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Imrie, R. M.

Publications and source records attributed to Imrie, R. M..

6 recordsLinked to original sources

Examining interactions between the microbiome and viral infection across Drosophila species

Microbiomes can influence the outcomes of virus infection, while viral infections can disrupt microbiome composition. These reciprocal interactions may contribute to patterns of host susceptibility, but it remains unclear whether microbiome-virus interactions are consistent across host species, or whether host evolutionary relationships influence microbiome variation and its association with viral susceptibility. Here, we investigate interactions between bacterial microbiomes and Drosophila C virus (DCV) infection across 32 Drosophilidae host species, using experimental infections and 16S rRNA amplicon sequencing. Using phylogenetic mixed models, we tested for phylogenetic structure in microbiome diversity and composition, and whether specific bacterial taxa were associated with among-species variation in viral load. Drosophilidae microbiomes were consistently dominated by a small number of bacterial genera and showed limited phylogenetic structuring. DCV infection was associated with a small reduction in bacterial richness, but microbiome composition was only weakly affected by wounding or infection and largely dominated by within-species variation. However, specific taxa were associated with large differences in viral replication, including reduced DCV load in flies harbouring Streptococcus before infection or Bacillus during infection. These results suggest that, at least in the conditions used in this study, microbiome composition may not generate strong, generalisable host phylogenetic patterns in virus susceptibility.

evolutionary biology↗

Bacterial phylogeny explains variation in virulence but not phage efficacy in vivo

The continuing emergence of antimicrobial resistance (AMR) poses one of the most urgent threats to public health in the 21st century, causing [~]1.2 million deaths per year. A promising alternative to traditional antimicrobials is phage therapy, which has proved effective in the treatment of antimicrobial-resistant infections, including methicillin-resistant Staphylococcus aureus (MRSA). However, considerable variation in the outcome of phage therapy remains, with phage that show high efficacy in vitro often showing little to no effect when applied in vivo. To allow for the efficient clinical use of phage, it is vital to understand how both bacterial virulence and phage efficacy vary in vivo and determine how well in vitro and in vivo measures of phage efficacy correlate. Here, we infected 4,968 Galleria mellonella larvae with 64 phylogenetically diverse Staphylococcaceae isolates, both with and without co-inoculation of the bacteriophage ISP, and recorded mortality and melanisation over 24 hours. We found that bacterial virulence varied among Staphylococcaceae strains, and that a large proportion of this variation could be explained by the evolutionary relationships between bacteria. These results indicate that pathogen phylogeny may be a useful tool for explaining variation in both the severity of clinical infections and the virulence of novel emerging pathogens. The addition of phage significantly improved the survival of G. mellonella larvae, with an average 15.2% increase in endpoint survival and 10.1% reduction in endpoint melanisation across Staphylococcaceae strains. Phage efficacy in vivo showed phylogenetic repeatability, but no detectable phylogenetic heritability across bacteria species, in contrast to previous in vitro studies of phage infections. Concurrently, we found no evidence of a correlation between in vivo and in vitro measures of phage efficacy across bacterial isolates, demonstrating that environment plays a major role in determining the outcomes of bacteria-phage interactions. This highlights that caution should be used when extrapolating from in vitro measures of phage efficacy to select phages for therapeutic uses.

microbiology↗

Positive correlations in susceptibility to a diverse panel of viruses across host species

Our ability to predict the emergence of novel viruses relies on there being generalisable patterns in the susceptibilities of hosts to novel infections. Studies investigating variation in susceptibility among host species have consistently shown that closely related hosts share similar susceptibilities to a given virus. However, the extent to which such phylogenetic patterns of susceptibility are correlated amongst diverse sets of viruses is unclear. Here, we investigate phylogenetic correlations in susceptibility among Drosophilidae hosts to a panel of eleven different invertebrate viruses, comprising seven unique virus species, six unique families, and both RNA and DNA viruses. The susceptibility of hosts to each pair of viruses tested was either positively correlated across host species or did not show evidence of correlation. No negative correlations, indicative of evolutionary trade-offs in host susceptibility to different viruses, were detected between any virus pairs. The strength of correlations were generally higher in viruses of the same species and family, consistent with virus phylogenetic patterns in host infectivity. Our results suggest that generalised host susceptibility can result in positive correlations, even between highly diverged viruses, while specialised interactions with individual viruses cause a stepwise decrease in correlation strength between viruses from the within-species, to the within-family, to the across-family level.

evolutionary biology↗

Investigating the outcomes of virus coinfection within and across host species

Interactions between coinfecting pathogens have the potential to alter the course of infection and can act as a source of phenotypic variation in susceptibility between hosts. This phenotypic variation may influence the evolution of host-pathogen interactions within host species and interfere with patterns in the outcomes of infection across host species. Here, we examine experimental coinfections of two Cripaviruses - Cricket Paralysis Virus (CrPV), and Drosophila C Virus (DCV) -across a panel of 25 Drosophila melanogaster inbred lines and 47 Drosophilidae host species. We find that interactions between these viruses alter viral loads across D. melanogaster genotypes, with a ~3 fold increase in the viral load of DCV and a ~2.5 fold decrease in CrPV in coinfection compared to single infection, but we find little evidence of a host genetic basis for these effects. Across host species, we find no evidence of systematic changes in susceptibility during coinfection, with no interaction between DCV and CrPV detected in the majority of host species. These results suggest that phenotypic variation in coinfection interactions within host species can occur independently of natural host genetic variation in susceptibility, and that patterns of susceptibility across host species to single infections can be robust to the added complexity of coinfection.

evolutionary biology↗

The host phylogeny determines viral infectivity and replication across Staphylococcus host species

Genetic similarity between eukaryotic host species is an important determinant of the outcome of virus host shifts, where a pathogen infects a novel host species. However, it is less clear if this is the case for prokaryotes where anti-virus defences can be transmitted by horizontal gene transfer and evolve rapidly. Understanding the patterns and determinants of cross-species transmissions may provide insights into the processes underlying pathogen emergence. Here, we measure the susceptibility of 64 strains of Staphylococcus bacteria (48 strains of S. aureus and 16 non-aureus species) 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 Staphylococcus species, suggesting that these phylogenetic effects are conserved both within and among host species. We find positive correlations between susceptibility assessed using a binary measure of plaque assay, OD, and qPCR, but not between the continuous component of plaque assay and any other method, suggesting that plaque assays alone may be inadequate to assess host range. 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.

evolutionary biology↗

Earl Grey: a fully automated user-friendly transposable element annotation and analysis pipeline

Transposable elements (TEs) are major components of eukaryotic genomes and are implicated in a range of evolutionary processes. Yet, TE annotation and characterisation remains challenging, particularly for non-specialists, since existing pipelines are typically complicated to install, run, and extract data from. Current methods of automated TE annotation are also subject to issues that reduce overall quality, particularly: (i) fragmented and overlapping TE annotations, leading to erroneous estimates of TE count and coverage; (ii) repeat models represented by short sections of total TE length, with poor capture of 5 and 3 ends. To address these issues, we present Earl Grey, a fully automated TE annotation pipeline designed for user-friendly curation and annotation of TEs in eukaryotic genome assemblies. Using nine simulated genomes and an annotation of Drosophila melanogaster, we show that Earl Grey outperforms current widely-used TE annotation methodologies in ameliorating the issues mentioned above, whilst scoring highly in benchmarking for TE annotation and classification, and being robust across genomic contexts. Earl Grey provides a comprehensive and fully automated TE annotation toolkit that provides researchers with paper-ready summary figures and outputs in standard formats compatible with other bioinformatics tools. Earl Grey has a modular format, with great scope for the inclusion of additional modules focussed on further quality control and tailored analyses in future releases.

bioinformatics↗