PHAGE THERAPY STRIKES BACK: PHAGE RESISTANCE AND SUPERBUGS ARE NOT THE END OF THE STORY

The radical decrease in the effectiveness of antibiotics and the emergence of antibiotic-resistant “Superbugs” has led the researchers worldwide in a pursuit of alternative techniques. Phage therapy emerges as a potential solution considering the numerous benefits over antibiotics like strain-specificity with no impact on the commensal microflora, high efficiency against hard-to-eradicate biofilms and ease of isolation.

Emergence of phage resistance can be thought to be a barrier while using phage therapy against superbugs. In case of antibiotics, following emergence of antibiotic resistance; a new compound needs to be formulated; which is usually a very difficult and time consuming process. Fortunately, in case of phages there are more than one ways to overcome such resistance. Here we demonstrate two such techniques: isolation of new phage and use of phage cocktails.

As described in Khalifa et al 2015, we isolated phage EFDG1 against VRE (Vancomycin resistant Enterococi) Enterococcus faecalis that was found to be highly effective against not only planktonic bacteria but also biofilms of the host bacteria. However, during our experiments mutants resistant to our EFDG1 phage evolved (EFDG1^r). To combat these resistant mutant EFDG1^r we isolated another phage EFLK1 using the same technique as before. EFLK1 was found to be effective against planktonic and biofilm cultures of both, EFDG1^r and VRE E. faecalis. The phage cocktail with equally concentration of EFDG1 and EFLK1was also found to be highly efficient. Even when the two forms of these bacteria were combined together as mixed culture, the phage cocktail was highly effective in killing them. Hence, phage therapy proves not only effective against Superbugs and their hard to eradicate biofilms but also their phage resistant mutants.