>Environmental structure drives resistance to phages and antibiotics during phage therapy and to invading lysogens during colonisation
Pub. online 28 February 2019. JorgeA. Moura de Sousa & Eduardo P. C. Rocha. www.nature.com/scientificreports
Microbial communities are shaped by bacteriophages through predation and lysogeny. A better understanding of the interactions between these processes across different types of environments is key to elucidate how phages mediate microbial competition and to design efficient phage therapies. We introduce an individual-based model (eVIVALDI) to investigate the role of environmental structure in the elimination of a population with a combined treatment of antibiotics and virulent phages, and in the invasion of a population of phage-sensitive bacteria by lysogens. We show that structured environments facilitate the emergence of double resistance, to antibiotics and phages, due to limited diffusion of phage particles and increased nutrient availability from dead cells. They also hinder phage amplification, thus decreasing the generation of phage genetic diversity and increasing the unpredictability of phage-bacteria arms-races. We used a machine learning approach to determine the variables most important for the invasion of sensitive populations by lysogens. They revealed that phage-associated traits and environmental structure are the key drivers of the process. Structured environments hinder invasions, and accounting for their existence improves the ft of the model to published in vivo experimental data. Our results underline environmental structure as key to understand in vivo phage-bacteria interactions.
Microbial Evolutionary Genomics, Institut Pasteur, CNRS, UMR3525, Paris, 75015, France. Correspondence and requests for materials should be addressed to J.A.M.d.S. (email: jorge-andre.sousa [at] pasteur.fr)
>Workshop on the therapeutic use of bacteriophages
Date:08/06/2015. Location:European Medicines Agency, London, UK. English only.
phage.workshop [at] ema.europa.eu
On 8 June 2015, the European Medicines Agency is organising a workshop on the therapeutic use of bacteriophages, bringing together experts and stakeholders from the academic, industrial and regulatory sectors to discuss different aspects of using bacteriophages to treat bacterial infections. The aim is to proactively discuss current issues and open questions and reflect on potential ways forward for this therapy with various stakeholders.
Workshop on the therapeutic use of bacteriophages - Summary (PDF/75.19 KB)
First published: 09/07/2015, Last updated: 09/07/2015. EMA/389257/2015
Agenda - Workshop on the therapeutic use of bacteriophages (PDF/68.67 KB)
First published: 21/05/2015 Last updated: 05/06/2015 EMA/265715/2015 Corr.
Presentation - A historical overview of the therapeutic use of bacteriophages (Andrzej Gorski) (PDF/2.93 MB)
First published: 22/06/2015 Last updated: 22/06/2015
Presentation - GMP phage production for clinical trials (Frenk Smrekar) (PDF/371.69 KB)
First published: 22/06/2015 Last updated: 22/06/2015
Presentation - GMP phage production for clinical trials (Laurent Bretaudeau) (PDF/882.15 KB)
First published: 22/06/2015 Last updated: 22/06/2015
Presentation - Current issues on quality of phage products (Alan Fauconnier) (PDF/1.02 MB)
First published: 22/06/2015 Last updated: 22/06/2015
Presentation - Changing phage cocktails to match developing resistance (Gilbert Verbeken) (PDF/1.37 MB)
First published: 22/06/2015 Last updated: 22/06/2015
Presentation - Considerations on regulatory aspects (Zigmars Sebris) (PDF/134.17 KB)
First published: 22/06/2015 Last updated: 22/06/2015
Presentation - Current clinical evidence for the therapeutic use of bacteriophages (Xavier Wittebole)(PDF/2.18 MB)
First published: 22/06/2015 Last updated: 22/06/2015
Presentation - Experience from the ongoing Phagoburn clinical trial (Patrick Jault) (PDF/5.92 MB)
First published: 22/06/2015 Last updated: 22/06/2015
Presentation - Experience from the Phagorburn clinical trial (Jerome Gabard) (PDF/371.21 KB)
First published: 22/06/2015 Last updated: 22/06/2015
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Presentation - A historical overview of the therapeutic use of bacteriophages (Andrzej Gorski), (English only) ... A video recording is now made available.