Virus-Host Interactions Gets Lousy: P1vir Phage Development Upon Impaired RNA Global Regulation in E. coli Cells

Bacteriophage P1 is one of the most commonly studied phages in molecular biology, and P1vir, its virulent derivative, has been widely used in almost every biotechnological laboratory as a useful genetic tool. Phage development depends on many host proteins and the cellular physiological state. In many cases, metabolic control is assessed by efficient and energy-saving riboregulation, and one of the major cellular hub of the global RNA regulation is the Hfq protein. Despite the fact that this factor was discovered as host factor necessary for Qß bacteriophage replication, the role of Hfq in phage biology has not been extensively studied. We have found that deletion of the hfq gene resulted in impaired development of P1vir, suggesting its important role, but not indispensability, in the phage biology. We demonstrate global changes in the host-virus transcriptome during the infection. We have found that at different times after infection of the wild type strain (10 and 20 min), numerous hosts genes have been downregulated. On the other hand, in the ?hfq mutant, relatively small number of genes has been downregulated. Furthermore, numerous viral genes have been downregulated in the ?hfq mutant, comparing to the wild-type cells. Our results demonstrate that deficiency in global RNA regulation severely affects phage P1vir development. Thus, observed impaired P1vir development can be explained by abolition of proper cell re-programming during infection and/or impaired phage gene expression. The Hfq protein, as a global RNA hub, occurs in Escherichia coli and its homologues are present in other bacteria and archeons. Therefore, we anticipate that our results put new light on Hfq as a global phage regulator. Overall design: To obtain a widespread and holistic overview of the virus–host interactions, we analyzed the transcriptome of both, the P1vir phage and the hfq and wild type hosts during the infection. Total RNA sequencing was performed to assess the changes in gene expression pattern at 0, 10 and 20 min of P1vir infection as wel as 0 min with no phage added.