Phage-specific metabolic reprogramming of virocells

Abstract

Ocean viruses are abundant and infect 20-40% of surface microbes. Infected cells, termed virocells, are thus a predominant microbial state. Yet, virocells and their ecosystem impacts are understudied, thus precluding their incorporation into ecosystem models. Here we investigated how unrelated bacterial viruses (phages) reprogram one host into contrasting virocells with different potential ecosystem footprints. We independently infected the marine Pseudoalteromonas bacterium with siphovirus PSA-HS2 and podovirus PSA-HP1. Time-resolved multi-omics unveiled drastically different metabolic reprogramming and resource requirements by each virocell, which were related to phage-host genomic complementarity and viral fitness. Namely, HS2 was more complementary to the host in nucleotides and amino acids, and fitter during infection than HP1. Functionally, HS2 virocells hardly differed from uninfected cells, with minimal host metabolism impacts. HS2 virocells repressed energy-consuming metabolisms, including motility and translation. Contrastingly, HP1 virocells substantially differed from uninfected cells. They repressed host transcription, responded to infection continuously, and drastically reprogrammed resource acquisition, central carbon and energy metabolisms. Ecologically, this work suggests that one cell, infected versus uninfected, can have immensely different metabolisms that affect the ecosystem differently. Finally, we relate phage-host genome complementarity, virocell metabolic reprogramming, and viral fitness in a conceptual model to guide incorporating viruses into ecosystem models.

Ecology of inorganic sulfur auxiliary metabolism in widespread bacteriophages

“…Despite their reduced genome size and limited coding capacity, phages are known for their ability to modulate host cells during infection, take over cellular metabolic processes and proliferate through a bacterial population, typically through lysis of host cells 7,8 . Phage-infected hosts, termed virocells, take on a distinct physiology compared to an uninfected state 9 . As many as 30-40% of all bacteria are assumed to be in a virocell state, undergoing phage-directed metabolism 10,11 .…”

Fundamental Difficulties Prevent the Reconstruction of the Deep Phylogeny of Viruses

“…However, this goal can be achieved in many different ways, sometimes contradictory, depending on the host and ecological situations. It could be via further genomic reduction (thus alleviating the energetic burden of DNA replication on the host) [ 61 ], by improving the efficiency of host infection (by innovating on virion structures and infection strategies) [ 12 ], by helping the host viability (thus increasing burst sizes) [ 62 , 63 ], or by using molecular defenses against viruses competing for the same host [ 64 ]. Such a complex web of evolutionary constraints is expected to generate a huge diversity of “optimal” solutions (sometimes involving moderate gene gains via horizontal transfers) resulting into the observed variety of viral gene contents without much apparent rationale.…”

Rethinking Phage Ecology by Rooting it Within an Established Plant Framework

“…Although the transcriptional profiles for 42 phages had previously been established 17,33, -no previous work has attempted to broadly compare these profiles across different phage groups. However, when analyzed as we have done here, these data present an excellent opportunity for comparative studies.…”

“…Genome-wide comparisons of phage genomes are difficult, as phage genes are extremely diverse, where typically less than 25% of genes within individual phage genomes have sequence similarities, and generally only within closely related groups. As each phage type will differentially impact the metabolic state of bacterial cells, 17 organizing phage genomes into functional niches will help us to identify certain genome and gene-wise features that are associated with lifestyles and ''phage types.'' This is what is widely done in plants where functional traits are associated with plants in specific environments.…”

“…One study that recognized ecological phage types within a genus focused on two phages that infect the marine bacterium Pseudoaltermonas. 17 This work examined the concept of a ''virocell'' and showed that two phages infected their bacterial host using contrasting strategies such that the infected bacteria had very different properties. The authors suggest that the complementarity between the two genomes (phage and host) drives the amount of cellular reprogramming that is needed, and the phage that was most distant from the bacteria in terms of nucleotide composition needed to carry our more bacterial transcriptional modification.…”