Phage tail protein methylation enabling the virus to bind to the surface of bacterial cells is vital for progeny infectivity

The importance of methylation-based protein modifications in viral infection remains largely unknown. Here, we show that phage tail protein methylation depending on a host-encoded enzyme, MepM, is vital for maintaining the viral infectivity. Inactivation of the mepM gene of Mycolicibacterium smegmatis ( M . smegmatis ) confers broad-spectrum phage resistance to the host. The absence of mepM does not affect primary infection but abolishes progeny phage infectivity. The phage tail protein Gp34 expressed in wild-type strain, but not in mepM- deleted strain, undergoes unique MepM-dependent methylation-based modifications at its ELS amino acid motif, enabling it to maintain strong binding to the surface of mycobacterial cells. Recombinant phages harboring mutant genes encoding Gp34 with altered amino acid residues at its methylation sites do not exhibit infectivity. Our findings provide original experimental data on the previously undefined mechanism by which bacteriophages utilize host-encoded enzymes for protein methylation to maintain infectivity.