Abstract

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. In this study, 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-y-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web application (Phage-Estimator of Lytic Function) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and nondestructive tool for quality control of phage preparations in academic and commercial settings.

Details

Title
Rapid assessment of changes in phage bioactivity using dynamic light scattering
Author
Dharmaraj, Tejas 1   VIAFID ORCID Logo  ; Kratochvil, Michael J 2   VIAFID ORCID Logo  ; Pourtois, Julie D 3   VIAFID ORCID Logo  ; Chen, Qingquan 1 ; Hajfathalian, Maryam 1 ; Hargil, Aviv 1 ; Yung-Hao, Lin 4   VIAFID ORCID Logo  ; Evans, Zoe 1   VIAFID ORCID Logo  ; Oromí-Bosch, Agnès 5 ; Berry, Joel D 5 ; McBride, Robert 5 ; Haddock, Naomi L 1 ; Holman, Derek R 6   VIAFID ORCID Logo  ; van Belleghem, Jonas D 1   VIAFID ORCID Logo  ; Chang, Tony H 1   VIAFID ORCID Logo  ; Barr, Jeremy J 7   VIAFID ORCID Logo  ; Lavigne, Rob 8   VIAFID ORCID Logo  ; Heilshorn, Sarah C 2   VIAFID ORCID Logo  ; Blankenberg, Francis G 9 ; Bollyky, Paul L 1   VIAFID ORCID Logo 

 Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Beckman Center for Molecular and Genetic Medicine , Stanford, CA 94305 , USA 
 Department of Materials Science and Engineering, Stanford University , Stanford, CA 94305 , USA 
 Department of Biology, Hopkins Marine Station, Stanford University , Pacific Grove, CA 93950 , USA 
 Department of Chemical Engineering, Stanford University , Stanford, CA 94305 , USA 
 Felix Biotechnology , South SanFrancisco, CA 94080 , USA 
 Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine , Stanford, CA 94305 , USA 
 School of Biological Sciences, Monash University , Clayton, VIC 3800 , Australia 
 Department of Biosystems, KU Leuven , Leuven 3001 , Belgium 
 Division of Pediatric Radiology and Nuclear Medicine, Department of Radiology, Lucile Packard Children's Hospital , Stanford, CA 94305 , USA 
Publication year
2023
Publication date
Dec 2023
Publisher
Oxford University Press
e-ISSN
27526542
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3191454595
Copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.