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 lambda S 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.