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Durham University

Institute of Advanced Study

Antibacterial Clay Therapy

Summary

Antimicrobial resistance is a global concern requiring innovative and lateral approaches to combat the threat to human health. New antimicrobial agents and materials are urgently needed to tackle increasingly drug resistant pathogens. For centuries, clay minerals have been employed in traditional medicine, either topically or by ingestion. Recent studies have verified that clays do possess unique antibacterial properties that offer considerable health benefits. The approach to
this project aims to merge empirical studies on the constituents and antibacterial properties of therapeutic clays, while also considering political, social and cultural contexts that may inform future medical applications.

As a starting point, we will evaluate clay from the Baku region of Azerbijan as an antibacterial agent with potential for the treatment of wound infections. The structure and composition of this clay will be specifically defined and its antibacterial efficacy assessed against representative bacterial species. As an integral part of the project, we will commence a broader, humanities-driven approach to investigate the poorly characterised usage of clays in the treatment of infections. There are many questions surrounding the different ways that clays are harnessed as therapies, for what types of infection and in what kinds of social interactions.

Term: Michaelmas Term

Principal Investigator: Dr Gary J. Sharples, Associate Professor, Department of Biosciences, gary.sharples@durham.ac.uk;
Principal Investigator: Dr Kim Jamie, Assistant Professor, Sociology, kimberly.jamie@durham.ac.uk


Project Description

A recent UK government report[1] predicted that antimicrobial resistance (AMR) is likely to overtake cancer as the leading cause of death over the next 30 years. Resistance to existing antimicrobial chemotherapeutics is an increasing global threat to the treatment of infectious diseases. Few novel drugs have been discovered in recent years to combat increasingly resistant bacteria and history has shown that evolution of resistance is inevitable. In this project, we propose an alternative approach that harnesses clay minerals to combat bacterial growth and promote wound healing irrespective of a protective biofilm or the antibiotic resistant capabilities of the pathogen.

Chronic wound infections involving tissue ulceration are a current and emerging clinical concern, particularly with the escalation in cases of diabetes and associated vascular impairment to extremities[2]. Diabetic foot ulcers, leg ulcers and pressure sores are common in healthcare settings and are estimated to cost around 3-5% of the annual NHS budget[3], [4], which for England in 2015/16 was estimated to be approximately £3.5-5.8 billion. Around 60% of chronic skin infections harbour bacterial biofilms[5] and impede healing due to their intrinsic resistance to immune responses, antibiotics and disinfectants. Current treatment regimes involve the removal of wound biofilms by debridement, making them more vulnerable to antibiotics, antiseptics and selective biocides[6]. Hospital acquired infections present a growing problem and post-operative wounds and ulcers, particularly in the elderly, are proving increasingly intractable to treatment. Consequently, there is considerable need for alternative therapies that do not rely on our dwindling number of effective antibiotics. This project offers a solution to the AMR predicament by harnessing a novel approach to wound treatment that cannot be subverted by evolving pathogens.

Clay minerals have been used for therapeutic purposes throughout history, with the first use of medicinal clay recorded in ancient Mesopotamia. Traditional medicine around the world, most notably in Asian and African countries as well as in France, still relies on the use natural clays. The antibacterial effect of such clays has been validated in numerous published articles[7] [8]. A striking example that generated considerable interest was the dramatic account of the healing of a patient with Buruli ulcer caused by Mycobacterium ulcerans[9]. Clays found at various localities in Azerbaijan have also been used for their therapeutic benefits, for example from outcrops of green clays in Surakhany village and Gilabi clay in Amircan, Mashtaga and Khashoxonu villages in Baku. Green Surakhany clays are used for internal and external treatments, for instance, as a compress for knee pain. Gilabi clays are only employed externally because they contain alkali elements, which could be harmful, especially for the stomach, when applied internally. However, a rigorous assessment of the antibacterial properties of these Azerbaijani clays is still lacking and the mineralogical properties underpinning the therapeutic role of these and other clays are still being debated. Questions remain over how these clays have been used historically in communities and how they are currently deployed in the context of a modern healthcare system. How was knowledge of clay’s beneficial properties originally determined, how were clays selected and how is this information disseminated to the next generation?

Most studies to date have invoked clay minerals' unique chemical and physical properties to explain the observed beneficial effects on infections[10]. As these finegrained, natural materials have particle dimensions of <2 μm, they can be delivered both internally and externally. One mode of antibacterial action relies on the adsorptive properties of clay minerals, which may interfere with nutrient uptake, metabolite efflux or cell envelope integrity. The adsorptive properties are determined by the clay mineral structure, which varies with the elemental composition of the clay mineral and the environment in which they were formed. The presence of metals in the structure of clay minerals, which consist of tetrahedral (Si, Al, Fe3+) and octahedral (Al, Fe2+, Fe3+, Mg) coordinated cations organised into either sheets or chains, gives rise to additional modes of action. The metal constituents of clay are known to interfere with bacterial metal homeostasis and to contribute to oxidative stress via the formation of reactive oxygen species[11]. Others have suggested alternative specific effects at the outer surface of gram-negative bacteria[12]. Regardless of the mode of action, clay minerals are increasingly recognised as novel, potent antibacterial agents.

The aim of this project is to assess the potential of Azerbaijani clays as a novel antimicrobial for external treatment of infections. To this end, we will relate the mineralogical composition of Azerbaijani clays to their therapeutic role and work towards identifying the underlying mechanism of antibacterial action. The natural sciences aspects will follow two parallel strands of investigation building on expertise of the partners in geochemistry and antibacterial modes of action. A third goal will be to initiate interactions with partners in anthropology and beyond to investigate traditional applications of clay in wound healing and/or geophagy in Azerbaijan and Africa. These three aims are summarized as follows:

1. An assessment of Azerbaijani clays for mineralogical parameters: elemental composition, redox chemistry and surface properties.

2. Evaluation of the antibacterial activity of these clays and the underlying mechanism of antibacterial action.

3. To investigate the use of therapeutic clays in Azerbaijan and Africa from an anthropological perspective.

The planned research requires expertise in diverse research areas, including mineralogy, microbiology, chemistry and anthropology which will be provided through the highly interdisciplinary team. To translate our findings from studying Azerbaijani clays to enable targeted clay exploration, we will also compare our results with those of French and Oregon clays studied previously[10, 11].



[1] J. O'Neill, Tackling drug-resistant infections globally: final report and recommendations of the review on antimicrobial resistance. Department of Health and the Wellcome Trust, UK. 2016.

[2] McInnes, A.D., Diabetic foot disease in the United Kingdom: about time to put feet first. J. Foot Ankle Res., 2012. 5: 26.

[3] Posnett, J. and P.J. Franks, The burden of chronic wounds in the UK. Nurs. Times, 2008. 104: 44-45.

[4] Phillips, C.J., et al., Estimating the costs associated with the management of patients with chronic wounds using linked routine data. Int. Wound J., 2016. 13: 1193-1197.

[5] James, G.A., et al., Biofilms in chronic wounds. Wound Repair Regen., 2008. 16: 37-44.

[6] Wolcott, R.D., J.P. Kennedy, and S.E. Dowd, Regular debridement is the main tool for

maintaining a healthy wound bed in most chronic wounds. J. Wound Care, 2009. 18: 54-56

[7] Carretero, M.I., Clay minerals and their beneficial effects upon human health. A review. Applied Clay Science, 2002. 21: 155-163.

[8] Williams, L.B. and S.E. Haydel, Evaluation of the medicinal use of clay minerals as antibacterial agents. Int. Geol. Rev., 2010. 52: 745-770.

[9] Williams, L.B., et al., Killer clays! Natural antibacterial clay minerals. Mineral. Soc. Bull., London, 2004. 139: 3

[10] Ghadiri, M., W. Chrzanowski, and R. Rohanizadeh, Biomedical applications of cationic clay minerals. RSC Advances, 2015. 5: 29467-29481.

[11] Morrison, K.D., R. Misra, and L.B. Williams, Unearthing theantibacterial mechanism of medicinal clay: a geochemical approach to combating antibiotic resistance. Sci. Rep., 2016. 6: 19043.

[12] Zarate-Reyes, L., et al., Antibacterial clay against gram-negative antibiotic resistant bacteria. J. Hazard. Mater., 2018. 342: 625-632.

IAS Fellows

Visiting Distinguished Scholar

IAS Antibacterial Clay Therapy: Team Members – July 2019

Elshan Abdullayev (French-Azerbaijani University, Baku, Azerbaijan) Kamal Badreshany (Department of Archaeology, Durham University, UK)
Clay mineralogy and geochemistry Geological characterization of ancient ceramics
https://www.researchgate.net/profile/Elshan_Abdullayev2 https://www.dur.ac.uk/archaeology/staff/?id=11825
Lynsay Blake (Department of Engineering, Durham University, UK) Hannah Brown (Department of Anthropology, Durham University, UK)
Microbial communities in the environment, waste treatment and extremophiles Medical anthropology; community-based health care and public health
https://www.dur.ac.uk/directory/profile/?id=17326 https://www.dur.ac.uk/anthropology/staff/academic/?id=11578
Hailiang Dong (Department of Geology and Environmental Earth Science, Miami University, USA) Chris Greenwell (Department of Earth Sciences, Durham University, UK)
Geomicrobiology; mineral-microbe interactions; life in extreme environments; bioremediation Surface chemistry, structure and properties of layered minerals
https://miamioh.edu/cas/academics/departments/geology/about/faculty-staff/dong/index.html https://www.dur.ac.uk/earth.sciences/staff/?id=5665
Kimberly Jamie (Department of Sociology, Durham University, UK) Irada Khalilova (Khazar University, Baku, Azerbaijan)
Medical sociology and sociology of work; complementary/alternative medicines Human cell biology; toxicology; contribution of reactive oxygen species to inflammation
https://www.dur.ac.uk/sociology/staff/profile/?id=12420 http://khazar.org/uploads/files/letters/CV_IradaKhalilova_2019.pdf
Sean McMahon (School of Physics and Astronomy, The University of Edinburgh, UK) Nor Ainy Mahyudin (Faculty of Food Science and Technology, Universiti Putra Malaysia)
Geobiology and astrobiology; importance of microbes in fossilisation of animal and plant tissues Antibacterial resistance and surfaces; biofilm formation
https://www.ph.ed.ac.uk/people/sean-mcmahon https://www.researchgate.net/profile/Nor_Ainy_Mahyudin
Rasoul Moradi (Khazar University, Baku, Azerbaijan) Papreen Nahar (Brighton and Sussex Medical School, Sussex University, UK)
Nanotechnology and water purification; drug discovery and delivery Medical anthropology; health inequality, antimicrobial resistance
http://khazar.org/uploads/files/engineering/CV%20Rasoul%20Moradi.pdf https://www.bsms.ac.uk/about/contact-us/staff/dr-papreen-nahar.aspx
Anke Neumann (School of Engineering, Newcastle University, UK) Robert Pal (Department of Chemistry, Durham University, UK)
Environmental chemistry; redox processes at mineral-water interfaces High resolution microscopy of eukaryotic and prokaryotic cells; nanomachines
https://www.ncl.ac.uk/engineering/staff/profile/ankeneumann.html#background https://www.dur.ac.uk/chemistry/staff/profile/?id=6011
Kevin Rosso (Pacific Northwest National Laboratory, Richland, USA) Gary Sharples (Department of Biosciences, Durham University, UK)
Redox chemistry of minerals and interactions with microbes Antibacterial compounds and surfaces; bacterial genome rearrangements
https://www.pnnl.gov/science/staff/staff_info.asp?staff_num=5642 https://www.dur.ac.uk/biosciences/about/schoolstaff/profile/?id=37

Project Events 2019/20

On Thursday 14th November (10am-4pm), a Social Theory and AMR workshop will be hosted to bring together social science and humanities colleagues with an interest in AMR. The workshop will explore how social scientists and humanities scholars have used social theory to make sense of AMR to date, and what the future of theorising AMR might be. The workshop is designed to be informal and conversational and colleagues from across disciplines are welcomed to attend and join the day-long workshop.

The convenors of this project, Dr Kim Jamie and Dr Gary Sharples are delighted to confirm the following speakers:


Catherine Will, University of Sussex

Christina Buse, University of York

Andrea Nunez Casal, Goldsmiths

Any colleague who wishes to participate can sign up at: https://www.eventbrite.co.uk/e/social-theory-and-amr-tickets-74103901765?utm_term=eventurl_text

If you have any questions, please contact Dr Kimberly Jamie.