bismuth-subsalicylate and bismuth-oxychloride

Previous studies have shown bismuth subsalicylate (BSS) has antimicrobial properties, but few studies have addressed the mechanism of action. Furthermore, following BSS ingestion other bismuth salts form throughout the gastrointestinal tract including bismuth oxychloride (BiOCl) that also act upon enteric pathogens. To further understand the antimicrobial activity of bismuth in infectious diarrhea, the antimicrobial effect of BSS and BiOCl on Clostridium difficile, Salmonella, Shigella, Shiga toxin-producing Escherichia coli strains and norovirus (NoV) were measured. Bacterial enteric pathogens in pure culture or in human fecal material were exposed to 35mg/ml BSS or BiOCl with or without a vehicle suspension. BSS and BiOCl treated samples were quantified and visualized by transmission electron microscopy. To measure the effect on NoV, reduction of infectious murine NoV (MNV), a surrogate for human NoV, and Norwalk virus RNA levels were measured by viral plaque assay and RT-qPCR, respectively. BSS and BiOCl reduced bacterial growth by 3-9 logs in all strains with majority resulting in populations of <10 cfu/ml within 24 h. Similar results were found when fecal material was included. Microscopy images detected bismuth on bacterial membranes and within the bacterial organisms at 30 min post-treatment. At 8.8mg/ml BSS and BiOCl reduced infectivity of MNV significantly by 2.7 and 2.0 log after 24 h of exposure. In addition, both BSS and BiOCl slightly reduced the level of Norwalk replicon-bearing cells suggesting that bismuth may inhibit NoV in vivo. Collectively, our results confirm and build on existing data that BSS has antimicrobial properties against a wide-range of diarrhea-causing pathogens.

Topics: Animals; Anti-Infective Agents; Bacterial Load; Bismuth; Clostridioides difficile; Enterobacteriaceae; Humans; Mice; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Transmission; Norovirus; Organometallic Compounds; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Salicylates; Viral Load; Viral Plaque Assay

The effects of sublethal concentrations of bismuth salts on bacterial invasion of mammalian cells were investigated. Pepto-Bismol, bismuth subsalicylate, and bismuth oxychloride, produced by interacting bismuth subsalicylate and simulated gastric juice, in suspension at concentrations as low as 1.4 mM significantly interfered with the invasion of RPMI-4788 cells by two different strains of Yersinia enterocolitica. Invasion of the mammalian epithelial cells by other enteric bacteria was also reduced significantly by some of these bismuth salts. Commercially obtained bismuth oxychloride, bismuth sulfide, and sodium salicylate had no affect on invasion by Y. enterocolitica. Exposure of Y. enterocolitica 8081c to Pepto-Bismol for as brief a time as 5 min was sufficient to produce the inhibitory effect. Removal of bismuth bound to bacteria by sodium potassium tartrate did not reverse the inhibition. Electron-dense deposits are observed in Y. enterocolitica 8081c exposed to bismuth subsalicylate, suggesting that interference of invasion may result from bismuth permeation of the bacterial cell wall.

Topics: Bacteria; Bismuth; Colony Count, Microbial; Gastrointestinal Diseases; Humans; Intestinal Mucosa; Organometallic Compounds; Salicylates; Tumor Cells, Cultured

Bismuth salts inhibited plaque formation of all enteric viruses tested, which included four strains of rotavirus and one strain each of echovirus, reovirus, and poliovirus. The compounds had no direct virucidal effect at concentrations ranging from 0.025 to 2.5 mg/ml, and the inhibitory effects were observed only at concentrations slightly below those that caused extensive cytotoxicity. Plaque inhibition appeared to result from interference with host cell functions, with secondary inhibition of virus production.

Topics: Animals; Bismuth; Cattle; Cells, Cultured; Enterovirus; Humans; Organometallic Compounds; Rotavirus; Salicylates; Tartrates; Viral Plaque Assay