Open AccessTolevamer, an Anionic Polymer, Neutralizes Toxins Produced by the BI/027 Strains of Clostridium difficile
Author(s) -
Paul L. Hinkson,
Carol Dinardo,
Daniel DeCiero,
Jeffrey D. Klinger,
Robert H. Barker
Publication year - 2008
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00041-08
Subject(s) - microbiology and biotechnology , clostridium difficile , clostridium difficile toxin a , toxin , clostridium difficile toxin b , biology , exotoxin , antibiotics , pore forming toxin , clostridium , cytotoxicity , clostridiaceae , antibody , enterotoxin , cell culture , bacteria , in vitro , virology , immunology , escherichia coli , microbial toxins , biochemistry , gene , genetics
Clostridium difficile -associated diarrhea (CDAD) is caused by the toxins the organism produces when it overgrows in the colon as a consequence of antibiotic depletion of normal flora. Conventional antibiotic treatment of CDAD increases the likelihood of recurrent disease by again suppressing normal bacterial flora. Tolevamer, a novel toxin-binding polymer, was developed to ameliorate the disease without adversely affecting normal flora. In the current study, tolevamer was tested for its ability to neutralize clostridial toxins produced by the epidemic BI/027 strains, thereby preventing toxin-mediated tissue culture cell rounding. The titers of toxin-containingC. difficile culture supernatants were determined using confluent cell monolayers, and then the supernatants were used in assays containing dilutions of tolevamer to determine the lowest concentration of tolevamer that prevented ≥90% cytotoxicity. Tolevamer neutralized toxins in the supernatants of allC. difficile strains tested. Specific antibodies against the large clostridial toxins TcdA and TcdB also neutralized the cytopathic effect, suggesting that tolevamer is specifically neutralizing these toxins and that the binary toxin (whose genes are carried by the BI/027 strains) is not a significant source of cytopathology against tissue culture cells in vitro.