Phage therapy - opportunities and challenges for its development in Colombia

Abstract

"Based on the challenges and opportunities we identified for phage therapy, this research aims to point out and narrow the obstacles and take advantage of the open doors to bring phage therapy to Colombia. In this sense, this work is divided into seven chapters that address a group of these challenges and opportunities using different bacteria as models. The first chapter presents the state of the art at the moment of initiating the thesis. By reviewing the literature, we recognized the historical aspects of phage therapy, what was the actual development in the world, in Latin America and in Colombia. This review process allowed the identification of the main challenges and opportunities for the phage therapy in Colombia. The second chapter summarizes the techniques necessary to work with phages. This knowledge and expertise were acquired using a Pseudomonas syringae pv. actinidiae model. In this case, bacteriophages were used successfully to control in vitro the plant pathogen causing canker in kiwifruit plantations in New Zealand. Techniques such as isolation, characterization, in vitro testing, Transmission Electron Microscopy, transduction assays, bacterial growth kinetics, cross-resistance assays, were learned and applied. The third chapter is about phage selection for phage therapy, where Pseudomonas aeruginosa was used as a model. Phage isolation, phage characterization, in vitro testing, and in vivo testing, were performed. This was the first practical approach to phage therapy in our lab. We learned the importance of establishing criteria for phage selection for therapy and categorize the characterization techniques according to its relevance for phage therapy. Chapters 4 and 6 present the interaction between different bacteria and their phages, looking for a deeper understanding of the long-term potential use of the phage therapy. The natural interaction between a phage and its host allows the system to evolve in such a way that an initially susceptible bacterial population can develop resistance. Reciprocally, the phage population might regain infectivity by overcoming the resistance barrier, coexisting in a given environment. These dynamics has been described as co-evolution [Buckling and Rainey, 2002]..."Introducción