ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1632267
The joint action of antibiotics, bacteriophage, and the innate immune response in the treatment of bacterial infections
Provisionally accepted
- Emory University, Atlanta, United States
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Studies of antimicrobial therapeutics have traditionally neglected the contribution of the host in determining the course of treatment and its outcome. One critical host element, which shapes the dynamics of treatment is the innate immune system. Studies of chemotherapeutics and complementary therapies such as bacteriophage (phage), are commonly performed with mice that purposely have an ablated innate immune system.Here, we generate a mathematical and computer-simulation model of the joint action of antibiotics, phage, and phagocytes. Our analysis of this model highlights the need for future studies to consider the role of the host's innate immune system in determining treatment outcomes. Critically, our model predicts that the conditions under which resistance to the treatment agent(s) will emerge are much narrower than commonly anticipate. We also generate a second model to predict the dynamics of treatment when multiple phages are used. This model provides support for the application of cocktails to treat infections rather than individual phages. Overall, this study provides hypotheses that can readily be tested experimentally with both in vitro and in vivo experiments.
Keywords: Conceptualization: BAB, TGG, BRL Methodology: BAB, BRL Investigation: BAB, BRL Visualization: TGG Funding Acquisition: BRL Project Administration: BAB, BRL Supervision: BAB, BRL Writing-Initial Draft: BAB, BRL Writing-Review & Editing: BAB
Received: 21 May 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Berryhill, Gil-Gil and Levin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bruce R Levin, Emory University, Atlanta, United States
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