title: Effective Sequestration of Clostridium difficile Protein Toxins by Calcium Aluminosilicate.
abstract: 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.
authors.affiliation: Nutrition and Food Science Department, Texas A&M University, College Station, Texas, USA joseph.sturino@gmail.com.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Sturino
authors.affiliation: Nutrition and Food Science Department, Texas A&M University, College Station, Texas, USA.
authors.forename: Karina
authors.initials: K
authors.lastname: Pokusaeva
authors.affiliation: Texas EnteroSorbents, Inc., Bastrop, Texas, USA Salient Pharmaceuticals Incorporated, Houston, Texas, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Carpenter
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D000077215:Clay; D016360:Clostridioides difficile / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity; D004768:Enterotoxins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D010316:Particle Size; D011485:Protein Binding; D012996:Solutions; D016060:Sorption Detoxification / Q000379:methods*
chemical_list: D000538:Aluminum Silicates; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D012996:Solutions; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D000077215:Clay