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Wottrich et al. Microbiome Res Rep 2024;3:27  https://dx.doi.org/10.20517/mrr.2023.42  Page 15 of 17

               Our work, along with previous research, demonstrates that there are likely multiple evolved mechanisms
               governing C. acnes resistance to phage infection, including the CRISPR-Cas system, restriction-
               modification systems, and SIE mechanisms [11,59,60,62,63] . An understanding of the mechanism(s) by which this
               resistance may be produced in bacteria that were previously capable of being lysed by phage may give rise to
               the exploitation of the phenomenon in the fine-tuning of phage-based therapeutics. Likewise, this approach
               would give rise to a more thorough understanding of infection in the context of the evolutionary life cycles
               that the phage can undergo to promote its propagation and the success of its survival.


               DECLARATIONS
               Acknowledgments
               The authors acknowledge the programmatic support for the present publication, which includes: the SEA-
               PHAGES program at the University of California, Los Angeles (UCLA), the Microbiology, Immunology,
               and Molecular Genetics department at UCLA, the UCLA Dermatology department, and the UCLA Dean of
               the Life Sciences. The authors acknowledge the support of Daniel Russel from the University of Pittsburg
               for his contributions regarding assembly and quality control. The authors also acknowledge the assistance of
               Dr. Kris Reddi from UCLA, as well as the intellectual assistance of Rocky Ng, Andrew Lund, Kindra Kelly-
               Scumpia, and Dr. Francie Mercer for their contributions to the study and assistance with quality control.


               Authors’ contributions
               Conceived and designed the project idea and experiments: Wottrich S, Parker JM
               Performed the early phage characterization experiments (restriction enzyme digest, electron microscopy,
               etc.): Wottrich S, Mendonca S, Safarpour C, Nguyen C
               Performed the superinfection and pseudolysogeny-related experiments (patch tests, qPCR, etc.): Wottrich S
               Analyzed the data and conducted bioinformatics analyses: Wottrich S, Parker JM
               Contributed reagents/materials/analysis tools: Marinelli LJ, Modlin RL, Parker JM
               Wrote the paper: Wottrich S
               Contributing edits and revisions: Parker JM
               Preparing materials and methods section of the paper, as well as proofreading: Wottrich S, Safarpour C,
               Nguyen C
               Performed bioinformatic and structure prediction analyses and contributed to the writing of the
               manuscript: Hancock SP


               Availability of data and materials
               The full annotated genome of phage Aquarius may be found at https://phagesdb.org/phages/Aquarius/.


               Financial support and sponsorship
               None.


               Conflicts of interest
               All authors declared that there are no conflicts of interest.


               Ethical approval and consent to participate
               Not applicable.

               Consent for publication
               Not applicable.
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