Plasmid-Specific Bacteriophages to mitigate the Spread of Antimicrobial Resistance in Used Water & the Environment (Phage POWER).

Project Information

Phage POWER

Grant agreement ID: 101026675

DOI

10.3030/101026675

Project closed

EC signature date 3 May 2021

Start date 1 September 2021

End date 31 August 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 219 312,00

EU contribution

€ 219 312,00

Coordinated by

DANMARKS TEKNISKE UNIVERSITET
Denmark

Periodic Reporting for period 1 - Phage POWER (Plasmid-Specific Bacteriophages to mitigate the Spread of Antimicrobial Resistance in Used Water & the Environment (Phage POWER).)

Reporting period: 2021-09-01 to 2023-08-31

Summary of the context and overall objectives of the project

Antimicrobial resistance (AMR) is a global public health concern that forebodes a dramatic scenario for the coming decades because pathogenic bacteria are increasingly resistant to the drugs used to kill them. This crisis is worsened by the ability of many antimicrobial-resistant bacteria to spread their antimicrobial resistance genes (ARGs) to other bacteria by horizontal transfer, and especially by the transfer of conjugative plasmids, pieces of DNA that can autonomously transfer and that often carry ARGs. Wastewater treatment plants receive many resistant bacteria carrying such plasmids and, therefore, these environments are suspected hotspots in the spread of clinically relevant ARGs while, at the same time, being control points that can be used to prevent the dissemination of resistance genes and resistant organisms to the environment.
Viruses that attack plasmid-bearing bacteria via plasmid-encoded structures have been described. They were mainly isolated several decades, but many of them are no longer available and have not been documented comprehensively. It has been demonstrated that they reduce the rate of conjugation in pure culture studies; however, their effect in microbial communities is still unknown. Can we leverage some of these natural ‘enemies’ of plasmids to mitigate the spread of AMR in the diverse microbial communities that are typical of biological water treatment? Can we fight evolution with evolution? This is the ambition of this project.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The research was divided into four packages: plasmid collection, phage isolation, phage characterization and phage efficiency assessment.
A collection of diverse plasmids involved in the dissemination of antibiotic resistance was prepared and transferred to a model bacterium to serve as prey for the phage isolation.
Phages infective and lytic towards diverse type of plasmids were isolated and characterized both genomically and phenotypically. Some of these phages were closely related to already known phages while other were novel and had a wide host range. They were then tested their effect in environmental bacterial communities, where we showed that several of these phages replicate efficiently in wastewater.
The multidisciplinary nature of the project is strong, involving a combination of environmental microbiology, molecular biology, metagenomics and virology.
During the reporting period, the progress of the project was according to the proposal. We obtained interesting results that were disseminated mainly through scientific conferences and publications in scientific journals.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The scientific work conducted during the project generated a lot of new knowledge about plasmid-specific phages and their potential to mitigate the presence of conjugative plasmids. One key takeaway was that these phages are diverse and very abundant in wastewater environments but that spiking such phages can still have an impact on wastewater microbial community and potentially reduce the abundance of conjugal plasmids. Therefore, they are worth continuing to study due to their potential to be used to combat AMR.
The plan for the exploitation and dissemination of research results proposed was largely followed during the fellowship. However, whereas, registration and a presentation on The European Researcher’s night was made to disseminate the awareness of AMR crisis in simple words to school students, the presentation was cancelled because COVID. As a result, the dissemination has mostly been directed towards the members of scientific community via several outlets listed below:

Publication in scientific journals:
• He, Z., Parra, B., Nesme, J., Smets, B.F. Dechesne, A. (2022) Quantification and fate of plasmid-specific bacteriophages in wastewater: beyond the F-coliphages. Water Research. 227, 119320.
• Parra, B., Cockx, B., Lutz, V.T. Brøndsted, L., Smets, B.F. Dechesne, A. (2023) Isolation and Characterization of two novel plasmid-specific bacteriophages PKM.Lu.22.1 and PKM.Hi.22.6. Microbiology Spectrum: Under review
• Parra, B., Laing-Carmona, J., Palomo, A., Smets, B.F. Dechesne, A. (2023) Isolation of novel plasmid-specific PRD1-like phages and assessment of the origin of these phages in wastewater. In preparation
• Parra, B., Nesme, J., Smets, B.F. Dechesne, A. (2023) Plasmid-specific phages and assessment of their effect in wastewater communities. In preparation

Scientific conferences:
• He, Z., Parra, B., Smets, B., Dechesne, A. DISTRIBUTION AND ABUNDANCE OF PLASMID- SPECIFIC BACTERIOPHAGES IN WASTEWATER SYSTEMS. Conference of The Danish Society for Microbiology. Copenhagen, Denmark, 2021.
• Parra, B., He, Z., Lutz, V.T. Brøndsted, L., Smets, B.F. Dechesne, A. Plasmid-Specific Bacteriophages to mitigate the Spread of Antimicrobial Resistance in Used Water & the Environment (Phage POWER). Conference of The Chilean Society of Microbiology (SOMICH), La Serena, Chile 2022.
• Parra, B., He, Z., Lutz, V.T. Brøndsted, L., Smets, B.F. Dechesne, A. Isolation and Genomic Characterization of Plasmid-specific Phages able to Infect Bacteria Carrying Diverse Conjugative Plasmids. Conference of The Danish Society for Microbiology, Copenhagen, Denmark 2022.
• Parra, B., He, Z., Lutz, V.T. Brøndsted, L., Smets, B.F. Dechesne, A. Plasmid-specific Phages to Reduce the Spread of Conjugative Plasmids Carrying Antimicrobial Resistance Genes in the Environment. Symposium in Bacterial genetics and ecology (BAGECO23), Copenhagen, Denmark 2023.
• Parra, B., He, Z., Lutz, V.T. Brøndsted, L., Smets, B.F. Dechesne, A. Plasmid-specific Phages to Reduce the Spread of Conjugative Plasmids Carrying Antimicrobial Resistance Genes in the Environment. Conference on Viruses of Microbes (VOM2023), Tbilisi, Georgia 2023.
• Vuong Van Hung Le, Zhuang Gong, Lorrie Maccario, Boris Parra, Arnaud Dechesne, Søren J. Sørensen, Joseph Nesme. On searching the receptor of plasmid-dependent PRD1-like bacteriophage. Conference on Viruses of Microbes (VOM2023), Tbilisi, Georgia 2023.

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