Metabolome restructuring reveals distinct virocell infection strategies in bacteriophage–host interaction

Abstract

Viral infection transforms microbial cells into metabolically reprogrammed “virocells,” yet the metabolic architecture underlying this transition remains poorly resolved. Here we investigate how bacteriophages reshape host metabolism in Cellulophaga baltica across time and phage types, uncovering coordinated metabolic reorganization during infection that includes pathway-level patterns consistent with membrane remodeling, amino-acid recycling, and redistribution of cellular resources. Temporal analyses further distinguished infection strategies: efficient phages produced structured, phased metabolic shifts indicative of controlled host reprogramming, whereas inefficient infection triggered abrupt metabolic collapse. These results suggest that the organization and timing of host metabolome restructuring represent defining features of the virocell state and may reflect underlying viral life-history strategies. These biological patterns were made accessible by an integrative annotation framework that combines previously validated computational tools, substantially expanding interpretable metabolite coverage beyond conventional approaches. This approach reveals coherent infection signatures that would otherwise remain hidden, demonstrating how expanded metabolite interpretability can uncover functional principles of virus–host interactions. The analytical strategy presented here is readily transferable to other virus–host systems and complex microbial communities, providing a path toward mechanistic interpretation of untargeted metabolomic data in microbial ecology.