[[File:EAEC Prager etal.jpg|thumb|Enteroaggregative E. coli strain EAEC 042 aggregates during infection of Hep-2 cells.]]
| name = Enteroaggregative Escherichia coli
'''Enteroaggregative ''Escherichia coli''''' ('''EAEC''' or '''EAggEC''') are a pathotype of ''[[Escherichia coli]]'' associated with acute and chronic diarrhea in both the developed and developing world.<ref>{{Cite journal|last=Nataro|first=J. P.|last2=Mai|first2=V.|last3=Johnson|first3=J.|last4=Blackwelder|first4=W. C.|last5=Heimer|first5=R.|last6=Tirrell|first6=S.|last7=Edberg|first7=S. C.|last8=Braden|first8=C. R.|last9=Morris|first9=J. G.|date=2006-08-15|title=Diarrheagenic Escherichia coli Infection in Baltimore, Maryland, and New Haven, Connecticut|url=https://academic.oup.com/cid/article/43/4/402/387393/Diarrheagenic-Escherichia-coli-Infection-in|journal=Clinical Infectious Diseases|language=en|volume=43|issue=4|pages=402–407|doi=10.1086/505867|pmid=16838226|issn=1058-4838}}</ref><ref>{{Cite journal|last=Hebbelstrup Jensen|first=Betina|last2=Olsen|first2=Katharina E. P.|last3=Struve|first3=Carsten|last4=Krogfelt|first4=Karen Angeliki|last5=Petersen|first5=Andreas Munk|date=2017-02-03|title=Epidemiology and Clinical Manifestations of Enteroaggregative Escherichia coli|journal=Clinical Microbiology Reviews|volume=27|issue=3|pages=614–630|doi=10.1128/CMR.00112-13|issn=0893-8512|pmc=4135892|pmid=24982324}}</ref> EAEC are defined by their "stacked-brick" pattern of adhesion to the human laryngeal epithelial cell line HEp-2.<ref>{{Cite journal|last=Nataro|first=J. P.|last2=Kaper|first2=J. B.|last3=Robins-Browne|first3=R.|last4=Prado|first4=V.|last5=Vial|first5=P.|last6=Levine|first6=M. M.|date=1987-09-01|title=Patterns of adherence of diarrheagenic Escherichia coli to HEp-2 cells|url=https://www.ncbi.nlm.nih.gov/pubmed?cmd=Retrieve&db=PubMed&list_uids=3313248&dopt=Abstract|journal=The Pediatric Infectious Disease Journal|volume=6|issue=9|pages=829–831|issn=0891-3668|pmid=3313248|doi=10.1097/00006454-198709000-00008}}</ref> The [[pathogenesis]] of EAEC involves the aggregation of and adherence of the bacteria to the intestinal [[mucosa]], where they elaborate [[enterotoxin]]s and [[cytotoxin]]s that damage host cells and induce [[inflammation]] that results in [[diarrhoea|diarrhea]].
| image = [[File:EAEC_Prager_etal.jpg|250px]]
| caption = Micrograph of Enteroaggregative ''Escherichia coli'' (EAEC)
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.<ref>{{Cite journal|last=Huang|first=David B.|last2=Mohanty|first2=Alakananda|last3=DuPont|first3=Herbert L.|last4=Okhuysen|first4=Pablo C.|last5=Chiang|first5=Tom|date=2006-10-01|title=A review of an emerging enteric pathogen: enteroaggregative Escherichia coli|journal=Journal of Medical Microbiology|volume=55|issue=Pt 10|pages=1303–1311|doi=10.1099/jmm.0.46674-0|issn=0022-2615|pmid=17005776}}</ref><ref>{{Cite journal|url=http://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/32/12/10.1086/320756/2/32-12-1706.pdf?Expires=1486430967&Signature=dS8rswpDqMQnSEzj5dNbpCXXyuO-j1hd5Ek3nwr5cGFvvDEt2gZnXfFiPvqUkyAe4uC6we~kLbpqSxEh0NXKE-UeRTCBZOfbpxdCMEqZx-cRqAI2D0-A62-CYXuutl8KL-aOddVvXXUY9feka9TYdwxGLF6rbb3URoMpw5GIRzGKcdxYPZNBW-FH9b1KBnFYtA4KPrwCm7qq5rgPQIiTa-8HK1~okuRkZRZbil6ffSNzWDMWtSJrOfw115GBDslzUfMsQUyDwzI0sGzpF9JMhga4owpkO8BBSBwVx9JmR-iT~BC0KlilWppwdCGKvVui7AEdCEHacZj20-iVSNsiNQ__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q|title=Enteroaggregative Escherichia coli as a Major Etiologic Agent in Traveler's Diarrhea in 3 Regions of the World|doi=10.1086/320756|pmid=11360211|vauthors=Adachi JA, Jiang ZD, Mathewson JJ, Verenkar MP, Thompson S, Martinez-Sandoval F, Steffen R, Ericsson CD, DuPont HL|journal=Clin Infect Dis|year=2001|volume=32|issue=12|pages=1706–9}}</ref> It has also been associated with chronic infections in the latter, as well as in immunocompromised hosts, such as [[HIV]]-infected individuals.<ref>{{cite journal|author=Huang, D. B. |displayauthors=etal |year=2006 |title=A review of an emerging enteric pathogen: enteroaggregative ''Escherichia coli'' |journal=Journal of Medical Microbiology |volume=55 |issue=10 |pages=1303–1311 |pmid=17005776 |doi=10.1099/jmm.0.46674-0 }}</ref> Awareness of EAEC was increased by a [[2011 Germany E. coli O104:H4 outbreak|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 [[Verotoxin-producing Escherichia coli|Shiga toxin-producing ''Escherichia coli'']], which often encode the adhesin intimin).<ref>{{Cite journal|last=Kalita|first=Anjana|last2=Hu|first2=Jia|last3=Torres|first3=Alfredo G.|date=2017-02-01|title=Recent advances in adherence and invasion of pathogenic Escherichia coli|journal=Current Opinion in Infectious Diseases|volume=27|issue=5|pages=459–464|doi=10.1097/QCO.0000000000000092|issn=0951-7375| pmc=4169667 |pmid=25023740}}</ref><ref>{{cite journal|author1=Nadia Boisen|author2=Angela R. Melton-Celsa|author3=Flemming Scheutz|author4=Alison D. O'Brien|author5=James P. Nataro|year=2015|title=Shiga toxin 2a and Enteroaggregative ''Escherichia coli''—a deadly combination|journal=Gut Microbes|volume=6|issue=4|pages=272–278|doi=10.1080/19490976.2015.1054591|pmid=26039753|pmc=4615819}}</ref> The putative cause of the outbreak were sprouted fenugreek seeds.<ref>{{Cite web|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6250a3.htm|title=Outbreak of Escherichia coli O104:H4 Infections Associated with Sprout Consumption — Europe and North America, May–July 2011|website=www.cdc.gov|language=en|access-date=2017-02-01}}</ref>
| field = [[Infectious disease]]
| synonyms = EAEC
Strains of EAEC are highly genetically heterogeneous, and the identification of virulence factors important for pathogenesis has proven difficult.<ref>{{Cite journal|last=Harrington|first=Susan M.|last2=Dudley|first2=Edward G.|last3=Nataro|first3=James P.|date=2006-01-01|title=Pathogenesis of enteroaggregative Escherichia coli infection|journal=FEMS Microbiology Letters|language=en|volume=254|issue=1|pages=12–18|doi=10.1111/j.1574-6968.2005.00005.x|pmid=16451173|issn=1574-6968}}</ref> 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.<ref>{{Cite journal|last=Ruan|first=Xiaosai|last2=Crupper|first2=Scott S.|last3=Schultz|first3=Bruce D.|last4=Robertson|first4=Donald C.|last5=Zhang|first5=Weiping|date=2012-08-15|title=Escherichia coli Expressing EAST1 Toxin Did Not Cause an Increase of cAMP or cGMP Levels in Cells, and No Diarrhea in 5-Day Old Gnotobiotic Pigs|journal=PLOS ONE|volume=7|issue=8|pages=e43203|doi=10.1371/journal.pone.0043203|issn=1932-6203| pmc=3419656 |pmid=22905235}}</ref>
More recently, a study of symptomatic children in Mali has led to increased interest in specific sets of EAEC virulence factors. The study utilized Classification and Regression Tree analysis, or CART analysis, to identify sets of EAEC factors which were implicated in virulence amongst pediatric patients who presented with acute diarrhea. The researchers found that a subset which encoded the gene for the cryptic serine protease SepA, previously described in ''Shigella'', and lacking the transcriptional regulator of hemolysin expression, ''rmoA'' were associated with virulence. Furthermore, a set of EAEC which encoded the flagellar antigen H33 and the EAST-1 toxin were associated with diarrhea. These results and more recent efforts have suggested that a specific set of virulence determinants may be more important in pathogenesis of EAEC than the presence or absence of singular virulence factors.<ref>{{Cite journal|last=Boisen|first=Nadia|last2=Scheutz|first2=Flemming|last3=Rasko|first3=David A.|last4=Redman|first4=Julia C.|last5=Persson|first5=Søren|last6=Simon|first6=Jakub|last7=Kotloff|first7=Karen L.|last8=Levine|first8=Myron M.|last9=Sow|first9=Samba|date=2012-02-01|title=Genomic Characterization of Enteroaggregative Escherichia coli From Children in Mali|journal=The Journal of Infectious Diseases|volume=205|issue=3|pages=431–444|doi=10.1093/infdis/jir757|issn=0022-1899| pmc=3256949 |pmid=22184729}}</ref>
| onset = 1-3 days after exposure
| duration = 3-10 days
== References ==
| causes = [[Escherichia coli]] infection
{{reflist}}
| risks = Poor sanitation, contaminated food or water
'''Enteroaggregative ''Escherichia coli''''' ('''EAEC''' or '''EAggEC''') is a distinct [[pathotype]] of the bacterium ''[[Escherichia coli]]'' (''E. coli'') that is associated with both acute and chronic [[diarrhea]] in individuals from both the [[developed world|developed]] and [[developing world]]. EAEC is recognized for its characteristic adherence pattern and the damage it causes to the intestinal mucosa.
== Characteristics ==
EAEC is defined by its unique ''stacked-brick'' pattern of adhesion to [[HEp-2 cells]], which are derived from a human laryngeal epithelial carcinoma cell line. This pattern is observed in vitro and is used as a diagnostic criterion for identifying this pathotype.
== Pathogenesis ==
The disease process of EAEC involves:
* Adherence to the [[intestinal mucosa]] using aggregative [[fimbriae]].
* Formation of a biofilm that enhances colonization and protects the bacteria from the host immune system.
* Production of [[enterotoxins]] and [[cytotoxins]] that disrupt the [[intestinal epithelium]].
* Induction of an [[inflammatory response]], leading to mucosal damage and diarrhea.
== Clinical Significance ==
EAEC has been implicated in a wide range of diarrheal illnesses, including:
* Persistent diarrhea in children
* Traveler’s diarrhea
* Diarrhea in immunocompromised individuals, such as patients with [[HIV/AIDS]]
It is also a known contributor to [[malnutrition]] in young children due to chronic gastrointestinal inflammation and nutrient loss.
== Diagnosis ==
Diagnosis of EAEC may involve:
* Stool culture followed by adherence assays using HEp-2 or HeLa cells.
* Molecular methods such as [[polymerase chain reaction]] (PCR) to detect EAEC-specific genes (e.g., ''aggR'', ''aaiC'').
== Treatment ==
Management generally includes:
* [[Oral rehydration therapy]] to prevent dehydration.
* In some cases, [[antibiotics]] such as [[ciprofloxacin]] or [[rifaximin]] may be prescribed, particularly in severe or persistent cases, although antibiotic resistance is an emerging concern.
Enteroaggregative Escherichia coli (EAEC or EAggEC) is a distinct pathotype of the bacterium Escherichia coli (E. coli) that is associated with both acute and chronic diarrhea in individuals from both the developed and developing world. EAEC is recognized for its characteristic adherence pattern and the damage it causes to the intestinal mucosa.
EAEC is defined by its unique stacked-brick pattern of adhesion to HEp-2 cells, which are derived from a human laryngeal epithelial carcinoma cell line. This pattern is observed in vitro and is used as a diagnostic criterion for identifying this pathotype.
In some cases, antibiotics such as ciprofloxacin or rifaximin may be prescribed, particularly in severe or persistent cases, although antibiotic resistance is an emerging concern.
