A surface enolase participates in Borrelia burgdorferi-plasminogen interaction and contributes to pathogen survival within feeding ticks.
Borrelia burgdorferi, a tick-borne bacterial pathogen, causes a disseminated infection involving multiple organs known as Lyme disease. Surface proteins can directly participate in microbial virulence by facilitating pathogen dissemination via interaction with host factors. We show here that a fraction of the B. burgdorferi chromosomal gene product BB0337, annotated as enolase or phosphopyruvate dehydratase, is associated with spirochete outer membrane and is surface exposed. B. burgdorferi enolase, either in a recombinant form or as a membrane-bound native antigen, displays enzymatic activities intrinsic to the glycolytic pathway. However, the protein also interacts with host plasminogen, potentially leading to its activation and resulting in B. burgdorferi-induced fibrinolysis. As expected, enolase displayed consistent expression in vivo, however, with a variable temporal and spatial expression during spirochete infection in mice and ticks. Despite an extracellular exposure of the antigen and a potential role in host-pathogen interaction, active immunization of mice with recombinant enolase failed to evoke protective immunity against subsequent B. burgdorferi infection. In contrast, enolase immunization of murine hosts significantly reduced the acquisition of spirochetes by feeding ticks, suggesting that the protein could have a stage-specific role in B. burgdorferi survival in the feeding vector. Strategies to interfere with the function of surface enolase could contribute to the development of novel preventive measures to interrupt the spirochete infection cycle and reduce the incidences of Lyme disease.
Department of Veterinary Medicine, University of Maryland, College Park, Maryland 20742, USA.
Sarah Veloso
SV
Nogueira
Alexis A
AA
Smith
Jin-Hong
JH
Qin
Utpal
U
Pal
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000201:enzymology* / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D005260:Female; D005342:Fibrinolysis; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D051379:Mice; D008809:Mice, Inbred C3H; D050296:Microbial Viability; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D013987:Ticks / Q000382:microbiology*
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D010958:Plasminogen; D010751:Phosphopyruvate Hydratase