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Carboxyl groups in Clostridium perfringens epsilon toxin
1Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Microbial Pathogenesis
|December 1, 1987
Summary
Modifying carboxyl groups on Clostridium perfringens epsilon toxin with agents like norleucine methyl ester (NME) significantly reduces its lethal activity. At least four surface carboxyl groups are crucial for maintaining the toxin's lethality.
Area of Science:
- Microbiology
- Toxicology
- Protein Chemistry
Background:
- Clostridium perfringens epsilon toxin is a potent lethal agent.
- Carboxyl groups on toxin surfaces are potential targets for modification.
- Understanding the role of these groups is key to developing antitoxins.
Purpose of the Study:
- To investigate the role of carboxyl groups in epsilon toxin's lethality.
- To determine the effect of chemical modification on toxin activity.
- To identify critical carboxyl groups for maintaining lethal activity.
Main Methods:
- Carbodiimide-nucleophile procedure using norleucine methyl ester (NME), glycine methyl ester, and taurine.
- Assessing toxin lethality before and after chemical modification.
- Circular dichroism spectroscopy to analyze structural changes.
- Antigen-antibody reactions to evaluate toxin-antitoxin binding.
Main Results:
- Incorporation of 3-4 modifying agents reduced epsilon toxin lethality to ~10%.
- Incorporation of 6-7 agents resulted in complete loss of lethal activity.
- Circular dichroism and toxin-antitoxin binding showed no significant differences between native and modified toxins.
- At least 4 of the 7 surface carboxyl groups are essential for lethal activity.
Conclusions:
- Surface carboxyl groups are critical for the lethal activity of epsilon toxin.
- Modification of these groups can attenuate or abolish toxin lethality.
- The structural integrity of the toxin, as assessed by CD and antibody binding, is largely maintained despite modifications impacting lethality.