Overview
My PhD, supervised by Dr Ben Longdon and Professor Angus Buckling, focuses on exploring the evolutionary and molecular factors that underpin virus host range (the phylogenetic breadth of hosts a pathogen can infect) and virus host shifts (where a pathogen jumps from one host species to another). Using a panel of 64 different Staphylococcus strains spanning 18 species and a broad host range bacteriophage (ISP) currently used for the treatment of antibiotic resistant S. aureus, we aim to use experimental evolution to ask fundamental questions about what influences the ability of viruses to infect novel host species.
I previously completed several research projects as part of my undergraduate studies at the University of Birmingham and my postgraduate studies at the London School of Hygiene and Tropical Medicine. With the McNally lab (Birmingham) , I analysed clinical samples to determine the prevalence of Carbapenemase-Producing Enterobacteriaceae (CPE) and determine whether lineages causing extra-intestinal infection were the same as those carried as commensal organisms. With the Shannon-Lowe lab (Birmingham), I investigated the role of cues in the stromal microenvironment in triggering Epstein-Barr virus latency and reactivation. Most recently, as part of the virology group at the Animal and Plant Health Agency, Weybridge I contributed to a study investigating the fitness of genotypes of Influenza A that emerged following reassortment of H7N9 and H9N2, two low pathogenicity avian influenza viruses that are co-circulating in China. The preprint of this work can be found here (https://doi.org/10.1101/2021.04.05.438444).
Qualifications
PhD Biological Sciences, Centre for Ecology and Conservation, University of Exeter (2019 onwards)
MSc Control of Infectious Disease, London School of Hygiene and Tropical Medicine (2018-2019)
BSc (Hons) Biomedical Science, University of Birmingham (2015-2018)
Publications
Key publications | Publications by category | Publications by year
Publications by category
Journal articles
Walsh SK, Imrie RM, Longdon B, Buckling A (In Press). The host phylogeny determines viral infectivity and replication across Staphylococcus host species.
PLoS PathogensAbstract:
The host phylogeny determines viral infectivity and replication across Staphylococcus host species
Virus host shifts, where a virus transmits to and infects a novel host species, are a major source of emerging infectious disease. Genetic similarity between eukaryotic host species has been shown to be an important determinant of the outcome of virus host shifts, but it is unclear if this is the case for prokaryotes where anti-virus defences can be transmitted by horizontal gene transfer and evolve rapidly. Here, we measure the susceptibility of 64 strains of Staphylococcaceae bacteria (48 strains of Staphylococcus aureus and 16 non-S. aureus species spanning 2 genera) to the bacteriophage ISP, which is currently under investigation for use in phage therapy. Using three methods – plaque assays, optical density (OD) assays, and quantitative (q)PCR – we find that the host phylogeny explains a large proportion of the variation in susceptibility to ISP across the host panel. These patterns were consistent in models of only S. aureus strains and models with a single representative from each Staphylococcaceae species, suggesting that these phylogenetic effects are conserved both within and among host species. We find positive correlations between susceptibility assessed using OD and qPCR and variable correlations between plaque assays and either OD or qPCR, suggesting that plaque assays alone may be inadequate to assess host range. Furthermore, we demonstrate that the phylogenetic relationships between bacterial hosts can generally be used to predict the susceptibility of bacterial strains to phage infection when the susceptibility of closely related hosts is known, although this approach produced large prediction errors in multiple strains where phylogeny was uninformative. Together, our results demonstrate the ability of bacterial host evolutionary relatedness to explain differences in susceptibility to phage infection, with implications for the development of ISP both as a phage therapy treatment and as an experimental system for the study of virus host shifts.
Abstract.
Publications by year
In Press
Walsh SK, Imrie RM, Longdon B, Buckling A (In Press). The host phylogeny determines viral infectivity and replication across Staphylococcus host species.
PLoS PathogensAbstract:
The host phylogeny determines viral infectivity and replication across Staphylococcus host species
Virus host shifts, where a virus transmits to and infects a novel host species, are a major source of emerging infectious disease. Genetic similarity between eukaryotic host species has been shown to be an important determinant of the outcome of virus host shifts, but it is unclear if this is the case for prokaryotes where anti-virus defences can be transmitted by horizontal gene transfer and evolve rapidly. Here, we measure the susceptibility of 64 strains of Staphylococcaceae bacteria (48 strains of Staphylococcus aureus and 16 non-S. aureus species spanning 2 genera) to the bacteriophage ISP, which is currently under investigation for use in phage therapy. Using three methods – plaque assays, optical density (OD) assays, and quantitative (q)PCR – we find that the host phylogeny explains a large proportion of the variation in susceptibility to ISP across the host panel. These patterns were consistent in models of only S. aureus strains and models with a single representative from each Staphylococcaceae species, suggesting that these phylogenetic effects are conserved both within and among host species. We find positive correlations between susceptibility assessed using OD and qPCR and variable correlations between plaque assays and either OD or qPCR, suggesting that plaque assays alone may be inadequate to assess host range. Furthermore, we demonstrate that the phylogenetic relationships between bacterial hosts can generally be used to predict the susceptibility of bacterial strains to phage infection when the susceptibility of closely related hosts is known, although this approach produced large prediction errors in multiple strains where phylogeny was uninformative. Together, our results demonstrate the ability of bacterial host evolutionary relatedness to explain differences in susceptibility to phage infection, with implications for the development of ISP both as a phage therapy treatment and as an experimental system for the study of virus host shifts.
Abstract.
Refresh publications
