title: Bismuth-mediated disruption of the glycocalyx-cell wall of Helicobacter pylori: ultrastructural evidence for a mechanism of action for bismuth salts.
abstract: The mechanism of bismuth's bactericidal activity against Helicobacter pylori was investigated using transmission electron microscopy (TEM) and analytical electron microscopy (AEM); time-kill kinetic methods evaluated the effect of excess divalent cations. TEM analysis of untreated H. pylori revealed a normal morphology. In contrast, H. pylori exposed to bismuth salts had swollen, distorted cells with membrane-cell wall blebbing and a cytoplasm containing electron-dense, sometimes crystalline aggregates. By AEM, swollen cells contained bismuth at the cell periphery, whereas bacillary forms contained cytoplasmic bismuth localizations. Time-kill studies showed that the bactericidal activity of bismuth could be prevented by pretreatment with divalent cations. The effects of bismuth salts on the glycocalyces-cell walls of H. pylori with reversal of bactericidal activity by divalent cations are identical to those produced by other polycationic agents on various gram-negative bacilli. We conclude that disruption of the glycocalyces-cell walls of H. pylori is one mechanism of action for bismuth salts.
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232-5310, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Stratton
authors.forename: R R
authors.initials: RR
authors.lastname: Warner
authors.forename: P E
authors.initials: PE
authors.lastname: Coudron
authors.forename: N A
authors.initials: NA
authors.lastname: Lilly
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001729:Bismuth / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects / Q000648:ultrastructure; D019276:Glycocalyx / Q000187:drug effects / Q000648:ultrastructure; D016480:Helicobacter pylori / Q000187:drug effects* / Q000648:ultrastructure*; D007700:Kinetics; D008854:Microscopy, Electron / Q000379:methods; D009942:Organometallic Compounds / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; C002791:bismuth tripotassium dicitrate; D001729:Bismuth