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H2020Individual fellowship2018–2020

ProphARG · Evolution of Prophages that carry Antibiotic Resistance Genes (ARGs) and their host-bacteria in response to antibiotics and increased lytic activity

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2018-09-01 → 2020-08-31
EU contribution
€187,420
Participants
1
Scheme
MSCA-IF

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Results in brief

Evolution of Prophages that carry Antibiotic Resistance Genes (ARGs) and their host-bacteria in response to antibiotics and increased lytic activity

Antibiotic resistance genes (ARGs) can spread horizontally by mobile genetic elements, such as prophages, i.e. viruses that can incorporate their own genetic material into the bacterial chromosome (then called lysogen). Prophages can increase their hosts’ fitness through additional genes, such as ARGs and by their ability to kill phage-susceptible competitors. However, spontaneous or environment-dependent prophage induction can also be costly for the lysogen. In addition, ARGs often come with additional costs, especially in the absence of the selective antibiotic. A better understanding of how prophage-associated fitness effects of antibiotic resistant lysogens vary across environments is key to elucidate how prophages contribute to the ecology and evolution of antimicrobial resistance. At the start of the project, the I set out to address the following questions: (1) How does the net fitness effect of prophage carriage vary across different antibiotic concentrations? (2) Are these effects specific to prophages that encode ARGs? (3) Are prophages more beneficial in environments where lysis is more frequent? (4) In which environments is the acquisition of ARG-carrying prophages by susceptible strains most likely?

Data: CORDIS, © European Union

Project objective

In the European Union, 25,000 deaths per year are caused by multidrug resistant bacteria. This trend is predicted to increase with ever increasing misuse and overuse of antibiotics, which accelerates the evolution of antibiotic resistance (AR). An important mechanism of transferring antibiotic resistance genes (ARGs) among bacteria are temperate bacteriophages (prophages), viruses that can incorporate their own genetic material into the bacterial chromosome, thereby providing their bacterial host (which is now called a ‘lysogen’) with additional genes, such as ARGs. Despite their vast abundance in nature, our understanding of the evolution of ARG-carrying prophages is still incomplete. Therefore I will study the evolution of ARG-carrying prophages and their host bacteria. Specifically, using constructed lysogens (carrying prophage lambda+ARG) of E. coli bacteria, I will (1) use competitive fitness assays to determine the costs/benefits for bacteria of carrying prophages that encode AR and how these costs depend on environmental antibiotic concentrations and the frequency with which the prophage enters the lytic cycle (i.e. the prophage becomes active, replicates and lyses the host cell). (2) I will follow the evolution of these lysogens that carry AR-encoding prophages using a serial transfer experiment in the presence/absence of antibiotics and compounds that induce phage lysis. (3) I will sequence the evolved lysogens including their prophage genomes to detect underlying genomic changes associated with bacterial adaptation to prophage carriage. I predict that the net effect of a prophage that encodes an ARG on the growth and evolution of its host bacterium will strongly depend on both the frequency with which the phage enters the lytic cycle and the costs/benefits of the ARG. By using a novel approach that has been neglected so far (evolution of ARG-carrying prophages) this project will improve our understanding of AR evolution.

Original text from CORDIS.

Participants

  • EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH · ZuerichCoordinatorSwitzerland

Links

Data: CORDIS, © European Union