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Contribution of the outer surface proteins of Borrelia burgdorferi s.l. to the pathogenesis of Lyme disease
Umeå University, Faculty of Medicine, Microbiology.ORCID iD: 0000-0001-7175-1336
1994 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Borrelia burgdorferi s. l. is a spirochete which causes the multisystemic disorder Lyme disease. As the borreliae lack toxin production, the pathogenicity is thought to involve, at least in part, molecules from the outer surface. Most Lyme disease Borrelia strains express two major outer surface lipoproteins, OspA (31 kD) and OspB (34 kD), on their surface. However, some strains lack the expression of OspA and OspB, but express a smaller 21 to 25 kD OspC protein instead. This thesis focuses on the importance of these proteins in the pathogenesis of Lyme disease.

Biochemical and immunochemical studies of the OspA and OspB proteins from strains of various geographic origins show considerable differences in the apparent molecular weights and in their reactivities to monoclonal antibodies. The cloning and sequencing of the ospAB opérons from strains of different origins has demonstrated that the heterogeneity is found also at the DNA level Comparison of the ospAB sequences allows the classification of the strains into three types, which coincide with the recent species designations, B. burgdorferi sensu stricto, B. afzelii and B. garinii The genes are located on a linear plasmid about 50 kb in size, and are cotranscribed as a single message.

The expression of the osp operon in different strains was studied by Western blot and Northern blot analysis. The ospAB operon of strains expressing varying amounts of the Osp proteins was cloned and sequenced. The DNA sequence was found to be >99% identical. The regulation appears to be primarily at the transcriptional level.

In patients who have received incomplete treatment, B. burgdorferi have been isolated several years after the onset of the disease. As mentioned above, the ospAB loci of different strains show considerable heterogeneity, and it has been speculated that the spirochetes evade the host’s immune system by antigenic variation of the Osp proteins. In a mouse model system it was shown that no variation of the osp genes occurs over the course of an infection, and that other escape mechanisms must be used.

The OspB proteins in particular have been shown to be very heterogeneous in different isolates. The MAb 84C recognizes a wide variety of B. burgdorferi strains, and the binding epitope was mapped to a conserved region in the carboxyl terminus of the OspB protein with putative structural and/or functional importance.

It is well known that antibodies can kill bacteria in the presence of complement and phagocytes. Some antibodies seem to have a bactericidal effect by themselves. H6831 is a monoclonal antibody recognizing the OspB protein of some B. burgdorferi strains. The bactericidal action of univalent FAb fragments from H6831 was further characterized, and the binding epitope was mapped to a very heterogeneous region of the carboxyl end of the OspB protein.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 1994. , 79 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 413
Keyword [en]
Borrelia burgdorferi, Lyme disease, Osp proteins, ospAB operon, gene regulation, pathogenicity
National Category
Microbiology in the medical area
URN: urn:nbn:se:umu:diva-100569ISBN: 91-7174-938-1OAI: diva2:792997
Public defence
1994-10-07, Föreläsningssalen, byggnad 6L, Institutionen för Mikrobiologi, Umeå universitet, Umeå, 09:00

Diss. (sammanfattning) Umeå : Umeå universitet, 1994, härtill 5 uppsatser

Available from: 2015-03-17 Created: 2015-03-04 Last updated: 2016-08-22Bibliographically approved
List of papers
1. Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins.
Open this publication in new window or tab >>Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins.
1992 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 60, no 5, 1845-53 p.Article in journal (Refereed) Published
Abstract [en]

Biochemical and immunochemical studies of the outer membrane proteins of Borrelia burgdorferi have shown that the OspA and OspB proteins from strains of different geographic origins may differ considerably in their reactivities with monoclonal antibodies and in their apparent molecular weights. To further characterize this variation in Osp proteins between strains, the osp operons and deduced translation products from two strains, one from Sweden (ACAI) and one from eastern Russia (Ip90), were studied. Polyacrylamide gel electrophoresis and Western blot (immunoblot) analyses confirmed differences between ACAI, Ip90, and the North American strain B31 in their Osp proteins. The sequences of the ospA and ospB genes of ACAI and Ip90 were compared with that of the previously studied osp operon of B31 (S. Bergström, V. G. Bundoc, and A. G. Barbour, Mol. Microbiol. 3:479-486, 1989). The osp genes of ACAI and Ip90, like the corresponding genes of B31, were found on plasmids with apparent sizes of about 50 kb and are cotranscribed as a single unit. Pairwise comparisons of the nucleotide sequences revealed that the ospA genes of ACAI and Ip90 were 85 and 86% identical, respectively, to the ospA gene of strain B31 and 86% identical to each other. The ospB sequences of these two strains were 79% identical to the ospB gene of B31 and 81% identical to each other. There was significantly greater similarity between the ospA genes of the three different strains than there was between the ospA and ospB genes within each strain. These studies suggest that the duplication of osp genes in B. burgdorferi occurred before the geographical dispersion of strains represented by ACAI, Ip90, and B31.

Place, publisher, year, edition, pages
American Society for Microbiology, 1992
National Category
Immunology in the medical area Infectious Medicine
urn:nbn:se:umu:diva-82024 (URN)1563773 (PubMedID)
Available from: 2013-10-25 Created: 2013-10-25 Last updated: 2016-08-22Bibliographically approved

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