Biology subjects

Jameson, E.

Publications and source records attributed to Jameson, E..

10 recordsLinked to original sources

bioRxiv2026

Large scale antibiotic-phage synergy studies reveal key combinations for urinary tract infection and urosepsis treatments

The growing problem of AMR infections in healthcare has prompted the search for alternative treatments, with increasing interest in bacteriophages. However, most bacteriophage-antibiotic interactions are incompletely understood, and the benefits of combining them remains context dependent. In this study, we screened thousands of phage-antibiotic combinations to assess interaction outcomes in clinical E. coli and K. pneumoniae isolates. By integrating bacteriophages into an existing, scalable clinical MIC determination platform, we identified shifts in antibiotic MIC and susceptibility, revealing patterns of additivity and antagonism. Overall, interactions showed a species-specific profile; additive interactions predominated, particularly for E. coli. Hierarchical clustering highlighted frequent positive interactions between {beta}-lactams and Tequatroviruses. Notably, closely related phages sometimes displayed divergent phenotypes, indicating that interaction outcomes cannot be inferred solely from taxonomic relatedness or genomic similarity. Taken together, these results establish a foundation for rational, evidence-based development of phage-antibiotic therapies to restore and broaden treatment options against multidrug-resistant infections.

microbiology↗

bioRxiv2025

In-vivo Efficacy of a Phage Cocktail Therapy that Targets ESBL-producing Klebsiella Urinary Tract Infections Clinical Isolates

Uropathogenic Klebsiella pneumoniae strains, are of major concern of with respect to antimicrobial resistance, which has sparked interest in phage therapy as an alternative, or compliment to antibiotics. However, very limited in vivo data on phage therapy safety and efficacy for treating UTIs is available. To address this, we developed a model to test these parameters for a phage cocktail optimised for Extended Spectrum Beta-Lactamases (ESBL)-producing Klebsiella UTI strains. Female C57BL/6J mice were infected with K. pneumoniae Top52 then received a single dose of the purified therapeutic phages, with observations over seven days. Results showed a significant reduction of bacterial burden in urine, bladder, and kidney samples starting from 4 h post-treatment until Day 7. Phage treatment also reduced local inflammation within the bladder. Additionally, cytokine profile demonstrated an increase in anti-inflammatory IL-10 and a decrease in pro-inflammatory IL-6, indicating a synergy between phage and the host immune response.

microbiology↗

bioRxiv2023

Bacteriophage cocktail shows no toxicity and improves the survival of Galleria mellonella infected with Klebsiella spp.

Klebsiella spp. are causative agents of healthcare associated infections in patients who are immunocompromised and use medical devices. The antibiotic resistance crisis has led to an increase in infections caused by these bacteria, which can develop into potentially life-threatening illness if not treated swiftly and effectively. Thus, new treatment options for Klebsiella are urgently required. Phage therapy can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria infections. The aim of the present study was to produce a safe and effective phage cocktail treatment against K. pneumoniae and K. oxytoca, both in liquid in vitro culture and an in vivo Galleria mellonella infection model. The phage cocktail was significantly more effective at killing K. pneumoniae and K. oxytoca strains compared with monophage treatments. Preliminary phage cocktail safety was demonstrated through application in the in vivo G. mellonella model: where the phage cocktail induced no toxic side effects in G. mellonella. In addition, the phage cocktail significantly improved the survival of G. mellonella when administered as a prophylactic treatment, compared with controls. In conclusion, our phage cocktail was demonstrated to be safe and effective against Klebsiella spp. in the G. mellonella infection model. This provides a strong case for future treatment for Klebsiella infections, either as an alternative, or adjunct to, antibiotics.

microbiology↗

bioRxiv2023

Phages prevent biofilm formation on catheters under flow

Biofilms pose a significant challenge in medical settings, leading to persistent infections. Phage therapy has shown promise in biofilm eradication, but its effectiveness under dynamic flow conditions remains unclear. Here we use two novel phages isolated on Klebsiella, Llofrudd and Samara, and characterized their genomes, host range and virulence. In this study, we built a simple catheterised bladder model with flow to investigate the impact of phage treatment on biofilm viability in a flow-based catheter model. Our analyses demonstrate that phages Llofrudd and Samara are the same species and infect a limited number of strains (3/222), but across three species: Klebsiella aerogenes, Klebsiella pneumoniae and E. coli. Phage treatment significantly reduced E. coli biofilm viability in catheters both in static conditions and under flow, highlighting the potential of phage therapy as an intervention strategy for catheter associated urinary tract infections (CAUTI).

microbiology↗

bioRxiv2022

Ecological and evolutionary patterns of virus-host interactions throughout a grassland soil depth profile

BackgroundSoil microbes play pivotal roles in global carbon cycling, however the fundamental interactions between microbes and their infecting viruses remain unclear. This is exacerbated with soil depth, where the patterns of viral dispersal, ecology, and evolution are markedly underexplored. To investigate viral communities across soil depth, we leveraged a publicly available metagenomic data set sampled from grassland soil in northern California. Results10,196 non-redundant vOTUs were recovered from soil sampled from 20 cm to 120 cm below the surface. Viral prevalence was high throughout the soil depth profile, with viruses infecting dominant soil phyla, including Actinomycetota. Contrary to leading hypotheses, lysogeny did not dominate in the soil viral communities. Viral diversity was investigated at both the population-level (i.e., macro diversity) and strain-level (i.e., micro diversity) to reveal diverse ecological and evolutionary patterns of virus-host interactions in surface and subsurface soil. ConclusionsBy investigating viral micro diversity in soil for the first time, we have uncovered patterns of antagonistic co-evolution across both surface and subsurface soils. Furthermore, we have provided evidence of soil viruses augmenting the remineralisation of soil carbon. While we continue to yield a more comprehensive understanding of soil viral ecology, our work appeals to future researchers to continue to investigate subsurface viral communities.

ecology↗

bioRxiv2022

Crop management shapes the diversity and activity of DNA and RNA viruses in the rhizosphere

BackgroundThe rhizosphere is a hotspot for microbial activity and contributes to ecosystem services including plant health and biogeochemical cycling. The activity of microbial viruses, and their influence on plant-microbe interactions in the rhizosphere, remains undetermined. Given the impact of viruses on the ecology and evolution of their host communities, determining how soil viruses influence microbiome dynamics is crucial to build a holistic understanding of rhizosphere functions. ResultsHere, we aimed to investigate the influence of crop management on the composition and activity of bulk soil, rhizosphere soil, and root viral communities. We combined viromics, metagenomics, and metatranscriptomics on soil samples collected from a 3-year crop rotation field trial of oilseed rape (Brassica napus L.). By recovering 1,059 dsDNA viral populations and 16,541 ssRNA bacteriophage populations, we expanded the number of underexplored Leviviricetes genomes by > 5 times. Through detection of viral activity in metatranscriptomes, we uncovered evidence of "Kill-the-Winner" dynamics, implicating soil bacteriophages in driving bacterial community succession. Moreover, we found the activity of viruses increased with proximity to crop roots and identified that soil viruses may influence plant-microbe interactions through the reprogramming of bacterial host metabolism. We have provided the first evidence of crop rotation-driven impacts on soil microbial communities extending to viruses. To this aim, we present the novel principal of "viral priming", which describes how the consecutive growth of the same crop species primes viral activity in the rhizosphere through local adaptation. ConclusionsOverall, we reveal unprecedented spatial and temporal diversity in viral community composition and activity across root, rhizosphere soil and bulk soil compartments. Our work demonstrates that the roles of soil viruses need greater consideration to exploit the rhizosphere microbiome for food security, food safety, and environmental sustainability.

ecology↗

bioRxiv2021

The component parts of bacteriophage virions accurately defined by a machine-learning approach built on evolutionary features.

Antimicrobial resistance (AMR) continues to evolve as a major threat to human health and new strategies are required for the treatment of AMR infections. Bacteriophages (phages) that kill bacterial pathogens are being identified for use in phage therapies, with the intention to apply these bactericidal viruses directly into the infection sites in bespoke phage cocktails. Despite the great unsampled phage diversity for this purpose, an issue hampering the roll out of phage therapy is the poor quality annotation of many of the phage genomes, particularly for those from infrequently sampled environmental sources. We developed a computational tool called STEP3 to use the "evolutionary features" that can be recognized in genome sequences of diverse phages. These features, when integrated into an ensemble framework, achieved a stable and robust prediction performance when benchmarked against other prediction tools using phages from diverse sources. Validation of the prediction accuracy of STEP3 was conducted with high-resolution mass spectrometry analysis of two novel phages, isolated from a watercourse in the Southern Hemisphere. STEP3 provides a robust computational approach to distinguish specific and universal features in phages to improve the quality of phage cocktails, and is available for use at http://step3.erc.monash.edu/. IMPORTANCEIn response to the global problem of antimicrobial resistance there are moves to use bacteriophages (phages) as therapeutic agents. Selecting which phages will be effective therapeutics relies on interpreting features contributing to shelf-life and applicability to diagnosed infections. However, the protein components of the phage virions that dictate these properties vary so much in sequence that best estimates suggest failure to recognize up to 90% of them. We have utilised this diversity in evolutionary features as an advantage, to apply machine learning for prediction accuracy for diverse components in phage virions. We benchmark this new tool showing the accurate recognition and evaluation of phage components parts using genome sequence data of phages from under-sampled environments, where the richest diversity of phage still lies.

microbiology↗

bioRxiv2020

Isolation and chacterisation of Klebsiella phages for phage therapy

Klebsiella is a clinically important pathogen causing a variety of antimicrobial resistant infections in both community and nosocomial settings, particularly pneumonia, urinary tract infection and sepsis. Bacteriophage (phage) therapy is being considered as a primary option for the treatment of drugresistant infections of these types. We report the successful isolation and characterisation of 30 novel, genetically diverse Klebsiella phages. The isolated phages span six different phage families and nine genera, representing both lysogenic and lytic lifestyles. Individual Klebsiella phage isolates infected up to 11 of the 18 Klebsiella capsule types tested, and all 18 capsule-types were infected by at least one of the phages. Of the Klebsiella-infecting phages presented in this study, the lytic phages are most suitable for phage therapy, based on their broad host range, high virulence, short lysis period and given that they encode no known toxin or antimicrobial resistance genes. Importantly, when applied alone, none of the characterised phages were able to suppress the growth of Klebsiella for more than 12 hours, with some phages only able to suppress growth for 3 hours, likely due to inherent ease of Klebsiella to generate spontaneous phage-resistant mutants. This indicates that for successful phage therapy, a cocktail of multiple phages would be necessary to treat Klebsiella infections.

microbiology↗

bioRxiv2020

CAUTI's Next Top Model - model dependent Klebsiella biofilm inhibition by bacteriophages and antimicrobials

Klebsiella infections, including catheter associated urinary tract infections, are a considerable burden on health care systems. This is due to their difficulty to treat, caused by antimicrobial resistance and their ability to form biofilms. In this study, we investigated the use of a Klebsiella phage cocktail to reduce biofilm viability. We used two methodologies to investigate this, a standard 96-well plate assay and a more complicated Foley catheter-based model. The phage cocktail was used alone and in combination with clinically relevant antibiotic treatments. Viability was measured by both a resazurin based stain and colony forming unit counts, of cells sloughed off from the biofilm. We showed that phage infection dynamics and host survival vary significantly in different standard laboratory media, presumably due to the expression of different surface receptors and capsule composition by the bacteria effecting phage binding. This underscores the importance of a realistic model for developing phage therapyWe demonstrate that bacteriophage-based treatments are a viable option for preventing Klebsiella colonisation and biofilm formation on urinary catheters. Phage cocktails were able to significantly reduce the amount of biofilm that formed when they were present during early biofilm formation. The phages used in this study were unable to significantly reduce a pre-formed mature biofilm, despite encoding depolymerases. Phages applied together with antimicrobial treatments, showed synergistic interactions, in some cases the combined treatment was much more effective than antimicrobial treatments alone.We show that phage cocktails have the potential to prevent Klebsiella biofilms in catheters, if used early or as a preventative treatment and will work well alongside standard antibiotics in the treatment of catheter-associated urinary tract infections (CAUTI).Competing Interest StatementThe authors have declared no competing interest.View Full Text

microbiology↗

bioRxiv2018

Riding the wave of genomics, to investigate aquatic coliphage diversity and activity

Bacteriophages infecting Escherichia coli have been used as a proxy for faecal matter and water quality from a variety of environments. However, the diversity of coliphages that are present in seawater remains largely unknown, with previous studies largely focusing on morphological diversity. Here, we isolated and characterised coliphages from three coastal locations in the UK and Poland. This revealed a surprising genetic diversity, with comparative genomics and phylogenetic analysis of phage isolates facilitating the identification of putative new species within the genera RB69virus and T5virus and a putative new genus within the subfamily Tunavirinae. Furthermore, by combining this genomic data with proteomic and host range analyses a number of phage structural proteins were identified, one of which is likely to be responsible for the observed differences in host range.

microbiology↗