Phage Therapy Modifies Bacterial Resistance to Antibiotic Sensitivity

Objectives: Enteroccocus faecalis (E. faecalis) is one of the most prevalent nosocomial pathogen worldwide. Vancomycin resistant E. faecalis (VRE) has arisen 20 years ago, and ever since, it is known to be a serious threat worldwide. Phage therapy offers an alternative way for combating multidrug resistant bacteria. Previously, a synergistic effect between phages and antibiotics was described. We isolated efficient phages against E. faecalis known as EFDG1 and EFLK1. The null hypothesis here was that combined treatment of phage and vancomycin could reverse VRE bacterial resistance.
Methods: VRE bacterial sensitivity was determined using vancomycin E-test before and after phage treatment. Vancomycin activity against VRE bacteria that survived phage attack was evaluated in logarithmic growth using an ELISA reader. Additionally, the effect of combined treatment of phages and vancomycin was visualized using scanning electron microscopy; evaluated in planktonic as well as in biofilm using an ELISA reader, and the number of surviving bacteria was evaluated by (CFU/mL) and SGP (survivor growth on plate scale).
Results: E- test and Elisa readings showed that VRE bacteria that survived phage treatment became sensitive to vancomycin. Phages with vancomycin showed an additive effect, leading to eradication of the VRE at certain dose combinations, where antibiotic alone was ineffective. The Bacteria killing was evident in planktonic cultures as well as in biofilm. Scanning electron microscopy showed massive lysis, degradation and biofilm deformation after the combined treatment. Currently, we are deciphering the mechanism behind this phenomenon.
Conclusions: Vancomycin antibiotics efficacy can be reversed using phage therapy against VRE bacterial contamination.