Details of Award
NERC Reference : NE/N01992X/1
A quantitative method to evaluate AMR distribution in complex communities based on methylome profiling
Grant Award
- Principal Investigator:
- Dr JM Ritchie, University of Surrey, Microbial & Cellular Sciences
- Co-Investigator:
- Dr JI Jimenez, Imperial College London, Life Sciences
- Grant held at:
- University of Surrey, Microbial & Cellular Sciences
- Science Area:
- Atmospheric
- Earth
- Freshwater
- Marine
- Terrestrial
- Overall Classification:
- Unknown
- ENRIs:
- Environmental Risks and Hazards
- Science Topics:
- Antibiotic resistance
- Methylation
- Microbial communities
- Environmental Microbiology
- Metagenomics
- Single molecule sequencing
- Genomics
- Abstract:
- Antimicrobial resistance (AMR) inhibits our ability to deal with once easy-to-treat bacterial infections. AMR can be acquired by disease-causing bacteria from other organisms living in the same environment that do not pose a threat to our health e.g. in our intestines, which is home to trillions of bacteria. The acquisition of AMR by some harmful bacteria will enable these organisms to survive antibiotic exposure whereas as sensitive organisms, both beneficial and harmful to us, are killed. This means that the use of antibiotics, even at low levels, can promote the expansion of resistant populations in niches where there is little competition from other microorganisms. Understanding the chain of events taking place during transmission of AMR is essential to inform more effective treatments and to rationalise use of our current repertoire of antibiotics. Unfortunately, methods for studying transmission are largely based on being able to grow the organism in the laboratory, something that is only possible for a relatively small number of species. As a consequence, all the events in which non-culturable species - those that cannot be grown in the lab - are involved are missing from our studies. Only recently, methods based on the production of fluorescent proteins have been used to understand transmission events in the environment and they have already given insights into previously unknown bacterial interactions. These methods are however limited to those conditions in which the fluorescent proteins work, which are largely dependent on the presence of oxygen. Specific anaerobic niches crucial in antibiotic treatments such as the intestine cannot be analysed using this methodology. We propose an alternative approach to monitor transmission of AMR in complex bacterial populations like the gut microbiota. This method is based on the analysis of changes in the DNA of resistant populations in response to changes in environmental conditions such as during treatment with antibiotics. We will take advantage of the presence of other genes that can be transferred together with AMR to do this. These genes encode for enzymes called methyltransferases that produce permanent modifications in the DNA of the recipient cell. Monitoring the presence or absence of those modifications by a new sequencing technology will be used as proof of the acquisition of AMR. Since this method works in a high-throughput fashion, we can monitor thousands of species in a single experiment. In that way we will generate a complete dynamic picture of the main AMR interactions in the community and the rate at which these occur. If successful, this new technique will help us to determine the flow of AMR in the natural environment, identifying potential reservoirs that favour the development of resistance. These results could be used to design tailored-made treatments to optimise the way that we use antibiotics to minimise the spread of AMR.
- NERC Reference:
- NE/N01992X/1
- Grant Stage:
- Completed
- Scheme:
- Directed (Research Programmes)
- Grant Status:
- Closed
- Programme:
- AMR
This grant award has a total value of £145,098
FDAB - Financial Details (Award breakdown by headings)
| DI - Other Costs | Indirect - Indirect Costs | DA - Investigators | DA - Estate Costs | DI - Staff | DI - T&S | DA - Other Directly Allocated |
|---|---|---|---|---|---|---|
| £19,150 | £56,211 | £6,542 | £12,663 | £46,004 | £1,211 | £3,317 |
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