This perspective paper follows up on earlier communications on bacteriophage therapy that we wrote as a multidisciplinary and intercontinental expert-panel when we first met at a bacteriophage conference hosted by the Eliava Institute in Tbilisi, Georgia in 2015. In the context of a society that is confronted with an ever-increasing number of antibiotic-resistant bacteria, we build on the previously made recommendations and specifically address how the Nagoya Protocol might impact the further development of bacteriophage therapy. By reviewing a number of recently conducted case studies with bacteriophages involving patients with bacterial infections that could no longer be successfully treated by regular antibiotic therapy, we again stress the urgency and significance of the development of international guidelines and frameworks that might facilitate the legal and effective application of bacteriophage therapy by physicians and the receiving patients. Additionally, we list and comment on several recently started and ongoing clinical studies, including highly desired double-blind placebo-controlled randomized clinical trials. We conclude with an outlook on how recently developed DNA editing technologies are expected to further control and enhance the efficient application of bacteriophages.

• Keywords
• CRISPR CAS, Nagoya Protocol, antibiotic resistance, bacteriophage therapy, bacteriophages,
• Publication type
• Journal Article MeSH

Five bacteriophages (Kpn5, Kpn12, Kpn13, Kpn17 and Kpn22), each having specificity against Klebsiella pneumoniae strain B5055, were isolated from sewage samples and characterized in terms of growth characteristics, genetic material, morphology and structural proteins. Adsorption rate as well as single step growth curve experiments showed variation among phages. Restriction enzyme digestion of DNA confirmed the presence of double stranded DNA as well as the heterogeneous nature of genetic material. RAPD-PCR was performed to further distinguish these closely related phages. Their genome fingerprint confirmed their diversity. Transmission electron microscopy, on the other hand, showed their morphological similarity; they were assigned to family Podoviridae, order Caudovirales on the basis of their head and tail morphology. Structural proteins resolved on SDS-PAGE showed the presence of similar major outer membrane proteins. The bacteriophages, belonging to Podoviridae family with short stumpy tails, were found to be nontoxic to mice. They showed maximum count in various organs at 6 h post inoculation, which persisted till 36 h. These phages thus have the potential to be used for phage therapy.

• MeSH
• Animal Structures virology   MeSH
• Bacteriophages classification   isolation & purification   physiology   ultrastructure   MeSH
• DNA Fingerprinting MeSH
• DNA, Viral genetics   MeSH
• DNA genetics   MeSH
• Electrophoresis, Polyacrylamide Gel MeSH
• Genetic Variation MeSH
• Genotype MeSH
• Klebsiella pneumoniae virology   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Sewage virology   MeSH
• Podoviridae classification   isolation & purification   physiology   ultrastructure   MeSH
• Virus Attachment MeSH
• Random Amplified Polymorphic DNA Technique MeSH
• Microscopy, Electron, Transmission MeSH
• Virion ultrastructure   MeSH
• Viral Proteins analysis   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA, Viral MeSH
• DNA MeSH
• Sewage MeSH
• Viral Proteins MeSH