Bacteriophages reinvented: tiny killers, life savers and detectives

Antibiotic resistance is a challenge for health care worldwide, and effective strategies to control drug-resistant bacteria are needed. While bacteriophages offer great host specificity and killing activity, their therapeutic potential is naturally limited by narrow host-ranges, insufficient antimicrobial activity, lysogeny, and rapid emergence of resistance. This can be overcome by design, engineering, assembly, and rebooting of synthetic phage genomes. We developed a bacterial L-form surrogate host platform, and use recombination-based engineering of large phage genomes supported by CRISPR-Cas based counterselection. Besides bacteriophages, another very successful approach is to harness the bacteriolytic enzymes encoded by phages, such as endolysins and depolymerases.