c Clostridium difficile is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for C. difficile infection. Toxin A (TcdA) and toxin B (TcdB) are nearly indispensable virulence factors for Clostridium difficile pathogenesis. Given the toxin-centric mechanism by which C. difficile pathogenesis occurs, the selective sequestration with neutralization of TcdA and TcdB by nonantibiotic 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 nonswelling M-1 (CAS UPSN M-1), is capable of sequestering TcdA and TcdB in vitro. The following major findings were derived from the present study. First, we show that CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Second, we show that CAS UPSN M-1's affinity for TcdA is greater than its affinity for TcdB. Last, we show that CAS UPSN M-1 exhibited limited binding affinity for nontarget proteins. Taken 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 proinflammatory effects of luminal TcdA and TcdB.C lostridium difficile is a leading cause of antibiotic-associated diarrhea (AAD) and is the etiologic agent responsible for C. difficile-associated infection (CDI). CDI typically starts as a mild diarrhea but rapidly degenerates into a variety of potentially lifethreatening conditions, including sepsis syndrome and pseudomembranous colitis (1). In the United States, approximately 330,000 cases of CDI are estimated to occur each year (2); however, the incidence of C. difficile infection continues to increase (2, 3). The increasing CDI rates highlight the fact that the current infection control procedures and treatment options are insufficient.In the health care setting, C. difficile endospores are transmitted to patients via the fecal-oral route (4). Following exposure, the host's gastrointestinal microbiota typically either quells a nascent C. difficile infection or suppresses it to subclinical levels (5). As a result of the latter, approximately 20% of hospitalized adults become asymptomatic C. difficile carriers, and the carriage rates approach 50% for patients in long-term care (6-9). The likelihood of development of CDI increases in patients with dysbiotic gastrointestinal microbiota, since C. difficile can thrive in the dysbiotic niche (5, 10). This dysbiosis is often the result of nonspecific chemotherapies that are used to treat conditions unrelated to C. difficile infection (e.g., antibacterial agents or antineoplastic drugs).The antibiotics metronidazole and vancomycin are currently used to treat CDI (11). Unfortunately, given the conflicting roles of antibiotics in the establishment and resolution of CDI, C. difficile AAD recurs in up to 1 in 5 patients (12)...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.