Inhibition of host cell division by T5 protein 008 (Hdi)

Bacteriophages (phages) have evolved effective methods of exploiting host-cell machinery by redirecting molecular pathways. In this study, we describe an inhibitor of bacterial growth, T5.008, encoded by the T5 phage. High-throughput sequencing of genomic DNA from bacterial mutants resistant to T5.008 identified mutations in the Escherichia coli ftsZ gene, suggesting that T5.008 targets the cell division protein FtsZ. We validated this finding by replacing a residue in FtsZ with one that confers protection from T5.008 inhibition. We used time-lapse microscopy to show that T5.008 interferes with FtsZ ring formation and stability, thereby inhibiting division. We also demonstrated that phages expressing T5.008 can prevent host division before lysis much more efficiently than those lacking T5.008. We also showed that T5.008 provides a competitive advantage to the T5 phage. This strategy of inhibiting division during phage infection likely enables T5 phage to utilize host-cell resources efficiently.