Switches controlling bacteriophage lysis of the lyme disease spirochete

The National Institute of Allergy and Infectious Diseases awarded The University of Kentucky Research Foundation $420,063 on February 18, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to identify and functionally characterize bacterial and phage proteins that control BB-1 bacteriophage production in Lyme disease spirochetes.

The funded research targets the molecular switches governing the transition of BB-1 bacteriophages from dormant plasmid replication to lytic bacteriophage production within Borrelia burgdorferi, the causative agent of Lyme disease. All known Lyme disease spirochetes naturally carry BB-1 bacteriophages as 32-kilobase circular plasmids (CP32s), which remain under tight regulatory control. The spirochete's rpos alternative sigma factor plays a role in this control, but the complete regulatory mechanisms remain uncharacterized. The Research Foundation will leverage the Stevenson Lab's more than thirty years of experience characterizing Lyme spirochete regulatory networks to identify functional characterization of the bacterial and phage proteins governing BB-1 induction. These findings are intended to support development of improved Lyme disease therapies through endogenous prophage induction and spirochete lysis.

Work is performed in Lexington, Kentucky, with a period of performance extending from February 18, 2026 through January 31, 2028. The award is classified as a Project Grant under the assistance type structure.

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.