Combining a novel phenotypic virulence screen with genomic approaches to uncover bacterial acquisition of multi-drug resistance and virulence in aquat

Lead Research Organisation: University of Exeter
Department Name: School of Postgraduate Medicine

Abstract

Combining a novel phenotypic virulence screen with genomic approaches to uncover bacterial acquisition of multi-drug resistance and virulence in aquatic environments

Poor microbiological water quality poses a major threat to environmental and human health and is likely to deteriorate through climate change and changes in land use. Worryingly, the global increase in antimicrobial resistance (AMR) could mean that exposure to contaminated waters leads to infections that are very hard or impossible to treat. The role of the natural environment in the dissemination of, and selection for, AMR through pollution with resistant bacteria, antibiotic residues, biocides and heavy metals is increasingly appreciated. The risk to human health posed by resistant bacteria present in the environment are likely to be significant. There is evidence for a range of pathogens that AMR and virulence genes can be carried on the same mobile genetic elements, and these could potentially spread between species. However, we currently know very little about the diversity and distribution of multidrug-resistant pathogens in aquatic environments.

In this project, we will selectively isolate pathogenic bacteria by directly injecting environmental samples into the Wax Moth larva Galleria mellonella, a well-established model for the mammalian innate immune system. Combining these assays with antibiotic selection and the ability to mobilise plasmids from freshwater microbial communities into model recipient bacteria will enable capture of novel plasmids carrying both AMR and virulence genes. Using both Illumina and Nanopore technologies to sequence chromosomes and plasmids of bacterial clones isolated from Galleria will give detailed information on pathogen identity, origin (i.e. hospital- or environment-associated) and carriage of known virulence- and antibiotic resistance genes. Functional genomics will be employed to identify unknown virulence and antibiotic resistance genes. Prevalence of multi-drug resistance and virulence will be related to catchment scale variables and point and diffuse sources of pollution.

Although microbiologically safe water is considered a fundamental human right, it is not exactly clear what it constitutes and how it is best monitored. This project will employ novel approaches enabling us to characterize the diversity and prevalence of antibiotic resistant pathogenic bacteria and their ecological drivers to ultimately assess human infection risk.

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