Engineering Bacteriophages as Versatile Biologics

• Published in: Trends in microbiology (Regular ed.) 2019-04, Vol.27 (4), p.355-367
• Main Authors: Kilcher, Samuel, Loessner, Martin J.
• Format: Article
• Language: English
• Subjects: Bacteria; bacteriophage; Biological evolution; Biopharmaceuticals; Cell walls; Drug development; Engineering; Genetic modification; genome engineering; Modular design; Molecular biology; Multidrug resistance; Phage display; phage therapy; Phages; synthetic biology; Viruses
• ISSN: 0966-842X; 1878-4380
• DOI: 10.1016/j.tim.2018.09.006

Viruses of bacteria (bacteriophages or phages) are highly evolved nanomachines that recognize bacterial cell walls, deliver genetic information, and kill or transform their targets with unparalleled specificity. For a long time, the use of genetically modified phages was limited to phage display approaches and fundamental research. This is mostly because phage engineering has been a complex and time-consuming task, applicable for only a few well characterized model phages. Recent advances in sequencing technology and molecular biology gave rise to rapid and precise tools that enable modification of less-well-characterized phages. These methods will pave the way for the development of modular designer-phages as versatile biologics that efficiently control multidrug-resistant bacteria and provide novel tools for pathogen detection, drug development, and beyond. The increasing prevalence of antibiotic-resistant pathogenic bacteria has sparked renewed interest in bacteriophage therapy. Synthetic biology methods allow design, straightforward construction, and testing of engineered bacteriophages that target both Gram-positive and Gram-negative bacteria. Phages with small genomes are easier to engineer using synthetic methods, while recombination-based approaches are currently the method of choice for larger phages. The efficiency, safety, and therapeutic suitability of phage-based antimicrobials can be specifically tailored through targeted phage engineering. In contrast to non-modified viruses, engineered phages offer intellectual property protection opportunities that may fuel the commercial implementation of phage therapy in many countries.