Serologic proteome analysis of Borrelia burgdorferi membrane-associated proteins.
Lyme disease, a global health concern, is caused by infection with Borrelia burgdorferi, B. afzelii, or B. garinii. The spirochete responsible for the disease in the United States is B. burgdorferi and is spread by the bite of an infected Ixodes tick. We utilized multiple two-dimensional gel techniques combined with proteomics to reveal the full humoral immune response of mice and Lyme patients to membrane-associated proteins isolated from Borrelia burgdorferi. Our studies indicated that a subset of immunogenic membrane-associated proteins (some new and some previously identified) was recognized by mice experimentally infected with Borrelia burgdorferi either by low-dose needle inoculation or by tick infestation. Moreover, the majority of these immunogenic membrane-associated proteins were recognized by sera from patients diagnosed with early-disseminated Lyme disease. These included RevA, ErpA, ErpP, DbpA, BmpA, FtsZ, ErpB, LA7, OppA I, OppA II, OppA IV, FlhF, BBA64, BBA66, and BB0323. Some immunogens (i.e., BBI36/38) were more reactive with sera from mice than Lyme patients, while additional membrane proteins (i.e., FlaB, P66, LA7, and Hsp90) were recognized more strongly with sera from patients diagnosed with early-localized, early-disseminated, or late (chronic)-stage Lyme disease. We were able to examine the humoral response in Lyme patients in a temporal fashion and to identify the majority of immunoreactive proteins as the disease progresses from early to late stages. This serologic proteome analysis enabled the identification of novel membrane-associated proteins that may serve as new diagnostic markers and, more importantly, as second-generation vaccine candidates for protection against Lyme disease.
Nowalk
Andrew J
AJ
Department of Molecular Genetics and Biochemistry, W1145 Biomedical Science Tower, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15261, USA.
Gilmore
Robert D
RD
Carroll
James A
JA
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D025065:Borrelia burgdorferi / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology*; D051379:Mice; D005810:Multigene Family / Q000276:immunology; D020543:Proteome / Q000032:analysis* / Q000276:immunology*; D040901:Proteomics / Q000379:methods*
D000942:Antigens, Bacterial; D008565:Membrane Proteins; D020543:Proteome