Endogenous Linear Plasmids lp28-4 and lp25 Are Required for Infectivity and Restriction Protection in the Lyme Disease Spirochete Borrelia mayonii

Timothy Casselli, Yvonne Tourand, Kaitlyn Gura, Brian Stevenson, Wolfram R. Zückert, Catherine A. Brissette

Research output: Contribution to journalArticlepeer-review

Abstract

Borrelia mayonii is a newly recognized causative agent of Lyme disease in the Upper Midwestern United States, with distinct clinical presentations compared to classical Lyme disease caused by other Lyme Borrelia species. However, little is known about the B. mayonii genetic determinants required for establishing infection or perpetuating disease in mammals. Extrachromosomal plasmids in Borrelia species often encode proteins necessary for infection and pathogenesis, and spontaneous loss of these plasmids can lead to the identification of virulence determinant genes. Here, we describe infection of Lyme disease-susceptible C3H mice with B. mayonii, and show bacterial dissemination and persistence in peripheral tissues. Loss of endogenous plasmids, including lp28-4, lp25, and lp36 correlated with reduced infectivity in mice. The apparent requirement for lp28-4 during murine infection suggests the presence of a novel virulence determinant, as this plasmid does not encode homologs of any known virulence determinant. We also describe transformation and stable maintenance of a self-replicating shuttle vector in B. mayonii, and show that loss of either lp25 or lp28-4 correlated with increased transformation competency. Finally, we demonstrate that linear plasmids lp25 and lp28-4 each encode functional restriction modification systems with distinct but partially overlapping target modification sequences, which likely accounts for the observed decrease in transformation efficiency when those plasmids are present. Taken together, this study describes a role for endogenous plasmids in mammalian infection and restriction protection in the Lyme disease spirochete Borrelia mayonii.

Original languageEnglish
JournalInfection and Immunity
Volume91
Issue number3
DOIs
StatePublished - Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 American Society for Microbiology. All Rights Reserved.

Keywords

  • Borrelia mayonii
  • Lyme disease
  • infection
  • plasmids
  • restriction modification systems
  • virulence determinants

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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