Bulletin of the American Physical Society
2023 APS March Meeting
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session K08: Ecological Dynamics III
3:00 PM–6:00 PM,
Tuesday, March 7, 2023
Room: Room 131
Sponsoring
Unit:
DBIO
Chair: Antun Skanata, Syracuse University
Abstract: K08.00006 : Multi-strain phage-induced clearance of Pseudomonas aeruginosa*
4:24 PM–4:36 PM
Presenter:
Jacopo Marchi
(Georgia Institute of Technology)
Authors:
Jacopo Marchi
(Georgia Institute of Technology)
Sophia Zborowsky
(Institute Pasteur)
Laurent Debarbieux
(Institute Pasteur)
Joshua S Weitz
(Georgia Institute of Technology)
result, phages – viruses that exclusively infect and
lyse bacteria – are increasingly considered as a therapeutic
alternative to treat bacterial infections. But, bacteria can develop
resistance against phages during treatment leading to adverse clinical
outcomes. Mixtures of multiple phages (i.e., 'cocktails') have been
proposed as a means to minimize the chance that the emergence of a
phage-resistant bacterial mutant leads to therapeutic failure. Here, we
address quantitatively how to design a phage cocktail efficient against
Pseudomonas aeruginosa infections. We study the efficacy of a cocktail
composed of two phages that bind to different bacterial receptors, via a
combination of vitro experiments and nonlinear dynamics models. We show
that the phage cocktail can control the bacterial population and utilize
model-data comparisons to shed light on physiological mechanisms
underlying emergent population dynamics. We leverage these findings to
analyze a theoretical model of in vivo infection dynamics, where
therapeutic phage and the innate immune system can work synergistically to
prevent infection. We quantify the therapy outcome in a single- or
double-phage treatment as a function of phage traits and immune strength.
*This work was supported by grants from the National Institutes of Health (1R01AI46592-01 to JSW and LD), from the Conseil Régional Ile de France Chaire Blaise Pascal (to JSW) and from Agence Nationale de la Recherche (ANR-19-AMRB-0002 to LD)
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