The bacteriolytic activity of the putative holin Gp52 of bacteriophage Phi11 requires its N-terminal transmembrane...

Gene gp52 of bacteriophage Phi11 encodes a putative holin ("GeneID:1258070"). Holins are bacteriophage proteins that control host cell lysis and determine the timing of the phage's infectious cycle. This study assessed the effect of overexpressing Gp52 and its mutants upon the growth rate and morphology of Escherichia coli. Gp52 caused aggressive host cell lysis, while two of the deletion mutants caused a decline in lytic potency. Lysis was completely abolished by the third mutant, which lacked the N-terminal domain and the two putative transmembrane domains. This is a first-hand study reporting the domain-dependent antibacterial activity of Gp52 and could contribute to the development of novel therapeutic interventions targeting bacterial membrane integrity, especially in the context of rising antimicrobial resistance. Impact statement We studied the functional domains of Phi11 holin and their impact on host lysis. The identification of the smallest region of holin which can lyse bacterial cells will open doors for novel phage-based therapies, thereby circumventing traditional antibiotics and benefiting both the scientific community and society's fight against antimicrobial resistance.