Adaptive loss of tRNA gene expression leads to phage resistance in a marine cyanobacterium

Bacterial resistance against phage infection is a topic of significant interest, yet little is known for ecologically relevant systems. Here we investigate the mechanisms underlying intracellular resistance of marine Synechococcus WH5701 to the Syn9 cyanophage. Despite possessing restriction-modification and Gabija defense systems, neither contributed to resistance. Instead, resistance was primarily driven by insufficient levels of the LeuTAA tRNA, preventing translation of key phage genes. This resulted from a dramatic reduction in transcripts of both cellular and phage encoded LeuTAA tRNAs. Restoring cellular tRNA expression rendered the cyanobacterium sensitive to infection. This study revealed a passive intracellular mode of resistance, that is distinct from currently known active innate and adaptive defense systems, demonstrating their importance for bacteria-phage interactions. We propose an evolutionary scenario whereby changes in cell codon usage, acquisition of tRNAs by the phage and loss of cell and phage tRNA expression resulted in an effective means of cyanophage resistance, highlighting the dynamic interplay between bacteria and phages in shaping their co-evolutionary trajectories.