Details of Award
NERC Reference : NE/N019261/1
Impact of stereochemistry of antimicrobial agents on their environmental fate, biological potency and the emergence of resistance
Grant Award
- Principal Investigator:
- Professor B Kasprzyk-Hordern, University of Bath, Chemistry
- Co-Investigator:
- Professor EJ Feil, University of Bath, Biology and Biochemistry
- Co-Investigator:
- Dr SE Lewis, University of Bath, Chemistry
- Grant held at:
- University of Bath, Chemistry
- Science Area:
- Freshwater
- Terrestrial
- Overall Classification:
- Unknown
- ENRIs:
- Biodiversity
- Environmental Risks and Hazards
- Global Change
- Natural Resource Management
- Pollution and Waste
- Science Topics:
- Water pollution
- Pollution
- Wastewater treatment
- Catchment management
- Water Quality
- Earth & environmental
- Pollution/pollution control
- Earth & environmental
- Pollutant pathways
- Pollutant transport
- Abstract:
- This project aims to understand and address the impact of stereoisomerism of antimicrobial agents in their environmental cycle on mechanisms behind the development of antimicrobial resistance. The risk of promotion of antibiotic resistant bacteria is by far the greatest human health concern with regards to medicinal products in the environment. The continuous introduction of sub-inhibitory quantities of antimicrobial agents (AAs) to the environment is believed to be directly linked with antimicrobial resistance (AMR). Unfortunately, there is little knowledge of mechanisms in the environment and influencing factors due to the multi-dimensional nature of the AMR problem. There are several research gaps that need to be addressed including research into contaminated habitats (e.g. wastewater) where AAs, co-selecting agents, bacteria carrying resistance determinants and favourable conditions for bacterial growth prevail at the same time. Furthermore, the stereochemistry of AAs (which is key in defining their biological potency) has never been studied in the context of their environmental fate and effects. This is an oversight as changes in stereoisomeric profile of AAs throughout their environmental cycle will lead to (and be influenced by) changes in the composition and structure of microbial communities present in the environment. This might further contribute to the development of AMR, a phenomenon that has never been the subject of investigation in the context of stereochemistry of AAs. This project postulates that stereochemistry of AAs determines their environmental fate and biological effects. It also hypothesizes that two enantiomers of the same AA should be recognised as two different substances that can elicit different responses leading to changes in the environmental fate and effects of the drug. The project will: 1. Verify the mechanisms of (stereoselective) transformation of chiral antimicrobial agents and their metabolites during wastewater treatment and in receiving waters 2. Identify resistant bacterial taxa responsible for (stereoselective) degradation of antimicrobial agents and to study the development of antimicrobial resistance at stereoisomeric level 3. Recommend changes to ERA via inclusion of AAs (and their stereochemistry) and ARGs as AMR indicators The stereochemistry of AAs is complex, as many of the semi-synthetic agents are marketed as mixtures of diastereomers and a number of synthetic agents are used as racemates. In this project we will focus on ofloxacin and chloramphenicol, but we will also consider other synthetic quinolones, Beta-lactams (e.g. amoxicillin) and carbapenems (e.g. meropenem). Considering the importance of better understanding environmental and human health impacts from chiral pollutants such as AAs and the need for the development of new solutions tackling AMR, this project has the potential to lead to groundbreaking research with long term scientific, technological and societal impact.
- NERC Reference:
- NE/N019261/1
- Grant Stage:
- Completed
- Scheme:
- Directed (Research Programmes)
- Grant Status:
- Closed
- Programme:
- AMR
This grant award has a total value of £161,599
FDAB - Financial Details (Award breakdown by headings)
| DI - Other Costs | Indirect - Indirect Costs | DA - Investigators | DA - Estate Costs | DI - Staff | DA - Other Directly Allocated | DI - T&S |
|---|---|---|---|---|---|---|
| £9,711 | £55,054 | £11,639 | £21,328 | £55,624 | £2,579 | £5,665 |
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