Esteves, Nathaniel C.Scharf, Birgit E.2025-06-102025-06-102024-07-312045-232210.1038/s41598-024-68747-3 (PII)https://hdl.handle.net/10919/135452Serratia marcescens is an opportunistic human pathogen that produces a vibrant red pigment called prodigiosin. Prodigiosin has implications in virulence of S. marcescens and promising clinical applications. We discovered that addition of the virulent flagellotropic bacteriophage χ (Chi) to a culture of S. marcescens stimulates a greater than fivefold overproduction of prodigiosin. Active phage infection is required for the effect, as a χ-resistant strain lacking flagella does not respond to phage presence. Via a reporter fusion assay, we have determined that the addition of a χ-induced S. marcescens cell lysate to an uninfected culture causes a threefold increase in transcription of the pig operon, containing genes essential for pigment biosynthesis. Replacement of the pig promoter with a constitutive promoter abolished the pigmentation increase, indicating that regulatory elements present in the pig promoter likely mediate the phenomenon. We hypothesize that S. marcescens detects the threat of phage-mediated cell death and reacts by producing prodigiosin as a stress response. Our findings are of clinical significance for two main reasons: (i) elucidating complex phage-host interactions is crucial for development of therapeutic phage treatments, and (ii) overproduction of prodigiosin in response to phage could be exploited for its biosynthesis and use as a pharmaceutical.13 page(s)application/pdfenCreative Commons Attribution 4.0 InternationalFlagellaGene expressionGenetic transcriptionPhage therapySerratia marcescensBacteriophagesProdigiosinGene Expression Regulation, BacterialOperonPigments, BiologicalPromoter Regions, GeneticArticle - Refereedhttps://doi.org/10.1038/s41598-024-68747-3141Scharf, Birgit [0000-0001-6271-8972]390854602045-2322