Novel bioelectronic sensors of antimicrobial resistance

Lead Research Organisation: University of York
Department Name: Electronics

Abstract

Antimicrobial resistance (AMR) has been identified as a major threat to public health worldwide. The recent O'Neill report predicts that the cost of AMR may be as high as 300 million premature deaths and up to $100 trillion lost to the global economy by 2050. The need for reliable diagnostic technologies is critical if we are to preserve the efficacy of existing antibiotics and the life span of new therapeutics.

The aim of this studentship is to develop a hand-held device that will optimise the treatment of bacterial infections by providing clinicians with a better tool for assessing bacterial susceptibility.

We will achieve this by developing a test that monitors the activity of enzymes associated with bacterial resistance, focusing specifically on beta-lactamases expressed by pathogenic E. Coli. The test will operate by monitoring the turnover of surface-immobilised beta-lactam antibiotics. By creating an array of different antibiotics, each immobilised on an individually addressable electrode, it is possible to uniquely determine the specific resistance profile of an E. Coli strain, and thus identify the most appropriate antibiotic.

The research aligns with the AMR cross-council initiative that particularly targets EPS research, and with the recently launched EPSRC/BBSRC/MRC "Technology Touching Life" initiative. Furthermore, "Biophysics" is one of only 12 "growth" areas in the EPSRC portfolio and our work fits squarely into the "Healthy Nation" vision expressed in the EPSRC Delivery Plan.

This research is a collaboration between multiple academic departments at York, specifically the Departments of Physics Chemistry, Biology and Health Economics. Furthermore, the project parners with a range of stakeholders including clinical consultants Mr Adrian Evans (gynaecology) and Dr Neil Todd (microbiology) at the York Teaching Hospital NHS Trust, and TRANSLATE, a regional programme to support the commercialisation and adoption of medical technology.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509802/1 01/10/2016 31/03/2022
1947363 Studentship EP/N509802/1 01/10/2017 31/03/2021 Callum Silver
 
Description The project focusses on discovering a new method by which to determine beta-lactam resistance in bacteria. Beta-lactams are class of antibiotics which inhibit cell wall cross-linking. One mechanism that bacteria have evolved to become resistant to these antibiotics is through the production of beta-lactamase enzymes, which break apart the beta-lactam antibiotics. By detecting the presence of these enzymes, we can infer resistance in patient's samples. Our work up until this point has shown that it is possible to immobilise a beta-lactam antibiotic onto a surface, allowing the molecules to be used as probes for a variety of surface-based biosensors. By exposing the immobilised antibiotic to beta-lactamase enzymes, and observing changes in the immobilised drugs, we have shown that they can serve as functional probes for beta-lactamase enzymes. Furthermore, we have shown that these immobilised antibiotics remain functional in complex samples, such as human urine. Carrying out tests directly on patients samples will dramatically reduce the time to diagnosis for beta-lactam resistance.
Exploitation Route There are a variety of biosensors that this immobilised antibiotic could work with. I am currently working towards implementing these drugs onto an Ion-sensitive-Field-Effect-Transistor, which would allow the detection of a pH change due to the breakdown of the beta-lactam. This chemistry is also compatible with many surface-based biosensors. For example, work is currently being done to implement it onto photonic sensors which rely on changes in surface refractive index. Eventually, this chemistry may fit into more commercial biosensors that would allow for more point-of-care use.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://www.york.ac.uk/news-and-events/news/2019/research/new-way-test-drug-resistant-infections/
 
Description PhD Spotlight competition alongside the York Talks 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The work was recently presented at the 'PhD Spotlight Competition' which ran alongside the York Talks at the University of York. The competition runs every year and allows the general public to engage with the research done by PhD students at the university. Ten Students are given exhibition stands to allow them to show off their research to the general public. The exhibition stands have to be of a level which is accessible by anyone from schoolchildren to university professors.
Year(s) Of Engagement Activity 2018
URL https://www.york.ac.uk/research/graduate-school/updates/2018/phd-spotlight-2019/