Cyanophage infection-induced metabolic alterations in freshwater bloom-forming Microcystis aeruginosa

Freshwater cyanophages has been shown to co-exploit host cellular resources to meet their energy and material requirements, which is in contrast with marine cyanophages that in many cases actively reprogram host metabolism via auxiliary metabolic genes (AMGs). Here, we investigated the infection of Microcystis aeruginosa by the cyanophage LMM01 (previously Ma-LMM01), integrating physiological, proteomic, and metabolomic analyses. Consistent with the previous infection transcriptome analysis, we observed no changes in host protein abundance during viral DNA replication. Metabolome profiling, however, revealed significant phage-induced modulation of M. aeruginosa metabolism. Photosynthetic activity remained largely stable until the major cell lysis event (up to 48 h post infection, hpi) pointing toward the absence of physiological stress during infection. The observed slight photoinhibition and altered electron transport dynamics suggests enhanced cyclic electron flow, potentially sustaining ATP supply for viral replication. Together, the LMM01 infection, characterized by a stable proteome, induced however significant changes in metabolic flux and metabolite pool sizes. This suggests that LMM01 achieves its resource requirement through post-translational modulation with resource co-exploitation and re-allocation rather than transcriptional or translational reprogramming. Such in-depth understanding the cyanophage impact on the physiology of infected population expands the current knowledge of how viruses alter host metabolism in ecologically important cyanobacteria.