Influence of Escherichia coli Shiga Toxin on the Mammalian Central Nervous System

2010 ◽  
pp. 1-19 ◽  
Author(s):  
Fumiko Obata
Keyword(s):  
Escherichia Coli ◽  
Central Nervous System ◽  
Nervous System ◽  
Shiga Toxin ◽  
Mammalian Central Nervous System

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 Therapeutic Strategies to Protect the Central Nervous System against Shiga Toxin from Enterohemorrhagic Escherichia coli

2020 ◽  
Vol 19 (1) ◽  
pp. 24-44 ◽  
Author(s):  
Jorge Goldstein ◽  
Krista Nuñez-Goluboay ◽  
Alipio Pinto
Keyword(s):  
Escherichia Coli ◽  
Central Nervous System ◽  
Nervous System ◽  
Shiga Toxin ◽  
Inflammatory Responses ◽  
Clinical Signs ◽  
Enterohemorrhagic Escherichia Coli ◽  
Cns Injury ◽  
Immune System Activation ◽  
The Central Nervous System

: Infection with Shiga toxin-producing Escherichia coli (STEC) may cause hemorrhagic colitis, hemolytic uremic syndrome (HUS) and encephalopathy. The mortality rate derived from HUS adds up to 5% of the cases, and up to 40% when the central nervous system (CNS) is involved. In addition to the well-known deleterious effect of Stx, the gram-negative STEC releases lipopolysaccharides (LPS) and may induce a variety of inflammatory responses when released in the gut. Common clinical signs of severe CNS injury include sensorimotor, cognitive, emotional and/or autonomic alterations. In the last few years, a number of drugs have been experimentally employed to establish the pathogenesis of, prevent or treat CNS injury by STEC. The strategies in these approaches focus on: 1) inhibition of Stx production and release by STEC, 2) inhibition of Stx bloodstream transport, 3) inhibition of Stx entry into the CNS parenchyma, 4) blockade of deleterious Stx action in neural cells, and 5) inhibition of immune system activation and CNS inflammation. Fast diagnosis of STEC infection, as well as the establishment of early CNS biomarkers of damage, may be determinants of adequate neuropharmacological treatment in time.

scholarly journals Promoter Sequence of Shiga Toxin 2 (Stx2) Is Recognized In Vivo, Leading to Production of Biologically Active Stx2

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Leticia V. Bentancor ◽  
Maria P. Mejías ◽  
Alípio Pinto ◽  
Marcos F. Bilen ◽  
Roberto Meiss ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Central Nervous System ◽  
Nervous System ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Biologically Active ◽  
Eukaryotic Cells ◽  
Content Type ◽  
Uremic Syndrome

ABSTRACTShiga toxins (Stx) are the main agent responsible for the development of hemolytic-uremic syndrome (HUS), the most severe and life-threatening systemic complication of infection with enterohemorrhagicEscherichia coli(EHEC) strains. We previously described Stx2 expression by eukaryotic cells after they were transfectedin vitrowith thestx2gene cloned into a prokaryotic plasmid (pStx2). The aim of this study was to evaluate whether mammalian cells were also able to express Stx2in vivoafter pStx2 injection. Mice were inoculated by hydrodynamics-based transfection (HBT) with pStx2. We studied the survival, percentage of polymorphonuclear leukocytes in plasma, plasma urea levels, and histology of the kidneys and the brains of mice. Mice displayed a lethal dose-related response to pStx2. Stx2 mRNA was recovered from the liver, and Stx2 cytotoxic activity was observed in plasma of mice injected with pStx2. Stx2 was detected by immunofluorescence in the brains of mice inoculated with pStx2, and markers of central nervous system (CNS) damage were observed, including increased expression of glial fibrillary acidic protein (GFAP) and fragmentation of NeuN in neurons. Moreover, anti-Stx2B-immunized mice were protected against pStx2 inoculation. Our results show that Stx2 is expressedin vivofrom the wildstx2gene, reproducing pathogenic damage induced by purified Stx2 or secondary to EHEC infection.IMPORTANCEEnterohemorrhagic Shiga toxin (Stx)-producingEscherichia coli(EHEC) infections are a serious public health problem, and Stx is the main pathogenic agent associated with typical hemolytic-uremic syndrome (HUS). In contrast to the detailed information describing the molecular basis for EHEC adherence to epithelial cells, very little is known about how Stx is released from bacteria in the gut, reaching its target tissues, mainly the kidney and central nervous system (CNS). In order to develop an efficient treatment for EHEC infections, it is necessary to understand the mechanisms involved in Stx expression. In this regard, the present study demonstrates that mammals can synthesize biologically active Stx using the natural promoter associated with the Stx-converting bacteriophage genome. These results could impact the comprehension of EHEC HUS, since local eukaryotic cells transduced and/or infected by bacteriophage encoding Stx2 could be an alternative source of Stx production.

scholarly journals Steroid Pulse Therapy for Severe Central Nervous System Involvement in Shiga Toxin-Producing Escherichia coli-Related Hemolytic Uremic Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Chiara Rosazza ◽  
Alberto M Cappellari ◽  
Cristiano Gandini ◽  
Elisa Scola ◽  
Gianluigi Ardissino
Keyword(s):  
Escherichia Coli ◽  
Central Nervous System ◽  
Nervous System ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Pulse Therapy ◽  
Steroid Pulse Therapy ◽  
High Dose ◽  
Steroid Pulse ◽  
Uremic Syndrome

We report on the case of a 7-year-old boy with Shiga toxin-producing Escherichia coli-related hemolytic uremic syndrome (STEC-HUS), initially presenting with abdominal pain as the only clinical feature and thus requiring differential diagnosis with a surgical emergency. Diagnosis of STEC-HUS was made with the appearance of bloody diarrhea and renal function impairment, and the clinical picture rapidly progressed to multiorgan failure. Relatively late and severe central nervous system (CNS) involvement was present, characterized by subacute encephalitis progressing to coma, which became apparent when the acute phase of thrombotic microangiopathy was resolving. Therefore, neurologic manifestations were thought to be related to reperfusion damage to the CNS and high-dose IV steroid pulse therapy was empirically administered. Following this therapeutic scheme, neurologic involvement resolved with no sequelae. This case offers several points of discussion on the clinical presentation and the diagnostic approach to STEC-HUS, on the related neurologic complications, and on a novel approach to their management.

Recent Advances in the Pharmacology of Excitatory Amino Acids in the Mammalian Central Nervous System

Excitotoxins ◽  
1983 ◽  
pp. 43-54 ◽  
Author(s):  
J. Davies ◽  
R. H. Evans ◽  
A. W. Jones ◽  
K. N. Mewett ◽  
D. A. S. Smith ◽  
...  
Keyword(s):  
Amino Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Excitatory Amino Acids ◽  
Mammalian Central Nervous System ◽  
Recent Advances

scholarly journals Suppurative infectious diseases of the central nervous system in domestic ruminants

2017 ◽  
Vol 37 (8) ◽  
pp. 820-828 ◽  
Author(s):  
Guilherme Konradt ◽  
Daniele M. Bassuino ◽  
Klaus S. Prates ◽  
Matheus V. Bianchi ◽  
Gustavo G.M. Snel ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Infectious Diseases ◽  
Neurological Disease ◽  
Etiologic Agent ◽  
Domestic Ruminants ◽  
The Central Nervous System ◽  
Positive Immunostaining

ABSTRACT: This study describes suppurative infectious diseases of the central nervous system (CNS) in domestic ruminants of southern Brazil. Reports from 3.274 cattle, 596 sheep and 391 goats were reviewed, of which 219 cattle, 21 sheep and 7 goats were diagnosed with central nervous system inflammatory diseases. Suppurative infectious diseases of the CNS corresponded to 54 cases (28 cattle, 19 sheep and 7 goats). The conditions observed consisted of listerial meningoencephalitis (8 sheep, 5 goats and 4 cattle), suppurative leptomeningitis and meningoencephalitis (14 cattle, 2 goats and 1 sheep), cerebral (6 cattle and 2 sheep), and spinal cord (7 sheep) abscesses, and basilar empyema (4 cattle and 1 sheep). Bacterial culture identified Listeria monocytogenes (9/54 cases), Escherichia coli (7/54 cases), Trueperella pyogenes (6/54 cases) and Proteus mirabilis (1/54 cases). All cases diagnosed as listeriosis through histopathology yielded positive immunostaining on immunohistochemistry, while 12/17 of the cases of suppurative leptomeningitis and meningoencephalitis presented positive immunostaining for Escherichia coli. Meningoencephalitis by L. monocytogenes was the main neurological disease in sheep and goats, followed by spinal cord abscesses in sheep. In cattle, leptomeningitis and suppurative meningoencephalitis was the most frequent neurological disease for the species, and E. coli was the main cause of these lesions. Basilar empyema, mainly diagnosed in cattle, is related to traumatic injuries, mainly in the nasal cavity, and the main etiologic agent was T. pyogenes.

Sign in / Sign up

Export Citation Format

Share Document