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Rapid assessment of changes in phage bioactivity using dynamic light scattering

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scatter...

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Autores principales: Dharmaraj, Tejas, Kratochvil, Michael J., Pourtois, Julie D., Chen, Qingquan, Hajfathalian, Maryam, Hargil, Aviv, Lin, Yung-Hao, Evans, Zoe, Oromí-Bosch, Agnès, Berry, Joel D., McBride, Robert, Haddock, Naomi L., Holman, Derek R., van Belleghem, Jonas D., Chang, Tony H., Barr, Jeremy J., Lavigne, Rob, Heilshorn, Sarah C., Blankenberg, Francis G., Bollyky, Paul L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327207/
https://www.ncbi.nlm.nih.gov/pubmed/37425882
http://dx.doi.org/10.1101/2023.07.02.547396
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author Dharmaraj, Tejas
Kratochvil, Michael J.
Pourtois, Julie D.
Chen, Qingquan
Hajfathalian, Maryam
Hargil, Aviv
Lin, Yung-Hao
Evans, Zoe
Oromí-Bosch, Agnès
Berry, Joel D.
McBride, Robert
Haddock, Naomi L.
Holman, Derek R.
van Belleghem, Jonas D.
Chang, Tony H.
Barr, Jeremy J.
Lavigne, Rob
Heilshorn, Sarah C.
Blankenberg, Francis G.
Bollyky, Paul L.
author_facet Dharmaraj, Tejas
Kratochvil, Michael J.
Pourtois, Julie D.
Chen, Qingquan
Hajfathalian, Maryam
Hargil, Aviv
Lin, Yung-Hao
Evans, Zoe
Oromí-Bosch, Agnès
Berry, Joel D.
McBride, Robert
Haddock, Naomi L.
Holman, Derek R.
van Belleghem, Jonas D.
Chang, Tony H.
Barr, Jeremy J.
Lavigne, Rob
Heilshorn, Sarah C.
Blankenberg, Francis G.
Bollyky, Paul L.
author_sort Dharmaraj, Tejas
collection PubMed
description Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-year-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web-application (Phage-ELF) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and non-destructive tool for quality control of phage preparations in academic and commercial settings.
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spelling pubmed-103272072023-07-08 Rapid assessment of changes in phage bioactivity using dynamic light scattering Dharmaraj, Tejas Kratochvil, Michael J. Pourtois, Julie D. Chen, Qingquan Hajfathalian, Maryam Hargil, Aviv Lin, Yung-Hao Evans, Zoe Oromí-Bosch, Agnès Berry, Joel D. McBride, Robert Haddock, Naomi L. Holman, Derek R. van Belleghem, Jonas D. Chang, Tony H. Barr, Jeremy J. Lavigne, Rob Heilshorn, Sarah C. Blankenberg, Francis G. Bollyky, Paul L. bioRxiv Article Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-year-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web-application (Phage-ELF) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and non-destructive tool for quality control of phage preparations in academic and commercial settings. Cold Spring Harbor Laboratory 2023-07-02 /pmc/articles/PMC10327207/ /pubmed/37425882 http://dx.doi.org/10.1101/2023.07.02.547396 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Dharmaraj, Tejas
Kratochvil, Michael J.
Pourtois, Julie D.
Chen, Qingquan
Hajfathalian, Maryam
Hargil, Aviv
Lin, Yung-Hao
Evans, Zoe
Oromí-Bosch, Agnès
Berry, Joel D.
McBride, Robert
Haddock, Naomi L.
Holman, Derek R.
van Belleghem, Jonas D.
Chang, Tony H.
Barr, Jeremy J.
Lavigne, Rob
Heilshorn, Sarah C.
Blankenberg, Francis G.
Bollyky, Paul L.
Rapid assessment of changes in phage bioactivity using dynamic light scattering
title Rapid assessment of changes in phage bioactivity using dynamic light scattering
title_full Rapid assessment of changes in phage bioactivity using dynamic light scattering
title_fullStr Rapid assessment of changes in phage bioactivity using dynamic light scattering
title_full_unstemmed Rapid assessment of changes in phage bioactivity using dynamic light scattering
title_short Rapid assessment of changes in phage bioactivity using dynamic light scattering
title_sort rapid assessment of changes in phage bioactivity using dynamic light scattering
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327207/
https://www.ncbi.nlm.nih.gov/pubmed/37425882
http://dx.doi.org/10.1101/2023.07.02.547396
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