Defeating antibiotic- and phage-resistant Enterococcus faecalis using a phage Cocktail in vitro and in a clot model

Leron Khalifa, Daniel Gelman, Mor Shlezinger, Axel Lionel Dessal, Shunit Coppenhagen-Glazer, Nurit Beyth, Ronen Hazan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


The deteriorating effectiveness of antibiotics is propelling researchers worldwide towards alternative techniques such as phage therapy: curing infectious diseases using viruses of bacteria called bacteriophages. In a previous paper, we isolated phage EFDG1, highly effective against both planktonic and biofilm cultures of one of the most challenging pathogenic species, the vancomycin-resistant Enterococcus (VRE). Thus, it is a promising phage to be used in phage therapy. Further experimentation revealed the emergence of a mutant resistant to EFDG1 phage: EFDG1r. This kind of spontaneous resistance to antibiotics would be disastrous occurrence, however for phage-therapy it is only a minor hindrance. We quickly and successfully isolated a new phage, EFLK1, which proved effective against both the resistant mutant EFDG1r and its parental VRE, Enterococcus faecalis V583. Furthermore, combining both phages in a cocktail produced an additive effect against E. faecalis V583 strains regardless of their antibiotic or phage-resistance profile. An analysis of the differences in genome sequence, genes, mutations, and tRNA content of both phages is presented. This work is a proof-of-concept of one of the most significant advantages of phage therapy, namely the ability to easily overcome emerging resistant bacteria.

Original languageAmerican English
Article number326
JournalFrontiers in Microbiology
Issue numberFEB
StatePublished - 28 Feb 2018

Bibliographical note

Publisher Copyright:
© 2018 Khalifa, Gelman, Shlezinger, Dessal, Coppenhagen-Glazer, Beyth and Hazan.


  • Antibiotic-resistance
  • Bacteriophages
  • Enterococcus faecalis
  • Phage cocktail
  • Phage therapy
  • Phage-resistance


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