EAGER: Antibacterial clay effects on pathogenic biofilms

EAGER：抗菌粘土对致病生物膜的作用

基本信息

批准号：
1719325
负责人：
Lynda Williams
金额：
$ 24.08万
依托单位：
Arizona State University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1719325&HistoricalAwards=false
关键词：
EAGER Antibacterial clay effects pathogenic

项目摘要

Recent research by the investigator on clays that kill human pathogens, including antibiotic resistant strains like methicillin resistant S. aureus (MRSA), has documented their common characteristics. Worldwide, only 5-10 % of clays studied to date are antibacterial when hydrated and tested in vitro. Most antibacterial clays are from hydrothermally altered volcanics, where volcanogenic fluids produce minerals containing reduced metals. Ferruginous illite-smectite (I-S) is the most common clay mineral, although kaolins dominate some samples. Antibacterial clay mineral assemblages may also contain non-clay reduced Fe-minerals (e.g., pyrite) that oxidize, causing damage to cell membranes and intracellular proteins. The key is that the clay mineral assemblage buffers the hydration water to pH and Eh conditions that release metals critical to the antibacterial process, allowing interaction with the bacteria. Antibacterial clays also exchange structural ions with the bacterial membrane that weaken bacterial defenses. This research will take this new understanding of the antibacterial process, to the next level by testing their effect on biofilms. Infectious diseases in humans commonly form biofilms, which are communities of bacteria more resistant to antibiotics than the "free floating" bacterial suspensions tested. The effectiveness of antibacterial clay on biofilms is an important step in supporting the costly testing of the bactericidal effect in animal trials. If antibacterial clay is effective against biofilms, in vivo testing may lead to design of new treatments for antibiotic resistant bacteria, with potential applications in wound dressings, medical implants (joint replacements, catheters), animal feed stocks, agricultural pathogens, and production of antibacterial building materials. The scientific goal of this research is to document the effect of an antibacterial clay previously tested against a broad spectrum of planktonic human pathogens, on biofilms most common to infectious diseases. In collaboration with infectious disease researchers at the Mayo Clinic (Rochester, MN), the investigator will develop protocols for the application of clays to biofilms and evaluate conditions that lead to, or limit, their antibacterial activity. Clinical isolates of common and antibiotic resistant bacterial strains will be tested. The investigator has demonstrated that antibacterial clays release metals (Aluminum, Iron) that act together to damage cell membranes and intracellular proteins so they will monitor the interaction of these metals with the biofilms. Standard methods for testing antibiotics must be modified for testing natural clay because the minerals, while releasing metals, are not completely dissolved and therefore will affect spectroscopic evaluations of bacterial viability. Furthermore, the investigator found that metal speciation in various growth media affect results by limiting metal reactivity with bacteria. Therefore, healthy biofilms grown on Teflon disks will be incubated with clay suspensions and cultures will be evaluated for viability by serial dilution and plate counting. If successful, this project will bridge the gap between mineralogy and medicine promoting applications of clay or its derivatives to antibiotic resistant infections. This will enhance development of medical protocols for evaluating minerals that improve human health. The ultimate benefit to society will be to establish an economical and safe natural mineral cure for antibiotic-resistant infections. Proof of the antibacterial activity and safety for applications in wound care may lead to an economic use of clays to treat wounds, or to development of new medicines that incorporate similar antibacterial properties.

研究者对杀死人类病原体的粘土的最新研究，包括耐甲氧西林金黄色葡萄球菌（MRSA）等抗生素菌株，已经记录了它们的共同特征。在全球范围内，迄今为止研究的粘土中只有5-10％的粘土在体外水合和测试时是抗菌性的。大多数抗菌粘土来自水热改变的火山，火山液产生含有减少金属的矿物质。铁石 - 丝岩（I-S）是最常见的粘土矿物，尽管考林占主导地位。抗菌粘土矿物组合物还可能包含氧化氧化的非粘土降低的Fe-Minerals（例如黄铁矿），从而损害细胞膜和细胞内蛋白质。关键是，粘土矿物组合将水合水缓冲到pH和EH条件下，释放对抗菌过程至关重要的金属，从而可以与细菌相互作用。抗菌粘土还将结构离子与细菌防御的细菌膜交换。这项研究将通过测试其对生物膜的影响，将对抗菌过程的新理解提升到一个新的水平。人类中的传染病通常形成生物膜，这些疾病是细菌的群落，对抗生素具有比测试的“游离浮动”细菌悬浮液更具耐药性。抗菌粘土对生物膜的有效性是支持动物试验中对杀菌作用的昂贵测试的重要一步。如果抗菌粘土对生物膜有效，则体内测试可能会导致设计新的抗生素耐药细菌治疗方法，并在伤口敷料，医疗植入物（关节置换剂，导管），动物饲料储备，农业病原体和产生抗细菌材料的产生中潜在应用。这项研究的科学目标是记录先前对广泛的浮游人类病原体，对传染病最常见的生物膜的抗菌粘土的影响。与Mayo诊所（明尼苏达州罗切斯特）的传染病研究人员合作，研究人员将开发用于将粘土应用于生物膜上的方案，并评估导致或限制其抗菌活性的状况。将测试常见和抗生素抗性细菌菌株的临床分离株。研究者表明，抗菌粘土释放金属（铝，铁），它们一起起作用，以损害细胞膜和细胞内蛋白质，因此它们将监测这些金属与生物膜的相互作用。必须修改用于测试抗生素的标准方法以测试天然粘土，因为矿物质虽然释放金属并非完全溶解，因此会影响细菌生存能力的光谱评估。此外，研究者发现，各种生长培养基中的金属物种形成通过限制了与细菌的金属反应性来影响结果。因此，将在特氟龙磁盘上生长的健康生物膜与粘土悬浮液一起孵育，并且将通过连续稀释和板块计数评估培养物的生存能力。如果成功，该项目将弥合矿物学和医学之间的差距，促进粘土或其衍生物在抗生素耐药性感染中的应用。这将增强用于评估改善人类健康的矿物质的医疗方案的开发。对社会的最终好处是建立一种经济和安全的自然矿物质治疗抗生素耐药性感染。在伤口护理中应用的抗菌活性和安全性证明可能会导致经济使用粘土来治疗伤口，或开发融合了类似抗菌特性的新药物。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Anatomy of an Antibacterial Clay Deposit

抗菌粘土沉积物的解剖

DOI：
发表时间：
2018
期刊：
Program and abstracts for Clay Minerals Society ... Annual Meeting
影响因子：
0
作者：
Morrison, K.D.;Williams, L.B.
通讯作者：
Williams, L.B.

In vitro Anti-Biofilm Activity of Oregon Mineral Technologies Blue Clay

Oregon Mineral Technologies Blue Clay 的体外抗生物膜活性

DOI：
发表时间：
2018
期刊：
Directory and constitution - American Society for Microbiology
影响因子：
0
作者：
Caflisch, K.M.;Schmidt-Malan, S.M.;Mandrekar, J.N.;Karau, M.J.;Nicklas, J.P.;Patel, R.
通讯作者：
Patel, R.

Antibacterial activity of reduced iron clay against pathogenic bacteria associated with wound infections