Enteroaggregative Escherichia coli | |
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Specialty | Infectious disease |
Enteroaggregative Escherichia coli (EAEC or EAggEC) are a pathotype of Escherichia coli which cause acute and chronic diarrhea in both the developed and developing world. [1] [2] They may also cause urinary tract infections. [2] EAEC are defined by their "stacked-brick" pattern of adhesion to the human laryngeal epithelial cell line HEp-2. [3] The pathogenesis of EAEC involves the aggregation of and adherence of the bacteria to the intestinal mucosa, where they elaborate 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 are reported as the second most common cause of traveler's diarrhea, second only to Enterotoxigenic E. coli, and a common cause of diarrhea amongst pediatric populations. [4] [5] It has also been associated with chronic infections in the latter, as well as in immunocompromised hosts, such as HIV-infected individuals. [6] Awareness of EAEC was increased by a serious outbreak in Germany during 2011, causing over 5000 cases and at least 50 fatalities. The pathogen responsible was found to be an EAEC O104:H4 strain which was lysogenized by a Shiga toxin encoding phage (typically associated with Shiga toxin-producing Escherichia coli, which often encode the adhesin intimin). [7] [8] The putative cause of the outbreak were sprouted fenugreek seeds. [9]
Strains of EAEC are highly genetically heterogeneous, and the identification of virulence factors important for pathogenesis has proven difficult. [10] Many EAEC encode a transcriptional factor named aggR (aggregative regulator), part of the AraC family of transcription activators. AggR regulates many plasmid, as well chromosomally encoded, virulence factors, that include genes implicated 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. However, further studies of these factors have failed to elucidate their role in pathogenesis. [11]
Diarrhea is still an important disease burden worldwide. It causes considerable childhood mortality in the developing world and is correlated with morbidity (or of relating to disease) and substation health care costs in industrialized countries. E. coli is a bacterium that is normally found in the human intestine, but some strains of bacteria can cause illness and infection.[ citation needed ] Subgroups of diarrheagenic Escherichia coli (DEC) are the following: enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enterotoxigenic E.coli (ETEC), Shiga toxin-producing E. coli (STEC) and Enteroaggregative E. coli (EAEC). [2]
Enteroaggregative Escherichia coli (EAEC) is a type of strain from E.coli. E.coli causes intestinal infections, some intestinal infections include diarrhea, fever and abdominal pain. Most severe cases can lead to bloody diarrhea, dehydration or even kidney failure. People with weakened immune systems, young children, older adults and pregnant women are at increased risks for developing these complications. Symptoms of intestinal infection usually begin between 8 and 52 hours after you have been infected with E.coli, [2] this is the incubation period. The incubation period is the time between catching an infection and symptoms appearing. [12]
Symptoms:
Bloody diarrhea has only been observed in children, and only rarely. [2] On the other hand, the STEC-EAEC hybrid strain identified in the 2011 Germany outbreak caused bloody diarrhea. [13] Common sources of infection include:
Diagnosis of infectious diarrhea and identification of antimicrobial resistance 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 pathogens can not be cultured. For culture-positive samples, antimicrobial resistance testing takes an additional 12–24 hours to perform.[ citation needed ]
Current point of care molecular diagnostic tests can identify EAEC and antimicrobial resistance in the identified strains much faster than culture and sensitivity testing. Microarray-based platforms can identify EAEC and AMR genes in two hours or less with high sensitivity and specificity, but the size of the test panel (i.e., total pathogens and AMR 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.[ citation needed ]
Antibiotics are a type of medicine that is used to destroy or inhibit the growth of microorganisms. [14] Antibiotics are not recommended in mild cases, but doctors may prescribe them in moderate to severe illness.
Studies have suggested that azithromycin or ciprofloxacin, may be the most effective antibiotics when treating Enteroaggregative E.coli (EAEC) infections. If either antibiotic isn't effective after 24 hours, a 3-day course of rifaximin is recommended. Unfortunately, resistance toward ciprofloxacin in Enteroaggregative E.coli (EAEC) strains has been reported in several studies. [15]
For most people treatments include rest and the intake of fluids. Patients with profuse diarrhea or vomit should be rehydrated by drinking much water or by drinking rehydration solutions such as Rehydralyte or Pedialyte. [16]
EAEC is transmitted through the fecal-oral route and primarily contaminated by food and water. [17] EAEC has been associated with many symptoms such as diarrhea in some individuals and intestinal colonization in others. [18] Because many strains of EAEC have been identified, it is difficult to identify the mechanism of its pathogenesis. Most candidate virulence genes are not always connected with disease. [10] The model of EAEC pathogenesis comprises three stages: Stage 1 is the attachment of the intestinal mucosa by aggregative adherence fimbriae (AAF) and other adhering projections, Stage 2 an increase in mucus that covers EAEC on its surface of enterocytes is found; Stage 3 evocation of an inflammatory response, mucosal toxicity, and intestinal secretion as well as a release of toxins exist.[ citation needed ]
Stage One: Aggregative adherence factors (AAF) are responsible for the adhesion to the intestinal mucosa. AAF are made up of three fimbriae encoded by the pAA plasmid; aagaafAagg-3. aggA is in charge of aggregative phenotype and human erythrocyte haemagglutination of EAEC. aafA allows EAEC to adhere to the intestinal mucosa. agg-3 serves as an adhesion. MAP, three-membrane associated proteins, are essential in the EAEC adherence to haemagglutination of animal cells. [10]
Stage two: After AAF factors in stage 1, adherence to the mucosa is characterized by the presence a biofilm. The production of biofilm is regulated by AggR and demands several genes. The loss of biofilm production and diffuse adherence pattern was reported in EAEC at a pH of 4.0. Many studies reveal that EAEC are capable of surviving in the mucus layer. This evidence can support why malnourished children who are infected with EAEC and live in poor conditions develop mucoid stools and prolonged diarrhea. [10]
Stage Three: Cytotoxic effects are found in the release of toxins in EAEC as well as an elicitation of the inflammatory response, mucosal toxicity, and intestinal secretion. EAEC toxins are destructive to the intestinal villi and enterocytes. There are three toxins found in EAEC; plasmid encoded toxin (Pet), heat-stable toxin (EAST1), and Shigella enterotoxin 1 (ShET1). [10]
E. coli has been involved as agents of diarrheal disease since 1920. Enteroaggregative Escheichia coli (EAEC) was first found in 1987, in a child in Lima, Peru. [19] Since 1987, Enteroaggregative Escheichia coli (EAEC) has been recognized as agents of diarrhea in industrialized and developing countries. Enteroaggregative Escheichia coli (EAEC) is most commonly found in developing countries due to less developed industrial base and low human development (HDI) compared to other countries. India, Jamaica and Mexico are the most commonly risked countries.[ citation needed ]
Escherichia coli ( ESH-ə-RIK-ee-ə KOH-lye) is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes such as EPEC, and ETEC are pathogenic and can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. Most strains are part of the normal microbiota of the gut and are harmless or even beneficial to humans (although these strains tend to be less studied than the pathogenic ones). For example, some strains of E. coli benefit their hosts by producing vitamin K2 or by preventing the colonization of the intestine by pathogenic bacteria. These mutually beneficial relationships between E. coli and humans are a type of mutualistic biological relationship — where both the humans and the E. coli are benefitting each other. E. coli is expelled into the environment within fecal matter. The bacterium grows massively in fresh fecal matter under aerobic conditions for three days, but its numbers decline slowly afterwards.
Escherichia coli O157:H7 is a serotype of the bacterial species Escherichia coli and is one of the Shiga-like toxin–producing types of E. coli. It is a cause of disease, typically foodborne illness, through consumption of contaminated and raw food, including raw milk and undercooked ground beef. Infection with this type of pathogenic bacteria may lead to hemorrhagic diarrhea, and to kidney failure; these have been reported to cause the deaths of children younger than five years of age, of elderly patients, and of patients whose immune systems are otherwise compromised.
Dysentery, historically known as the bloody flux, is a type of gastroenteritis that results in bloody diarrhea. Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation. Complications may include dehydration.
Shigella is a genus of bacteria that is Gram-negative, facultatively anaerobic, non–spore-forming, nonmotile, rod-shaped, and is genetically closely related to Escherichia. The genus is named after Kiyoshi Shiga, who discovered it in 1897.
Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial origin of dysentery caused by Shigella dysenteriae. Shiga-like toxin (SLT) is a historical term for similar or identical toxins produced by Escherichia coli. The most common sources for Shiga toxin are the bacteria S. dysenteriae and some serotypes of Escherichia coli, which include serotypes O157:H7, and O104:H4.
Enteritis is inflammation of the small intestine. It is most commonly caused by food or drink contaminated with pathogenic microbes, such as Serratia, but may have other causes such as NSAIDs, radiation therapy as well as autoimmune conditions like coeliac disease. Symptoms include abdominal pain, cramping, diarrhoea, dehydration, and fever. Related diseases of the gastrointestinal system involve inflammation of the stomach and large intestine.
Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney injury, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea progresses. Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. Adults, especially the elderly, may present a more complicated presentation. Complications may include neurological problems and heart failure.
Coliform bacteria are defined as either motile or non-motile Gram-negative non-spore forming bacilli that possess β-galactosidase to produce acids and gases under their optimal growth temperature of 35–37 °C. They can be aerobes or facultative aerobes, and are a commonly used indicator of low sanitary quality of foods, milk, and water. Coliforms can be found in the aquatic environment, in soil and on vegetation; they are universally present in large numbers in the feces of warm-blooded animals as they are known to inhabit the gastrointestinal system. While coliform bacteria are not normally causes of serious illness, they are easy to culture, and their presence is used to infer that other pathogenic organisms of fecal origin may be present in a sample, or that said sample is not safe to consume. Such pathogens include disease-causing bacteria, viruses, or protozoa and many multicellular parasites. Every drinking water source must be tested for the presence of these total coliform bacteria.
Shigella flexneri is a species of Gram-negative bacteria in the genus Shigella that can cause diarrhea in humans. Several different serogroups of Shigella are described; S. flexneri belongs to group B. S. flexneri infections can usually be treated with antibiotics, although some strains have become resistant. Less severe cases are not usually treated because they become more resistant in the future. Shigella are closely related to Escherichia coli, but can be differentiated from E.coli based on pathogenicity, physiology and serology.
Enterotoxigenic Escherichia coli (ETEC) is a type of Escherichia coli and one of the leading bacterial causes of diarrhea in the developing world, as well as the most common cause of travelers' diarrhea. Insufficient data exists, but conservative estimates suggest that each year, about 157,000 deaths occur, mostly in children, from ETEC. A number of pathogenic isolates are termed ETEC, but the main hallmarks of this type of bacterium are expression of one or more enterotoxins and presence of fimbriae used for attachment to host intestinal cells. The bacterium was identified by the Bradley Sack lab in Kolkata in 1968.
The discovery of disease-causing pathogens is an important activity in the field of medical science. Many viruses, bacteria, protozoa, fungi, helminths, and prions are identified as a confirmed or potential pathogen. In the United States, a Centers for Disease Control and Prevention program, begun in 1995, identified over a hundred patients with life-threatening illnesses that were considered to be of an infectious cause but that could not be linked to a known pathogen. The association of pathogens with disease can be a complex and controversial process, in some cases requiring decades or even centuries to achieve.
Enteroinvasive Escherichia coli (EIEC) is a type of pathogenic bacteria whose infection causes a syndrome that is identical to shigellosis, with profuse diarrhea and high fever. EIEC 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.
A novel strain of Escherichia coli O104:H4 bacteria caused a serious outbreak of foodborne illness focused in northern Germany in May through June 2011. The illness was characterized by bloody diarrhea, with a high frequency of serious complications, including hemolytic–uremic syndrome (HUS), a condition that requires urgent treatment. The outbreak was originally thought to have been caused by an enterohemorrhagic (EHEC) strain of E. coli, but it was later shown to have been caused by an enteroaggregative E. coli (EAEC) strain that had acquired the genes to produce Shiga toxins, present in organic fenugreek sprouts.
Escherichia coli O104:H4 is an enteroaggregative Escherichia coli strain of the bacterium Escherichia coli, and the cause of the 2011 Escherichia coli O104:H4 outbreak. The "O" in the serological classification identifies the cell wall lipopolysaccharide antigen, and the "H" identifies the flagella antigen.
Shigatoxigenic Escherichia coli (STEC) and verotoxigenic E. coli (VTEC) are strains of the bacterium Escherichia coli that produce Shiga toxin. Only a minority of the strains cause illness in humans. The ones that do are collectively known as enterohemorrhagic E. coli (EHEC) and are major causes of foodborne illness. When infecting the large intestine of humans, they often cause gastroenteritis, enterocolitis, and bloody diarrhea and sometimes cause a severe complication called hemolytic-uremic syndrome (HUS). Cattle are an important natural reservoir for EHEC because the colonised adult ruminants are asymptomatic. This is because they lack vascular expression of the target receptor for Shiga toxins. The group and its subgroups are known by various names. They are distinguished from other strains of intestinal pathogenic E. coli including enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC), and diffusely adherent E. coli (DAEC).
Escherichia coli is a gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms (endotherms). Most E. coli strains are harmless, but pathogenic varieties cause serious food poisoning, septic shock, meningitis, or urinary tract infections in humans. Unlike normal flora E. coli, the pathogenic varieties produce toxins and other virulence factors that enable them to reside in parts of the body normally not inhabited by E. coli, and to damage host cells. These pathogenic traits are encoded by virulence genes carried only by the pathogens.
In biology, a pathogen, in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.
Campylobacter coli is a Gram-negative, microaerophilic, non-endospore-forming, S-shaped bacterial species within genus Campylobacter. In humans, C. coli can cause campylobacteriosis, a diarrhoeal disease which is the most frequently reported foodborne illness in the European Union. C. coli grows slowly with an optimum temperature of 42 °C. When exposed to air for long periods, they become spherical or coccoid shaped.
Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.