Enteroaggregative Escherichia coli

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Enteroaggregative Escherichia coli
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.

Contents

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]

Classification

Developing Countries in 2007 Developing countries 2007.jpg
Developing Countries in 2007

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]

Symptoms and Causes

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

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 ]

Treatment

Chemical structure of ciprofloxacin Ciprofloxacin.svg
Chemical structure of ciprofloxacin

Antibiotics is a type of medicine that is used to destroy or inhibit the growth of microorganisms. [14] Studies have suggested that fluoroquinolone, especially ciprofloxacin, may be the most effective antibiotic when treating Enteroaggregative E.coli (EAEC) infections, patients treated with ciprofloxacin had significant reductions in duration of diarrhea. Unfortunately resistance toward ciprofloxacin in Enteroaggregative E.coli (EAEC) strains has been reported in several studies.[ citation needed ]

For most people treatments include, rest and the intake of fluids. For patients with profuse diarrhea or vomit should be rehydrated by drinking much water or by drinking rehydration solutions such as Rehydralyte or Pedialyte. [15]

Pathogenesis

E. coli fimbriae E. coli fimbriae.png
E. coli fimbriae

EAEC is transmitted through the fecal-oral route and primarily contaminated by food and water. [16] EAEC has been associated with many symptoms such as diarrhea in some individuals and intestinal colonization in others. [17] 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]

History

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. [18] 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 ]

Related Research Articles

<i>Escherichia coli</i> Enteric, rod-shaped, gram-negative bacterium

Escherichia coli ( ESH-ə-RIK-ee-ə KOH-ly) 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.

<i>Escherichia coli</i> O157:H7 Serotype of the bacteria Escherichia coli

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.

<i>Shigella</i> Genus of bacteria

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.

<span class="mw-page-title-main">Shiga toxin</span> Family of related toxins

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 (STEC), which includes serotypes O157:H7, and O104:H4.

Virulence is a pathogen's or microorganism's ability to cause damage to a host.

<span class="mw-page-title-main">Hemolytic–uremic syndrome</span> Group of blood disorders related to bacterial infection

Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney failure, 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.

<span class="mw-page-title-main">Coliform bacteria</span> Group of bacterial species

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.

Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor.

<i>Shigella flexneri</i> Species of bacterium

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.

Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:

<span class="mw-page-title-main">Intimin</span>

Intimin is a virulence factor (adhesin) of EPEC and EHEC E. coli strains. It is an attaching and effacing (A/E) protein, which with other virulence factors is necessary and responsible for enteropathogenic and enterohaemorrhagic diarrhoea.

Escherichia coli O104:H21 is a rare serotype of Escherichia coli, a species of bacteria that lives in the lower intestines of mammals. Although there are many serotypes of E. coli, when in animals, there are benefits or do not cause disease. Some serotypes of E. coli have been recognized as pathogenic to humans, e.g. E. coli O157:H7, E. coli O121 and E. coli O104:H21.

The discovery of disease-causing pathogens is an important activity in the field of medical science. Many viruses, bacteria, protozoa, fungi, helminthes and prions are identified as a confirmed or potential pathogen. In the United States, a Centers for Disease Control 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.

2011 Germany <i>E. coli</i> O104:H4 outbreak 2011 foodborne illness outbreak in northern Germany

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 is 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).

Pathogenic <i>Escherichia coli</i> Strains of E. coli that can cause disease

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.

Campylobacter coli is a Gram-negative, microaerophilic, non-endospore-forming, S-shaped bacterial species within genus Campylobacter. In humans, it 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.

P fimbriae or P pili or Pap are chaperone-usher type fimbrial appendages found on the surface of many Escherichia coli bacteria. The P fimbriae is considered to be one of the most important virulence factor in uropathogenic E. coli and plays an important role in upper urinary tract infections. P fimbriae mediate adherence to host cells, a key event in the pathogenesis of urinary tract infections.

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