The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin

Fujinaga, Yukako; Inoue, Kaoru; Watanabe, Sadahiro; Yokota, Kenji; Hirai, Yoshikazu; Nagamachi, Eiko; Oguma, Keiji

doi:10.1099/00221287-143-12-3841

Cited by 146 publications

(100 citation statements)

References 21 publications

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“…Structural comparison of the N-terminal module of LSL, with known folds using the DALI algorithm (21), revealed a high homology with proteins known to interact with sugars, for example, the hemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum (22) blance of the N-terminal module of LSL with sugar-binding domains of toxins that exert their cytotoxic action by binding glycoproteins; particularly, the hemagglutinin component (HA1), which has been shown to increase the toxicity of C. botulinum neurotoxin by binding to oligosaccharides lining the intestine (30,31), or abrin and the closely related deadly plant toxin ricin (20), which bind their target membranes through a ␤-trefoil motif. The emergence of this structural motif in toxins from diverse sources could suggest a mechanism of evolution involving the association of discrete stable functional modules into a final modular protein with toxic character.…”

Section: Resultsmentioning

confidence: 99%

Structural Analysis of the Laetiporus sulphureus Hemolytic Pore-forming Lectin in Complex with Sugars

Mancheño

Tateno

Goldstein

et al. 2005

Journal of Biological Chemistry

113

111

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LSL is a lectin produced by the parasitic mushroom Laetiporus sulphureus, which exhibits hemolytic and hemagglutinating activities. Here, we report the crystal structure of LSL refined to 2.6-Å resolution determined by the single isomorphous replacement method with the anomalous scatter (SIRAS) signal of a platinum derivative. The structure reveals that LSL is hexameric, which was also shown by analytical ultracentrifugation. The monomeric protein (35 kDa) consists of two distinct modules: an N-terminal lectin module and a pore-forming module. The lectin module has a ␤-trefoil scaffold that bears structural similarities to those present in toxins known to interact with galactose-related carbohydrates such as the hemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum, abrin, and ricin. On the other hand, the C-terminal pore-forming module (composed of domains 2 and 3) exhibits three-dimensional structural resemblances with domains 3 and 4 of the ␤-pore-forming toxin aerolysin from the Gram-negative bacterium Aeromonas hydrophila, and domains 2 and 3 from the ⑀-toxin from Clostridium perfringens. This finding reveals the existence of common structural elements within the aerolysin-like family of toxins that could be directly involved in membrane-pore formation. The crystal structures of the complexes of LSL with lactose and N-acetyllactosamine reveal two dissacharide-binding sites per subunit and permits the identification of critical residues involved in sugar binding.

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Section: Resultsmentioning

confidence: 99%

Structural Analysis of the Laetiporus sulphureus Hemolytic Pore-forming Lectin in Complex with Sugars

Mancheño

Tateno

Goldstein

et al. 2005

Journal of Biological Chemistry

113

111

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“…In nature BoNTs are found as progenitor toxins containing the neurotoxin and nontoxic associated proteins, probably responsible for protecting the neurotoxin from environmental factors. 17 Genes encoding BoNTs can be located on the chromosome or on extrachromosomal elements, such as plasmids or bacteriophages. [18][19][20] Specifically, toxin genes for group III organisms are carried by bacteriophages that exert an unstable lysogenic cycle.…”

Section: Bont-producing Clostridia and Their Toxinsmentioning

confidence: 99%

Management of Animal Botulism Outbreaks: From Clinical Suspicion to Practical Countermeasures to Prevent or Minimize Outbreaks

Anniballi

Fiore

Löfström

et al. 2013

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, an

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“…Because it was speculated that ligation may cause tissue damage, these toxins were inoculated into the small intestine without ligation. Only the 16 S toxin bound obviously to the epithelial cells and time to death after injection with 16 S toxin was measurably shorter compared with 12 S toxin or neurotoxin [13]. Furthermore, in a way comparable to 16 S toxin, recombinant proteins of HA1 and HA3 could bind both epithelial cells and erythrocytes [14,15].…”

Section: Introductionmentioning

confidence: 97%

Mucosal immunisation with Clostridium botulinum type C 16 S toxoid and its non-toxic component

Mahmut¹,

Inoue

Fujinaga³

et al. 2002

Journal of Medical Microbiology

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Clostridium botulinum types C and D produce a 16 S (500 kDa) toxin that is formed by conjugation of neurotoxin with a non-toxic component (nonTox). The amino acid sequences of type C and D nonTox components are almost identical. In a previous report it was proposed that nonTox is necessary for the effective absorption of the toxin from the small intestine. This suggested the hypothesis that mucosal immunity against nonTox in the small intestine might prevent the absorption of both C-and D-16 S toxins. The nonTox was purified from a mutant strain, (C)-N71, that does not produce neurotoxin. This nonTox or detoxified C-16 S toxin were mixed with adjuvant (a mutant form of heat-labile toxin of Escherichia coli), and inoculated into mice via the nasal or oral route, or both. The mice inoculated nasally four times with nonTox or toxoid produced high levels of antibodies (including IgA) against the immunogens, both in intestinal fluids and sera. When these nonTox-immunised mice were challenged orally with 2 and 20 oral minimum lethal doses (MLD) of C-or D-16 S toxins, the same results were obtained with both C and D; the mice survived after challenge with 2 MLD of either C or D but were killed by 20 MLD of either toxin although the time to death was significantly longer than in the control non-immunised mice. These results indicate that the local anti-nonTox antibodies reduce absorption of both C-and D-16 S toxins from the small intestine. The C-16 S toxoid-immunised mice showed similar behaviour with type D toxin challenge, probably due to the same mechanism, but were protected against 20 MLD of C-16 S toxin.

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The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin

Cited by 146 publications

References 21 publications

Structural Analysis of the Laetiporus sulphureus Hemolytic Pore-forming Lectin in Complex with Sugars

Structural Analysis of the Laetiporus sulphureus Hemolytic Pore-forming Lectin in Complex with Sugars

Management of Animal Botulism Outbreaks: From Clinical Suspicion to Practical Countermeasures to Prevent or Minimize Outbreaks

Mucosal immunisation with Clostridium botulinum type C 16 S toxoid and its non-toxic component

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