For self-funded PhD and MSc by Research project enquires please contact Dr Jonathan Butler ([email protected])

1. Novel antimicrobial fabrics for use within wound care management.

Antimicrobial resistance is a major global issue. It is estimated that by 2050, mortality rates associated with antimicrobial resistant infections will exceed 10 million people per annum, superseding cancer as the leading cause of global mortality. Healthcare associated infections (HCAIs) are a major cause of morbidity and mortality, and it is estimated that between 7% and 10% of hospitalised patients will develop such an infection type. Methicillin-Resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are prevailing causes of skin and soft tissue infections. Developing antimicrobial textiles and wound dressings is one method of reducing the transmission of pathogens in healthcare environments, whilst assisting the healing process and promoting local antisepsis. We have identified natural fabrics which have inherent antimicrobial properties against MRSA. Furthermore, we have developed encapsulation technology to manufacture nanofibres with slow releasing antimicrobial properties. We now aim to exploit these for use within the healthcare setting for wound care management. This project aims to determine the mechanism of antimicrobial activity of these fabrics and evaluate the commercial potential for healthcare use with the ultimate aim of developing an applied product.

References

Lu, H., Butler, J.A., Britten, N.S., Venkatraman, P.D. and Rahatekar, S.S. (2021) Natural Antimicrobial Nano Composite Fibres Manufactured from a Combination of Alginate and Oregano Essential Oil. Nanomaterials, 11(2062), 1-17.

Butler, J.A., Slate, A.J., Todd, D.B., Airton, D., Hardman, M., Hickey, N.A., Scott, K. and Venkatraman, P.D. (2021) A traditional Ugandan Ficus natalensis bark cloth exhibits antimicrobial activity against Methicillin‐Resistant Staphylococcus aureus. Journal of Applied Microbiology, 131(1), 2-10.

2. Antimicrobial activity of novel metallotherapeutic agents against medically-relevant bacterial pathogens.

Antimicrobial resistance in bacteria is an ever-increasing global problem. Very few novel antimicrobial agents are being introduced into the clinical setting, partly due to the complexity of licensing regulations and the cost involved in such research. Compounds based on metals from the Platinum-group including, Ruthenium (Ru), Rhodium and Platinum have previously been exploited for use in anticancer chemotherapy and are now being explored for use as antimicrobial agents. We have identified several highly active Ru-based compounds, which individually demonstrated potent selective antibacterial activity against multidrug resistant bacterial pathogens including MRSA and P. aeruginosa. This project now aims to validate the potential for use as topical and systemic treatment options and understand the mechanisms of cellular antimicrobial activity by using physical (microscopy), biochemical (cellular leakage assays, membrane permeation assays) and molecular (DNA –binding assays, qRT-PCR, RNA-seq) techniques.

References

Southam, H.M., Butler, J.A., Chapman, J.A. and Poole, R.K. (2017) The microbiology of Ruthenium complexes. Advances in Microbial Physiology 71, 1-96.

3. Combatting antimicrobial resistance: Small-molecule inhibitors (SMIs) as precision anti-virulence agents.

Antimicrobial resistance (AMR) is an ever-increasing global problem and it is estimated that deaths associated with AMR infections will exceed 10 million by 2050, superseding cancer as the leading cause of global mortality. Traditional antibiotics display antimicrobial activity through direct targeting of key bacterial cellular processes such as cell wall formation, which are essential for viability but are susceptible to resistance generation. In contrast, one approach to combatting AMR is the development of novel anti-virulence agents, which target pathogen specific virulence-related traits, such as enzymes involved in the generation of post-translational modifications. We have identified lead SMIs and now aim to use virtual screening, microbiological, cell culture and in vivo assays to determine the anti-virulence effects.

References

Rasko, D.A., and Sperandio, V. (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nature Reviews Drug Discovery 9, 117-128.

4. Molecular basis for attachment, colonisation and survival of the foodborne pathogen Campylobacter jejuni.

Campylobacter jejuni is the worldwide leading cause of human bacterial enteric disease. The molecular mechanisms by which C. jejuni attach, colonise and survive on surfaces, especially during food preparation, are poorly understood. Bipolar flagella play a key role in virulence and are composed of FlaA and FlaB protein subunits. These are extensively modified by glycan sugar moieties during the process of glycosylation, which is implicated in immune evasion and providing structural stability to the flagellum filament. This study is investigating the role of glycosylation in mediating attachment to a range of domestic and industrial food preparation surfaces, in order to help develop novel intervention strategies which reduce the risk of transmission.

References 

Burnham, P.M. and Hendrixson, D.R. (2018) Campylobacter jejuni: collective components promoting a successful enteric lifestyle. Nature Reviews Microbiology 16, 551-565.

Hitchen, P., Brzostek, J., Panico, M., Butler, J.A., Morris, H.R., Dell, A. and Linton, D. (2010) Modification of the Campylobacter jejuni flagellin glycan by the product of the Cj1295 homopolymeric tract containing gene. Microbiology, 156(7), 1953-1962.

Undergraduate teaching

Cell and Molecular Biology (L4) - Unit Leader

Infection Science (L5)

Integrated Pathology (L5)

Medical Microbiology (L6)

Project Dissertations (L6) 

Postgraduate teaching (MSc level)

Management and Control of Infectious Diseases

Human Infectious Diseases

Recent Advance in Biomedical Research

Research Ethics and Methods in Biomedical Sciences 

Project Dissertations 

PhD programme

Principal Supervisor 

(2019-present) ‘Ruthenium metallotherapeutics for targeted antimicrobial chemotherapy’

(2017-2022) ‘Novel Ruthenium metal-based complexes as antimicrobial agents’

Co-Supervisor

(2019-present) ‘Determining the antimicrobial resistance of bacterial isolates from clinical environments’

(2018-present) ‘Wound infection following hepatopancreatobiliary (HPB) surgery - A measure of predictive surgical and transmission factors on patient outcomes’ 

(2018-present) ‘Cleaning and surface modification of fabrics and washing machine components to deter biofouling and biofilm formation’

(2016 - 2020) ‘The use of metal ions and graphene-based compounds as novel antimicrobials against multidrug resistant Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus.

MSc by Research programme 

(2021-present) ‘Combatting antimicrobial resistance: novel targets, molecules and modalities’

(2020-present) ‘Combatting antimicrobial resistance: Small molecular inhibitors as anti-virulence agents’

(2020-2021) ‘Probiotic formulations as antimicrobial and antiadhesive agents’

M BioMed Sci Biomedical Science

(2021-present) ‘Antimicrobial activity of Ficus natalensis backcloth on a range of bacterial pathogens’

MSc Medical Microbiology / Biomedical Science

2021-present

‘Combatting antimicrobial resistance: Small-molecule inhibitors as precision anti-virulence agents’

‘Beyond The Gut: Use of probiotics as alternatives to chemical cleaning agents or disinfectants’

2020-21

‘The efficacy of using Silver nanoparticles as an antibacterial against Gram-positive vs Gram-negative bacteria’

‘Quinolone synergism for bactericidal effects against Pseudomonas aeruginosa in vitro and in vivo: a systematic review and meta-analysis’

2019-20

‘In comparison to open surgery, laparoscopic approach decreases the occurrence of surgical site infections for colorectal surgery – a systematic review and meta-analysis’

‘An evaluation of polyethylene-glycol for antimicrobial textile applications’

‘An analysis of the antimicrobial activity of Ficus natalensis bark cloth with a subsequent meta-analysis comparing organic and inorganic compounds as active agents in textiles’

‘Role of pathogenic bacteria in the clinical settings - a systematic review’ 

2018-19

‘A molecular genetic analysis for the role of flagella in the attachment and survival of Campylobacter jejuni mutants on steel food preparation surfaces and host invasion’    

‘Investigation into the relative effects of Cj1163 targeted gene deletion for the pathogenic bacterium Campylobacter jejuni in the presence of Zinc nanoparticles with relation to survival and virulence.’         

‘Molecular basis for attachment, colonisation and pathogenesis of the foodborne pathogen Campylobacter jejuni’

2017-18

‘Mechanisms of activity of novel Ruthenium based antimicrobials’ 

‘An investigation into the antibiotic efficacy of novel Ruthenium Compounds on a variety of microorganisms’

‘Assessing the role of Campylobacter jejuni cj1163 gene in mediating survival responses’

Britten, N.S. and Butler, J.A. (2022) Ruthenium metallotherapeutics: novel approaches to combatting parasitic infections. Current Medicinal Chemistry, 29(31), 5159-5178

Lu, H., Butler, J.A., Britten, N.S., Venkatraman, P.D. and Rahatekar, S.S. (2021). Natural antimicrobial nano composite fibres manufactured from a combination of alginate and oregano essential oil. Nanomaterial, 11(8), 2062.

Slate, A.J., Hickey, N.A., Butler, J.A., Wilson, D., Liauw, C.M. Banks, C.E. and Whitehead, K.A. (2021) Additive manufactured graphene-based electrodes exhibit beneficial performances in Pseudomonas aeruginosa microbial fuel cells. Journal of Power Sources, 499, 229938.

Butler, J.A., Slate, A.J., Todd, D.B., Airton, D., Hardman, M., Hickey, N.A., Scott, S. and Venkatraman, P.D. (2021). A traditional Ugandan Ficus natalensis bark cloth exhibits antimicrobial activity against Methicillin‐Resistant Staphylococcus aureus. Journal of Applied Microbiology, 131(1), 2-10.

Zare, M., Zare, M., Butler, J.A. and Ramakrishna, S. (2021) Nanoscience-led antimicrobial surface engineering to prevent infections. ACS Applied Nano Materials, 4(5), 4269-4283.

Slate, A.J., Karaky, N., Crowther, G.S., Butler, J.A., Banks, C.E., McBain, A.J. and Whitehead, K.A. (2021) Graphene matrices as carriers for metal ions against antibiotic susceptible and resistant bacterial pathogens. Coatings, 11(3), 352.

Butler, J.A, Osbourne, L., El Mohtadi, M. and Whitehead, K.A. (2020) Graphene derivatives potentiate the activity of antibiotics against Enterococcus faecium, Klebsiella pneumoniae and Escherichia coli. AIMS Bioengineering, 7(2), 106-113.

Liauw, C.M., Slate, A.J., Butler, J.A., Wilson-Nieuwenhuis, J.S.T., Deisenroth, T., Preuss, A., Verran, J. and Whitehead, K.A. (2020) The effect of surface hydrophobicity on the attachment of fungal conidia to substrates of polyvinyl acetate and polyvinyl alcohol. Journal of Polymers and the Environment, 20, 1450-1464.

Karaky, N., Kirby, A., McBain, A.J., Butler, J.A., El Mohtadi, M., Banks, C.E. and Whitehead, K.A. (2020) Metal ions and graphene-based compounds as alternative treatment options for burn wounds infected by antibiotic-resistant Pseudomonas aeruginosa. Archives in Microbiology, 202(5), 995-1004.

Hickey, N.A., Whitehead, K.A., Shalamanova, L., Butler, J.A. and Taylor, R.L. (2019) A Novel Microbiological Medium for the growth of periodontitis Associated Pathogens. Journal of Microbiological Methods,163, 105647. 

Liu, X., Sun, B., Kell, R.E.M., Southam, H.M., Butler, J.A., Li, X., Poole, R.K., Keene, F.R. and Collins, J.G. (2018) The antimicrobial activity of mononuclear ruthenium(II) complexes containing the dppz ligand. ChemPlusChem, 83(7), 643-650.

Sun, B., Southam, H.M., Butler, J.A., Poole, R., Burgun, A., Tarzia, A., Keene, F.R., and Collins, J.G. (2018) Synthesis, isomerisation and biological properties of mononuclear ruthenium complexes containing the bis[4(4′-methyl-2,2′-bipyridyl)]-1,7-heptane ligand. Dalton Transactions 47(7), 2422-2434.

Akhidime, I.D., Saubade, F., Benson, P., Butler, J.A., Olivier, S., Kelly, P., Verran, J. and Vagg-Whitehead, K.A. (2018) The antimicrobial effect of metal substrates on food pathogens. Food and Bioproducts Processing,113, 68-76.

Jervis, A.J., Wood, A.G., Cain, J.A., Butler, J.A., Frost, H., Lord, E., Langdon, R., Cordwell, S.J., Wren, B.W. and Linton, D. (2018). Functional analysis of the Helicobacter pullorum N-linked protein glycosylation system. Glycobiology 28(4), 233-244.

Verran, J. Haigh, C., Brooks, J., Butler, J.A., and Redfern J. (2018) Fitting the message to the location: engaging adults with antimicrobial resistance in a World War 2 air raid shelter. Journal of Applied Microbiology, 125(4), 1008-1016.

Rana, N., Jesse, H.E., Tinajero-Trejo, M., Butler, J.A., Tarlit, J.D., von und zur Mühlen, M.L., Nagel, C., Schatzschneider, U. and Poole R.K. (2017). A Manganese photoactivated carbon monoxide-releasing molecule [Mn(CO)₃(tpa-κ³N)]Br enhances antibiotic effects on a multi-drug resistant Escherichia coli. Microbiology 163(10), 1477-1489.

Vaidya, M.Y., McBain, A.J., Butler, J.A., Banks, C.E., Whitehead, K.A. (2017). Antimicrobial efficacy and synergy of metal ions against Enterococcus faecium, Klebsiella pneumoniae and Acinetobacter baumannii in planktonic and biofilm phenotypes. Scientific Reports. 7(1), 5911.

Southam, H.M., Butler, J.A., Chapman, J.A. and Poole, R.K. (2017) The microbiology of Ruthenium complexes. Advances in Microbial Physiology 71, 1-96.

Jervis, A.J., Butler, J.A., Wren, B.W. and Linton, D. (2015) Chromosomal integration vectors allowing flexible expression of foreign genes in Campylobacter jejuni. BMC Microbiology 15(230), 1-9.

Jervis, A.J., Butler, J.A., Lawson, A., Langdon, R., Wren, B. and Linton, D. (2012). Characterization of the structurally diverse N-linked glycans of Campylobacter species. Journal of Bacteriology, 194(9), 2355-2362.

Hitchen, P., Brzostek, J., Panico, M., Butler, J.A., Morris, H.R., Dell, A. and Linton, D. (2010) Modification of the Campylobacter jejuni flagellin glycan by the product of the Cj1295 homopolymeric tract containing gene. Microbiology, 156(7), 1953-1962.

Selected conference presentations

Butler, J.A., Slate, A.J., Todd, D.B., Airton, D., Hardman, M., Hickey, N.A., Ahmed, S.M., Scott, K., Venkatraman, P.D. (2022) Natural antimicrobial fabrics for use within wound care management. The Microbiology Society Annual Conference, Belfast, UK.

Ralif, L., Britten, T., Lewis, A.M., McLaughlin, M.G. and Butler, J.A. (2022) Small-molecule inhibitors as precision anti-virulence agents. The Microbiology Society Annual Conference, Belfast, UK.

Britten, N.S. and Butler, J.A. (2022) Antimicrobial activity of Ruthenium-based metallotherapeutics against Pseudomonas aeruginosa. The Microbiology Society Annual Conference, Belfast, UK

Scott, K., Venkatraman P.D., Butler, J.A and Spurgin K. (2021) Restorative fashion: the healing powers of the mutuba tree. Curative Things: Medicine / Fashion / Art, Leeds Arts University, UK.

Britten, N.S. and Butler, J.A (2021) Biocidal activity of Ruthenium metallotherapeutics against Pseudomonas aeruginosa. 18th International Biodeterioration and Biodegradation Symposium, online. [Awarded best poster]

Sustainable fabric made from tree bark could cut MRSA infection rates (phys.org)