Alternative approaches to medicine are stock-in-trade in the ASU laboratory of microbiologist Shelley Haydel. So when ASU senior Jenny Koehl joined Haydel's investigative team seeking firsthand knowledge of how basic research is done, how drugs are tested and potential cures produced, she found it and much more.
With the guidance of Tanya Cunningham, a graduate student mentor, Koehl has helped advance understanding about the antibacterial activity of clay minerals and their ability to kill what the best antibiotics on the market can't touch.
Haydel's group, part of the School of Life Sciences, in the College of Liberals Arts and Sciences, and the Biodesign Institute at ASU, did the work in collaboration with Jack Summers, an inorganic chemist at Western Carolina University. They uncovered two factors that control the antibacterial activity. Their article, "pH-dependent metal ion toxicity influences the antibacterial activity of two natural mineral mixtures" was published March 1 in the journal Public Library of Science (PLoS) ONE.
"This work sets a baseline from which to look for potential mechanisms of antibacterial action," said Cunningham, lead author, who is now a research technician with the Fred Hutchinson Cancer Research Center in Seattle.
"We need helpful alternatives, natural approaches to antibacterial cures, because there is bacterial resistance to drugs," Koehl said. "Knowing the mechanisms of action will help us develop our own topical treatments."
Clay has had a role in human health as ancient as man. However, specific identification of the mechanisms underlying this antibacterial activity has been elusive, until now.
The Haydel-Summers collaborative has added clarity to these distinctly muddy waters by screening more than 50 mineral mixtures (and aqueous extractions from them, known as leachates) marketed as health and cosmetic products using pathogens Escherichia coli, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa. Only two mineral mixtures of significantly different compositions (and their leachates) were discovered to possess antibacterial traits.
Clay minerals often are recognized as the slimy slurry of minerals that slicks rivers' banks. Understanding clay's structure is integral to answering questions about the mechanisms behind its antibacterial activity. Negatively charged surfaces attract positively charged elements, such as iron, copper, silver and other metals. In turn, water is absorbed between layers of the crystal structure creating a cation sandwich with aqueous filling or interlayer.
Antibacterial activity in leachates, extracted from the mineral mixtures, confirm that the antibacterial activity is chemically-based, rather than a result of physical interactions with microbes.
Because of the tendency of clay to attract multivalent ions, particularly metals, the scientists next examined the leachates' chemistry and antibacterial activity in the presence of chelators, which bind metals. The researchers also used thiourea, a hydroxyl radical scavenger, at various pH levels. Chelation of the minerals with ethylenediaminetetraacetic acid (EDTA) or desferrioxamine eliminated or reduced toxicity, respectively.
Further testing of the mineral leachates confirmed that there are higher concentrations of chemically-accessible metal ions in leachates from antibacterial samples than from non-bactericidal mineral samples.
