Effective sequestration of Clostridium difficile protein toxins by calcium aluminosilicate.
AUTHORS
- PMID: 26149988 [PubMed].
ABSTRACT
Clostridium difficile is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for C. difficile infection. TcdA and TcdB are nearly indispensible virulence factors for Clostridium difficile pathogenesis. Given the toxin-centric mechanism by which C. difficile pathogenesis occurs, the selective sequestration and neutralization of TcdA and TcdB by non-antibiotic agents represents a novel mode of action to prevent or treat C. difficile-associated disease. In this preclinical study, we used quantitative enzyme immunoassays to determine the extent by which a novel drug, calcium aluminosilicate uniform particle size Novasil (CAS UPSN M-1), is capable of sequestering TcdA and TcdB in vitro. The following major findings were derived from the present study: Firstly, CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Secondly, we show that CAS UPSN M-1’s affinity for TcdA is greater than its affinity for TcdB. Lastly, we show that CAS UPSN M-1 exhibited limited binding affinity for non-target therapeutic proteins. Together, these results suggest that ingestion of calcium aluminosilicate might protect gastrointestinal tissues from antibiotic- or chemotherapy-induced C. difficile infection by neutralizing the cytotoxic and pro-inflammatory effects of luminal TcdA and TcdB.
Clostridium difficile is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for C. difficile infection. TcdA and TcdB are nearly indispensible virulence factors for Clostridium difficile pathogenesis. Given the toxin-centric mechanism by which C. difficile pathogenesis occurs, the selective sequestration and neutralization of TcdA and TcdB by non-antibiotic agents represents a novel mode of action to prevent or treat C. difficile-associated disease. In this preclinical study, we used quantitative enzyme immunoassays to determine the extent by which a novel drug, calcium aluminosilicate uniform particle size Novasil (CAS UPSN M-1), is capable of sequestering TcdA and TcdB in vitro. The following major findings were derived from the present study: Firstly, CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Secondly, we show that CAS UPSN M-1’s affinity for TcdA is greater than its affinity for TcdB. Lastly, we show that CAS UPSN M-1 exhibited limited binding affinity for non-target therapeutic proteins. Together, these results suggest that ingestion of calcium aluminosilicate might protect gastrointestinal tissues from antibiotic- or chemotherapy-induced C. difficile infection by neutralizing the cytotoxic and pro-inflammatory effects of luminal TcdA and TcdB.
Tags: Alumni Publications 2015