EVOLUTION FOR EFFICACY: “TRAINING” ANTI-STREPTOCOCCUS MUTANS PHAGES

Reut Kraitman 2 Hadar Ben-Zaken 2 Shunit Copenhagen-Glazer 2 Nurit Beyth 1 Ronen Hazan 2
1Department of Prosthodontics,, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
2Faculty of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel

Introduction: Bacterial resistance crisis calls for new measures in antibacterial therapy. Bacteriophages, or phages, are the most abundant organisms found in nature that kill bacteria. Streptococcus mutans is a significant contributor to dental caries, a worldwide oral health problem that cannot be solved by antibiotics. Thus, phage therapy can be beneficial against S. mutans. In this study, we demonstrate on a S. mutans phage one of the advantages of phage therapy; the ability to improve phages efficacy by evolutionary process. To this end, we used anti S. mutans phage, SmHBZ, previously isolated in our lab, which showed low efficacy expressed in low killing and narrow range of targets.


Materials and Methods:
The PFU/mL of the phage and the CFU/mL of the bacteria were evaluated before each experiment on BHI agar plates. “Training” was performed by exposure the phages to sensitive S. mutans bacteria on BHI agar plates followed by selection the biggest and clearest plaques appeared. This process was repeated for several cycles. Efficacy of the newly trained phages was re-evaluated on the sensitive and resistant S. mutans bacteria.


Results:
The newly trained phages demonstrated better efficacy, expressed in much more transparent and huge plaques on sensitive S. mutans. Moreover, the trained phages formed plaques on previously resistant bacteria even from other serotypes. While the original phage was effective only against serotype C, the trained phages killed also S. mutans of serotypes E, and F.


Conclusion:
In contrast to antibiotics, phage activity can be improved by evolutionary “training” process. This is a very promising result that constitutes a basis for the potential of personal phage therapy.









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