Unearthing the Antibacterial Mechanism of Medicinal Clay: A Geochemical Approach to Combating Antibiotic Resistance

Sci Rep. 2016 Jan 8;6:19043. doi: 10.1038/srep19043.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aluminum / chemistry
  • Aluminum / pharmacology*
  • Aluminum Silicates / chemistry
  • Aluminum Silicates / pharmacology*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cations, Divalent
  • Clay
  • Drug Resistance, Bacterial / drug effects*
  • Drug Resistance, Bacterial / genetics
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Escherichia coli Proteins / antagonists & inhibitors*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Gene Expression
  • Humans
  • Hydrogen Peroxide / chemistry
  • Hydrogen Peroxide / metabolism
  • Hydrogen-Ion Concentration
  • Hydroxyl Radical / chemistry
  • Hydroxyl Radical / metabolism
  • Iron / chemistry
  • Iron / pharmacology*
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Microbial Sensitivity Tests
  • Mud Therapy / methods
  • Oxidation-Reduction
  • Protein Folding / drug effects
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / growth & development
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / growth & development
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / genetics
  • Staphylococcus epidermidis / growth & development

Substances

  • Aluminum Silicates
  • Anti-Bacterial Agents
  • Cations, Divalent
  • Escherichia coli Proteins
  • Membrane Proteins
  • Hydroxyl Radical
  • Hydrogen Peroxide
  • Aluminum
  • Iron
  • Clay