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Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model

Leron Khalifa1, Daniel Gelman1, Mor Shlezinger1,2

  • 1Faculty of Dental Sciences, Hadassah School of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.

Frontiers in Microbiology
|March 16, 2018
PubMed

Insights

Phage therapy offers a solution to antibiotic resistance. Researchers developed a phage cocktail effective against vancomycin-resistant Enterococci (VRE) and its resistant mutants, showcasing phage therapy

Area of Science:

  • Microbiology and Virology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Antibiotic resistance is a growing global health threat.
  • Phage therapy, using bacteriophages to treat bacterial infections, is a promising alternative.
  • Vancomycin-resistant Enterococci (VRE) are a particularly challenging pathogen.

Purpose of the Study:

  • To investigate phage therapy as a strategy against VRE.
  • To address the challenge of phage-resistant bacterial mutants.
  • To analyze phage characteristics for therapeutic applications.

Main Methods:

  • Isolation and characterization of bacteriophage EFDG1 against VRE.
  • Isolation and characterization of a new phage, EFLK1, effective against EFDG1-resistant VRE.
  • Genomic analysis of both phages (EFDG1 and EFLK1).
  • Evaluation of a phage cocktail comprising EFDG1 and EFLK1.

Main Results:

  • Phage EFDG1 showed efficacy against planktonic and biofilm VRE.
  • A resistant VRE mutant (EFDG1r) emerged, but was successfully targeted by a new phage, EFLK1.
  • A phage cocktail of EFDG1 and EFLK1 demonstrated an additive effect against VRE, irrespective of resistance.
  • Genomic comparison revealed differences in sequence, genes, mutations, and tRNA content between the two phages.

Conclusions:

  • Phage therapy can overcome emerging bacterial resistance.
  • A dual-phage cocktail strategy is effective against VRE and its resistant strains.
  • Genomic analysis provides insights into phage-bacterial interactions and resistance mechanisms.
Keywords:
Enterococcus faecalisantibiotic-resistancebacteriophagesphage cocktailphage therapyphage-resistance

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