Bacteriophage-Encoded Small RNAs: Emerging Tools for Phage Therapy and Antibacterial Intervention

Bacteriophages (phages) are viruses that specifically infect bacteria and play a central role in shaping microbial communities and bacterial evolution. Beyond their protein-coding genes, phage genomes were found recently to encode small RNAs (sRNAs) that act post-transcriptionally to regulate host and viral gene expression. These phage-encoded sRNAs can influence infection dynamics, modulate host physiology, and determine the balance between lytic and lysogenic cycles. A prominent example is the phage lambda sRNA PreS, which enhances phage DNA replication by increasing translation of the host dnaN mRNA, linking host replication capacity to phage propagation. This review examines emerging evidence that phage-encoded sRNAs constitute a versatile and underappreciated class of molecular tools. We discuss how such RNAs could be repurposed as precision antibacterial agents in an era of increasing antibiotic resistance and outline key challenges and opportunities for developing RNA-based alternatives to conventional phage therapy.