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

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. In conclusion, discovery of this bactericidal mechanism demonstrated by natural clays should guide designs of new mineral-based antibacterial agents.
Authors:
 [1] ;  [2] ;  [3]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division
  2. Arizona State Univ., Tempe, AZ (United States). School of Life Sciences
  3. Arizona State Univ., Tempe, AZ (United States). School of Earth & Space Exploration
Publication Date:
Grant/Contract Number:
EAR-1123931; R21-AT003618; NIGMS-R01-048167; EAR-1352996
Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Research Org:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org:
USDOE; National Science Foundation (NSF); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1259512