Language
English
Publication Date
6-3-2025
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2423286122
PMID
40445752
PMCID
PMC12146767
PubMedCentral® Posted Date
5-30-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, providing almost complete protection against a second lethal infection for animals treated with phage therapy. The activity also reduced infection burden an astounding billion-fold over the control. Reinfection protection requires phage lytic killing of its target bacterium but is independent of additional phage therapy. The effect is not driven by phage alone, lingering phage resistors, or a sublethal inoculum. In vitro phage-lysed bacteria provide partial protection, suggesting a combination of phage-induced lytic activity and immune stimulation by phage treatment is responsible for the effect. These observations imply certain phages may induce host adaptive responses following the lysis of the infecting bacteria. This work suggests phage therapy may contain a dual-action effect, an initial treatment efficacy followed by a long-term protection against reoccurring infection, a therapeutic-vaccination mechanism of action.
Keywords
Phage Therapy, Animals, Bacteriophages, Reinfection, Mice, Bacterial Infections, ExPEC, immunity, phage therapy, sepsis
Published Open-Access
yes
Recommended Citation
Xing, Yikun; Hernandez Santos, Haroldo J; Qiu, Ling; et al., "Phage-Induced Protection Against Lethal Bacterial Reinfection" (2025). Faculty and Staff Publications. 4820.
https://digitalcommons.library.tmc.edu/baylor_docs/4820
Included in
Health Services Research Commons, Medical Molecular Biology Commons, Medical Specialties Commons, Virology Commons