E. coli Pathotypes- ETEC, EPEC, EHEC, EAEC, EIEC, DAEC

Escherichia coli (E. coli) is a type of bacteria that belongs to the family Enterobacteriaceae, which includes gram-negative, rod-shaped, and facultatively anaerobic organisms. E. coli is one of the most common and diverse bacterial species that can be found in the environment, foods, and intestines of humans and animals. E. coli can be easily altered genetically and is widely used as a model organism in molecular biology and biotechnology.

Most E. coli strains are harmless or even beneficial to their hosts, as they can produce vitamin K2, prevent the colonization of pathogenic bacteria, and contribute to the normal microbiota of the gut. However, some strains of E. coli can cause serious diseases, such as foodborne illness, urinary tract infections, sepsis, meningitis, and abscesses. These pathogenic strains are classified into six main types based on their virulence factors and clinical features: enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), Shiga toxin-producing E. coli (STEC), enteroinvasive E. coli (EIEC), and diffusely-adherent E. coli (DAEC).

E. coli is transmitted mainly through the fecal-oral route, by ingestion of contaminated food or water, or by contact with infected surfaces or persons. The bacteria can grow rapidly in fresh fecal matter under aerobic conditions, but their numbers decline slowly afterward. E. coli can also survive outside the body for a limited amount of time, which makes them potential indicator organisms to test environmental samples for fecal contamination. However, some strains of E. coli can persist and grow in the environment for longer periods of time.

E. coli is a chemoheterotroph that requires a source of carbon and energy for its growth and metabolism. Under favorable conditions, it can reproduce by binary fission every 20 minutes. E. coli has a circular chromosome of about 4.6 million base pairs and several plasmids that carry genes for antibiotic resistance, virulence factors, or metabolic functions. E. coli can also exchange genetic material with other bacteria by horizontal gene transfer mechanisms such as transformation, transduction, or conjugation.

E. coli has been one of the most intensively studied microorganisms for over 60 years and has provided valuable insights into many aspects of biology, genetics, biochemistry, and biotechnology. However, E. coli also remains a major public health concern due to its ability to cause various infections and outbreaks that can be life-threatening or have long-term complications [^3 ^]. Therefore, it is important to understand the diversity, ecology, pathogenesis, diagnosis, prevention, and treatment of E. coli infections.

Escherichia coli (E. coli) is one of the many groups of bacteria that live in the intestines of healthy humans and most warm-blooded animals. E. coli bacteria help maintain the balance of normal intestinal flora (bacteria) against harmful bacteria and synthesize or produce some vitamins. However, there are hundreds of types or strains of E. coli bacteria. Different strains of E. coli have different distinguishing characteristics. Some strains are harmless and beneficial, while others can cause intestinal and extraintestinal infections in humans.

The normal intestinal flora of E. coli consists of hundreds of different serotypes, which are classified based on their antigenic properties. The most common serotypes are O (somatic), H (flagellar), and K (capsular). The normal intestinal flora of E. coli is usually acquired during birth and early infancy from the mother and the environment. The normal intestinal flora of E. coli can vary depending on factors such as age, diet, health status, and antibiotic use.

The normal intestinal flora of E. coli plays an important role in human health and physiology. Some of the functions of the normal intestinal flora of E. coli include:

• Competing with pathogenic bacteria for nutrients and attachment sites on the intestinal mucosa, thus preventing colonization and infection by harmful bacteria.

• Producing short-chain fatty acids (SCFAs) from dietary fiber, which can be used as an energy source by the host cells and modulate the intestinal pH and motility.

• Synthesizing vitamins such as vitamin K, biotin, folic acid, and vitamin B12, which are essential for blood clotting, metabolism, DNA synthesis, and nervous system function.

• Stimulating the development and maturation of the immune system, especially the gut-associated lymphoid tissue (GALT), which is responsible for producing antibodies and regulating inflammation.

• Modulating the expression of genes involved in metabolism, immunity, and inflammation in the host cells through direct or indirect interactions.

The normal intestinal flora of E. coli is usually harmless and beneficial to the host, but it can also become pathogenic under certain conditions. For example, some strains of E. coli can acquire virulence genes from other bacteria through horizontal gene transfer, such as plasmids or bacteriophages. These virulence genes can encode toxins, adhesins, invasins, or other factors that enable the bacteria to cause disease in humans. Additionally, some strains of E. coli can translocate from the intestine to other sites in the body, such as the urinary tract, bloodstream, or central nervous system, where they can cause infections such as urinary tract infections (UTIs), sepsis, or meningitis. Furthermore, some strains of E. coli can disrupt the balance of the normal intestinal flora by producing toxins or inflammatory cytokines that damage the intestinal mucosa and alter the gut microbiota composition. These disruptions can lead to diarrhea or inflammatory bowel diseases (IBDs) such as ulcerative colitis or Crohn`s disease.

Therefore, Escherichia coli is a diverse group of bacteria that can be part of the normal intestinal flora or cause intestinal and extraintestinal infections in humans depending on their strain characteristics and host factors.

Escherichia coli is a versatile and adaptable bacterium that can cause a wide range of infections in humans and animals. Some of the factors that contribute to its effectiveness as a pathogen are:

• Genetic diversity: E. coli has a large and dynamic genome that can undergo frequent mutations, recombination, and horizontal gene transfer. This allows it to acquire new traits and adapt to different environments and hosts. For example, some E. coli strains have acquired genes encoding toxins, adhesins, invasins, and other virulence factors from other bacteria or phages, enabling them to cause specific diseases such as diarrhea, urinary tract infections, sepsis, meningitis, etc.

• Colonization ability: E. coli can colonize various sites in the human body, such as the intestinal tract, the urinary tract, the respiratory tract, the bloodstream, and the central nervous system. It can also survive and persist in the environment, such as in water, soil, food, and animal feces. To colonize these sites, E. coli can express different surface structures that facilitate attachment to host cells or extracellular matrix components. For example, E. coli can produce fimbriae (pili), flagella, capsules, lipopolysaccharides (LPS), and outer membrane proteins that mediate adhesion, motility, biofilm formation, and immune evasion.

• Invasion and dissemination ability: Some E. coli strains can invade host cells and tissues and cause damage by producing toxins or inducing inflammation. For example, enteroinvasive E. coli (EIEC) can invade and destroy the colonic epithelium by using a plasmid-encoded type III secretion system that injects effector proteins into host cells. Shiga toxin-producing E. coli (STEC) can produce potent cytotoxins that inhibit protein synthesis and cause cell death in various organs, especially the kidneys. Enterohemorrhagic E. coli (EHEC) can also cause attaching and effacing lesions on the intestinal mucosa by using a chromosomal pathogenicity island called the locus of enterocyte effacement (LEE) that encodes a type III secretion system and effector proteins. Some E. coli strains can also cross the intestinal barrier and enter the bloodstream or the central nervous system, causing systemic infections such as sepsis or meningitis.

• Antimicrobial resistance: E. coli can acquire resistance to various antibiotics by carrying genes on plasmids, transposons, integrons, or chromosomes. These genes can encode enzymes that inactivate or modify antibiotics (e.g., beta-lactamases), efflux pumps that expel antibiotics from the cell, or mutations that alter the target sites of antibiotics (e.g., ribosomes). Antimicrobial resistance can limit treatment options and increase the morbidity and mortality of E. coli infections.

These factors make E. coli a formidable pathogen that poses significant challenges to public health and clinical management.

Sepsis is a life-threatening condition that occurs when the body`s response to an infection causes damage to its own tissues and organs. Sepsis can lead to shock, organ failure, and death if not treated promptly and effectively.

One of the most common causes of sepsis is a bacterial infection, especially by gram-negative rods. Gram-negative rods are a group of bacteria that have a thin cell wall and a negative charge on their outer membrane. They can produce endotoxins, which are lipopolysaccharides (LPS) that trigger inflammation and coagulation in the host.

Among the gram-negative rods that cause sepsis, Escherichia coli (E. coli) is the most prevalent. E. coli is a normal inhabitant of the human intestinal tract, but some strains can cause infections in other parts of the body, such as the urinary tract, the bloodstream, the lungs, or the abdomen. These strains are often resistant to multiple antibiotics and have various virulence factors that enable them to adhere to, invade, and damage the host cells.

Other gram-negative rods that are frequently isolated from patients with sepsis include Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter spp., Proteus spp., and Serratia spp. These bacteria can also cause nosocomial infections (infections acquired in hospitals or healthcare settings) and are often associated with underlying conditions such as diabetes, immunosuppression, malignancy, or trauma.

The diagnosis of sepsis caused by gram-negative rods is based on clinical criteria and microbiological tests. Blood cultures are the gold standard for identifying the causative agent, but they may take several hours or days to yield results. Therefore, empirical antibiotic therapy is usually initiated as soon as possible based on the suspected source of infection and the local antimicrobial resistance patterns.

The treatment of sepsis caused by gram-negative rods requires a combination of supportive measures and appropriate antibiotics. Supportive measures include fluid resuscitation, vasopressors, oxygen therapy, mechanical ventilation, renal replacement therapy, and source control (e.g., drainage of abscesses or removal of foreign bodies). Appropriate antibiotics should be chosen based on the results of blood cultures and susceptibility tests and should cover both aerobic and anaerobic gram-negative rods. The duration of antibiotic therapy depends on the severity of sepsis, the source of infection, and the clinical response.

The prevention of sepsis caused by gram-negative rods involves infection control measures such as hand hygiene, sterilization of medical devices, isolation of infected patients, and judicious use of antibiotics. Vaccines against some gram-negative rods (e.g., Neisseria meningitides or Haemophilus influenzae type b) are also available and recommended for certain populations at risk.

Sepsis caused by gram-negative rods is a serious and potentially fatal condition that requires prompt recognition and management. E. coli is the most common gram-negative rod isolated from patients with sepsis, but other bacteria, such as Klebsiella pneumoniae or Pseudomonas aeruginosa, can also cause sepsis. The treatment of sepsis involves supportive measures and appropriate antibiotics based on blood cultures and susceptibility tests. The prevention of sepsis involves infection control measures and vaccination when indicated.

Urinary tract infections (UTIs) are among the most common bacterial infections in humans, affecting millions of people every year. UTIs can involve the lower urinary tract (cystitis) or the upper urinary tract (pyelonephritis) and can cause symptoms such as dysuria, frequency, urgency, hematuria, flank pain, fever, and sepsis.

The majority of UTIs are caused by Escherichia coli, a gram-negative rod that normally inhabits the gastrointestinal tract. E. coli accounts for more than 80% of all community-acquired UTIs and about 50% of hospital-acquired UTIs. Other bacteria that can cause UTIs include Klebsiella, Proteus, Enterococcus, Staphylococcus saprophyticus, and Pseudomonas.

The pathogenesis of UTIs involves several steps: colonization of the periurethral area by E. coli from the fecal flora, the ascension of the bacteria into the bladder via the urethra, attachment of the bacteria to the uroepithelial cells, invasion and replication of the bacteria in the bladder mucosa, and dissemination of the bacteria to the kidneys via the ureters.

E. coli strains that cause UTIs have specific virulence factors that enable them to adhere to and invade the urinary tract. These include:

• Fimbriae: hair-like appendages that mediate binding to specific receptors on the uroepithelial cells. The most important fimbriae for UTIs are type 1 fimbriae (which bind to mannose residues) and P fimbriae (which bind to globoseries glycolipids).

• Capsule: a polysaccharide layer that protects the bacteria from phagocytosis and complement-mediated killing. The most common capsule for UTIs is K1 (which mimics host cell antigens).

• Hemolysin: a toxin that lyses red blood cells and damages uroepithelial cells. Hemolysin also activates inflammatory cytokines and chemokines that recruit neutrophils to the site of infection.

• Siderophores: molecules that scavenge iron from the host and transport it to the bacteria. Iron is essential for bacterial growth and metabolism. The most common siderophores for UTIs are aerobactin and enterobactin.

The diagnosis of UTIs is based on clinical signs and symptoms, urinalysis, and urine culture. Urinalysis can reveal pyuria (presence of leukocytes), bacteriuria (presence of bacteria), hematuria (presence of blood), nitrite (indicating nitrate-reducing bacteria), and leukocyte esterase (indicating leukocyte enzymes). A urine culture can identify the causative organism and its antibiotic susceptibility.

The treatment of UTIs depends on the severity and location of the infection, the patient`s age, sex, medical history, and local antibiotic resistance patterns. The general principles of treatment are:

• Empiric therapy: initial antibiotic therapy based on the most likely causative organism and its susceptibility. Empiric therapy should be started as soon as possible after diagnosis and adjusted according to urine culture results.

• Definitive therapy: tailored antibiotic therapy based on urine culture results and clinical response. Definitive therapy should be continued until the infection is eradicated and symptoms are resolved.

• Symptomatic relief: supportive measures such as hydration, analgesics, antipyretics, and cranberry juice (which may prevent bacterial adhesion).

• Prevention: measures to reduce the risk of recurrent or complicated UTIs such as good hygiene, adequate fluid intake, voiding after sexual intercourse, avoiding spermicides and diaphragms, prophylactic antibiotics for high-risk patients, and treatment of underlying conditions such as diabetes or urinary obstruction.

UTIs caused by E. coli are common and potentially serious infections that require prompt diagnosis and treatment. By understanding the pathogenesis and virulence factors of E. coli, clinicians can select appropriate antibiotics and prevent complications such as pyelonephritis, sepsis, renal scarring, and chronic kidney disease.

: Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med 2002;113 Suppl 1A:5S-13S.

Gastroenteritis is an inflammation of the stomach and intestines that causes diarrhea, vomiting, abdominal pain, and cramps. It can be caused by various infectious agents, such as viruses, bacteria, parasites, and toxins.

Among the bacterial causes of gastroenteritis, Escherichia coli (E. coli) is a prominent one. E. coli is a gram-negative rod-shaped bacterium that normally lives in the intestines of humans and animals. However, some strains of E. coli have acquired genes that enable them to cause intestinal infection.

The strains of E. coli that cause gastroenteritis are subdivided into six pathotypes based on their epidemiology, clinical features, and virulence factors. These pathotypes are:

• Enterotoxigenic E. coli (ETEC): The most common cause of traveler`s diarrhea and a major cause of diarrheal disease in developing countries. It produces heat-labile and heat-stable toxins that stimulate fluid secretion in the small intestine.

• Enteropathogenic E. coli (EPEC): A common cause of infantile diarrhea and outbreaks in nurseries, especially in low-resource settings. It adheres to the intestinal mucosa and causes attaching and effacing lesions that disrupt the brush border epithelium.

• Enteroaggregative E. coli (EAEC): A heterogeneous group of strains that adhere to the intestinal mucosa in a stacked-brick pattern and produce toxins and biofilms. It causes persistent and acute diarrhea, especially in children and travelers to developing countries.

• Shiga toxin–producing E. coli (STEC): Also known as verocytotoxin-producing E. coli (VTEC) or enterohemorrhagic E. coli (EHEC), it produces Shiga toxins that damage the intestinal mucosa and cause bloody diarrhea (hemorrhagic colitis). It can also cause hemolytic uremic syndrome (HUS), a serious complication characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. The most common strain of this pathotype is E. coli O157:H7, which is often transmitted by undercooked ground beef, unpasteurized milk or juice, contaminated water or vegetables, or person-to-person contact.

• Enteroinvasive E. coli (EIEC): A rare cause of gastroenteritis that invades and destroys the colonic epithelium, causing watery or bloody diarrhea. It is closely related to Shigella and is mainly found in low- and middle-income countries.

• Diffusely adherent E. coli (DAEC): A poorly understood pathotype that adheres to the intestinal mucosa in a diffuse pattern and expresses fimbriae that may contribute to its pathogenesis. It is associated with diarrhea in children aged 2-6 years, but it can also be part of the normal intestinal flora in children and adults.

E. coli gastroenteritis can be diagnosed by stool culture, polymerase chain reaction (PCR) testing, or detection of toxins or antigens. Treatment is usually supportive, with oral or intravenous rehydration and electrolyte replacement. Antibiotics are not routinely recommended, except for some cases of ETEC or EIEC infection or for patients with severe or systemic illness. Prevention measures include proper hygiene, safe food handling and cooking, pasteurization of milk and juice, chlorination of water, and vaccination against ETEC for travelers to high-risk areas.

E. coli gastroenteritis is a significant public health problem worldwide, causing morbidity and mortality, especially among children, the elderly, and immunocompromised individuals[^2 ^][ ^5 ^]. Therefore, it is important to recognize its causes, symptoms, diagnosis, treatment, and prevention.

References:

E. coli is a diverse group of bacteria that can be classified into different pathotypes based on their virulence factors, modes of transmission, clinical manifestations, and associated serotypes. The pathotypes of E. coli that cause gastroenteritis are collectively known as diarrheagenic E. coli (DEC). There are six major pathotypes of DEC: enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), Shiga toxin–producing E. coli (STEC), enteroinvasive E. coli (EIEC), and diffusely adherent E. coli (DAEC). Each pathotype has a distinct mechanism for causing diarrhea and can affect different age groups and geographic regions.

• ETEC is the most common cause of traveler`s diarrhea and endemic diarrhea in developing countries. It produces heat-labile and/or heat-stable toxins that stimulate intestinal secretion and inhibit absorption, resulting in watery diarrhea.

• EPEC is mainly associated with infantile diarrhea and outbreaks in nurseries and daycare centers. It adheres to the intestinal epithelium and causes attaching and effacing (A/E) lesions that disrupt the microvilli and impair absorption, leading to watery diarrhea.

• EAEC is responsible for persistent diarrhea in children and adults, especially in developing countries. It forms aggregative adherence fimbriae (AAF) that enable it to form biofilms on the intestinal mucosa and secrete toxins and cytokines that induce inflammation and mucosal damage, causing watery or mucoid diarrhea.

• STEC is also known as verotoxigenic E. coli (VTEC) or enterohemorrhagic E. coli (EHEC). It produces Shiga toxins that inhibit protein synthesis and damage the intestinal epithelium and the vascular endothelium, causing bloody diarrhea and hemolytic uremic syndrome (HUS). The most notorious serotype is O157:H7, which is often transmitted by contaminated food or water.

• EIEC is closely related to Shigella and causes a similar disease. It invades and destroys the colonic epithelium, causing inflammation, ulceration, and dysentery. It is more common in tropical and subtropical regions and affects mainly children and immunocompromised adults.

• DAEC is a heterogeneous group of strains that adhere diffusely to the intestinal epithelium. It is not clear whether it is a true pathogen or a commensal strain, but some studies have suggested that it may cause diarrhea in children by interfering with the normal function of the epithelial cells.

These pathotypes of E. coli can be distinguished by various laboratory methods, such as serotyping, detection of virulence genes or toxins, or adherence patterns on cultured cells. However, these methods are not always available or reliable, so clinical diagnosis and treatment should be based on the patient`s history, symptoms, and epidemiological factors.

Escherichia coli (E. coli) is a diverse group of bacteria that can cause various diseases in humans and animals. Some strains of E. coli are harmless and are part of the normal intestinal flora, while others are pathogenic and can cause diarrhea or extraintestinal infections. The pathogenic strains of E. coli that cause diarrhea is classified into six pathotypes based on their distinct epidemiological and clinical features, specific virulence determinants, and association with certain serotypes. These pathotypes are:

• Enterotoxigenic E. coli (ETEC): These strains produce heat-labile and/or heat-stable enterotoxins that stimulate fluid secretion in the small intestine, causing watery diarrhea. ETEC is a major cause of traveler`s diarrhea and endemic diarrhea in developing countries, especially in infants and children.

• Enteropathogenic E. coli (EPEC): These strains adhere to the intestinal mucosa and cause attaching and effacing (A/E) lesions that disrupt the microvilli and impair absorption. EPEC is mainly associated with infantile diarrhea in developing countries but can also cause sporadic cases or outbreaks in developed countries.

• Enteroaggregative E. coli (EAEC): These strains form aggregative adherence fimbriae (AAF) that enable them to form a stacked-brick pattern on the epithelial cells of the small intestine and colon. EAEC also produces various toxins and biofilm components that contribute to mucosal damage and inflammation. EAEC is implicated in persistent and acute diarrhea in children and adults in developing countries, as well as in traveler`s diarrhea.

• Shiga toxin-producing E. coli (STEC): These strains produce Shiga toxins (Stx1 and/or Stx2) that inhibit protein synthesis and damage endothelial cells, leading to bloody diarrhea and hemolytic uremic syndrome (HUS), a life-threatening complication characterized by hemolytic anemia, thrombocytopenia, and renal failure. STEC can also cause A/E lesions similar to EPEC. The most common serotype of STEC is O157:H7, but other serotypes such as O26, O103, O111, O121, O145, and O104:H4 have also been associated with outbreaks.

• Enteroinvasive E. coli (EIEC): These strains invade and destroy the colonic epithelium, causing inflammatory diarrhea with fever, abdominal cramps, and blood and leukocytes in stool specimens. EIEC is closely related to Shigella species and shares many virulence genes with them. EIEC is rare in both developed and developing countries.

• Diffusely adherent E. coli (DAEC): These strains adhere to the epithelial cells in a diffuse pattern mediated by fimbriae called F1845 or Afa/Dr. DAEC is considered a heterogeneous group of strains that may be involved in diarrhea in children aged 2-6 years in developing countries but can also be asymptomatic intestinal microbiota strains in children and adults.

These six pathotypes of diarrheagenic E. coli are responsible for a significant burden of morbidity and mortality worldwide, especially among children under five years of age. Therefore, it is important to identify them accurately for epidemiological surveillance, clinical management, and prevention strategies.

Enterotoxigenic E. coli (ETEC) is one of the most common causes of bacterial diarrheal disease in developing countries and in travelers to these countries. It causes acute watery diarrhea in infants and adults by producing two classes of enterotoxins: heat-stable toxins (STa and STb) and heat-labile toxins (LT-I, LT-II). These toxins act on the intestinal epithelial cells and stimulate the secretion of fluids and electrolytes, leading to dehydration and loss of nutrients.

ETEC is transmitted by food or water contaminated with animal or human feces. The infection requires a high inoculum, so the person-to-person spread is rare. ETEC strains are characterized by the presence of colonization factors (CFs), which are fimbrial or non-fimbrial surface proteins that mediate the attachment of the bacteria to the intestinal mucosa. There are more than 25 different CFs identified, and some ETEC strains may express more than one CF. The most common CFs associated with human disease are CFA/I, CFA/II, and CFA/IV.

The symptoms of ETEC infection usually develop after a 1- to 2-day incubation period and last for an average of 3 to 5 days. The typical clinical presentation is watery, non-bloody diarrhea and abdominal cramps; nausea and vomiting may also occur. The severity of the disease varies depending on the host factors, such as age, immune status, nutritional status, and previous exposure to ETEC. In some cases, ETEC infection can cause severe dehydration, especially in young children and elderly people, and may result in death if not treated promptly.

The diagnosis of ETEC infection is based on the detection of the toxins or the CFs in stool samples by various methods, such as enzyme immunoassays, polymerase chain reactions, or cell culture assays. However, these methods are not widely available or standardized and may have low sensitivity or specificity. Therefore, the diagnosis is often presumptive based on the clinical and epidemiological features of the illness.

The treatment of ETEC infection consists mainly of oral rehydration therapy to replace the fluids and electrolytes lost due to diarrhea. Antibiotics may be indicated for patients with severe symptoms, high-risk groups (such as immunocompromised patients, pregnant women, or travelers), or outbreaks. The choice of antibiotics depends on the local resistance patterns and the availability of the drugs. Some commonly used antibiotics are fluoroquinolones, azithromycin, rifampin, or doxycycline.

The prevention of ETEC infection relies on the improvement of sanitation and hygiene practices, such as washing hands with soap frequently, drinking safe water, and avoiding or safely preparing foods that could be contaminated with feces. Vaccines against ETEC are under development, but none are currently licensed for human use. Some vaccines target the toxins or the CFs or both and aim to induce protective immune responses in the intestinal mucosa. However, there are many challenges in developing effective and safe vaccines against ETEC, such as the diversity of the strains, the lack of correlates of protection, and the ethical issues of testing vaccines in vulnerable populations.

References:

Enteropathogenic E. coli (EPEC) is a group of E. coli strains that cause infantile diarrhea, especially in developing countries. They are also associated with sporadic cases of diarrhea in adults and travelers to endemic areas.

EPECs are transmitted by the fecal-oral route through contaminated food, water, or surfaces. They can also spread from person to person in households or daycare centers.

EPEC are characterized by their ability to form attaching and effacing (A/E) lesions on the intestinal epithelium, similar to some Shiga toxin–producing E. coli (STEC). However, unlike STEC, EPEC does not produce Shiga toxins or other enterotoxins.

The pathogenesis of EPEC involves two steps: initial adherence and intimate attachment. First, EPEC adheres to the intestinal mucosa by using plasmid-encoded bundle-forming pili (BFP), which mediate the formation of microcolonies on the epithelial surface. Second, EPEC attaches intimately to the host cells by using a type III secretion system (T3SS), which injects effector proteins into the host cytoplasm. These effectors induce actin rearrangement and pedestal formation under the bacterial attachment site, resulting in the loss of microvilli and disruption of the epithelial barrier.

The A/E lesions caused by EPEC impair the absorption of nutrients and water by the intestinal cells, leading to watery diarrhea. EPEC can also induce inflammation and apoptosis of the epithelial cells, contributing to tissue damage and mucosal ulceration.

The symptoms of EPEC infection usually appear within 12 to 72 hours after ingestion of the bacteria and last for 3 to 14 days. The clinical manifestations include watery diarrhea, fever, vomiting, abdominal cramps, and dehydration. In some cases, EPEC infection can cause persistent diarrhea and malnutrition in infants, leading to growth retardation and increased mortality.

The diagnosis of EPEC infection is based on the detection of specific virulence factors or genes in stool samples. The most commonly used methods include polymerase chain reaction (PCR) for the detection of the eye gene (encoding intimin) or the bfp gene (encoding BFP), immunofluorescence assay for the detection of BFP on bacterial cells, or cell culture assay for the detection of A/E lesions on cultured epithelial cells.

The treatment of EPEC infection consists mainly of supportive care, such as oral rehydration therapy or intravenous fluids for severe dehydration. Antibiotics are not routinely recommended for EPEC infection, as they may not shorten the duration of diarrhea or prevent complications. However, antibiotics may be considered for patients with severe or persistent symptoms, immunocompromised patients, or patients with a high risk of transmission.

The prevention of EPEC infection relies on improving sanitation and hygiene practices, such as washing hands with soap and water before eating or preparing food, drinking safe water or boiling it before use, avoiding raw or undercooked food, and disposing of human and animal feces properly. Breastfeeding can also protect infants from EPEC infection by providing maternal antibodies and enhancing their immune systems. Vaccines against EPEC are currently under development and may offer a promising strategy for reducing the burden of this disease in the future.

Enteroaggregative E. coli (EAEC) are a heterogeneous group of strains that cause acute and chronic diarrhea in both developed and developing countries. They may also cause urinary tract infections. EAEC are defined by their "stacked-brick" pattern of adhesion to the human laryngeal epithelial cell line HEp-2.

The pathogenesis of EAEC involves the aggregation and adherence of the bacteria to the intestinal mucosa, where they produce enterotoxins and cytotoxins that damage host cells and induce inflammation that results in diarrhea. EAEC is now recognized as an emerging enteric pathogen. In particular, EAEC is reported as the second most common cause of traveler`s diarrhea, second only to Enterotoxigenic E. coli, and a common cause of diarrhea among pediatric populations. It has also been associated with chronic infections in immunocompromised hosts, such as HIV-infected individuals.

Awareness of EAEC was increased by a serious outbreak in Germany in 2011, causing over 5000 cases and at least 50 fatalities. The pathogen that is responsible was found to be an EAEC O104:H4 strain that had acquired the Shiga toxin gene from Shiga toxin–producing E. coli (STEC), which often encodes the adhesin intimin. The putative cause of the outbreak was sprouted fenugreek seeds.

Strains of EAEC are highly genetically diverse, and the identification of virulence factors important for pathogenesis has proven difficult. Many EAECs encode a transcriptional factor named aggR (aggregative regulator), part of the AraC family of transcription activators. AggR regulates many plasmid and chromosomally encoded virulence factors which include genes involved in aggregative adherence fimbriae biogenesis and toxin production. Several toxins have been linked to EAEC virulence, including ShET1 (Shigella enterotoxin 1), Pet (plasmid‐encoded toxin), and EAST-1 (entero-aggregative heat-stable enterotoxin 1). However, further studies of these factors have failed to elucidate their role in pathogenesis.

Diagnosis of EAEC infection is based on the detection of the characteristic adherence pattern on HEp-2 cells or the identification of specific molecular markers by PCR, such as eggs, aaiC, aatA, or AAF. Treatment of EAEC infection is mainly supportive, with rehydration therapy and nutritional support. Antibiotics may be considered for severe or persistent cases, but resistance is common among EAEC strains. Prevention of EAEC infection relies on good hygiene practices, safe food handling, and avoiding consumption of contaminated water or food.

Shiga toxin–producing E. coli (STEC) are a group of E. coli strains that produce one or more types of Shiga toxins (Stx), also known as verotoxins or Shiga-like toxins. These toxins can damage the lining of the intestine and cause bloody diarrhea, abdominal cramps, and sometimes fever. Some STEC strains can also cause a serious complication called hemolytic uremic syndrome (HUS), which is characterized by hemolytic anemia, thrombocytopenia, and acute kidney failure.

STEC strains are classified into different serotypes based on their O antigen (somatic) and H antigen (flagellar). The most common and well-known serotype is O157:H7, which is responsible for many outbreaks of foodborne illness worldwide. However, there are many other non-O157 STEC serotypes that can also cause human disease, such as O26, O45, O103, O111, O121, and O145. A 2011 outbreak in Germany was caused by a rare STEC serotype, O104:H4, which had both enteroaggregative and enterohemorrhagic properties.

STEC infections are usually acquired through the consumption of contaminated food or water or through contact with animals or persons who carry the bacteria. Cattle are an important reservoir for STEC, as they can harbor the bacteria in their intestines without showing any symptoms. Other animals, such as sheep, goats, deer, and pigs, can also carry STEC. Foods that have been implicated in STEC outbreaks include undercooked ground beef, raw milk, unpasteurized juice, fresh produce, and cheese. Water sources that have been contaminated by animal or human feces can also transmit STEC.

The pathogenesis of STEC infection involves the attachment of the bacteria to the intestinal mucosa by various adhesins, such as intimin or fimbriae. Some STEC strains can also form attaching and effacing (A/E) lesions on the epithelial cells, similar to enteropathogenic E. coli (EPEC), by using a type III secretion system encoded by a chromosomal pathogenicity island called the locus of enterocyte effacement (LEE). The LEE-positive STEC strains are also known as enterohemorrhagic E. coli (EHEC).

The main virulence factor of STEC is the production of Shiga toxins, which are encoded by genes located on bacteriophages that can be transferred among different E. coli strains. There are two types of Shiga toxins: Stx1 and Stx2, which have different subtypes with varying degrees of toxicity. The toxins bind to specific receptors on the surface of endothelial cells, especially in the kidneys and the central nervous system. They then enter the cells and inhibit protein synthesis by cleaving a specific adenine residue on the 28S rRNA of the 60S ribosomal subunit. This leads to cell death and tissue damage, resulting in bloody diarrhea and HUS.

The diagnosis of STEC infection is based on the detection of Shiga toxins or their genes in stool samples by enzyme immunoassays or polymerase chain reaction assays. Serotyping of isolated E. coli strains can also be performed to identify the specific serotype involved in the infection. The treatment of STEC infection is mainly supportive, as antibiotics may increase the risk of HUS by inducing toxin release from lysed bacteria. Fluid and electrolyte replacement may be needed to prevent dehydration and shock. Patients with HUS may require dialysis or blood transfusions.

The prevention of STEC infection relies on proper hygiene and food safety practices. These include washing hands before and after handling food or animals; cooking meat thoroughly; avoiding cross-contamination between raw and cooked foods; refrigerating perishable foods promptly; drinking pasteurized milk and juice; washing fruits and vegetables before eating; avoiding swallowing water from lakes or pools; and reporting any cases of bloody diarrhea to health authorities. Vaccines against some STEC serotypes are under development but are not yet available for human use.

Enteroinvasive E. coli (EIEC) is a rare type of pathogenic E. coli that cause a syndrome similar to shigellosis, with profuse diarrhea and high fever. EIECs are highly invasive, and they use adhesin proteins to bind to and enter intestinal cells. They produce no toxins but severely damage the intestinal wall through mechanical cell destruction. EIEC is closely related to Shigella, and they share some virulence genes and phenotypic properties.

The disease caused by EIEC is transmitted by fecal-oral exposure to contaminated food, water, or surfaces. Person-to-person spread can also occur. The bacteria invade and destroy the colonic epithelium, producing inflammation and ulceration of the mucosa. A series of genes on a plasmid mediates bacterial invasion into the colonic epithelium (pInv genes). The bacteria then lyse the phagocytic vacuole and replicate in the cell cytoplasm. Movement within the cytoplasm and into adjacent epithelial cells is regulated by the formation of actin tails.

The onset of disease may be as rapid as a few hours after ingestion of EIEC, and although most infections resolve after a few days, persistent diarrhea requiring hospitalization can occur. A minority of patients progress to the dysenteric form of the disease, consisting of fever, abdominal cramps, and blood and leukocytes in stool specimens. Diagnosis is made by detection of EIEC by culture or molecular methods.

EIEC is one of the six pathotypes of diarrheagenic E. coli, along with enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), Shiga toxin–producing E. coli (STEC), and diffusely-adherent E. coli (DAEC). These pathotypes are defined by their distinct epidemiological and clinical features, specific virulence determinants, and association with certain serotypes.

Diffusely-adherent E. coli (DAEC) are a heterogeneous group of E. coli strains that are characterized by their ability to adhere to epithelial cells in a diffuse pattern, covering the entire cell surface. DAEC strains are mostly associated with the Afa/Dr family of adhesins, which mediate the attachment to the host cells. However, other adhesins and virulence factors have also been described for DAEC.

The role of DAEC as a cause of diarrhea is still controversial, as these strains can also be found as part of the normal intestinal microbiota in healthy individuals. Some studies have suggested that DAEC may be more prevalent in children with diarrhea than in controls, especially in developing countries and in children aged 2-6 years. However, other studies have failed to find such an association or have reported conflicting results.

The pathogenesis and pathogenicity of DAEC are not well understood, but it is thought that DAEC may cause diarrhea by interfering with the normal function of the intestinal epithelium, inducing inflammation, and producing toxins. Some DAEC strains have also been shown to invade epithelial cells and cause cell death. The clinical manifestations of DAEC infection may range from mild to moderate watery diarrhea, with or without fever, abdominal pain, and vomiting.

The diagnosis of DAEC infection is based on the detection of the diffuse adherence pattern on cultured epithelial cells (HeLa or HEp-2) or the presence of specific adhesin genes by molecular methods. However, these methods are not widely available or standardized, and there is no single marker that can identify all DAEC strains. Therefore, the epidemiology and burden of DAEC infection remain unclear.

The treatment and prevention of DAEC infection are similar to those of other diarrheagenic E. coli infections. Antibiotics may be indicated for severe or persistent cases, but their use should be guided by susceptibility testing and local resistance patterns. Oral rehydration therapy is essential to prevent dehydration and electrolyte imbalance. Hygienic measures such as washing hands, drinking safe water, and avoiding raw or undercooked foods can help reduce the risk of exposure to DAEC and other enteric pathogens.

1. Diffusely adherent E. coli (DAEC)

Diffusely-adherent E. coli (DAEC) are a heterogeneous group of E. coli strains that are characterized by their ability to adhere to cultured epithelial cells in a diffuse pattern, covering the entire cell surface. About 75% of DAEC strains harbor adhesins from the Afa/Dr family, which are responsible for this adherence phenotype. These adhesins can also mediate binding to extracellular matrix proteins and human decay-accelerating factor (DAF), a complement regulator.

The role of DAEC as a diarrheagenic pathotype of E. coli is still controversial, as these strains can also be found as asymptomatic intestinal microbiota in children and adults. However, some studies have suggested that DAEC can cause diarrhea, especially in children aged 2-6 years, and may also be associated with persistent diarrhea and growth retardation in developing countries. The pathogenesis and virulence mechanisms of DAEC are not fully understood, but some factors have been proposed, such as:

• The production of cytotoxins, hemolysins, and siderophores that may damage the intestinal epithelium and compete for iron.

• The induction of inflammatory cytokines and chemokines that may recruit immune cells and cause tissue damage.

• The alteration of tight junctions and barrier function that may increase intestinal permeability and facilitate the translocation of bacteria and toxins.

• The modulation of host cell signaling pathways that may affect cell survival, proliferation, differentiation, and apoptosis.

The diagnosis of DAEC infection is based on the detection of the diffuse adherence pattern on cultured epithelial cells or the presence of specific genes encoding for Afa/Dr adhesins or other virulence factors. However, these methods are not widely available or standardized, and there is no single molecular marker that can identify all DAEC strains. Therefore, the epidemiology and clinical relevance of DAEC remain unclear and require further investigation.

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