Disease relevance of eae

• Norepinephrine was effective in promoting cecal adherence of a non-O157 E. coli strain as well as E. coli O157:H7 eae or espA mutant strains that are incapable of intimate mucosal attachment [1].
• Enterohemorrhagic E. coli (EHEC) strains also possess an eae gene and are capable of intimate attachment and microvillus effacement in vitro and in animal models [2].
• The predicted amino acid sequence derived from the nucleotide sequence of eae shows significant homology to that of the invasin of Yersinia pseudotuberculosis [3].
• However, in spite of being eae negative, STEC strains belonging to serogroup O113 have frequently been associated with cases of severe STEC disease, including hemolytic-uremic syndrome (HUS) [4].
• Our findings suggest that the eae locus of C. freundii biotype 4280 is necessary for AE activity and has a role in the pathogenesis of transmissible murine colonic hyperplasia [5].

High impact information on eae

• Intimate attachment in vivo was restored when the EHEC eae gene or the eaeA gene of EPEC was introduced into the mutant on a plasmid [2].
• Other non-invasive EPEC mutants (eae) are still able to induce Hp90 tyrosine phosphorylation and to initiate aggregation of the tyrosine phosphorylated proteins and some cytoskeleton components [6].
• Using TnphoA mutagenesis we have identified a chromosomal gene (eae, for E. coli attaching and effacing) that is necessary for this activity [3].
• SdiA has a DNA-binding motif in its C-terminal part and can bind to the promoter regions of the esp and eae genes in vitro [7].
• The 90 kDa protein was revealed to be intimin, a protein product of the eae gene, which is required for the EPEC attaching/effacing phenotype, suggesting a direct interaction of TrcA with intimin in the cytoplasmic compartment [8].

Chemical compound and disease context of eae

• The bacterial isolate was an enteropathogenic E. coli isolate which did not contain the adherence factor (EAF) but possessed the attaching-effacing eae gene, was able to invade HeLa cells in a gentamicin invasion assay, and also invaded rabbit intestinal cells [9].
• Thus, eae-positive, necrotoxigenic, and verotoxigenic (except for nalidixic acid) E. coli strains were significantly more sensitive to nalidixic acid, enoxacin, and enrofloxacin than nonfimbriated, nontoxigenic, eae-negative strains [10].
• We conclude that enteropathogenic E. coli strains that possess the eae gene are a common cause of diarrhea in Spanish rabbit farms and that the rhamnose-negative highly pathogenic strains of serotype O103:K-:H2 and biotype B14 are especially predominant [11].
• The strains were initially identified as Hafnia alvei with a commercial identification system and were reported to contain the eae gene of enteropathogenic Escherichia coli [12].
• The 32 sorbitol-positive strains tested negative for stx genes and belonged to the serotypes O157:H2, O157:H7, O157:H8, O157:H12, O157:H19, O157:H25, O157:H27, O157:H38, O157:H43, O157:H45, and O157:H-. All O157:H45 strains harbored the eae subtype alpha 1 and therefore seem to be atypical enteropathogenic E. coli strains [13].

Biological context of eae

• The predicted amino acid sequence of the EHEC eae gene shared 31% identity and 51% similarity with invasin of Yersinia pseudotuberculosis [14].
• The intimin (eae) gene is part of a pathogenicity island, a 35-kb segment of DNA that has been acquired independently in different groups of pathogens [15].
• We amplified their complete eae genes, contrasting them with those of SLT-producing E. coli O157 by restriction fragment length polymorphism analysis and nucleotide sequence analysis of a 400-bp stretch of the 3' end of eae [16].
• However, it was absent from the genome of all 37 O157:H7/H(-), 14 O111:H(-), 13 O103:H2, and 13 O145:H(-) STEC isolates, all of which were positive for eae [17].
• Sequences homologous to those of an eae gene probe were detected in EPEC, RDEC-1, and EHEC isolates [18].

Anatomical context of eae

• The genes encoding the proteins for A/E lesion formation are located on a pathogenicity island, termed the locus of enterocyte effacement (LEE), which contains eae encoding intimin as well as the type III secretion system and effector genes [19].
• HeLa cell adherence, actin aggregation, and invasion by nonenteropathogenic Escherichia coli possessing the eae gene [20].
• LEE contains the eae gene, which encodes intimin, an outer membrane protein which mediates the intimate attachment of bacteria to the host epithelial cell surface, and eae is routinely used as a marker for LEE-positive STEC strains [21].
• Following washing out of the nonadherent bacteria, while wild-type EHEC bacteria developed MC for another 2 to 3 h on Caco-2 cells, the eae mutant diffusely adhered throughout the infection without forming MC [22].
• Complementing the eae gene mutation in CVD206 (derived from EPEC strain E2348/69) with EPEC eaealpha (encoding intimin-alpha) restored the ability to colonize small intestinal mucosa like the parent strain [23].

Associations of eae with chemical compounds

• Moreover, eae-positive strains were significantly more sensitive to enoxacin and enrofloxacin than F5-positive strains [10].
• VTEC O26 strains from calves were characterized by the presence of the vtx1, eae, and ehxA genes, whereas vtx2 was associated with VTEC O2 and provisional serogroup E40874 [24].
• All nine human isolates obtained were sorbitol negative, carried the verocytotoxin 2 and eae genes, and produced verocytotoxin and enterohaemolysin [25].
• The isolates did not ferment sorbitol, rhamnose, sucrose or melibiose; they belonged to serogroup O86:K61, produced cytolethal distending toxin (CLDT) and possessed the eae gene sequence [26].
• Serotype-specific detection of STEC O26 was achieved by selecting cefixime-tellurite-resistant, MUG-fluorescent, rhamnose-nonfermenting colonies, which carried stx1, eae beta, irp2, and wzx gene sequences [27].

Other interactions of eae

• Supernatants of wild-type EPEC strain E2348/69 and its isogenic mutants deficient in TTSS (escN) and in production of intimin (eae), grown in Luria-Bertani broth, elicited similar amounts of IL-8 secretion by T84 cells [28].
• Based on gene typing, we observed 7 different eae espA espB tir pathotypes among the 12 STEC strains and described the new espAbetav variant [29].
• Treatment of vesicles with exogenous DNase hydrolyzed surface-associated DNA; PCR demonstrated that vesicles contain DNA encoding the virulence genes eae, stx1 and stx2, and uidA, which encodes for beta-galactosidase [30].
• The three strains with the H32 fliC RFLP pattern belonged to serotype O26:H32, and all were eae negative [31].
• The ureC gene was more frequent among STEC isolates harbouring eae than among those lacking eae (p < 0.0001) [32].

Analytical, diagnostic and therapeutic context of eae

• To assess the role of the EHEC eae gene in intimate attachment, we constructed an eae deletion/insertion mutation in wild-type EHEC O157:H7 strain 86-24 by using linear electroporation of a recombinant allele [2].
• Based on these considerations, we developed a panel of specific primers to investigate the eae heterogeneity of the variable 3' region by using PCR amplification [33].
• In the second study, a control group and volunteers who had previously ingested either the O127:H6 strain or an isogenic eae deletion mutant of that strain were challenged with the homologous wild-type strain [34].
• We have now studied 13 STEC O157:H7 strains and 1 O55:H7 strain that were epidemiologically unrelated, that originated from six countries on two continents, and that had different profiles when analyzed by multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, and PCR for stx and eae [35].
• By serotyping and determination of the virulence-associated factors Shiga toxin (stx1 stx2 stx2 variants), intimin (eae), and EHEC hemolysin (Hly(EHEC)), three distinctive groups of O118 human pathogens were identified [36].

References