From Host to Phage Metabolism: Hot Tales of Phage T4’s Takeover of E. coli

Abstract

The mechanisms by which bacteriophage T4 converts the metabolism of its E. coli host to one dedicated to progeny phage production was the subject of decades of intense research in many labs from the 1950s through the 1980s. Presently, a wide range of phages are starting to be used therapeutically and in many other applications, and also the range of phage sequence data available is skyrocketing. It is thus important to re-explore the extensive available data about the intricacies of the T4 infection process as summarized here, expand it to looking much more broadly at other genera of phages, and explore phage infections using newly-available modern techniques and a range of appropriate environmental conditions.

Phage-specific metabolic reprogramming of virocells

“…For both phages, the structural genes were transcribed late ( Supplementary Fig. S5d, g; Supplementary Tables S1 and S2), as commonly observed [51], but HS2's relative protein abundances of the late transcribed and predicted structural genes were higher than those of HP1 ( Supplementary Fig. S8).…”

“…Further, their host takeover capacity differed. The predicted peptidoglycan modification genes encoded by HP1 [24] were expressed immediately, followed by its host takeover genes (e.g., MazG, σ-70 transcriptional factor) and DNA metabolism genes (e.g., helicases, nucleases, and T7-like DNA polymerases (DNAP)) known to degrade host DNA, recycle nucleotides, and replicate phage DNA [51] ( Supplementary Fig. S5a-c and Supplementary Table S1).…”

“…A common vision of lytic phage infection is one of a phage hijacking its host, commandeering its functions, and turning it into a phage reproduction machine until lysis [51]. Though phages are commonly now perceived as efficient masters of their microbial hosts [3], the nuances of host responses are likely many and varied with respect to interaction and takeover strategies [51,62], including direct AMG-driven metabolic reprogramming [3,93].…”

“…A common vision of lytic phage infection is one of a phage hijacking its host, commandeering its functions, and turning it into a phage reproduction machine until lysis [51]. Though phages are commonly now perceived as efficient masters of their microbial hosts [3], the nuances of host responses are likely many and varied with respect to interaction and takeover strategies [51,62], including direct AMG-driven metabolic reprogramming [3,93]. Beyond needing increased diversity of studied phage-host model systems, incorporating phages into ecosystem models will require transitioning from studying the individual phage and host towards evaluating virocells [5][6][7], especially when phage-specific responses impact the ecosystem (e.g., different resource acquisition, nutrient transportation or production).…”

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

“…The early genes, which we define as those that show peak expression at 4 minutes post infection, consist mostly of short genes averaging less than 330bp and encoding hypothetical proteins (Fig 2 and S3 Table). It is difficult to infer the function of these genes, but there are several short immediate early genes in other phage systems that are known to have a role in host cell takeover [43,44]. The next grouping, middle early genes with peak expression at 8 minutes post infection, is mostly comprised of nucleotide metabolism genes including ICP1's DNA polymerase (Fig 2 and S3 Table).…”