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| 2. |
- Békassy, Zivile, et al.
(författare)
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Intestinal damage in enterohemorrhagic Escherichia coli infection.
- 2011
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Ingår i: Pediatric Nephrology. - : Springer Science and Business Media LLC. - 1432-198X .- 0931-041X. ; oct, s. 2059-2071
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Tidskriftsartikel (refereegranskat)abstract
- Enterohemorrhagic Escherichia coli (EHEC) infection leads to marked intestinal injury. Sigmoid colon obtained from two children during EHEC infection exhibited abundant TUNEL-positive cells. To define which bacterial virulence factors contribute to intestinal injury the presence of Shiga toxin-2 (Stx2), intimin and the type III secretion system were correlated with symptoms and intestinal damage. C3H/HeN mice were inoculated with Stx2-producing (86-24) and non-producing (87-23) E. coli O157:H7 strains and 86-24 mutants lacking eae, encoding intimin (strain UMD619) or escN regulating the expression of type III secretion effectors (strain CVD451). Severe symptoms developed in mice inoculated with 86-24 and 87-23. Few mice inoculated with the mutant strains developed severe symptoms. Strain 86-24 exhibited higher fecal bacterial counts, followed by 87-23, whereas strains UMD619 and CVD451 showed minimal fecal counts. More TUNEL-positive cells were found in proximal and distal colons of mice inoculated with strain 86-24 compared with strains 87-23 and CVD451 (p
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| 3. |
- Calderon Toledo, Carla, et al.
(författare)
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Cross-Reactive Protection against Enterohemorrhagic Escherichia coli Infection by Enteropathogenic Escherichia coli in a Mouse Model.
- 2011
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Ingår i: Infection and Immunity. - 1098-5522. ; 79:6, s. 2224-2233
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Tidskriftsartikel (refereegranskat)abstract
- Enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli are related attaching and effacing (A/E) pathogens. The genes responsible for the A/E pathology are encoded in a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). Both pathogens share a high degree of homology in the LEE and additional 'O' islands. EHEC prevalence is much lower in EPEC endemic areas. This may be due to the development of antibodies against common EPEC and EHEC antigens. This study investigated the hypothesis that EPEC infections may protect against EHEC infections. We used a mouse model to inoculate BALB/c mice intragastrically, first with EPEC, followed by EHEC (E. coli O157:H7). Four control groups received either a non-pathogenic E. coli (NPEC) strain followed by EHEC (NPEC/EHEC), alternatively PBS/EHEC, EPEC/PBS or PBS/PBS. Mice were monitored for weight loss and symptoms. EPEC colonized the intestine after challenge and mice developed serum antibodies to intimin and E. coli secreted protein B (encoded in the LEE). Prechallenge with an EPEC strain had a protective effect after EHEC infection as few mice developed mild symptoms, from which they recovered. These mice had an increase in body weight similar to control animals and tissue morphology exhibited mild intestinal changes and normal renal histology. All mice that were not pre-challenged with the EPEC strain developed mild to severe symptoms after EHEC infection, weight loss as well as intestinal and renal histopathological changes. These data suggest that EPEC may protect against EHEC infection in this mouse model.
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| 4. |
- Calderon Toledo, Carla, et al.
(författare)
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Shiga toxin-mediated disease in MyD88-deficient mice infected with Escherichia coli O157:H7.
- 2008
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 173:5, s. 1428-1439
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptors (TLRs) are key factors of innate immunity that detect pathogen invasion and trigger a host response. TLR4 can mediate a response through adaptor molecules, MyD88 or TRIF. In the present study, streptomycin-treated MyD88(-/-), Tlr4(-/-), Trif (Lps2/Lps2), and C57BL/6 wild-type (WT) mice were infected with either Shiga toxin (Stx)-producing or non-producing Escherichia coli O157:H7. Moderate to severe clinical signs of disease developed in MyD88(-/-) (n = 21/21), Tlr4(-/-) (n = 12/16), Trif (Lps2/Lps2) (n = 7/15) and WT mice (n = 6/20) infected with Stx-producing E. coli O157:H7 but not in mice inoculated with the Stx non-producing strain (n = 0/54, P < 0.001). MyD88(-/-) mice infected with Stx-producing E. coli O157:H7 developed the most severe disease and had the highest bacterial burden. Hematological analysis of sick MyD88(-/-) mice showed reduced red blood cell counts and reticulocytosis, suggesting hemolysis. Thrombocytopenia developed in MyD88(-/-), Trif (Lps2/Lps2), and WT mice, and creatinine levels were elevated in both MyD88(-/-) and WT mice infected with the Stx-producing strain. Renal histopathology showed evidence of glomerular capillary congestion, tubular desquamation, and fibrinogen deposition, and intestinal histopathology showed mucosal injury, edema, and inflammation in sick mice. Administration of purified Stx2 to MyD88(-/-) and WT mice led to severe disease in both groups, suggesting that MyD88(-/-) mice are not more sensitive to Stx than WT mice. As MyD88(-/-) mice developed the most severe disease hematological and pathological changes, the results suggest that dysfunctional innate immune responses via MyD88 enhanced Stx-induced disease.
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| 5. |
- Calderon Toledo, Carla
(författare)
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Studies of the pathogenesis of Enterohemorrhagic Escherichia coli infections: pathogen virulence factors and host response
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Enterohemorrhagic Escherichia coli (EHEC) is a highly virulent pathogen that can cause diarrhea and a life-threatening disease known as hemolytic uremic syndrome. EHEC possess an array of virulence factors that can exert severe consequences in the host. Shiga toxin constitutes a key virulence factor. Enteropathogenic Escherichia coli (EPEC) is a leading cause of infant diarrhea. EHEC and EPEC are related pathogens that share considerable homology regarding virulence factors. The aim of this study was to describe host-pathogen interactions during EHEC infection using established mouse models. Host detection of infection requires the activation of the innate immune system. Toll-like receptors (TLRs) can detect microbial motifs and initiate a signaling cascade leading to an inflammatory response with the goal to eradicate the pathogen. TLR4 recognizes bacterial lipopolysaccharide and can signal through two pathways that utilize the MyD88 and TRIF adaptor molecules, respectively. In this study MyD88-deficient mice infected with a Shiga toxin-producing E. coli O157:H7 strain developed severe symptoms and an increased bacterial burden, suggesting that the MyD88-dependent pathway is essential for an effective response against EHEC infection and in its absence Shiga toxin-mediated disease is amplified. The adaptive immune response provides long-lasting immunity against subsequent infection. A previous inoculation with EPEC resulted in a protective effect against a subsequent EHEC infection in mice, suggesting a cross-reactive immunity presumably against multiple factors shared by both pathogens. If EHEC bacteria overcome these host immune barriers an intestinal colonization process begins. The expression of intimin and an intact type three secretion system were shown to be necessary for intestinal colonization and virulence in mice. Shiga toxin secreted in the intestinal tract was shown to promote colonization and contribute to intestinal damage and cell death. Subsequently Shiga toxin can translocate the intestinal barrier targeting organs such as the kidney. Shiga toxin was demonstrated in kidneys of mice infected with a Shiga toxin-producing E. coli O157:H7 strain suggesting that the toxin could promote renal damage and severe symptoms.
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| 6. |
- Toledo, Carla Calderon, et al.
(författare)
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Circulation of enterotoxigenic Escherichia coli (ETEC) isolates expressing CS23 from the environment to clinical settings
- 2023
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Ingår i: mSystems. - 2379-5077. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of infant diarrhea in low- and middle-income countries (LMICs). Diarrheal pathogens are transmitted through environmental reservoirs; however, the bacterial clones that spread across the human-environment interface remain unexplored. We aimed to determine the relationship and clonal dissemination of ETEC between children with diarrhea and polluted water samples from a local river in La Paz, Bolivia. By using WGS and the PhenePlates phenotypic system to analyze ETEC strains, we showed that ST218 and ST410 LT+STh ETEC expressing the colonization factor (CF) CS23 were found with high frequency in both samples. The CS23 ETEC isolates were found within several STs, E. coli phylogroups, and across ETEC lineages. Comparative genomic evaluation and PhenePlate screening of globally distributed clinical ETEC strains suggest that the CS23 gene is likely carried on plasmids acquired independently of the bacterial chromosomal background. Clinical strains were more often multidrug-resistant (MDR) than environmental isolates and harbored the class 1 integron-integrase gene intI1 next to the MDR cassettes. Retrospective analysis of antibiotic resistance in ETEC revealed a high frequency of MDR in clinical isolates. The LT+STh CS23 environmental ETEC isolates, showed an increased biofilmability at environmental temperature, equal cytotoxicity, and significantlylower adherence to human epithelial cells compared to ETEC expressing other CFs. Together, we suggest that CS23 is more prevalent in ETEC than previously estimated, and the Choqueyapu River is a reservoir for LT+STh CS23 ETEC containing strains capable of causing diarrheal cases in children.
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