title: Unearthing the Antibacterial Mechanism of Medicinal Clay: A Geochemical Approach to Combating Antibiotic Resistance.
abstract: Natural antibacterial clays, when hydrated and applied topically, kill human pathogens including antibiotic resistant strains proliferating worldwide. Only certain clays are bactericidal; those containing soluble reduced metals and expandable clay minerals that absorb cations, providing a capacity for extended metal release and production of toxic hydroxyl radicals. Here we show the critical antibacterial components are soluble Fe(2+) and Al(3+) that synergistically attack multiple cellular systems in pathogens normally growth-limited by Fe supply. This geochemical process is more effective than metal solutions alone and provides an alternative antibacterial strategy to traditional antibiotics. Advanced bioimaging methods and genetic show that Al(3+) misfolds cell membrane proteins, while Fe(2+) evokes membrane oxidation and enters the cytoplasm inflicting hydroxyl radical attack on intracellular proteins and DNA. The lethal reaction precipitates Fe(3+)-oxides as biomolecular damage proceeds. Discovery of this bactericidal mechanism demonstrated by natural clays should guide designs of new mineral-based antibacterial agents.
authors.affiliation: Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Morrison
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287 USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Misra
authors.affiliation: School of Earth &Space Exploration, Arizona State University, Tempe, AZ 85287 USA.
authors.forename: Lynda B
authors.initials: LB
authors.lastname: Williams
mesh_terms: D000535:Aluminum / Q000737:chemistry / Q000494:pharmacology*; D000538:Aluminum Silicates / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002413:Cations, Divalent; D000077215:Clay; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000737:chemistry / Q000494:pharmacology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D009094:Mud Therapy / Q000379:methods; D010084:Oxidation-Reduction; D017510:Protein Folding / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development
chemical_list: D000538:Aluminum Silicates; D000900:Anti-Bacterial Agents; D002413:Cations, Divalent; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D000535:Aluminum; D007501:Iron; D000077215:Clay