Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Civil Engineering, University of British Columbia, Vancouver, British Columbia, Canada.
mBio. 2020 Oct 6;11(5):e02350-20. doi: 10.1128/mBio.02350-20.
Worldwide increases in antibiotic resistance and the dearth of new antibiotics have created a global crisis in the treatment of infectious diseases. These concerns highlight the pressing need for novel antimicrobial agents. Natural clay minerals have a long history of therapeutic and biomedical applications and have lately received specific attention for their potent antimicrobial properties. In particular, Kisameet clay (KC) has strong antibacterial activity against a variety of multidrug-resistant (MDR) bacterial pathogens Here, we have extended the known spectrum of activity of KC by demonstrating its efficacy against two major fungal pathogens, and In addition, KC also exhibits potent activity against the opportunistic bacterial pathogen , a model organism for infection. Moreover, aqueous KC leachates (KC-L) exhibited broad-spectrum antibacterial activity, eradicated Gram-negative and Gram-positive biofilms, and prevented their formation. The mechanism(s) underlying KC antibacterial activity appears to be complex. Adjusting KC-L to neutral pH rendered it inactive, indicating a contribution of pH, although low pH alone was insufficient for its antibacterial activity. Treatment of KC minerals with cation-chelating agents such as EDTA, 2,2'-bipyridyl, and deferoxamine reduced the antibacterial activity, while supplementation of KC-L with these chelating agents eliminated the inhibitory activity. Together, the data suggest a positive role for divalent and trivalent cations, including iron and aluminum, in bacterial inhibition by KC. Collectively, these studies demonstrate the range of KC bioactivity and provide a better understanding of the mechanism underlying its antibacterial effects. The escalating emergence of multidrug-resistant (MDR) bacteria, together with the paucity of novel antimicrobial agents in antibiotic development, is recognized as a worldwide public health crisis. Kisameet clay (KC), found in British Columbia (BC), Canada, is a clay mineral with a long history of therapeutic applications among people of the First Nations. We previously reported the antibacterial activity of KC against a group of MDR clinical pathogens. Here, we demonstrate its activity against two major human-pathogenic fungal species, as well as against bacterial biofilms, which underlie many recalcitrant bacterial infections. In these studies, we also identified several geochemical characteristics of KC, such as metal ions and low pH, which are involved in its antibacterial activity. These findings provide a better understanding of the components of KC antibacterial activity and a basis for developing defined preparations of this clay mineral for therapeutic applications.
全球范围内抗生素耐药性的增加和新抗生素的匮乏给传染病的治疗带来了全球性危机。这些问题凸显了开发新型抗菌药物的迫切需求。天然粘土矿物在治疗和生物医学应用方面有着悠久的历史，最近因其强大的抗菌特性而受到特别关注。特别是基斯梅特粘土 (KC) 对多种多药耐药 (MDR) 细菌病原体具有很强的抗菌活性。在这里，我们通过证明其对两种主要真菌病原体 和 的功效，扩展了 KC 的已知活性谱。此外，KC 还对机会性细菌病原体 表现出强大的活性， 是 感染的模型生物。此外，水性 KC 浸出液 (KC-L) 表现出广谱抗菌活性，根除革兰氏阴性和革兰氏阳性生物膜，并防止其形成。KC 抗菌活性的机制似乎很复杂。将 KC-L 调节至中性 pH 会使其失去活性，表明 pH 起作用，尽管单独的低 pH 不足以发挥其抗菌活性。用 EDTA、2,2'-联吡啶和去铁胺等阳离子螯合剂处理 KC 矿物可降低其抗菌活性，而向 KC-L 中添加这些螯合剂可消除抑制活性。综上所述，数据表明二价和三价阳离子（包括铁和铝）在 KC 抑制细菌方面发挥了积极作用。这些研究共同证明了 KC 的生物活性范围，并提供了对其抗菌作用机制的更好理解。多药耐药 (MDR) 细菌的不断出现，加上抗生素开发中新型抗菌药物的匮乏，被认为是全球公共卫生危机。基斯梅特粘土 (KC) 是一种粘土矿物，在加拿大不列颠哥伦比亚省 (BC) 被发现，在原住民中有着悠久的治疗应用历史。我们之前报道过 KC 对一组 MDR 临床病原体的抗菌活性。在这里，我们证明了它对两种主要的人类致病性真菌物种以及对抗细菌生物膜的活性，细菌生物膜是许多难治性细菌感染的基础。在这些研究中，我们还确定了 KC 的一些地球化学特征，例如金属离子和低 pH 值，这些特征参与了其抗菌活性。这些发现提供了对 KC 抗菌活性成分的更好理解，并为开发这种粘土矿物的明确治疗应用制剂奠定了基础。
