Bacteriophages, viruses that specifically target and kill bacteria, hold great potential as antimicrobial agents against multidrug-resistant bacterial infections. However, the advancement of phage therapy is hindered by a lack of understanding regarding the molecular mechanisms underlying bacteriophage-mediated hijacking of host gene expression machinery. Our group´s recent results suggest previously unknown host transcriptional profiles and active transcription of E. coli genes during infection. Here, we evaluate the influence of various viral and host factors, including nucleases, RNA structures, protein-RNA interactions, and RNA modifications, on the regulation of RNA stability and degradation during T4 phage infection of E. coli.

Our lab's experiments, employing dual RNA sequencing, unveiled the dynamic regulation of RNA stability in both host and phage transcripts during the infection process [1]. For the first time, these investigations allowed us to simultaneously and comprehensively analyse the transcriptomes of the T4 phage and its bacterial host, E. coli. To elucidate the specific molecular mechanisms responsible for RNA processing during T4 infection, we examined the functional roles of potential candidates, such as nucleases and RNA-binding proteins, in regulating RNA stability. We utilized diverse host strains lacking the expression of RNA processing enzymes and conducted phenotype screenings, including lysis and burst size assays. We identified several host RNA processing enzymes that show specific regulation of phage infection.

Further investigations including transcriptomics and proteomics of the identified candidates could deepen our understanding of the mechanism of phage infection, crucial for advancing phage therapy. This study makes significant contributions to understand the functional role of RNA-processing enzymes in host-phage interactions, potentially paving the way for innovative approaches to combat bacterial infections, particularly those caused by drug-resistant strains.

[1] Wolfram-Schauerte, M., Pozhydaieva, N., Viering, M., Glatter, T., & Höfer, K. (2022). Integrated Omics Reveal Time-Resolved Insights into T4 Phage Infection of E. coli on Proteome and Transcriptome Levels. Viruses, 14(11), 2502.