A Novel Laminin-Binding Protein Mediates Microbial-Endothelial Cell Interactions and Facilitates Dissemination of Lyme Disease Pathogens

Sandhya Bista, Preeti Singh, Quentin Bernard, Xiuli Yang, Thomas Hart, Yi Pin Lin, Chrysoula Kitsou, Vipin Singh Rana, Fuming Zhang, Robert J. Linhardt, Kai Zhnag, Darrin R. Akins, Lucy Hritzo, Yuri Kim, Dennis J. Grab, J. Stephen Dumler, Utpal Pal

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Borrelia burgdorferi conserved gene products BB0406 and BB0405, members of a common B. burgdorferi paralogous gene family, share 59% similarity. Although both gene products can function as potential porins, only BB0405 is essential for infection. Here we show that, despite sequence homology and coexpression from the same operon, both proteins differ in their membrane localization attributes, antibody accessibility, and immunogenicity in mice. BB0406 is required for spirochete survival in mammalian hosts, particularly for the disseminated infection in distant organs. We identified that BB0406 interacts with laminin, one of the major constituents of the vascular basement membrane, and facilitates spirochete transmigration across host endothelial cell barriers. A better understanding of how B. burgdorferi transmigrates through dermal and tissue vascular barriers and establishes disseminated infections will contribute to the development of novel therapeutics to combat early infection.

Original languageEnglish
Pages (from-to)1438-1447
Number of pages10
JournalJournal of Infectious Diseases
Volume221
Issue number9
DOIs
StatePublished - 7 Apr 2020
Externally publishedYes

Keywords

  • BB0406
  • Borrelia burgdorferi
  • Laminin
  • Pathogen dissemination

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