Antimicrobial properties of Kisameet clay, a natural clay mineral from British Columbia, Canada

The dearth of new antibiotics and the widespread emergence of multi-drug resistant (MDR) bacteria have created a global crisis in medicine and highlighted the drastic need for novel antimicrobial agents. Natural clay minerals with a long history of therapeutic and biomedical applications have recently received increasing attention due to recent studies on their potent antibacterial activity. Kisameet clay (KC), a natural clay deposit found in British Columbia, Canada, has been used by local First Nation people for medicinal purposes for generations. This research investigates the antimicrobial properties of KC, the spectrum of activity, and the mechanism(s) underlying its antibacterial action. In order to characterize KC antimicrobial activity and define its active components, a series of integrated microbiological, chemical, and mineralogical studies have been performed. This study revealed that aqueous suspensions of KC exhibit in vitro broad-spectrum antimicrobial activity against a variety of MDR bacterial pathogens, including the ESKAPE pathogens and Cystic fibrosis clinical isolates. Moreover, two major fungal pathogens, Candida albicans and Cryptococcus neoformans were also susceptible to KC. In addition, KC aqueous leachates (KC-L) show potent bactericidal activity in which low-pH plays a key role. Treatment of KC minerals and KC-L with cation-chelating agents indicates roles for divalent and trivalent cations, more specifically iron and aluminum. Further studies suggest that the bactericidal activity of KC-L is due to multiple modes of action. The low-pH buffered environment, rich in a combination of released metal ions, can synergistically challenge treated bacteria to maintain their metal homeostasis, while aluminum-related impairment of outer membrane (OM) permeability may exacerbate this situation. KC-L can, concurrently, stress multiple bacterial components, cause metal intoxication and consequential cell damage, impair OM and destabilize the cell membrane structure. Furthermore, it induces oxidative stress, generates hydrogen peroxide, and damages DNA, which collectively leads to lethal pleiotropic effects in treated bacteria. Further studies detected KC-L-related transcriptional modulation in oxidative- and envelope- stress responses, DNA damage, metal detoxification pathways, or efflux pump function. Better understanding of the principal components of KC antibacterial activity may permit the formulation of defined, active preparations of this natural clay mineral for therapeutic applications.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat