Development of natural and engineered bacteriophages as antimicrobials

Abstract

One of the major public health concerns of the modern day is the emergence and spread of extensively antibiotic-resistant pathogens. We have already seen the arrival of infections caused by bacteria resistant to all available antibiotics in the therapeutic arsenal. In addition, we have learned much of the incredible importance of the microbial communities that cohabit our bodies, and of how perturbations to these communities can lead to long-lasting health effects. Bacteriophages may provide a solution for both of these problems, in that they are narrow-spectrum and can be used to specifically kill target microbes without disrupting whole community structure through off-target effects. Here, various approaches to creating phage-based therapeutics are explored, including the isolation and application of naturally occurring wild-type phages, the conversion of temperate phages to obligately lytic phages to permit their use as a resource in phage therapeutics, and the creation of programmable, sequence-specific antimicrobials through phage-mediated genetic payload delivery. These efforts are expected to contribute to the field by expanding the approaches available to develop next-generation, phage-based antimicrobials.