Compositions and methods to inactivate and/or reduce production of microbial toxins
The present invention is related to compositions and methods to treat, ameliorate and/or prevent morbidity and/or mortality from microbial infections. In particular, bacterial infections that are associated with the production and release of bacterial toxins. For example, many Clostridia bacteria, such as Clostridium difficile , release toxins resulting in tissue and organ damage and death, even after antibiotic therapy that either reduces or eliminates the bacteria. In particular, various peptides, polypeptides, and proteins are disclosed herein that either inactivate Clostridium difficile toxin and/or reduce Clostridium difficile toxin production.
1. A method, comprising:
a) providing;
i) a patient comprising a Clostridia toxin;
ii) a therapeutic cationic polypeptide selected from the group consisting of protamine, a protamine fragment comprising a plurality of arginine amino acid clusters, protamine III-2, polyarginine and polylysine;
b) administering said therapeutic polypeptide to said patient; and
c) inactivating said bacterial toxin with said cationic polypeptide.
2. The method of claim 1 , wherein said bacterial toxin is systemic.
3. The method of claim 1 , wherein said bacterial toxin is localized to the colon.
4. The method of claim 1 , wherein said Clostridia toxin is selected from the group consisting of a C. difficile Toxin B and a C. difficile Toxin A.
5. The method of claim 1 , wherein said inactivating comprises a specific binding between said bacterial toxin and said cationic protein.
6. The method of claim 1 , wherein said inactivating comprising a non-specific binding between said bacterial toxin and said cationic protein.
7. The method of claim 1 , wherein said administering is selected from at least one group consisting of parenterally and/or via enema or suppository.
8. The method of claim 1 , wherein said method further comprises administering an antibiotic before step (b).
9. The method of claim 1 , wherein said method further comprises administering a toxin production inhibitor before step (b).
10. The method of claim 1 , wherein said cationic polypeptide is formulated into a pharmaceutical composition.