''Escherichia coli'' ( ; commonly abbreviated ''E. coli'') is a

gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...

rod-shaped Bacterial cellular morphologies are the shapes that are characteristic of various types of bacteria and often key to their identification. Their direct examination under a light microscope enables the classification of these bacteria (and archae ...

bacterium Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...

that is commonly found in the lower

intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

warm-blooded Warm-blooded is a term referring to animal species whose bodies maintain a temperature higher than that of their environment. In particular, homeothermic species (including birds and mammals) maintain a stable body temperature by regulating ...

organisms (endotherms). Most ''E. coli'' strains are harmless, but pathogenic varieties cause serious

food poisoning Foodborne illness (also known as foodborne disease and food poisoning) is any illness resulting from the contamination of food by pathogenic bacteria, viruses, or parasites, as well as prions (the agents of mad cow disease), and toxins such ...

septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International C ...

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...

, or urinary tract infections in

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

s. Unlike normal flora ''E. coli'', the pathogenic varieties produce toxins and other

virulence factor Virulence factors (preferably known as pathogenicity factors or effectors in botany) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following: * c ...

s 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 Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the g ...

, 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 organism Indicator organisms are used as a proxy to monitor conditions in a particular environment, ecosystem, area, habitat, or consumer product. Certain bacteria, fungi and helminth eggs are being used for various purposes. Types Indicator bacteria ...

s 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 A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Mo ...

, and an important species in the fields of

biotechnology Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...

and

microbiology Microbiology () is the branches of science, scientific study of microorganisms, those being of unicellular organism, unicellular (single-celled), multicellular organism, multicellular (consisting of complex cells), or non-cellular life, acellula ...

, where it has served as the host organism for the majority of work with

recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...

. German paediatrician and bacteriologist Theodor Escherich discovered ''E. coli'' in 1885, and it is now classified as part of the

Gammaproteobacteria ''Gammaproteobacteria'' is a class of bacteria in the phylum ''Pseudomonadota'' (synonym ''Proteobacteria''). It contains about 250 genera, which makes it the most genus-rich taxon of the Prokaryotes. Several medically, ecologically, and scienti ...

l family

Enterobacteriaceae Enterobacteriaceae is a large family (biology), family of Gram-negative bacteria. It includes over 30 genera and more than 100 species. Its classification above the level of Family (taxonomy), family is still a subject of debate, but one class ...

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 Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...

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 (LPS) molecules, which consists of: # O antigen, a polymer of immunogenic repeating

oligosaccharide An oligosaccharide (; ) is a carbohydrate, saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including Cell–cell recognition, cell recognition and ce ...

s (1–40 units) # Core region of phosphorylated nonrepeating oligosaccharides #

Lipid A Lipid A is a lipid component of an endotoxin held responsible for the toxicity of gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide (LPS), also called endotoxin molecule, and its hydrophobic nature allows ...

(endotoxin) 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 (now K84), O94, and O122; groups 174 to 181 are provisional (O174=OX3 and O175=OX7) or are under investigation (176 to 181 are STEC/VTEC). Additionally subtypes exist for many O groups (''e.g.'' O128ab and O128ac). 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 (cld) gene encodes the regulator of lipopolysaccharide O-chain length.

K antigen

The acidic capsular polysaccharide (CPS) 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 (while a small in-between subset (K3, K10, and K54/K96) has been classified as group III). The former (I) consist of 100 kDa (large) capsular polysaccharides, while the latter (II), associated with extraintestinal diseases, are under 50 kDa in size. Group I K antigens are only found with certain O-antigens (O8, O9, O20, and O101 groups), they are further subdivided on the basis of absence (IA, similar to that of ''Klebsiella'' species in structure) or presence (IB) of amino sugars and some group I K-antigens are attached to the lipid A-core of the lipopolysaccharide (K_LPS), in a similar way to O antigens (and being structurally identical to O antigens in some instances are only considered as K antigens when co-expressed with another authentic O antigen). Group II K antigens closely resemble those in

gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...

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 (K1, K2a/ac, K3, K4, K5, K6, K7 (=K56), K8, K9 (=O104), K10, K11, K12 (K82), K13(=K20 and =K23), K14, K15, K16, K18a, K18ab (=K22), K19, K24, K26, K27, K28, K29, K30, K31, K34, K37, K39, K40, K41, K42, K43, K44, K45, K46, K47, K49 (O46), K50, K51, K52, K53, K54 (=K96), K55, K74, K84, K85ab/ac (=O141), K87 (=O32), K92, K93, K95, K97, K98, K100, K101, K102, K103, KX104, KX105, and KX106).

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 (H13 and H22 were not ''E. coli'' antigens but from ''

Citrobacter freundii ''Citrobacter'' is a genus of Gram-negative, aerobic, rod-shaped coliform bacteria of the Enterobacteriaceae family. ''Citrobacter'' spp. cause opportunistic infections (including urinary tract infections, gastroenteritis, and bacteremia). ...

'', and H50 was found to be the same as H10).

Role in disease

In humans and in

domestic animal This page gives a list of domesticated animals, also including a list of animals which are or may be currently undergoing the process of domestication and animals that have an extensive relationship with humans beyond simple predation. This includ ...

s, virulent strains of ''E. coli'' can cause various diseases. In humans:

gastroenteritis Gastroenteritis, also known as infectious diarrhea, is an inflammation of the Human gastrointestinal tract, gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of ...

urinary tract infection A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...

, and

neonatal In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...

. In rarer cases, virulent strains are also responsible for hemolytic-uremic syndrome,

peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and covering of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One pa ...

mastitis Mastitis is inflammation of the breast or udder, usually associated with breastfeeding. Symptoms typically include local pain and redness. There is often an associated fever and general soreness. Onset is typically fairly rapid and usually occ ...

, gram-negative

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

and

sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

Gastrointestinal infection

Certain strains of ''E. coli'', such as O157:H7, O104:H4, O121, O26, O103, O111, O145, and O104:H21, produce potentially lethal

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

Food poisoning Foodborne illness (also known as foodborne disease and food poisoning) is any illness resulting from the contamination of food by pathogenic bacteria, viruses, or parasites, as well as prions (the agents of mad cow disease), and toxins such ...

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 enterotoxin In molecular biology, the heat-labile enterotoxin family includes ''Escherichia coli'' heat-labile enterotoxin (Elt or LT) and cholera toxin (Ctx) secreted by ''Vibrio cholerae''. lt is so named because it is inactivated at high temperatures. ...

s. 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 Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...

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 Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

. LT is secreted by the Type 2 secretion pathway. If ''E. coli'' bacteria escape the intestinal tract through a perforation (for example from an

ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughin ...

, a

ruptured appendix Appendicitis is inflammation of the Appendix (anatomy), appendix. Symptoms commonly include right lower abdominal pain, nausea, vomiting, fever and anorexia (symptom), decreased appetite. However, approximately 40% of people do not have these t ...

, or due to a surgical error) and enter the abdomen, they usually cause

that can be fatal without prompt treatment. However, ''E. coli'' are extremely sensitive to such

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

streptomycin Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, Mycobacterium avium complex, ''Mycobacterium avium'' complex, endocarditis, brucellosis, Burkholderia infection, ''Burkholderia'' i ...

gentamicin Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis amo ...

. 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 disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

and

ulcerative colitis Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...

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

Epidemiology of gastrointestinal infection

Transmission of pathogenic ''E. coli'' often occurs via fecal–oral transmission. Common routes of transmission include: unhygienic food preparation, farm contamination due to manure fertilization, irrigation of crops with contaminated

greywater Greywater (or grey water, sullage, also spelled gray water in the United States) refers to domestic wastewater generated in households or office buildings from streams without fecal contamination, i.e., all streams except for the wastewater fro ...

or raw

sewage Sewage (or domestic sewage, domestic wastewater, municipal wastewater) is a type of wastewater that is produced by a community of people. It is typically transported through a sewerage, sewer system. Sewage consists of wastewater discharged fro ...

, feral pigs on cropland, or direct consumption of sewage-contaminated water. Dairy and beef cattle are primary reservoirs of ''E. coli'' O157:H7, and they can carry it asymptomatically and shed it in their feces. Food products associated with ''E. coli'' outbreaks include

cucumber The cucumber (''Cucumis sativus'') is a widely-cultivated creeping vine plant in the family Cucurbitaceae that bears cylindrical to spherical fruits, which are used as culinary vegetables.U.S. Food and Drug Administration, the fecal-oral cycle of transmission can be disrupted by cooking food properly, preventing cross-contamination, instituting barriers such as gloves for food workers, instituting health care policies so food industry employees seek treatment when they are ill, pasteurization of juice or dairy products and proper

hand washing Hand washing (or handwashing), also known as hand hygiene, is the act of cleaning one's hands with soap, soap or handwash and water to remove viruses, bacteria, microorganisms, dirt, grease, and other harmful or unwanted substances stuck to th ...

requirements. Shiga toxin-producing ''E. coli'' (STEC), specifically serotype O157:H7, have also been transmitted by flies, as well as direct contact with farm animals, petting zoo animals, and airborne particles found in animal-rearing environments.

Urinary tract infection

Uropathogenic ''E. coli'' (UPEC) is responsible for approximately 90% of

s (UTI) seen in individuals with ordinary anatomy. In ascending infections, fecal bacteria colonize the

urethra The urethra (: urethras or urethrae) is the tube that connects the urinary bladder to the urinary meatus, through which Placentalia, placental mammals Urination, urinate and Ejaculation, ejaculate. The external urethral sphincter is a striated ...

and spread up the urinary tract to the

bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the bladder is a distens ...

as well as to the

kidneys In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...

(causing

pyelonephritis Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications ...

), or the

prostate The prostate is an male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemica ...

in males. Because women have a shorter urethra than men, they are 14 times more likely to suffer from an ascending UTI. Uropathogenic ''E. coli'' use P fimbriae (

-associated pili) to

bind BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name Daemon (computing), daemon''), performs both of the main DNS server roles, acting ...

urinary tract urothelial cells and colonize the bladder. These adhesins specifically bind D-galactose-D-galactose moieties on the P blood-group antigen of

erythrocytes Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

and uroepithelial cells. Approximately 1% of the human population lacks this receptor, and its presence or absence dictates an individual's susceptibility or non-susceptibility, respectively, to ''E. coli'' urinary tract infections. Uropathogenic ''E. coli'' produce alpha- and beta-hemolysins, which cause

lysis Lysis ( ; from Greek 'loosening') is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ...

of urinary tract cells. Another virulence factor commonly present in UPEC is the Dr family of adhesins, which are particularly associated with

cystitis A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra ( urethritis) while upper urinary tract infections affect the kidney (py ...

and pregnancy-associated

.Identified Virulence Factors of UPEC : Adherence
State Key Laboratory for Moleclular Virology and Genetic Engineering, Beijing. Retrieved July 2011 The Dr adhesins bind ''Dr blood group antigen'' (Dr^a) which is present on decay accelerating factor (DAF) on erythrocytes and other cell types. There, the Dr adhesins induce the development of long cellular extensions that wrap around the bacteria, accompanied by the activation of several

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

cascades, including activation of PI-3 kinase. UPEC can evade the body's innate immune defences (e.g. the

complement system The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...

) by invading superficial umbrella cells to form intracellular bacterial communities ( IBCs). They also have the ability to form K antigen, capsular polysaccharides that contribute to

biofilm A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...

formation. Biofilm-producing ''E. coli'' are recalcitrant to immune factors and

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

therapy, and are often responsible for chronic urinary tract infections. K antigen-producing ''E. coli'' infections are commonly found in the upper urinary tract. Descending infections, though relatively rare, occur when ''E. coli'' cells enter the upper urinary tract organs (

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

ureters The ureters are tubes composed of smooth muscle that transport urine from the kidneys to the urinary bladder. In an adult human, the ureters typically measure 20 to 30 centimeters in length and about 3 to 4 millimeters in diameter. They are lin ...

) from the blood stream.

Neonatal meningitis (NMEC)

It is produced by a serotype of ''Escherichia coli'' that contains a capsular antigen called K1. The colonization of the newborn's intestines with these strains, that are present in the mother's vagina, lead to bacteremia, which leads to

. And because of the absence of the IgM antibodies from the mother (these do not cross the placenta because FcRn only mediates the transfer of IgG), plus the fact that the body recognizes as self the K1 antigen, as it resembles the cerebral glycopeptides, this leads to a severe meningitis in the neonates.

Possible role in colorectal cancer

Some ''E. coli'' strains contain a polyketide synthase genomic island (''pks''), which encodes a multi-enzymatic machinery that produces colibactin, a substance that damages DNA. About 20% of humans are colonized with ''E. coli'' that harbor the ''pks'' island. Colibactin can cause

cellular senescence Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of appro ...

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

by damaging DNA. However, the mucosal barrier prevents ''E. coli'' from reaching the surface of enterocytes.

Mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins ( glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in ...

production diminishes in the presence of inflammation. Only when some inflammatory condition co-occurs with ''E. coli'' infection is the bacterium able to deliver colibactin to enterocytes and induce tumorogenesis.

Animal diseases

In animals, virulent strains of ''E. coli'' are responsible of a variety of diseases, among others

and

in newborn calves, acute

dairy cow Dairy cattle (also called dairy cows) are cattle bred with the ability to produce large quantities of milk, from which dairy products are made. Dairy cattle generally are of the species ''Bos taurus''. Historically, little distinction was m ...

s, colibacillosis also associated with chronic respiratory disease with Mycoplasma where it causes perihepatitis, pericarditis, septicaemic lungs, peritonitis etc. in

poultry Poultry () are domesticated birds kept by humans for the purpose of harvesting animal products such as meat, Eggs as food, eggs or feathers. The practice of animal husbandry, raising poultry is known as poultry farming. These birds are most typ ...

, and Alabama rot in dogs. F5 (formerly K99) and F41 are two common fimbrial antigens found in strains that infect calves. Most of the serotypes isolated from poultry are pathogenic only for

bird Birds are a group of warm-blooded vertebrates constituting the class (biology), class Aves (), characterised by feathers, toothless beaked jaws, the Oviparity, laying of Eggshell, hard-shelled eggs, a high Metabolism, metabolic rate, a fou ...

s. So avian sources of ''E. coli'' do not seem to be important sources of infections in other animals. File:Colibacilôze pericorite al fibrene fritches.jpg, Colibacillosis in domestic chicken File:Mamite å colibacile laecea.jpg, Mastitis in cows

Laboratory diagnosis

Diagnosis of infectious diarrhea and identification of

antimicrobial resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resista ...

is performed using a stool culture with subsequent antibiotic sensitivity testing. It requires a minimum of 2 days and maximum of several weeks to culture gastrointestinal pathogens. The sensitivity (true positive) and specificity (true negative) rates for stool culture vary by pathogen, although a number of

human pathogen A human pathogen is a pathogen (microbe or microorganism such as a virus, bacterium, prion, or fungus) that causes disease in humans. The human physiological defense against common pathogens (such as ''Pneumocystis'') is mainly the responsibility ...

s can not be cultured. For culture-positive samples, antimicrobial resistance testing takes an additional 12–24 hours to perform. Current point of care molecular diagnostic tests can identify ''E. coli'' and antimicrobial resistance in the identified strains much faster than culture and sensitivity testing. Microarray-based platforms can identify specific pathogenic strains of ''E. coli'' and ''E. coli''-specific AMR genes in two hours or less with high sensitivity and specificity, but the size of the test panel (i.e., total pathogens and antimicrobial resistance genes) is limited. Newer metagenomics-based infectious disease diagnostic platforms are currently being developed to overcome the various limitations of culture and all currently available molecular diagnostic technologies. In stool samples, microscopy will show

rods, with no particular cell arrangement. Then, either MacConkey agar or EMB agar (or both) are inoculated with the stool. On MacConkey agar, deep red colonies are produced, as the organism is

lactose Lactose is a disaccharide composed of galactose and glucose and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from (Genitive case, gen. ), the Latin word for milk, plus the suffix ''-o ...

-positive, and fermentation of this sugar will cause the medium's pH to drop, leading to darkening of the medium. Growth on EMB agar produces black colonies with a greenish-black metallic sheen. This is diagnostic of ''E. coli''. The organism is also

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

positive, and grows on TSI slant with a (A/A/g+/H₂S-) profile. Also, IMViC is for ''E. coli''; as it is

indole Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...

-positive (red ring) and methyl red-positive (bright red), but VP-negative (no change-colourless) and

citrate Citric acid is an organic compound with the formula . It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relati ...

-negative (no change-green colour). Tests for toxin production can use mammalian cells in

tissue culture Tissue culture is the growth of tissue (biology), tissues or cell (biology), cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-s ...

, which are rapidly killed by shiga toxin. Although sensitive and very specific, this method is slow and expensive. Typically, diagnosis has been done by culturing on sorbitol-MacConkey medium and then using typing antiserum. However, current latex assays and some typing antisera have shown cross reactions with non-''E. coli'' O157 colonies. Furthermore, not all ''E. coli'' O157 strains associated with HUS are nonsorbitol fermentors. The Council of State and Territorial Epidemiologists recommend that clinical laboratories screen at least all bloody stools for this pathogen. The U.S. Centers for Disease Control and Prevention recommend that "''all stools submitted for routine testing from patients with acute community-acquired diarrhea (regardless of patient age, season of the year, or presence or absence of blood in the stool) be simultaneously cultured for E. coli O157:H7 (O157 STEC) and tested with an assay that detects Shiga toxins to detect non-O157 STEC''".

Antibiotic therapy and resistance

Bacterial infections are usually treated with

s. However, the antibiotic sensitivities of different strains of ''E. coli'' vary widely. As

organisms, ''E. coli'' are resistant to many antibiotics that are effective against

organisms. Antibiotics which may be used to treat ''E. coli'' infection include amoxicillin, as well as other semisynthetic penicillins, many

cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus '' Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibio ...

s, carbapenems, aztreonam, trimethoprim-sulfamethoxazole,

ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin ...

nitrofurantoin Nitrofurantoin, sold under the brand name Macrobid among others, is an antibacterial medication of the nitrofuran class used to treat urinary tract infections (UTIs), although it is not as effective for kidney infections. It is taken by mouth ...

and the

aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...

Antibiotic resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...

is a growing problem. Some of this is due to overuse of antibiotics in humans, but some of it is probably due to the use of antibiotics as growth promoters in animal feeds. A study published in the journal ''

Science Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divided into twoor threemajor branches: the natural sciences, which stu ...

'' in August 2007 found the rate of adaptative

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s in ''E. coli'' is "on the order of 10⁻⁵ per

genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

per generation, which is 1,000 times as high as previous estimates," a finding which may have significance for the study and management of bacterial antibiotic resistance. Antibiotic-resistant ''E. coli'' may also pass on the genes responsible for antibiotic resistance to other species of bacteria, such as ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...

'', through a process called

horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the e ...

. ''E. coli'' bacteria often carry

multiple drug resistance Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are ...

plasmids, and under stress, readily transfer those plasmids to other species. Mixing of species in the intestines allows ''E. coli'' to accept and transfer

plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...

s from and to other bacteria. Thus, ''E. coli'' and the other

enterobacteria Enterobacteriaceae is a large family (biology), family of Gram-negative bacteria. It includes over 30 genera and more than 100 species. Its classification above the level of Family (taxonomy), family is still a subject of debate, but one class ...

are important reservoirs of transferable antibiotic resistance.

Beta-lactamase strains

Resistance to beta-lactam antibiotics has become a particular problem in recent decades, as strains of bacteria that produce extended-spectrum

beta-lactamase Beta-lactamases (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapene ...

s have become more common. These beta-lactamase enzymes make many, if not all, of the

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

s and

s ineffective as therapy. Extended-spectrum beta-lactamase–producing ''E. coli'' (ESBL ''E. coli'') are highly resistant to an array of antibiotics, and infections by these strains are difficult to treat. In many instances, only two oral antibiotics and a very limited group of intravenous antibiotics remain effective. In 2009, a gene called New Delhi metallo-beta-lactamase (shortened NDM-1) that even gives resistance to intravenous antibiotic

carbapenem Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Si ...

, were discovered in

India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...

and

Pakistan Pakistan, officially the Islamic Republic of Pakistan, is a country in South Asia. It is the List of countries and dependencies by population, fifth-most populous country, with a population of over 241.5 million, having the Islam by country# ...

on ''E. coli'' bacteria. Increased concern about the prevalence of this form of " superbug" in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

has led to calls for further monitoring and a UK-wide strategy to deal with infections and the deaths. Susceptibility testing should guide treatment in all infections in which the organism can be isolated for culture.

Phage therapy

Phage therapy—viruses that specifically target pathogenic bacteria—has been developed over the last 80 years, primarily in the former

Soviet Union The Union of Soviet Socialist Republics. (USSR), commonly known as the Soviet Union, was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 until Dissolution of the Soviet ...

, where it was used to prevent diarrhea caused by ''E. coli''. Presently, phage therapy for humans is available only at the Phage Therapy Center in the Republic of Georgia and in

Poland Poland, officially the Republic of Poland, is a country in Central Europe. It extends from the Baltic Sea in the north to the Sudetes and Carpathian Mountains in the south, bordered by Lithuania and Russia to the northeast, Belarus and Ukrai ...

. However, on January 2, 2007, the United States FDA gave Omnilytics approval to apply its ''E. coli'' O157:H7 killing phage in a mist, spray or wash on live animals that will be slaughtered for human consumption. The

enterobacteria phage T4 Escherichia virus T4 is a species of bacteriophages that infect ''Escherichia coli'' bacteria. It is a double-stranded DNA virus in the subfamily '' Tevenvirinae'' of the family '' Straboviridae''. T4 is capable of undergoing only a lytic li ...

, a highly studied phage, targets ''E. coli'' for infection. While phage therapy as a treatment for ''E. coli'' is unavailable in the US, some commercially available dietary supplements contain strains of phage that target ''E. coli'' and have been shown to reduce ''E. coli'' load in healthy subjects. This is not considered phage therapy, however, because it does not involve selection of phages with activity against a patient's specific strain of bacterium.

Vaccination

Researchers have actively been working to develop safe, effective

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...

s to lower the worldwide incidence of ''E. coli'' infection. In March 2006, a vaccine eliciting an immune response against the ''E. coli'' O157:H7 O-specific polysaccharide conjugated to recombinant exotoxin A of ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

'' (O157-rEPA) was reported to be safe in children two to five years old. Previous work had already indicated it was safe for adults. A

phase III clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phase ...

to verify the large-scale

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...

of the treatment is planned. In 2006, Fort Dodge Animal Health (

Wyeth Wyeth Pharmaceuticals Inc. was a pharmaceutical company until it was purchased by Pfizer in 2009. The company was founded in Philadelphia, Pennsylvania, in 1860 as John Wyeth and Brother. Its headquarters moved to Collegeville, Pennsylvania, a ...

) introduced an effective, live, attenuated vaccine to control airsacculitis and

in chickens. The vaccine is a genetically modified avirulent vaccine that has demonstrated protection against O78 and untypeable strains. In January 2007, the Canadian biopharmaceutical company Bioniche announced it has developed a cattle vaccine which reduces the number of O157:H7 shed in manure by a factor of 1000, to about 1000 pathogenic bacteria per gram of manure. In April 2009, a Michigan State University researcher announced he had developed a working vaccine for a strain of ''E. coli''. Dr. Mahdi Saeed, Professor of epidemiology and infectious disease in MSU's colleges of Veterinary Medicine and Human Medicine, has applied for a patent for his discovery and has made contact with pharmaceutical companies for commercial production. In May 2018, a team led by researchers at Washington University School of Medicine collaborated with Johns Hopkins University to conduct a study which delves deeper into the known link between blood type and the severity of ''E. coli'' infection. Results of the study showed that "the bacterium is more likely to cause severe diarrhea in people with type A blood," and this finding may aid current and future efforts to develop an effective vaccine against the pathogenic strains of E. ''coli.''

References

External links

The danger in our salad bowls
- ''

Boston Globe ''The Boston Globe,'' also known locally as ''the Globe'', is an American daily newspaper founded and based in Boston, Massachusetts. The newspaper has won a total of 27 Pulitzer Prizes. ''The Boston Globe'' is the oldest and largest daily new ...

'' report on FDA oversight of outbreaks in the United States {{Authority control Escherichia coli Bird diseases Pathogenic bacteria Mammal diseases Infraspecific bacteria taxa