Phage-Steering Strategy to Fight Antibiotic Resistance

Please note applications are no longer being accepted for these positions

The global emergence of antibiotic resistance has led to renewed interest in bacteriophage therapy as an alternative and feasible option to control and potentially reverse antimicrobial resistance in different settings including medicine, agriculture, aquaculture, food industry and the environment (“one health approach”). While bacteriophage use has led to the emergence of phage-resistant bacteria, in some cases, their antibiotic-resistant phenotype was concomitantly reversed. This interesting phenomenon may represent an attractive way to re-establish the utility of antibiotics despite initial antimicrobial resistance.

This joint project aims to minimise the spread and impact of antimicrobial resistance through implementing bacteriophage therapy as an innovative and natural ‘evolutionary-based strategy’. In an international collaborative effort, we aim to develop high-throughput techniques to obtain specific phage resources, by characterizing the complex phage-bacteria-antibiotic interactions and by validating our approach as a proof of concept using well-established laboratory techniques. As target pathogen, multidrug-resistance Staphylococcus aureus and Escherichia coli strains will be used due to their high prevalence in humans, animals, food, surface water, and the environment in both low and high-income countries.

The University of Melbourne (UoM) based project will focus on using genomics methods to characterize the evolution and resistance to phages targeting globally representative, multi-drug resistant Staphylococcus aureus. The phage collection will be the starting point to investigate the potential of “phage steering” and to prove that relevant phages can represent a feasible option to innovatively improve the management of antimicrobial resistance. The candidate will study the selective pressure on bacteria by phages and look to evolutionary trade-offs between resistance to phages and either sensitivity to other antimicrobials or reduced bacterial virulence.

The Berlin University Alliance (BUA) project will focus on isolating and characterizing phages targeting multi-drug resistant Escherichia coli. The phage collection will be the starting point to investigate the potential of “phage steering” and to prove that relevant phages can represent a feasible option to innovatively improve the management of antimicrobial resistance. The candidate will study the selective pressure on bacteria by phages and look to evolutionary trade-offs between resistance to phages and either sensitivity to other antimicrobials or reduced bacterial virulence.

Project goals

The projects are divided in three objectives that will be carried out in consecutive years with the following specific aims:

1. Collection and isolation of phages targeting well characterized multidrug-resistant (MDR) S. aureus and E. coli isolates.
   • Phage isolation targeting diverse strains within existing well characterized bacterial collection of relevant S. aureus clinical isolates (UoM candidate) or E. coli clinical isolates (BUA candidate)
   • Evaluation of presence of virulent factors, CRISPR-Cas genes and antibiotic resistant genes profiles in S. aureus strains (UoM candidate) or E. coli strains (BUA candidate)
   • Host range determination of newly isolated and reference phages active against the MDR bacterial collection and analysis of genomic correlates of phage-host interactions.
2. In vitro evaluation of trade-off effects.
   • Evaluation of in vitro phage-resistance emergence in MDR bacterial strains.
   • Assessment of trade-off effects: determination of increased sensitivity of phage-resistant mutants to antibiotics and/or reduced virulence.
   • Characterization of phage-resistant mutants. Identification of gene mutations associated with the phage-resistant phenotypes.
3. Evaluation of combined exposure of MDR strains to phages and antibiotics.
   • Antibacterial assessment of the best phage candidates in combination with other phages and with different antibiotics.
   • Evaluation of what types of bacterial resistance will arise after exposure to mixture of phage and/or antibiotics.
   • Determination of longer-term bacterial evolutionary responses to antibiotic and phage to ensure treatment efficacy and prevention of resistance development.

Supervision team

• The University of Melbourne: Professor Ben Howden

• Charité – Universitätsmedizin Berlin, Germany - Berlin University Alliance (BUA): Professor Andrej Trampuz

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Who we are looking for

We are seeking a PhD candidate with the following skills:

• An undergraduate degree with Honours, or Masters, in Microbiology or Molecular Biology or a related field.
• Demonstrated experience in the field of Microbiology, Molecular Biology or Genomics.
• Demonstrated ability to work independently and as part of a team.
• Demonstrated time and project management skills.
• Demonstrated ability to write research reports or other publications to a publishable standard (even if not published to date).
• Excellent written and oral communication skills.
• Demonstrated organisational skills, time management and ability to work to priorities.
• Demonstrated problem-solving abilities.

Further details

• Two PhD projects are available. One candidate will be based at University of Melbourne (UoM) with a minimum twelve-month stay at Charité – Universitätsmedizin Berlin. The Berlin University Alliance (BUA) candidate will be based at Charité – Universitätsmedizin Berlin and will spend a minimum of 12 months at the University of Melbourne (UoM).
• The PhD candidate will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.
• Prof Ben Howden  at the University of Melbourne will contribute expertise in clinical microbiology, antimicrobial resistance and pathogen genomics and evolution.
• Prof Andrej Trampuz  at Charité – Universitätsmedizin Berlin will contribute expertise in the characterization of newly isolated bacteriophages and their co-evolution with MDR bacteria.
• The candidate will be enrolled in the Department of Microbiology and Immunology PhD program the University of Melbourne (Doherty Institute) and the Center for Musculoskeletal Surgery at Charité – Universitätsmedizin Berlin.

Please note applications are no longer being accepted for these positions