scholarly journals Gut–Kidney Axis on Chip for Studying Effects of Antibiotics on Risk of Hemolytic Uremic Syndrome by Shiga Toxin-Producing Escherichia coli

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 775
Author(s):  
Yugyeong Lee ◽  
Min-Hyeok Kim ◽  
David Rodrigues Alves ◽  
Sejoong Kim ◽  
Luke P. Lee ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Low Frequency ◽  
Kidney Cells ◽  
Number Of Patients ◽  
Relevant Situation ◽  
Shiga Toxin 2 ◽  
Uremic Syndrome ◽  
On Chip

Shiga toxin-producing Escherichia coli (STEC) infects humans by colonizing the large intestine, and causes kidney damage by secreting Shiga toxins (Stxs). The increased secretion of Shiga toxin 2 (Stx2) by some antibiotics, such as ciprofloxacin (CIP), increases the risk of hemolytic–uremic syndrome (HUS), which can be life-threatening. However, previous studies evaluating this relationship have been conflicting, owing to the low frequency of EHEC infection, very small number of patients, and lack of an appropriate animal model. In this study, we developed gut–kidney axis (GKA) on chip for co-culturing gut (Caco-2) and kidney (HKC-8) cells, and observed both STEC O157:H7 (O157) infection and Stx intoxication in the gut and kidney cells on the chip, respectively. Without any antibiotic treatment, O157 killed both gut and kidney cells in GKA on the chip. CIP treatment reduced O157 infection in the gut cells, but increased Stx2-induced damage in the kidney cells, whereas the gentamycin treatment reduced both O157 infection in the gut cells and Stx2-induced damage in the kidney cells. This is the first report to recapitulate a clinically relevant situation, i.e., that CIP treatment causes more damage than gentamicin treatment. These results suggest that GKA on chip is very useful for simultaneous observation of O157 infections and Stx2 poisoning in gut and kidney cells, making it suitable for studying the effects of antibiotics on the risk of HUS.

scholarly journals Cognitive deficits found in a pro-inflammatory state are independent of ERK 1/2 signaling in the murine brain hippocampus treated with Shiga toxin 2 from enterohemorrhagic Escherichia Coli

2020 ◽  
Author(s):  
Clara Berdasco ◽  
Alipio Pinto ◽  
Mariano Blake ◽  
Fernando Correa ◽  
Nadia A. Longo Carbajosa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Central Nervous System ◽  
Nervous System ◽  
Hemolytic Uremic Syndrome ◽  
Signaling Pathway ◽  
Shiga Toxin ◽  
Enterohemorrhagic Escherichia Coli ◽  
Shiga Toxin 2 ◽  
Uremic Syndrome ◽  
The Brain

AbstractShiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) produces hemorrhagic colitis, hemolytic uremic syndrome (HUS) and acute encephalopathy. The mortality rate in HUS increases significantly when the central nervous system (CNS) is involved. Besides, EHEC also releases lipopolysaccharide (LPS). Many reports have described cognitive dysfunctions in HUS patients, the hippocampus being one of the brain areas targeted by EHEC infection. In this context, a translational murine model of encephalopathy was employed to establish the deleterious effects of Stx2 and the contribution of LPS in the hippocampus. Results demonstrate that systemic administration of a sublethal dose of Stx2 reduced memory index and produced depression like behavior, pro-inflammatory cytokine release and NF-kB activation independent of the ERK 1/2 signaling pathway. On the other hand, LPS activated NF-kB dependent on ERK 1/2 signaling pathway. Cotreatment of Stx2 with LPS aggravated the pathologic state, while dexamethasone treatment succeeded in preventing behavioral alterations. Our present work suggests that the use of drugs such as corticosteroids or NF-kB signaling inhibitors may serve as neuroprotectors from EHEC infection.Author SummaryShiga toxin (Stx) from enterohemorrhagic Escherichia coli (EHEC) is one of the most virulent factors responsible for hemolytic uremic syndrome (HUS). Stx2, the endemic variant targets the brain, among other organs, thus inducing encephalopathies. Central nervous system (CNS) compromise was the main predictor of death in patients with HUS. Stx2 may exert a direct action in the CNS, by disrupting the neurovascular unit. In this context, we investigate the molecular signaling triggered by Stx2 in the murine brain hippocampus involved in inflammatory mechanisms that altered hippocampal-related cognitive behaviors. The present data underscore that the use of drugs such as dexamethasone or those blocking the cascade by preventing NF-kB translocation to the nucleus may serve as effective neuroprotectors with potentially beneficial use in the clinic.

scholarly journals Escherichia coli O157:H7 and O157:H−Strains That Do Not Produce Shiga Toxin: Phenotypic and Genetic Characterization of Isolates Associated with Diarrhea and Hemolytic-Uremic Syndrome

1999 ◽  
Vol 37 (11) ◽  
pp. 3491-3496 ◽  
Author(s):  
H. Schmidt ◽  
J. Scheef ◽  
H. I. Huppertz ◽  
M. Frosch ◽  
H. Karch
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Low Frequency ◽  
Diagnostic Methods ◽  
Gene Encoding ◽  
E Coli ◽  
Uremic Syndrome ◽  
Plasmid Genes ◽  
Phenotypic And Genetic Characterization

We have isolated one sorbitol-nonfermenting (SNF) Escherichia coli O157:H7 isolate and five sorbitol-fermenting (SF) E. coli O157:H− isolates that do not contain Shiga toxin (Stx) genes (stx). Isolates originated from patients with diarrhea (n = 4) and hemolytic-uremic syndrome (HUS) (n = 2). All isolates harbored a chromosomaleae gene encoding gamma-intimin as well as the plasmid genes E-hly and etp. The E. coliO157:H7 isolate was katP and espP positive. Respective sera obtained from the patient with HUS contained antibodies to the O157 lipopolysaccharide antigen. Thestx-negative E. coli O157:H7 isolate is genetically related to stx-positive SNF E. coliO157:H7. All stx-negative SF E. coliO157:H− isolates belong to the same genetic cluster and are closely related to stx-positive SF E. coliO157:H− isolates. Our data indicate thatstx-negative E. coli O157:H7/H−variants may occur at a low frequency and cannot be recognized by diagnostic methods that target Stx.

scholarly journals Whole-genome characterization of hemolytic uremic syndrome-causing Shiga toxin-producing Escherichia coli in Sweden

Virulence ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1296-1305
Author(s):  
Ying Hua ◽  
Milan Chromek ◽  
Anne Frykman ◽  
Cecilia Jernberg ◽  
Valya Georgieva ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Whole Genome ◽  
Genome Characterization ◽  
Uremic Syndrome

Outbreak of Shiga Toxin–Producing Escherichia coli (STEC) O104:H4 Infection in Germany Causes a Paradigm Shift with Regard to Human Pathogenicity of STEC Strains

2012 ◽  
Vol 75 (2) ◽  
pp. 408-418 ◽  
Author(s):  
LOTHAR BEUTIN ◽  
ANNETT MARTIN
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Outbreak Strain ◽  
Fenugreek Seeds ◽  
E Coli ◽  
Aggregative Adherence ◽  
Uremic Syndrome ◽  
Enterocyte Effacement ◽  
The Way

An outbreak that comprised 3,842 cases of human infections with enteroaggregative hemorrhagic Escherichia coli (EAHEC) O104:H4 occurred in Germany in May 2011. The high proportion of adults affected in this outbreak and the unusually high number of patients that developed hemolytic uremic syndrome makes this outbreak the most dramatic since enterohemorrhagic E. coli (EHEC) strains were first identified as agents of human disease. The characteristics of the outbreak strain, the way it spread among humans, and the clinical signs resulting from EAHEC infections have changed the way Shiga toxin–producing E. coli strains are regarded as human pathogens in general. EAHEC O104:H4 is an emerging E. coli pathotype that is endemic in Central Africa and has spread to Europe and Asia. EAHEC strains have evolved from enteroaggregative E. coli by uptake of a Shiga toxin 2a (Stx2a)–encoding bacteriophage. Except for Stx2a, no other EHEC-specific virulence markers including the locus of enterocyte effacement are present in EAHEC strains. EAHEC O104:H4 colonizes humans through aggregative adherence fimbrial pili encoded by the enteroaggregative E. coli plasmid. The aggregative adherence fimbrial colonization mechanism substitutes for the locus of enterocyte effacement functions for bacterial adherence and delivery of Stx2a into the human intestine, resulting clinically in hemolytic uremic syndrome. Humans are the only known natural reservoir known for EAHEC. In contrast, Shiga toxin–producing E. coli and EHEC are associated with animals as natural hosts. Contaminated sprouted fenugreek seeds were suspected as the primary vehicle of transmission of the EAHEC O104:H4 outbreak strain in Germany. During the outbreak, secondary transmission (human to human and human to food) was important. Epidemiological investigations revealed fenugreek seeds as the source of entry of EAHEC O104:H4 into the food chain; however, microbiological analysis of seeds for this pathogen produced negative results. The survival of EAHEC in seeds and the frequency of human carriers of EAHEC should be investigated for a better understanding of EAHEC transmission routes.

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