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Putative Pseudolysogeny-Dependent Phage Gene Implicated in the Superinfection Resistance of Cutibacterium acnes

Background Bacteriophage therapy is a promising option to minimize the risk of treatment-associated antibiotic resistance in Cutibacterium acnes. A novel phage (Aquarius) was isolated and analyzed to explore characteristics of C. acnes phages that may confer lysis-evasion properties. Materials and Methods Phage superinfection resistance assays were performed with a range of C. acnes phages, which were assayed for pseudolysogeny via phage release assays and episome PCR. Bioinformatics and qRT-PCR were used to identify candidate genes related to observed phenotypes. Results Assay findings indicated that infected C. acnes strains were broadly resistant to superinfection and were capable of forming stable pseudolysogens. A conserved Ltp family-like gene contained protein signatures which may be contributing to phage-mediated superinfection resistance in a pseudolysogeny-dependent manner. Conclusions C. acnes bacteria are capable of harboring phage pseudolysogens, and this phenomenon may result in superinfection resistance, necessitating consideration in targeting optimization of C. acnes phage-based therapy.