Description of a 111-kb pathogenicity island (PAI) encoding various virulence features in the enterohemorrhagic E. coli (EHEC) strain RW1374 (O103:H2) and detection of a similar PAI in other EHEC strains of serotype O103:H2

Jores, Joerg; Wagner, Sylke; Rumer, Leonid; Eichberg, J.; Laturnus, Claudia; Kirsch, Petra; Schierack, Peter; Tschäpe, Helmut; Wieler, Lothar H.

doi:10.1016/j.ijmm.2004.09.009

Cited by 22 publications

(24 citation statements)

References 36 publications

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“…In the VTEC O26:H11-related RDEC strains, LEE is immediately upstream of OI-122 (modules 2 and 3), cointegrated as a 58-kb mosaic island (33,44). A similar structure was found in EHEC serotype O103:H2 strains, where LEE is 43 kb downstream of OI-122 (modules 2 and 3), again physically linked in this 111-kb hybrid island (22). Given that the presence of both LEE and OI-122 is associated with the most pathogenic VTEC strains, the objective of this study was to investigate the patterns of acquisition of these genomic islands in VTEC.…”

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confidence: 68%

Genomic O Island 122, Locus for Enterocyte Effacement, and the Evolution of Virulent Verocytotoxin-ProducingEscherichia coli

et al. 2008

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The locus of enterocyte effacement (LEE) and genomic O island 122 (OI-122) are pathogenicity islands in verocytotoxin-producing Escherichia coli (VTEC) serotypes that are associated with outbreaks and serious disease. Composed of three modules, OI-122 may occur as "complete" (with all three modules) or "incomplete" (with one or two modules) in different strains. OI-122 encodes two non-LEE effector (Nle) molecules that are secreted by the LEE type III secretion system, and LEE and OI-122 are cointegrated in some VTEC strains. Thus, they are functionally linked, but little is known about the patterns of acquisition of these codependent islands. To examine this, we conducted a population genetics analysis, using multilocus sequence typing (MLST), with 72 VTEC strains (classified into seropathotypes A to E) and superimposed on the results the LEE and OI-122 contents of these organisms. The wide distribution of LEE and OI-122 modules among MLST clonal groups corroborates the hypothesis that there has been lateral transfer of both pathogenicity islands. Sequence analysis of a pagC-like gene in OI-122 module 1 also revealed two nonsynonymous single-nucleotide polymorphisms that could help discriminate a subset of seropathotype C strains and determine the presence of the LEE. A nonsense mutation was found in this gene in five less virulent strains, consistent with a decaying or inactive gene. The modular nature of OI-122 could be explained by the acquisition of modules by lateral transfer, either singly or as a group, and by degeneration of genes within modules. Correlations between clonal group, seropathotype, and LEE and OI-122 content provide insight into the role of genomic islands in VTEC evolution.Verocytotoxin-producing Escherichia coli (VTEC) and Shiga toxin-producing E. coli (STEC) are emerging zoonotic pathogens consisting of multiple serotypes, over 200 of which have been isolated from cases of human disease (48). Human infection by some VTEC serotypes, notably O157:H7, is associated with significant outbreaks and may lead to serious complications, such as hemorrhagic colitis and the hemolytic-uremic syndrome (HUS) (23,25,34). Karmali et al. (24) have classified VTEC into five seropathotype groups based on the relative frequency with which the serotypes are associated with serious and epidemic human disease (Table 1). There is a strong association between VTEC seropathotypes A and B that cause serious or epidemic disease and the presence of two genomic islands, the locus of enterocyte effacement (LEE), which is associated with the characteristic "attaching and effacing" lesions (20, 34), and genomic O island 122 (OI-122) (24).All of the virulence factors necessary for the formation of the attaching and effacing lesions in VTEC are encoded by the LEE pathogenicity island (18,20,34,47), which encodes the structural, accessory, and effector molecules of this type III secretion system (4,12,13,18,19). The LEE of VTEC serotype O157:H7 reference strain EDL 933, which is ϳ43.4 kb long, contains 41 open reading fram...

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confidence: 68%

Genomic O Island 122, Locus for Enterocyte Effacement, and the Evolution of Virulent Verocytotoxin-ProducingEscherichia coli

et al. 2008

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“…Parts of modules 4 and 5 (aec-61 to aec-78, with the exception of aec-65 and aec-66, which encode transposases) are also found with the same organization in the 111-kb PAI of the enterohemorrhagic E. coli strain RW1374 inserted at the pheV locus (34). Moreover, from aec-64 (located at the right end of module 4) to aec-81, very similar regions exist in the she pathogenicity island of Shigella flexneri 2a strain 301 inserted at the pheV locus, in genomic island I of E. coli strain Nissle 1917 inserted at the serX locus, and in two different islands of E. coli strain CFT073, inserted at the serX and pheV loci (1,27,65 (6,10).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, module 3 is probably nonfunctional. (34). This module is also present in the she pathogenicity island of Shigella flexneri 2a strain 301 inserted at the pheV locus, in genomic island I of E. coli strain Nissle 1917 inserted at the serX locus, and in two different genomic islands of E. coli strain CFT073, inserted at the serX and pheV loci (1,27,65).…”

Section: Vol 188 2006mentioning

confidence: 99%

A selC -Associated Genomic Island of the Extraintestinal Avian Pathogenic Escherichia coli Strain BEN2908 Is Involved in Carbohydrate Uptake and Virulence

Chouikha¹,

Germon²,

Brée³

et al. 2006

J Bacteriol

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The complete nucleotide sequence and genetic organization of a new genomic island (AGI-3) isolated from the extraintestinal avian pathogenic Escherichia coli strain BEN2908 is reported. This 49,600-bp island is inserted at the selC locus and contains putative mobile genetic elements such as a phage-related integrase gene, transposase genes, and direct repeats. AGI-3 shows a mosaic structure of five modules. Some of these modules are present in other E. coli strains and in other pathogenic bacterial species. The gene cluster aec-35 to aec-37 of module 1 encodes proteins associated with carbohydrates assimilation such as a major facilitator superfamily transporter (Aec-36), a glycosidase (Aec-37), and a putative transcriptional regulator of the LacI family (Aec-35). The aec-35 to aec-37 cluster was found in 11.6% of the tested pathogenic and nonpathogenic E. coli strains. When present, the aec-35 to aec-37 cluster is strongly associated with the selC locus (97%). Deletion of the aec-35-aec-37 region affects the assimilation of seven carbohydrates, decreases the growth rate of the strain in minimal medium containing galacturonate or trehalose, and attenuates the virulence of E. coli BEN2908 for chickens.Escherichia coli, a commensal inhabitant of the gastrointestinal tract of mammals and birds, is also the causative agent of several diseases in animals and human worldwide. Pathogenic E. coli strains have been divided into intestinal pathogenic E. coli and extraintestinal pathogenic E. coli (ExPEC) depending on the location of the infection they are causing. ExPEC strains are responsible for a variety of infections, including bacteremia, urinary tract infections, neonatal meningitis, pneumonia, deep surgical wound infections, endovascular infections, vertebral osteomyelitis, and septicemia (35, 54).Avian pathogenic Escherichia coli (APEC) strains belong to the ExPEC group. They are mainly responsible for a respiratory disease in poultry usually followed by a systemic infection and a fatal septicemia. Characteristic fibrinopurulent lesions are aerosacculitis, pericarditis, and perihepatitis. APEC strains can also be involved in localized infections such as omphalitis, salpingitis, swollen head syndrome, and cellulitis (2, 17). APEC isolates commonly belong to serogroups O1, O2, O5, O8, O18, O35, and O78 (4, 17). Various virulence factors of APEC strains, such as adhesins (F1 and P fimbriae and curli), anti-host defense factors (OmpA, Iss, lipopolysaccharide, and K1), iron acquisition systems (aerobactin, Iro proteins, yersiniabactin, and the Sit iron acquisition locus), autotransporters (Tsh and Vat), and the IbeA protein have been identified (20, 21, 25, 36-38, 42, 46, 50). Using various genomic approaches, several putative virulence factors of APEC strains have been identified (9,20,38,58). However, the above components cannot explain all the disease process, suggesting the existence of other, unidentified components.It is well described that pathogenicity factors can be encoded by mobile genetic elements (transpos...

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“…Given the central role of lymphostatin in the pathogenesis of mouse 10 and human enteric infection with Gramnegative bacteria, 11,47,48 inactivation of either glucosyltransferase or protease motif will result in a significant loss of virulence and susceptibility to host defense mechanisms, including gastrointestinal motility and the mucosal immune system. 49 It is therefore conceivable that therapeutic interventions in the form of specific immunoglobulins directed against lymphostatin and its enzymatic activities might provide an attractive alternative to antibiotics in treating intestinal injury and preventing extraintestinal manifestations of Gram-negative infection.…”

Section: Discussionmentioning

confidence: 99%

“…7 Lymphostatin is encoded for by the lifA gene, which is present in Chlamydia psittaci, Chlamydia muridarum, 8 EPEC, EHEC, 9 and C. rodentium. 10 Lymphostatin expression has been associated with high virulence, 11 and has the strongest statistical association with diarrhea caused by atypical EPEC strains. 12 lifA consists of 9669 bp in EPEC and 9627 bp in C. rodentium, and encodes for three enzymatic motifs: a glucosyltransferase, a protease, and an aminotransferase motif.…”

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The Bacterial Virulence Factor Lymphostatin Compromises Intestinal Epithelial Barrier Function by Modulating Rho GTPases

Babbin

Sasaki

Gerner-Schmidt

et al. 2009

The American Journal of Pathology

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Lymphocyte inhibitory factor A (lifA) in Citrobacter rodentium encodes the large toxin lymphostatin, which contains two enzymatic motifs associated with bacterial pathogenesis, a glucosyltransferase and a protease. Our aim was to determine the effects of each lymphostatin motif on intestinal epithelial-barrier function. In-frame mutations of C. rodentium lifA glucosyltransferase (CrGlM21) and protease (CrPrM5) were generated by homologous recombination. Infection of both model intestinal epithelial monolayers and mice with C. rodentium wild type resulted in compromised epithelial barrier function and mislocalization of key intercellular junction proteins in the tight junction and adherens junction. In contrast, CrGlM21 was impaired in its ability to reduce barrier function and influenced the tight junction proteins ZO-1 and occludin. CrPrM5 demonstrated decreased effects on the adherens junction proteins ␤-catenin and E-cadherin. Analysis of the mechanisms revealed that C. rodentium wild type differentially influenced Rho GTPase activation, suppressed Cdc42 activation, and induced Rho GTPase activation. CrGlM21 lost its suppressive effects on Cdc42 activation, whereas CrPrM5 was unable to activate Rho signaling. Rescue experiments using constitutively active Cdc42 or C3 exotoxin to inhibit Rho GTPase supported a role of Rho GTPases in the epithelial barrier compromise induced by C. rodentium. Taken together, our results suggest that lymphostatin is a bacterial virulence factor that contributes to the disruption of intestinal epithelial-barrier function via the modulation of Rho GTPase activities.

show abstract

Description of a 111-kb pathogenicity island (PAI) encoding various virulence features in the enterohemorrhagic E. coli (EHEC) strain RW1374 (O103:H2) and detection of a similar PAI in other EHEC strains of serotype O103:H2

Cited by 22 publications

References 36 publications

Genomic O Island 122, Locus for Enterocyte Effacement, and the Evolution of Virulent Verocytotoxin-ProducingEscherichia coli

Genomic O Island 122, Locus for Enterocyte Effacement, and the Evolution of Virulent Verocytotoxin-ProducingEscherichia coli

A selC -Associated Genomic Island of the Extraintestinal Avian Pathogenic Escherichia coli Strain BEN2908 Is Involved in Carbohydrate Uptake and Virulence

The Bacterial Virulence Factor Lymphostatin Compromises Intestinal Epithelial Barrier Function by Modulating Rho GTPases

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