Near Kisameet Bay on the central coast of British Columbia sits a deposit of clay that covers 5 acres and spans a depth up to 42 feet in places. This vast smear formed 10,000 years ago as glacial melt filled a granite basin and fine minerals silted out.
The ancient clay likely holds secrets to developing desperately needed 21st century antibiotics. This week, researchers at the University of British Columbia (UBC) report in mBio that the Kisameet clay possesses potent antibacterial activity that kills all six members of the ESKAPE group of pathogens—the bacteria responsible for the most deadly hospital-acquired infections.
The Kisameet Glacial Clay company, which owns the rights to the deposit situated on the Heiltsuk Nation’s traditional territory, approached Julian Davies to assess the antimicrobial activity of the clay. The Heiltsuk First Nation people had used the clay as a natural remedy, taken internally and applied to the skin, for several centuries.
“When we first started, we thought it was folk medicine,” says Davies, emeritus Professor of Microbiology at UBC in Vancouver. “But it turned out to be much more than that.”
As Davies and his graduate student Shekooh Behroozian began to dig into the history of the clay, they found that doctors in Vancouver had used it in the 1940s to successfully treat serious wounds and conditions such as duodenal ulcers, burns, and phlebitis. But the company wanted to know: “Is it real? Does this clay have antimicrobial activity?” says Davies. (image: Shekooh Behroozian (left) and Julian Davies test Kisameet clay against ESKAPE pathogens)
So the team started by testing Kisameet clay against the worst of the worst. The ESKAPE bacterial pathogens are all multi-drug resistant and cause excessive mortality from hospital-acquired infections. These six—Enterococcus faecium, Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii, Psuedomonas aeruginosa, and Enterobacter species —are the culprits behind serious urinary tract infections, wound infections, pneumonia, and sepsis.
“We clearly need new antimicrobial agents to treat these serious problems in hospitals,” says Davies. “Increasingly multi-drug resistant strains are being selected because of the overuse and misuse of antibiotics.”
Behroozian began by preparing a 1% clay suspension from dried clay to treat a collection of 16 ESKAPE strains from local hospitals. When the strains were incubated with the clay suspension, five of the group members were killed within 24 hours, and the sixth, Enterococcus faecium, was killed after 48 hours. Some strains began to die off after just 5 hours, indicating potent antibacterial activity.
“The first time we did it, such activity was surprising. But Shekooh has repeated it so many times now, we are really convinced,” says Davies. Nailing down the mechanism of the antimicrobial activity will be more difficult.
The clay is a complex mixture made up of about 24% by weight clay minerals, which are aluminum silicates, with various exchangeable metal ions and elemental sulfur. The team found that water-based extracts of the clay also possess broad-spectrum antimicrobial activity. In addition, the clay, much like soils, contains its own diverse community of microbes, which could be pumping out antimicrobial compounds. It is likely that the physical, chemical, and biological components of the clay are all important, and perhaps synergistic, for its activity.
“So far, we are sure that the mechanism of action is multifactorial,” says Behroozian. “And we know the antimicrobial activity is pH-dependent, with the clay showing the best activity at acidic pH.”
Other work in Davies’ lab has shown that clay suspensions are also active in killing the pathogenic yeast Candida albicans and clay extracts disrupt biofilm formation by S. aureus and P. aeruginosa. The team has not observed any resistance to the clay so far.
“It’s a dream that there could be isolates [in the clay] that make new antibiotics,” says Davies. But he acknowledges the many hurdles facing that effort. The first task is to do a microbiome analysis of the clay to find out if there are “any weird bugs that make something interesting and new,” says Davies. But culturing such microbes in the lab to isolate antimicrobial compounds has so far proven difficult. A second major task is to show that the clay has efficacy in animal models of infection.
“This could be another option for treating infectious diseases,” says Davies, but the clay must be tested for toxicity and its activity defined well enough to satisfy drug regulators.
Davies points to another mBio study that recently resurrected a natural remedy from the Middle Ages. This ancient stye remedy was a complex mixture of plant extracts and other components that proved effective in killing S. aureus in the lab.
The complexity of these natural remedies could be the key to their success, says Davies. “Natural medicines like clay have multifactorial modes of action that would require a pathogen to acquire multiple mutations to become resistant.”