Details of Award
NERC Reference : NE/X00550X/1
Understanding The Eco-evolutionary Drivers Of Antifungal Resistance In Opportunistic Fungal Pathogens
Grant Award
- Principal Investigator:
- Professor TL Gladding, The Open University, Faculty of Sci, Tech, Eng & Maths (STEM)
- Grant held at:
- The Open University, Faculty of Sci, Tech, Eng & Maths (STEM)
- Science Area:
- Atmospheric
- Terrestrial
- Overall Classification:
- Unknown
- ENRIs:
- Biodiversity
- Environmental Risks and Hazards
- Global Change
- Natural Resource Management
- Pollution and Waste
- Science Topics:
- Crop protection
- Fungicides
- Ecosystem services
- Evolutionary ecology
- Population Ecology
- Infectious disease
- Human pathogens
- Environment & Health
- Pathogenic microbes
- Decomposer fungi
- Pathogenic fungi
- Environmental Microbiology
- Antifungals
- Microbiology
- Abstract:
- Microbes in their environment are exposed to changing conditions, which select for the most fit variants. This continual process of adaptation leads to the genetic composition of populations shifting in space and time as the fittest mutations track change. Unfortunately, when selection is imposed by chemicals that are designed to kill microbes, then those that are genetically resistant rise in frequency; this results in the global problem of antimicrobial resistance evolving in the environment. While emerging antimicrobial resistance is widely recognised in bacteria, the emergence of fungi that are resistant to antifungal chemicals is underappreciated yet is compromising our ability to grow blight-free crops and to treat serious human fungal diseases -therefore presenting a classic One Health dilemma. The core focus of our project is Aspergillus species, common environmental moulds to which all humans are exposed due to their ubiquitous presence in the air. Of note, A. fumigatus affects millions of susceptible individuals worldwide (including those with COVID-19) and is increasingly causing disease that is resistant to the frontline azole antifungal drugs that are used to treat it. Crucially, this is the same class of chemicals is used by farmers as fungicides, which is driving a surge in azole-resistant A. fumigatus as this mould comes under selection by these chemicals in its natural environment. However, we currently have very little understanding of the landscape-scale pathways that lead to fungicide chemical residues accumulating to the concentrations that select for, and amplify, resistance in moulds. We understand even less about the consequences combinations of different fungicides on the emergence of resistance, or how interactions with the wider microbial community that may hinder (or help) the emergence of resistance. Our project will examine the nested anthropogenic drivers - agricultural practices and green-waste recycling - with the aim of understanding how they create hotspots of evolution for antifungal resistant pathogens. The moulds on which we will focus are embedded in complex microbial ecosystems and we will determine the impact of scale from country-wide distributions of the fungus, through the ecological succession seen in fungicide-rich mesocosm environments, and down to individual model microcosm models. To do this, we will couple field and laboratory studies with Bayesian-based statistical methods that take into account both evolutionary and ecological complexity within a spatially-explicit framework. In doing so, we will be able to identify, understand and link the key factors that lead to hotspots of fungicide-resistant moulds forming. The variables that we measure - landuse, fungicides, fungal genetics and microbial community ecology - will be integrated into a systems network analysis that links the usage of fungicides in the environment to ecological settings where resistance is selected for. These 'Bayesian probabilistic networks' are a powerful tool which will allow us predict hotspots for fungal drug-resistance, as well as allowing us to model methods to mitigate against this risk by reducing fungicide-inputs into specific 'pinch-points' that we identify. Ultimately, by dissecting the extended (unintentional) consequence of fungicide use as these chemicals drive the evolution of fungal antimicrobial resistance, our project will address this problem within its greater 'One Health' context. Our approach is urgently needed to develop the knowledge-base that is needed to understand the current risk as well as to mitigate the selection-pressure driving future emergence of fungal antimicrobial resistance in the environment.
- Period of Award:
- 1 Dec 2022 - 30 Nov 2026
- Value:
- £242,409 Split Award
Authorised funds only
- NERC Reference:
- NE/X00550X/1
- Grant Stage:
- Awaiting Event/Action
- Scheme:
- Directed (Research Programmes)
- Grant Status:
- Active
- Programme:
- Highlights
This grant award has a total value of £242,409
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 |
|---|---|---|---|---|---|---|
| £31,592 | £15,657 | £26,122 | £1,096 | £132,498 | £7,836 | £27,608 |
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