pH-Dependent Metal Ion Toxicity Influences the Antibacterial Activity of Two Natural Mineral Mixtures

Abstract

BackgroundRecent studies have demonstrated that several mineral products sold for medicinal purposes demonstrate antimicrobial activity, but little is known about the physicochemical properties involved in antibacterial activity.Methodology/Principal FindingsUsing in vitro mineral suspension testing, we have identified two natural mineral mixtures, arbitrarily designated BY07 and CB07, with antibacterial activity against a broad-spectrum of bacterial pathogens. Mineral-derived aqueous leachates also exhibited antibacterial activity, revealing that chemical, not physical, mineral characteristics were responsible for the observed activity. The chemical properties essential for bactericidal activity against Escherichia coli were probed by testing antibacterial activity in the presence of metal chelators, the hydroxyl radical scavenger, thiourea, and varying pH levels. Chelation of the BY07 minerals with EDTA or desferrioxamine eliminated or reduced BY07 toxicity, respectively, suggesting a role of an acid-soluble metal species, particularly Fe3+ or other sequestered metal cations, in mineral toxicity. This conclusion was supported by NMR relaxation data, which indicated that BY07 and CB07 leachates contained higher concentrations of chemically accessible metal ions than leachates from non-bactericidal mineral samples.Conclusions/SignificanceWe conclude that the acidic environment of the hydrated minerals significantly contributes to antibacterial activity by increasing the availability and toxicity of metal ions. These findings provide impetus for further investigation of the physiological effects of mineral products and their applications in complementary antibacterial therapies.

Inexpensive mineral copper materials with antibacterial surfaces

“…57 Unfortunately only a few deposits accumulated antibacterial clays of specific mineralogical and elemental composition 58,59 , which can resist bacteria such as E. coli, S. aureus, Pseudomonas aeruginosa, Salmonella typhimurium and others. 60 Recent studies undertaken by the University of Arizona 59 suggest that these clays supply iron to kill bacteria by generating radicals that attack cell components by a reaction analogous to Equation 1 in section 4. Since there are only a few natural clays with antibacterial properties, other clays have been made antibacterial by ion exchange and sorption of bactericidal ions such as silver, copper, cobalt and zinc.…”

Antimicrobial Biomimetics

“…This mineral particulate heated to 200 or 500 o C still retained bactericidal activity, whereas heated or nonheated cation-exchanged CsAg0 2 no longer killed E. coli. Natural mineral mixtures were recently identified with antibacterial activity against a broad-spectrum of bacterial pathogens (Cunningham et al, 2010). Mineralderived aqueous leachates also exhibited antibacterial activity, revealing that chemical, not physical, mineral characteristics were responsible for the observed activity.…”

Adaptation of the neutral bacterial comet assay to assess antimicrobial-mediated DNA double-strand breaks in Escherichia coli

“…We have identified a natural antibacterial clay mineral mixture, designated CB, which exhibits broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria, including MRSA (Cunningham et al, 2010). The soluble fraction, or leachate (CB-L), of CB maintains the antimicrobial properties of the clay, indicating a chemical, rather than physical, mechanism of induced toxicity (Cunningham et al, 2010).…”

“…We have identified a natural antibacterial clay mineral mixture, designated CB, which exhibits broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria, including MRSA (Cunningham et al, 2010). The soluble fraction, or leachate (CB-L), of CB maintains the antimicrobial properties of the clay, indicating a chemical, rather than physical, mechanism of induced toxicity (Cunningham et al, 2010). Because the aqueous suspensions of the CB clay minerals result in desorption of metal cations (including iron), a low pH environment, and the generation of reactive oxygen species (ROS) and hydrogen peroxide, we hypothesized that Fenton/Haber-Weiss reaction-mediated oxidative stress contributes to CB antimicrobial activity (Cunningham et al, 2010; Koehl and Haydel, unpublished results).…”

“…The soluble fraction, or leachate (CB-L), of CB maintains the antimicrobial properties of the clay, indicating a chemical, rather than physical, mechanism of induced toxicity (Cunningham et al, 2010). Because the aqueous suspensions of the CB clay minerals result in desorption of metal cations (including iron), a low pH environment, and the generation of reactive oxygen species (ROS) and hydrogen peroxide, we hypothesized that Fenton/Haber-Weiss reaction-mediated oxidative stress contributes to CB antimicrobial activity (Cunningham et al, 2010; Koehl and Haydel, unpublished results). The Fenton and Haber-Weiss reactions utilize iron and hydrogen peroxide to produce hydroxyl and superoxide radicals, which are known variations of ROS (Halliwell and Gutteridge, 1984).…”