and bacteriologist Theodor Escherich discovered E. coli in 1885, and it is now classified as part of the Gammaproteobacterial family Enterobacteriaceae.

Serotypes

Pathogenic E. coli strains can be categorized based on elements that can elicit an immune response in animals, namely:

O antigen: part of lipopolysaccharide layer
K antigen: capsule
H antigen: flagellin

For example, E. coli strain EDL933 is of the O157:H7 group.
Some, but not all, E. coli fimbrial antigens are also given names in the form of F followed by a number.

O antigen

The outer membrane of an E. coli cell contains millions of lipopolysaccharide molecules, which consists of:

O antigen, a polymer of immunogenic repeating oligosaccharides
Core region of phosphorylated nonrepeating oligosaccharides
Lipid A

The O antigen is used for serotyping E. coli and these O group designations go from O1 to O181, with the exception of some groups which have been historically removed, namely O31, O47, O67, O72, O93, O94, and O122; groups 174 to 181 are provisional or are under investigation. Additionally subtypes exist for many O groups.
Antibodies towards several O antigens cross-react with other O antigens and partially to K antigens not only from E. coli, but also from other Escherichia species and Enterobacteriaceae species.
The O antigen is encoded by the rfb gene cluster. rol gene encodes the regulator of lipopolysaccharide O-chain length.

K antigen

The acidic capsular polysaccharide is a thick, mucous-like, layer of polysaccharide that surrounds some pathogen E. coli.
There are two separate groups of K-antigen groups, named group I and group II. The former consist of 100 kDa capsular polysaccharides, while the latter, associated with extraintestinal diseases, are under 50 kDa in size.
Group I K antigens are only found with certain O-antigens, they are further subdivided on the basis of absence or presence of amino sugars and some group I K-antigens are attached to the lipid A-core of the lipopolysaccharide, in a similar way to O antigens.
Group II K antigens closely resemble those in gram-positive bacteria and greatly differ in composition and are further subdivided according to their acidic components, generally 20–50% of the CPS chains are bound to phospholipids.
In total there are 60 different K antigens that have been recognized, K8, K9, K10, K11, K12, K13, K14, K15, K16, K18a, K18ab, K19, K24, K26, K27, K28, K29, K30, K31, K34, K37, K39, K40, K41, K42, K43, K44, K45, K46, K47, K49, K50, K51, K52, K53, K54, K55, K74, K84, K85ab/ac, K87.

H antigen

The H antigen is a major component of flagella, involved in E. coli movement. It is generally encoded by the fliC gene
There are 53 identified H antigens, numbered from H1 to H56.

Role in disease

In humans and in domestic animals, virulent strains of E. coli can cause various diseases.
In humans: gastroenteritis, urinary tract infection, and neonatal meningitis. In rarer cases, virulent strains are also responsible for hemolytic-uremic syndrome, peritonitis, mastitis, gram-negative pneumonia and sepsis.

Gastrointestinal infection

Certain strains of E. coli, such as O157:H7, O104:H4, O121, O26, O103, O111, O145, and O104:H21, produce potentially lethal toxins. Food poisoning caused by E. coli can result from eating unwashed vegetables or poorly butchered and undercooked meat.
O157:H7 is also notorious for causing serious and even life-threatening complications such as hemolytic-uremic syndrome. This particular strain is linked to the 2006 United States E. coli outbreak due to fresh spinach.
The O104:H4 strain is equally virulent. Antibiotic and supportive treatment protocols for it are not as well-developed, as it has the ability to be very enterohemorrhagic like O157:H7, causing bloody diarrhea, but also is more enteroaggregative, meaning it adheres well and clumps to intestinal membranes. It is the strain behind the deadly June 2011 E. coli outbreak in Europe. Severity of the illness varies considerably; it can be fatal, particularly to young children, the elderly or the immunocompromised, but is more often mild.
Earlier, poor hygienic methods of preparing meat in Scotland killed seven people in 1996 due to E. coli poisoning, and left hundreds more infected.
E. coli can harbour both heat-stable and heat-labile enterotoxins. The latter, termed LT, contain one A subunit and five B subunits arranged into one holotoxin, and are highly similar in structure and function to cholera toxins. The B subunits assist in adherence and entry of the toxin into host intestinal cells, while the A subunit is cleaved and prevents cells from absorbing water, causing diarrhea. LT is secreted by the Type 2 secretion pathway.
If E. coli bacteria escape the intestinal tract through a perforation and enter the abdomen, they usually cause peritonitis that can be fatal without prompt treatment. However, E. coli are extremely sensitive to such antibiotics as streptomycin or gentamicin. Recent research suggests treatment of enteropathogenic E. coli with antibiotics may significantly increase the chance of developing haemolytic-uremic syndrome.
Intestinal mucosa-associated E. coli are observed in increased numbers in the inflammatory bowel diseases, Crohn's disease and ulcerative colitis. Invasive strains of E. coli exist in high numbers in the inflamed tissue, and the number of bacteria in the inflamed regions correlates to the severity of the bowel inflammation.
Gastrointestinal infections can cause the body to develop memory T cells to attack gut microbes that are in the intestinal tract. Food poisoning can trigger an immune response to microbial gut bacteria. Some researchers suggest that it can lead to inflammatory bowel disease.

Virulence properties

Enteric E. coli are classified on the basis of serological characteristics and virulence properties. The major pathotypes of E. coli that cause diarrhea are listed below.

Name	Hosts	Type of diarrhea	Description
Enterotoxigenic E. coli	causative agent of diarrhea in humans, pigs, sheep, goats, cattle, dogs, and horses	Watery	ETEC uses various colonization factors to bind enterocyte cells in the small intestine. ETEC can produce two proteinaceous enterotoxins: The larger of the two proteins, LT enterotoxin, is similar to cholera toxin in structure and function. The smaller protein, ST enterotoxin causes cGMP accumulation in the target cells and a subsequent secretion of fluid and electrolytes into the intestinal lumen. ETEC strains are noninvasive, and they do not leave the intestinal lumen. ETEC is the leading bacterial cause of diarrhea in children in the developing world, as well as the most common cause of traveler's diarrhea. Each year, there are estimated to be 840 million cases of ETEC in developing countries. About 280 million of these cases, as well as 325,000 deaths, are in children under the age of five.
Enteropathogenic E. coli	causative agent of diarrhea in humans, rabbits, dogs, cats and horses	Watery	Like ETEC, EPEC also causes diarrhea, but the molecular mechanisms of colonization and aetiology are different. EPEC lack ST and LT toxins, but they use an adhesin known as intimin to bind host intestinal cells. This pathotype has an array of virulence factors that are similar to those found in Shigella. Adherence to the intestinal mucosa causes a rearrangement of actin in the host cell, causing significant deformation. EPEC cells are moderately invasive and elicit an inflammatory response. Changes in intestinal cell ultrastructure due to "attachment and effacement" is likely the prime cause of diarrhea in those afflicted with EPEC.
Enteroaggregative E. coli	found only in humans	Watery	So named because they have fimbriae which aggregate tissue culture cells, EAEC bind to the intestinal mucosa to cause watery diarrhea without fever. EAEC are noninvasive. They produce a hemolysin and an ST enterotoxin similar to that of ETEC.
Enteroinvasive E. coli	found only in humans	Bloody or nonbloody	EIEC infection causes a syndrome that is identical to shigellosis, with profuse diarrhea and high fever.
Enterohemorrhagic E. coli	found in humans, cattle, and goats	Bloody or nonbloody	The most infamous member of this pathotype is strain O157:H7, which causes bloody diarrhea and no fever. EHEC can cause hemolytic-uremic syndrome and sudden kidney failure. It uses bacterial fimbriae for attachment, is moderately invasive and possesses a phage-encoded shiga toxin that can elicit an intense inflammatory response.
Adherent-Invasive E. coli	found in humans	-	AIEC are able to invade intestinal epithelial cells and replicate intracellularly. It is likely that AIEC are able to proliferate more effectively in hosts with defective innate immunity. They are associated with the ileal mucosa in Crohn's disease.