Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00326/full |
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| author | Leron Khalifa Daniel Gelman Mor Shlezinger Mor Shlezinger Axel Lionel Dessal Shunit Coppenhagen-Glazer Nurit Beyth Nurit Beyth Ronen Hazan |
| author_facet | Leron Khalifa Daniel Gelman Mor Shlezinger Mor Shlezinger Axel Lionel Dessal Shunit Coppenhagen-Glazer Nurit Beyth Nurit Beyth Ronen Hazan |
| author_sort | Leron Khalifa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T19:36:45Z |
| format | Article |
| id | doaj.art-dea01fd0bb504539975f3c7fb39dba35 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-11T19:36:45Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-dea01fd0bb504539975f3c7fb39dba352022-12-22T00:53:09ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-02-01910.3389/fmicb.2018.00326286413Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot ModelLeron Khalifa0Daniel Gelman1Mor Shlezinger2Mor Shlezinger3Axel Lionel Dessal4Shunit Coppenhagen-Glazer5Nurit Beyth6Nurit Beyth7Ronen Hazan8Faculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Prosthodontics, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Prosthodontics, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelThe 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.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00326/fullbacteriophagesEnterococcus faecalisantibiotic-resistancephage therapyphage-resistancephage cocktail |
| spellingShingle | Leron Khalifa Daniel Gelman Mor Shlezinger Mor Shlezinger Axel Lionel Dessal Shunit Coppenhagen-Glazer Nurit Beyth Nurit Beyth Ronen Hazan Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model Frontiers in Microbiology bacteriophages Enterococcus faecalis antibiotic-resistance phage therapy phage-resistance phage cocktail |
| title | Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model |
| title_full | Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model |
| title_fullStr | Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model |
| title_full_unstemmed | Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model |
| title_short | Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model |
| title_sort | defeating antibiotic and phage resistant enterococcus faecalis using a phage cocktail in vitro and in a clot model |
| topic | bacteriophages Enterococcus faecalis antibiotic-resistance phage therapy phage-resistance phage cocktail |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00326/full |
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