Variable VlsE Is Critical for Host Reinfection by the Lyme Disease Spirochete

PLoS One. 2013 Apr 8;8(4):e61226. doi: 10.1371/journal.pone.0061226. Print 2013.

Abstract

Many pathogens make use of antigenic variation as a way to evade the host immune response. A key mechanism for immune evasion and persistent infection by the Lyme disease spirochete, Borrelia burgdorferi, is antigenic variation of the VlsE surface protein. Recombination results in changes in the VlsE surface protein that prevent recognition by VlsE-specific antibodies in the infected host. Despite the presence of a substantial number of additional proteins residing on the bacterial surface, VlsE is the only known antigen that exhibits ongoing variation of its surface epitopes. This suggests that B. burgdorferi may utilize a VlsE-mediated system for immune avoidance of its surface antigens. To address this, the requirement of VlsE for host reinfection by the Lyme disease pathogen was investigated. Host-adapted wild type and VlsE mutant spirochetes were used to reinfect immunocompetent mice that had naturally cleared an infection with a VlsE-deficient clone. Our results demonstrate that variable VlsE is necessary for reinfection by B. burgdorferi, and this ability is directly related to evasion of the host antibody response. Moreover, the data presented here raise the possibility that VlsE prevents recognition of B. burgdorferi surface antigens from host antibodies. Overall, our findings represent a significant advance in our knowledge of immune evasion by B. burgdorferi, and provide insight to the possible mechanisms involved in VlsE-mediated immune avoidance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Borrelia burgdorferi / genetics
  • Borrelia burgdorferi / metabolism
  • Borrelia burgdorferi / physiology*
  • Immunity, Humoral
  • Immunization, Passive
  • Lipoproteins / genetics
  • Lipoproteins / metabolism*
  • Lyme Disease / immunology*
  • Male
  • Mice
  • Mutation
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Lipoproteins
  • VlsE protein, Borrelia burgdorferi

Grant support

This work was supported by an intramural grant from the College of Veterinary Medicine, Washington State University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.