ProphARG | Evolution and Spread of Antibiotic Resistance Encoded on Prophages


A worldwide increase of life-threatening antibiotic resistant pathogens is a major global health problem. This trend is predicted to increase with ever increasing misuse and overuse of antibiotics, which accelerates the evolution of antibiotic resistance. In addition, we are limited in controlling the spread of antibiotic resistance genes (ARGs) due to an incomplete understanding of the underlying ecological and evolutionary forces. One important mechanism of transferring ARGs between different bacteria are temperate bacteriophages (prophages), i.e., viruses that can incorporate their own genetic material into the bacterial chromosome, thereby providing their bacterial host (which is now called ‘lysogen’) with additional genes, such as ARGs. However, despite their vast abundance in nature, our understanding of the contribution of prophages to the spread of AR is still incomplete. 
Here at ETH Zürich we aim to unravel the ecological and evolutionary drivers influencing the evolution and spread of antibiotic resistance genes through prophages. We combine experimental evolution, whole genome sequencing and theoretical simulations of E. coli populations with and/ or without prophages to determine the costs and benefits as well as the transfer rate of prophage-encoded antibiotic resistance genes. 
The project is funded through a Marie Curie Individual Fellowship and an SNSF Ambizione Fellowship
Recent publications:

Bailey, Z.M.*, Igler, C., Wendling, C.C.* (2023) „Prophage maintenance is determined by environmental-dependent selective sweeps rather than mutational availability” biorxiv. https://doi.org/10.1101/2023.03.21.533645
Kupczok, A.*, Bailey, Z.M., Refardt, D., Wendling, C.C. (2022) “Co-transfer of functionally interdependent genes contributes to genome mosaicism in lambdoid phages” Microbial Genomics 8(11) https://doi.org/10.1099/mgen.0.000915

Igler, C., Schwyter, L., Gehrig, D., Wendling, C.C. (2022). „Conjugative plasmid transfer is limited by prophages but can be overcome by high conjugation rates”. Phil Trans B 377(1842) https://doi.org/10.1098/rstb.2020.0470

Wendling, C.C., Refardt, D., Hall, A.R. (2021) “Fitness benefits to bacteria of carrying prophages and prophage-encoded antibiotic-resistance genes peak in different environments” Evolution 75(2) https://doi.org/10.1111/evo.14153