Switches controlling bacteriophage lysis of the Lyme disease spirochete

About This Grant

ABSTRACT All Lyme disease spirochetes that are known to be capable of infecting humans and other mammals naturally carry BB-1 bacteriophages, which replicate as 32kb circular plasmids (“cp32s”). While cp32s are capable of producing bacteriophage particles, the switch from peaceful coexistence as a plasmid to lytic bacteriophage is under tight control. The spirochete's RpoS alternative sigma factor is involved, but nothing more is currently known about the control mechanisms. The Stevenson lab has over 30 years of experience with characterizing the regulatory networks of the Lyme spirochete, and non-phage aspects of cp32s. This proposal leverages our extensive experience to identify and functionally characterize bacterial and phage proteins that control BB-1 production. These are crucial steps toward developing improved therapies for treating Lyme disease through induction of the endogenous prophages and lysis of infecting spirochetes.