Genetically modified filamentous phage as bactericidal agents: a pilot study

Aims: To evaluate the ability of a filamentous phage encoding lethal proteins to kill bacteria without host‐cell lysis. Methods and Results: Bacterial survival was determined after infection of a growing Escherichia coli culture with phage M13 encoding either the restriction endonuclease BglII gene or modified phage λS holin genes. The genetically engineered phage exerted a high killing efficiency while leaving the cells structurally intact. When compared with a lytic phage, the release of endotoxin was minimized after infection with the genetically modified phages. Conclusions: Genetically engineered phage can be used for efficient killing, concomitantly minimizing endotoxin release. Significance and Impact of the Study: This feasibility study provides a possible strategy for the use of genetically engineered phage as bactericidal agents by optimizing the advantages and minimizing potential risks such as release of pyrogenic cell wall components.