# Protein Kinases in Mediating Phage-Bacteria Interactions
## 4 Phage-Encoded STKs in Phage-Bacteria Interactions [10]  
Not surprisingly, phages also encode kinases, playing critical roles in subverting host machinery to facilitate viral replication (Table 1; Figure 1B). A well-characterized example is T7 phage Gp0.7, a STK that phosphorylates multiple host _E. coli_ proteins to hijack cellular processes. Gp0.7 modifies the \(\delta\)' subunit of host RNA polymerase at Thr1068, promoting transcription termination at phage early genes and redirecting resources to viral middle/late gene expression [35; 36]. It also phosphorylates RNase III, enhancing its activity to process phage transcripts, and targets translation machinery--including elongation factor G, ribosomal protein S6, and initiation factors--to prioritize phage mRNA translation [36; 37]. Additionally, Gp0.7 destabilizes host RNA degradosome components like RNase E, stabilizing viral RNA [38]. These modifications optimize T7 replication, particularly under stress conditions (e.g., nutrient scarcity) [52], where Gp0.7 becomes essential for phage infection [10]. A recent preprint reported a much broad range of substrates of Gp0.7 and suggest that Gp0.7 is a hyper-promiscuous STK [39]. Another example is the lambdoid phage 933W, which encodes a unique tyrosine-phosphorylating kinase Stk\({}_{933\mathrm{W}}\), contrasting with typical serine/threonine-phosphorylating STKs. Stk\({}_{933\mathrm{W}}\) is activated during infection by the heterologous phage HK97, which expresses the protein Orf41 [40]. This interaction triggers Stk\({}_{933\mathrm{W}}\) autophosphorylation, leading to phage exclusion and protecting the bacterial population from secondary HK97 infections. A third example is the phage-encoded kinase JSS1_004 in _Salmonella_ phage JSS1, functioning as a versatile immune evasion factor that disrupts multiple bacterial defense systems to facilitate viral proliferation [42]. JSS1_004 employs its N-terminal Ser/Thr/Tyr kinase activity to phosphorylate key components of the host's DNA degradation (Dnd) system--specifically targeting the DndFGH complex--thereby subverting phosphorothioate-mediated self/non-self discrimination and DNA cleavage. Beyond Dnd, JSS1_004 broadly phosphorylates (likely similar to T7 Gp0.7) diverse bacterial immune pathways, including CRISPR-Cas, QatABCD, SIR2 + HerA, and DUF4297 + HerA, effectively neutralizing their defensive capabilities. This multisite phosphorylation strategy allows JSS1_004 to dismantle layered host defenses, enhancing phage survival even against combinatorial bacterial immunity. The widespread phylogenetic distribution of JSS1_004 homologs suggests that such kinase-driven immune evasion represents a conserved countermeasure among phages, enabling them to overcome complex resistance mechanisms and thrive in hostile host environments. These examples highlight the dual roles of phage kinases: T7 Gp0.7 reprograms transcription and translation for viral proliferation, while Stk\({}_{933\mathrm{W}}\) acts more as a defensive sentinel. These and the above mechanisms underscore the importance of phosphorylation in phage-host conflicts, offering insights into bacterial stress adaptation and potential therapeutic targets to facilitate phage replication. Notably, it is clear from above descriptions that defining the origin of kinases as strictly bacterial or phage-encoded presents a significant challenge due to the blurred boundaries between host and viral genomes. For instance, prophages are viral DNA integrated into bacterial chromosomes and complicate categorization, as their genes may become permanently fixed in the host genome over evolutionary time, functioning as bacterial genes. Similarly, phage defense islands often cluster with mobile genetic elements [53], suggesting that many of these genes originate from ancient prophages, transposons and integrative conjugative elements that are co-opted by bacteria and repurposed to combat related or novel phages.