Centre staff
Dr Keith Miller
Lecturer in medical microbiology
Phone 0114 225 3946
Email k.miller@shu.ac.uk
Research interests
There are currently severe clinical problems arising from the emergence of resistance to antibiotics in bacteria and the lack of new antibacterial agents to challenge the threat. Indeed, options to treat healthcare-associated infections are perilously limited as the organisms expand their ability to evade existing antibiotics by development of various resistance mechanisms. The discovery of new drugs active against these healthcare-associated pathogens is therefore essential to prevent a future medical and social catastrophe.
Development of novel antimicrobial agents
Investigation of light-activated antibacterial metal alloy surface coatings
This study investigates the utility of metal alloy coating materials in the elimination of potentially pathogenic contaminating bacteria. This product would have broad-ranging applications in healthcare and domestic hygiene.
Novel therapeutic agents from insect larvae
An investigation to isolate and characterise the antimicrobial component of larval secretions from a range of insect species is being conducted in collaboration with Dr Simona Francese and Kate Barnes of the University of Derby.
Development of antibiotic-resistance
Does the use of antineoplastic agents result in the development of extended spectrum β‑lactamases?
The extended‑spectrum cephalosporins have been in clinical use for over 20 years and underpin empirical therapy of serious bacterial infections. This role is increasingly compromised by the emergence of bacteria, such as the Enterobacteriaceae and Pseudomonas aeruginosa, resistant to these drugs through the production of extended‑spectrum beta‑lactamases (ESBLs). These bacteria frequently cause life‑threatening infections, particularly in oncology patients. The genes encoding for ESBLs arise by point mutations in common genes that code for narrow‑spectrum beta‑lactamases. The interaction between antineoplastic agents and extended‑spectrum cephalosporins and other b‑lactams may exacerbate the selection of resistance to these antibiotics. This project is seeking to determine the combinations of antineoplastic agent and b‑lactam that are least likely to produce ESBLs in potential pathogens in oncology patients.
Publications
Miller K, Dunsmore CJ, Leeds JA, Patching SG, Sachdeva M, Blake KL, Stubbings WJ, Simmons KJ, Henderson PJ, De Los Angeles J, Fishwick CW, Chopra I. (2010) Benzothioxalone derivatives as novel inhibitors of UDP-N-acetylglucosamine enolpyruvyl transferases (MurA and MurZ). Journal of Antimicrobial Chemotherapy 2010 Sep 22. [Epub ahead of print]
Ooi N, Miller K, Hobbs J, Rhys-Williams W, Love W, Chopra I. (2009). XF-73, a novel antistaphylococcal membrane-active agent with rapid bactericidal activity. Journal of Antimicrobial Chemotherapy 64(4): 735-40
Miller K, O'Neill AJ, Wilcox MH, Ingham E, Chopra I. (2008). Delayed development of linezolid resistance in Staphylococcus aureus following exposure to low levels of antimicrobial agents. Antimicrobial Agents and Chemotherapy. 52(6): 1940-4
Dunsmore CJ, Miller K, Blake KL, Patching SG, Henderson PJ, Garnett JA, Stubbings WJ, Phillips SE, Palestrant DJ, Angeles Jde L, Leeds JA, Chopra I, Fishwick CW. (2008). 2-Aminotetralones: novel inhibitors of MurA and MurZ. Bioorganic and Medicinal Chemistry Letters. 18(5): 1730-4
Miller K, Dunsmore CJ, Fishwick CW, Chopra I. (2008). Linezolid and tiamulin cross-resistance in Staphylococcus aureus mediated by point mutations in the peptidyl transferase center. Antimicrobial Agents and Chemotherapy. 52(5): 1737-42
Driffield KL, Bostock JM, Miller K, O'Neill AJ, Hobbs JK. Chopra I. (2006). Evolution of extended-spectrum β-lactamases in a MutS-deficient Pseudomonas aeruginosa hypermutator. Journal of Antimicrobial Chemotherapy. 58(4): 905-7
Miller K, Storey C, Stubbings WJ, Hoyle AM, Hobbs JK, Chopra I. (2005). Anti-staphylococcal activity of the novel cephalosporin CB-181963 (CAB-175). Journal of Antimicrobial Chemotherapy. 55(4): 579-82.
Miller K, O’Neill AJ, Chopra I. (2004). Escherichia coli hypermutators present an enhanced risk for emergence of antibiotic resistance during urinary tract infections. Antimicrobial Agents and Chemotherapy. 48(1), 23-29.
Chopra I, O’Neill AJ, Miller K. (2003). The role of mutators in the emergence of antibiotic-resistant bacteria. Drug Resistance Updates. 6, 137-145.
Miller K, O’Neill AJ, Chopra I. (2002). Response of Escherichia coli hypermutators to selection pressure with antimicrobial agents from different classes. Journal of Antimicrobial Chemotherapy. 49(6), 925-934.
Grants held
£112k in research funding as PI or as co-PI since 2008, including the following current grants
- 2010-2011 'CROWD (Controlled Release from Open Wound Dressings)'. Neil Bricklebank is principal investigator with Keith Miller, Chris Breen and Louise Freeman-Parry as co-investigators (Sheffield Hallam University), EPSRC funded EFL project grant - £36,820
- 2010-2013 'Identification and characterisation of antimicrobials from snake and scorpion venoms and haemolymph'. Keith Miller is principal investigator with Peter Strong and Tom Smith (Sheffield Hallam University), Sheffield Hallam Biomedical Research Centre (BMRC) funded - £ 62,779
- 2009-2010 Does the use of antineoplastic agents result in the development of extended spectrum β-lactamases? Keith Miller is principal investigator (Sheffield Hallam University), BMRC funded £12,312.
PhD students
- Patrick Harrison - Identification and charcterisation of antimicrobials from snake and scorpian venoms and haemolymph
- Louise Freeman-Parry - Antimicrobial (Biocidal) properties of wound dressings
