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Front. Microbiol. | doi: 10.3389/fmicb.2018.00326

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

 Leron Khalifa1, Daniel Gelman1, Mor Shlezinger1, 2,  Axel Dessal1, Shunit Coppenhagen-Glazer1,  Nurit Beyth2 and  Ronen Hazan1*
  • 1Faculty of Dental Medicine, Hebrew University of Jerusalem, Israel
  • 2Department of Prosthodontics, Hadassah Medical Center, Israel

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. A disastrous occurrence in the development of antibiotic resistance, it proved only a minor hindrance in phage development. We quickly and successfully isolated a new phage, EFLK1, which proved effective against both the resistant mutant EFDG1r and its parental VRE, E. 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.

Keywords: Bacteriophages, Enterococcus faecalis, antibiotic resistance, phage therapy, phage resistance, phage cocktail

Received: 08 Jun 2017; Accepted: 12 Feb 2018.

Edited by:

Rebecca Thombre, Modern College, India

Reviewed by:

Andrei A. Zimin, Institute of Biochemistry and Physiology of Microorganisms (RAS), Russia
Stephen T. Abedon, The Ohio State University, United States  

Copyright: © 2018 Khalifa, Gelman, Shlezinger, Dessal, Coppenhagen-Glazer, Beyth and Hazan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ronen Hazan, Hebrew University of Jerusalem, Faculty of Dental Medicine, Room 404, Dental School, Hadassah Campus, Jerusalem, 91120, <None>, Israel, ronenh@ekmd.huji.ac.il