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Keywords:

  • bacteriophage therapy;
  • lysis;
  • restrictionendonuclease

Abstract

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.