The interactome of Streptococcus pneumoniae and its bacteriophages show highly specific patterns of interactions among bacteria and their phages

Abstract

Although an abundance of bacteriophages exists, little is known about interactions between their proteins and those of their bacterial hosts. Here, we experimentally determined the phage-host interactomes of the phages Dp-1 and Cp-1 and their underlying protein interaction network in the host Streptococcus pneumoniae. We compared our results to the interaction patterns of E. coli phages lambda and T7. Dp-1 and Cp-1 target highly connected host proteins, occupy central network positions, and reach many protein clusters through the interactions of their targets. In turn, lambda and T7 targets cluster to conserved and essential proteins in E. coli, while such patterns were largely absent in S. pneumoniae. Furthermore, targets in E. coli were mutually strongly intertwined, while targets of Dp-1 and Cp-1 were strongly connected through essential and orthologous proteins in their immediate network vicinity. In both phage-host systems, the impact of phages on their protein targets appears to extend from their network neighbors, since proteins that interact with phage targets were located in central network positions, have a strong topologically disruptive effect and touch complexes with high functional heterogeneity. Such observations suggest that the phages, biological impact is accomplished through a surprisingly limited topological reach of their targets.

Virus-host protein-protein interactions of mycobacteriophage Giles

“…However, phage proteins attacking the same host pathway or protein may reflect shared infection strategies. For instance, we note that both Giles gp17 and Dp-1 gp9 appear to interact with the host PhoU protein 23 . Whether this interaction is relevant for the phage remains unclear though, given that Giles gp17 and Dp-1 gp9 are functionally unrelated (the function of Dp-1 gp9 is unknown; Giles gp17 is a putative tail assembly protein).…”

“…All Giles interactions are from this study. Phage Protein host Host protein Giles Gp17 M. smegmatis PhoU (MSMEG_5776) Dp-1 Gp9 S. pneumoniae PhoU (SP_1395) 23 Giles Gp17 M. smegmatis III taurine-pyruvate aminotransferase (MSMEG_1662) Lambda p45 E. coli class I and class II aminotransferases (P39389) 35 Giles Gp47 M. smegmatis PAPS reductase (MSMEG_1245) Lambda p37 E. coli PAPS reductase (P17854) 35 Giles Gp54 M. smegmatis glutamate synthase 1 (MSMEG_6459) Cp-1 Gp10 S. pneumoniae SP_1881, a glutamate racemase (P63640) 23 Giles Gp65 M. smegmatis ABC1 family protein (MSMEG_1954) Dp-1 Gp47 S. pneumoniae ABC transporter (SP_0687) 23 Giles Gp65 M. smegmatis succinate-semialdehyde dehydrogenase (MSMEG_6702) Lambda p80 E. coli succinyl-CoA synthetase (P0A836) 35 Giles Gp65 M. smegmatis glycosyltransferase protein (MSMEG_5641). Dp-1 Gp58 S. pneumoniae glycosyltransferase (SP_1606) 23 …”

Unraveling protein interactions between the temperate virus Bam35 and its Bacillus host using an integrative Yeast two hybrid-High throughput sequencing approach

“…Some of the first Y2H studies involving viruses addressed the interaction between bacteria and their phages. These include E. coli phages T7 and λ, Pseudomonas aeruginosa phages, Streptococcus pneumoniae phages Cp-1 and Dp-1, and mycobacteriophage Giles [36][37][38][39][40][41]. Other techniques for detecting PPIs, such as affinity purification coupled to mass spectrometry, have also significantly contributed to the study of phage-bacteria interactions [42,43].…”

“…All of them appear to share a tendency to interact with central "hub" proteins, highlighting their potential disruptive effect to the host metabolism. Another commonality is found in the targeting of proteins involved in transcription, replication, recombination, and repair functions [40].…”

Mycobacteriophage Fruitloop gp52 inactivates Wag31 (DivIVA) to prevent heterotypic superinfection

“…Elucidating gene functions is facilitated by constructing mutant phage derivatives in which specific phage genes have been deleted (Marinelli et al ., ), although many genes are not required for lytic growth and do not exhibit informative phenotypes (Pope et al ., ; Dedrick et al ., ). Other strategies to characterize gene functions include determining the patterns of interacting phage proteins (Blasche et al ., , Mehla et al ., ; Mariano et al ., ) and identification of phage‐encoded genes that are toxic to the bacterial host and identifying interacting host proteins (Liu et al ., ). This also has the potential to identify essential host genes and their exploitation as targets for antibiotic development (Liu et al ., ).…”