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1389 KiB

Open AccessArticle

Changes in Astrocyte Shape Induced by Sublytic Concentrations of the Cholesterol-Dependent Cytolysin Pneumolysin Still Require Pore-Forming Capacity

by Christina Förtsch, Sabrina Hupp, Jiangtao Ma, Timothy J. Mitchell, Elke Maier, Roland Benz and Asparouh I. Iliev

Toxins 2011, 3(1), 43-62; https://doi.org/10.3390/toxins3010043 - 7 Jan 2011

Cited by 22 | Viewed by 10676

Abstract

Streptococcus pneumoniae is a common pathogen that causes various infections, such as sepsis and meningitis. A major pathogenic factor of S. pneumoniae is the cholesterol-dependent cytolysin, pneumolysin. It produces cell lysis at high concentrations and apoptosis at lower concentrations. We have shown that [...] Read more.

Streptococcus pneumoniae is a common pathogen that causes various infections, such as sepsis and meningitis. A major pathogenic factor of S. pneumoniae is the cholesterol-dependent cytolysin, pneumolysin. It produces cell lysis at high concentrations and apoptosis at lower concentrations. We have shown that sublytic amounts of pneumolysin induce small GTPase-dependent actin cytoskeleton reorganization and microtubule stabilization in human neuroblastoma cells that are manifested by cell retraction and changes in cell shape. In this study, we utilized a live imaging approach to analyze the role of pneumolysin’s pore-forming capacity in the actin-dependent cell shape changes in primary astrocytes. After the initial challenge with the wild-type toxin, a permeabilized cell population was rapidly established within 20–40 minutes. After the initial rapid permeabilization, the size of the permeabilized population remained unchanged and reached a plateau. Thus, we analyzed the non-permeabilized (non-lytic) population, which demonstrated retraction and shape changes that were inhibited by actin depolymerization. Despite the non-lytic nature of pneumolysin treatment, the toxin’s lytic capacity remained critical for the initiation of cell shape changes. The non-lytic pneumolysin mutants W433F-pneumolysin and delta6-pneumolysin, which bind the cell membrane with affinities similar to that of the wild-type toxin, were not able to induce shape changes. The initiation of cell shape changes and cell retraction by the wild-type toxin were independent of calcium and sodium influx and membrane depolarization, which are known to occur following cellular challenge and suggested to result from the ion channel-like properties of the pneumolysin pores. Excluding the major pore-related phenomena as the initiation mechanism of cell shape changes, the existence of a more complex relationship between the pore-forming capacity of pneumolysin and the actin cytoskeleton reorganization is suggested. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

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609 KiB

Open AccessArticle

β-N-Methylamino-L-Alanine Induces Neurological Deficits and Shortened Life Span in Drosophila

by Xianchong Zhou, Wilfredo Escala, Spyridon Papapetropoulos and R. Grace Zhai

Toxins 2010, 2(11), 2663-2679; https://doi.org/10.3390/toxins2112663 - 3 Nov 2010

Cited by 23 | Viewed by 10097

Abstract

The neurotoxic non-protein amino acid, β-N-methylamino-L-alanine (BMAA), was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam. Recently, BMAA has been implicated as a fierce environmental factor that contributes to the etiology of Alzheimer’s and Parkinson’s diseases, [...] Read more.

The neurotoxic non-protein amino acid, β-N-methylamino-L-alanine (BMAA), was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam. Recently, BMAA has been implicated as a fierce environmental factor that contributes to the etiology of Alzheimer’s and Parkinson’s diseases, in addition to ALS. However, the toxicity of BMAA in vivo has not been clearly demonstrated. Here we report our investigation of the neurotoxicity of BMAA in Drosophila. We found that dietary intake of BMAA reduced life span, locomotor functions, and learning and memory abilities in flies. The severity of the alterations in phenotype is correlated with the concentration of BMAA detected in flies. Interestingly, developmental exposure to BMAA had limited impact on survival rate, but reduced fertility in females, and caused delayed neurological impairment in aged adults. Our studies indicate that BMAA exposure causes chronic neurotoxicity, and that Drosophila serves as a useful model in dissecting the pathogenesis of ALS/PDC. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

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206 KiB

Open AccessArticle

Protein Domain Analysis of C. botulinum Type A Neurotoxin and Its Relationship with Other Botulinum Serotypes

by Shashi K. Sharma, Uma Basavanna and Hem D. Shukla

Toxins 2010, 2(1), 1-9; https://doi.org/10.3390/toxins2010001 - 24 Dec 2009

Cited by 4 | Viewed by 12019

Abstract

Botulinum neurotoxins (BoNTs) are highly potent poisons produced by seven serotypes of Clostridium botulinum. The mechanism of neurotoxin action is a multistep process which leads to the cleavage of one of three different SNARE proteins essential for synaptic vesicle fusion and transmission [...] Read more.

Botulinum neurotoxins (BoNTs) are highly potent poisons produced by seven serotypes of Clostridium botulinum. The mechanism of neurotoxin action is a multistep process which leads to the cleavage of one of three different SNARE proteins essential for synaptic vesicle fusion and transmission of the nerve signals to muscles: synaptobrevin, syntaxin, or SNAP-25. In order to understand the precise mechanism of neurotoxin in a host, the domain structure of the neurotoxin was analyzed among different serotypes of C. botulinum. The results indicate that neurotoxins type A, C, D, E and F contain a coiled-coil domain while types B and type G neurotoxin do not. Interestingly, phylogenetic analysis based on neurotoxin sequences has further confirmed that serotypes B and G are closely related. These results suggest that neurotoxin has multi-domain structure, and coiled-coil domain plays an important role in oligomerisation of the neurotoxin. Domain analysis may help to identify effective antibodies to treat Botulinum toxin intoxication. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

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497 KiB

Open AccessArticle

Isolation and Chemical Characterization of a Toxin Isolated from the Venom of the Sea Snake, Hydrophis torquatus aagardi

by Masaya Nagamizu, Yumiko Komori, Kei-ichi Uchiya, Toshiaki Nikai and Anthony T. Tu

Toxins 2009, 1(2), 162-172; https://doi.org/10.3390/toxins1020162 - 8 Dec 2009

Cited by 7 | Viewed by 9709

Abstract

Sea snakes (family: Hydrophiidae) are serpents found in the coastal areas of the Indian and Pacific Oceans. There are two subfamilies in Hydrophiidae: Hydrophiinae and Laticaudinae. A toxin, aagardi toxin, was isolated from the venom of the Hydrophiinae snake, Hydrophis torquatus aagardi and [...] Read more.

Sea snakes (family: Hydrophiidae) are serpents found in the coastal areas of the Indian and Pacific Oceans. There are two subfamilies in Hydrophiidae: Hydrophiinae and Laticaudinae. A toxin, aagardi toxin, was isolated from the venom of the Hydrophiinae snake, Hydrophis torquatus aagardi and its chemical properties such as molecular weight, isoelectric point, importance of disulfide bonds, lack of enzymatic activity and amino acid sequence were determined. The amino acid sequence indicated a close relationship to the primary structure of other Hydrophiinae toxins and a significant difference from Laticaudinae toxins, confirming that primary toxin structure is closely related to sea snake phylogenecity. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

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Open AccessArticle

Comparison of Sea Snake (Hydrophiidae) Neurotoxin to Cobra (Naja) Neurotoxin

by Yumiko Komori, Masaya Nagamizu, Kei-ichi Uchiya, Toshiaki Nikai and Anthony T. Tu

Toxins 2009, 1(2), 151-161; https://doi.org/10.3390/toxins1020151 - 3 Dec 2009

Cited by 3 | Viewed by 11125

Abstract

Both sea snakes and cobras have venoms containing postsynaptic neurotoxins. Comparison of the primary structures indicates many similarities, especially the positions of the four disulfide bonds. However, detailed examination reveals differences in several amino acid residues. Amino acid sequences of sea snake neurotoxins [...] Read more.

Both sea snakes and cobras have venoms containing postsynaptic neurotoxins. Comparison of the primary structures indicates many similarities, especially the positions of the four disulfide bonds. However, detailed examination reveals differences in several amino acid residues. Amino acid sequences of sea snake neurotoxins were determined, and then compared to cobra neurotoxins by computer modeling. This allowed for easy comparison of the similarities and differences between the two types of postsynaptic neurotoxins. Comparison of computer models for the toxins of sea snakes and cobra will reveal the three dimensional difference of the toxins much clearer than the amino acid sequence alone. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

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Review

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483 KiB

Open AccessReview

Peptide Neurotoxins That Affect Voltage-Gated Calcium Channels: A Close-Up on ω-Agatoxins

by Emilie Pringos, Michel Vignes, Jean Martinez and Valerie Rolland

Toxins 2011, 3(1), 17-42; https://doi.org/10.3390/toxins3010017 - 4 Jan 2011

Cited by 45 | Viewed by 13849

Abstract

Peptide neurotoxins found in animal venoms have gained great interest in the field of neurotransmission. As they are high affinity ligands for calcium, potassium and sodium channels, they have become useful tools for studying channel structure and activity. Peptide neurotoxins represent the clinical [...] Read more.

Peptide neurotoxins found in animal venoms have gained great interest in the field of neurotransmission. As they are high affinity ligands for calcium, potassium and sodium channels, they have become useful tools for studying channel structure and activity. Peptide neurotoxins represent the clinical potential of ion-channel modulators across several therapeutic fields, especially in developing new strategies for treatment of ion channel-related diseases. The aim of this review is to overview the latest updates in the domain of peptide neurotoxins that affect voltage-gated calcium channels, with a special focus on ω-agatoxins. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

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997 KiB

Open AccessReview

Bacterial Toxins and the Nervous System: Neurotoxins and Multipotential Toxins Interacting with Neuronal Cells

by Michel R. Popoff and Bernard Poulain

Toxins 2010, 2(4), 683-737; https://doi.org/10.3390/toxins2040683 - 15 Apr 2010

Cited by 91 | Viewed by 20551

Abstract

Toxins are potent molecules used by various bacteria to interact with a host organism. Some of them specifically act on neuronal cells (clostridial neurotoxins) leading to characteristics neurological affections. But many other toxins are multifunctional and recognize a wider range of cell types [...] Read more.

Toxins are potent molecules used by various bacteria to interact with a host organism. Some of them specifically act on neuronal cells (clostridial neurotoxins) leading to characteristics neurological affections. But many other toxins are multifunctional and recognize a wider range of cell types including neuronal cells. Various enterotoxins interact with the enteric nervous system, for example by stimulating afferent neurons or inducing neurotransmitter release from enterochromaffin cells which result either in vomiting, in amplification of the diarrhea, or in intestinal inflammation process. Other toxins can pass the blood brain barrier and directly act on specific neurons. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

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1534 KiB

Open AccessReview

Sensing the Deadliest Toxin: Technologies for Botulinum Neurotoxin Detection

by Petr Čapek and Tobin J. Dickerson

Toxins 2010, 2(1), 24-53; https://doi.org/10.3390/toxins2010024 - 7 Jan 2010

Cited by 64 | Viewed by 23114 | Correction

Abstract

Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method [...] Read more.

Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method of BoNT detection is the mouse bioassay. While this assay is sensitive, it is slow, quite expensive, has limited throughput and requires sacrificing animals. Herein, we discuss and compare recently developed alternative in vitro detection methods and assess their ability to supplement or replace the mouse bioassay in the analysis of complex matrix samples. Full article

(This article belongs to the Special Issue Neurotoxins of Biological Origin)

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