enteroaggregative Escherichia coli
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Enteroaggregative ''Escherichia coli'' (EAEC or EAggEC) are a
pathotype A pathovar is a bacterial strain or set of strains with the same or similar characteristics, that is differentiated at infrasubspecific level from other strains of the same species or subspecies on the basis of distinctive pathogenicity to one o ...
of ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' which cause acute and chronic diarrhea in both the developed and developing world. They may also cause
urinary tract infections A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...
. EAEC are defined by their "stacked-brick" pattern of adhesion to the human laryngeal epithelial cell line HEp-2. The
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
of EAEC involves the aggregation of and adherence of the bacteria to the intestinal
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
, where they elaborate
enterotoxin An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines. Enterotoxins are chromosomally encoded or plasmid encoded exotoxins that are produced and secreted from several bacterial organisms. They are heat labi ...
s and
cytotoxin Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating c ...
s that damage host cells and induce
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
that results in
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
. 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. It has also been associated with chronic infections in the latter, as well as in immunocompromised hosts, such as
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
-infected individuals. 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 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 orig ...
encoding phage (typically associated with Shiga toxin-producing ''Escherichia coli'', which often encode the adhesin intimin). The putative cause of the outbreak were sprouted fenugreek seeds. Strains of EAEC are highly genetically heterogeneous, and the identification of virulence factors important for pathogenesis has proven difficult. 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.


Classification

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. The cause of infectious diarrhea is diarrheagenic Escheriachia coli (DEC) group. Subgroups of diarrheagenic Escheriachia coli (DEC) are the following: enteroinvasive ''E. coli'' (EIEC), enteropathogenic ''E. coli'' (EPEC), enterotoxigenic ''E.coli'' (ETEC),
Shiga is a Prefectures of Japan, prefecture of Japan located in the Kansai region of Honshu. Shiga Prefecture has a population of 1,412,916 (1 October 2015) and has a geographic area of . Shiga Prefecture borders Fukui Prefecture to the north, Gifu Pr ...
toxin-producing ''E. coli'' (STEC) and Enteroaggregative ''E. coli'' (EAEC). ''E. coli'' is a bacterium that is found in the intestines, its mostly harmless, but some strains of bacteria can cause illness and infection


Symptoms and Causes

Enteroaggregative Escheichia coli (EAEC) is a type of strain from ''
E.coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Esche ...
. 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'', this is the incubation period. The incubation period is the time between catching an infection and symptoms appearing. Symptoms: * abdominal cramping, pain or tenderness * watery or mucoidy diarrhea * nausea and vomiting, in some people Bloody diarrhea has only been observed in children, and only rarely. On the other hand, the STEC-EAEC hybrid strain identified in the 2011 Germany outbreak caused bloody diarrhea. The bacteria that causes the infection can enter your body in numerous ways * contaminated water – Human and animal feces may pollute ground and surface water, including streams, lakes, rivers, and water used to water or irrigate crops. Although public water systems use chlorine and other chemicals to kill such organisms like ''E. coli'', some outbreaks have been linked to contaminated water supplies. * contaminated food – most common way to get a ''E.coli'' infection is by eating contaminated food such as ground beef, unpasteurized milk and fresh produce. * improper food handling – by consuming raw food, or not cooking the food properly, especially meats and poultry. It can also be transmitted by not cleaning your cooking utensils properly, causing cross contamination. * person to person – ''E.coli'' can be easily transmitted from person to person, especially when infected children and adults don't wash their hands properly.


Diagnosis

Diagnosis of infectious diarrhea and identification of antimicrobial resistance is performed using a
stool culture A stool test is a medical diagnostic technique that involves the collection and analysis of fecal matter. Microbial analysis (culturing), microscopy and chemical tests are among the tests performed on stool samples. Collection Stool samples shoul ...
with subsequent
antibiotic sensitivity testing Antibiotic sensitivity testing or antibiotic susceptibility testing is the measurement of the susceptibility of bacteria to antibiotics. It is used because bacteria may have resistance to some antibiotics. Sensitivity testing results can allow ...
. 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 Clinical point of care (POC) is the point in time when clinicians deliver healthcare products and services to patients at the time of care. Clinical documentation Clinical documentation is a record of the critical thinking and judgment of a health ...
molecular diagnostic Molecular diagnostics is a collection of techniques used to analyze biological markers in the genome and proteome, and how their cells express their genes as proteins, applying molecular biology to medical testing. In medicine the technique i ...
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.


Treatment

Antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s is a type of medicine that is used to destroy or inhibit the growth of microorganisms. Studies have suggested that
fluoroquinolone A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as wel ...
, 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. 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 Pedialyte is an oral electrolyte solution manufactured by Abbott Laboratories and marketed for use in children. It was invented by Dr. Gary Cohen of Swampscott, Massachusetts. Description Pedialyte is designed to promote rehydration and electr ...
.


Pathogenesis

EAEC is transmitted through the fecal-oral route and primarily contaminated by food and water. EAEC has been associated with many symptoms such as diarrhea in some individuals and intestinal colonization in others. Because many strains of EAEC have been identified, it is difficult to identify the mechanism of its pathogenesis. Most candidate
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...
genes are not always connected with disease. The model of EAEC
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
comprises three stages: Stage 1 is the attachment of the intestinal
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
by aggregative adherence fimbriae (AAF) and other adhering projections, Stage 2 an increase in mucus that covers EAEC on its surface of
enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its ...
s is found; Stage 3 evocation of an
inflammatory response Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
, mucosal toxicity, and intestinal secretion as well as a release of toxins exist. 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; ''aag'' ''aafA'' ''agg-3''. aggA is in charge of aggregative phenotype and human
erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
haemagglutination Hemagglutination, or haemagglutination, is a specific form of agglutination that involves red blood cells (RBCs). It has two common uses in the laboratory: blood typing and the quantification of virus dilutions in a haemagglutination assay. Blood ...
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. Stage two: After AAF factors in stage 1, adherence to the mucosa is characterized by the presence a
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...
. 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. Stage Three:
Cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...
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 Intestinal villi (singular: villus) are small, finger-like projections that extend into the lumen of the small intestine. Each villus is approximately 0.5–1.6 mm in length (in humans), and has many microvilli projecting from the enterocy ...
and enterocytes. There are three toxins found in EAEC; plasmid encoded toxin (Pet), heat-stable toxin (EAST1), and ''
Shigella ''Shigella'' is a genus of bacteria that is Gram-negative, facultative anaerobic, non-spore-forming, nonmotile, rod-shaped, and genetically closely related to ''E. coli''. The genus is named after Kiyoshi Shiga, who first discovered it in 1897. ...
'' enterotoxin 1 (ShET1).


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. 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.


References

{{Escherichia coli Escherichia coli