Integrated omics reveal time-resolved insights into T4 phage infection of E. coli on proteome and transcriptome level

Bacteriophages are highly abundant viruses of bacteria. The major role of phages in shaping bacterial communities and their emerging medical potential as antibacterial agents has trig-gered a rebirth of phage research. To understand the molecular mechanisms by which phages hijack their host, omics technologies can provide novel insights into the organization of tran-scriptional and translational events occurring during the infection process. In this study, we ap-ply transcriptomics and proteomics to characterize the temporal patterns of transcription and protein synthesis during T4 phage infection of E. coli. We investigated the stability of E. coli-originated transcripts and proteins in the course of infection, identifying degradation of E. coli transcripts and preservation of the host proteome. Moreover, the correlation of the phage transcriptome and proteome reveals specific T4 phage mRNAs and proteins that are temporally decoupled, suggesting post-transcriptional and translational regulation mechanisms. This study provides the first comprehensive insights into the molecular takeover of E. coli by bacteriophage T4. This data set represents a valuable resource for future studies seeking to study molecular and regulatory events during infection. We created a user-friendly online tool, POTATO4, available to the scientific community to access gene expression patterns for E. coli and T4 genes. Overall design: Exponentially growing E. coli were infected with T4 phage and RNA was isolated after 1, 4, 7 and 20 min of infection. RNA from uninfected E. coli was isolated to monitor the E. coli transcriptome immediately before infection (control/reference sample). The isolated total RNA was depleted from rRNA and sequenced by RNA-Seq. Thereby, expression of T4 phage and E. coli genes throughout infection can be monitored.