Characterization of a Novel Lysogeny and Superinfection Immunity Mechanism in Arthrobacteriophages

Abstract

Viruses that replicate by infecting and killing bacteria, called bacteriophages (or just phages), are ubiquitous in nature and represent one of the largest reservoirs of genetic diversity on earth. A subset of phages have an alternative lifestyle where instead of infecting and immediately killing their bacterial host, they can integrate their genetic material with the host chromosome and become dormant in a process called lysogeny.

Most disease-causing bacteria are lysogens or polylysogens harboring one or more dormant phages. However, the systems diverse phages use to maintain stable lysogeny are not fully understood which limits our ability to harness their bacterial killing power in the treatment of disease. This is at a time when antimicrobial resistance is becoming widespread and new treatment options for bacterial disease, such as phages, are needed in clinics worldwide.

In this work, I characterize a brand new lysogen maintenance system in a group of phages that infect Arthrobacter globiformis which appear to use a DNA-binding protease to cleave the phage-encoded sigma factor responsible for reversing lysogeny and promoting bacterial killing. I also show how this system has naturally evolved in response to phage-phage competition.