A Single Recombinant Plasmid Expressing Two Major Outer Surface Proteins of the Lyme Disease Spirochete

Howe, Timothy R.; Mayer, Leonard W.; Barbour, Alan G.

doi:10.1126/science.3969554

Cited by 144 publications

(88 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These organisms have been characterized from the immunological, biochemical and molecular biological aspects (Barbour & Hayes, 1986;Barbour & Garon, 1987;Bergstrom et al, 1989;Howe et al, 1985;, and now the species B. burgdorferi is regarded as a heterogeneous one which encompasses diverse isolates from geographically distinct areas. Recently, on the basis of DNA homology, specific rRNA gene restriction pattern and protein electrophoresis patterns, three genospecies for the strains of B. burgdorferi have been proposed.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Borrelia species associated with Lyme disease by rRNA gene restriction fragment length polymorphism

Fukunaga¹,

Sohnaka²,

Yanagihara³

1993

Journal of General Microbiology

View full text Add to dashboard Cite

We investigated the usefulness of rRNA gene restriction fragment length polymorphism (RFLP) for grouping of the Burrelia isolates associated with Lyme disease or from ixodid ticks. Genomic DNA was digested with a restriction enzyme, blotted and hybridized with an r d (23s rRNA) gene probe. The sizes of the restriction bands showed a good correlation with the genotypes recently proposed, and BurreZia isolates of diverse geographic origin formed four distinct DNA groups. Group I included all of the USA isolates and some European isolates; group I1 contained European isolates and Asian isolates; group I11 comprised European and Asian isolates; group IV included Japanese isolates and an eastern Russian isolate. Groups I, I1 and I11 corresponded to Burrelia burgdorferi, B. garinii and group VS461, respectively. The RFLPs of Japanese isolates were rather divergent and some of the isolates were quite distinct from the USA and European isolates. RFLP analysis of the rRNA genes and flanking regions, using r r l gene probes as we reported here, may be useful in the taxonomic study of Burrelia.

show abstract

Section: Introductionmentioning

confidence: 99%

Analysis of Borrelia species associated with Lyme disease by rRNA gene restriction fragment length polymorphism

Fukunaga¹,

Sohnaka²,

Yanagihara³

1993

Journal of General Microbiology

View full text Add to dashboard Cite

show abstract

“…We immunized mice with recombinant B. burgdorferi outer surface protein A (OspA) (11,12), which is the basis of a currently available vaccine for dogs (13). B. burgdorferi commonly expresses OspA in tick, but not mouse hosts, and consequently, OspAvaccinated mice, even infected ones, develop antibodies that kill B. burgdorferi in the tick while it feeds (12,14,15).…”

mentioning

confidence: 99%

An ecological approach to preventing human infection: Vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle

Tsao

Wootton

Bunikis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

273

222

View full text Add to dashboard Cite

Many pathogens, such as the agents of West Nile encephalitis and plague, are maintained in nature by animal reservoirs and transmitted to humans by arthropod vectors. Efforts to reduce disease incidence usually rely on vector control or immunization of humans. Lyme disease, for which no human vaccine is currently available, is a commonly reported vector-borne disease in North America and Europe. In a recently developed, ecological approach to disease prevention, we intervened in the natural cycle of the Lyme disease agent (Borrelia burgdorferi) by immunizing wild white-footed mice (Peromyscus leucopus), a reservoir host species, with either a recombinant antigen of the pathogen, outer surface protein A, or a negative control antigen in a repeated field experiment with paired experimental and control grids stratified by site. Outer surface protein A vaccination significantly reduced the prevalence of B. burgdorferi in nymphal blacklegged ticks (Ixodes scapularis) collected at the sites the following year in both experiments. The magnitude of the vaccine's effect at a given site correlated with the tick infection prevalence found on the control grid, which in turn correlated with mouse density. These data, as well as differences in the population structures of B. burgdorferi in sympatric ticks and mice, indicated that nonmouse hosts contributed more to infecting ticks than previously expected. Thus, where nonmouse hosts play a large role in infection dynamics, vaccination should be directed at additional species.

show abstract

“…Included in this class of lipoproteins with unknown function is the tick-associated Outer Surface Protein A (OspA) 1 (6), which is in current use as a Lyme disease vaccine for humans (7). OspA is anchored to the outer membrane via an N-terminal triacyl-modified cysteine (8,9) and is intrinsically resistant to proteases such as trypsin, despite its surface accessibility and high lysine content (10 -12).…”

mentioning

confidence: 99%

Structural Conservation of Neurotropism-associated VspA within the Variable Borrelia Vsp-OspC Lipoprotein Family

Zückert

Kerentseva

Lawson

et al. 2001

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Vsp surface lipoproteins are serotype-defining antigens of relapsing fever spirochetes that undergo multiphasic antigenic variation to avoid the immune response. One of these proteins, VspA of Borrelia turicatae, is also associated with neurotropism in infected mice. Vsp proteins are highly polymorphic in sequence, which may relate to their specific antibody reactivities and host cell interactions. To determine whether sequence variations affect protein structure, we compared B. turicatae VspA with three related proteins: VspB of B. turicatae, Vsp26 of the relapsing fever agent Borrelia hermsii, and OspC of the Lyme disease spirochete Borrelia burgdorferi. Recombinant non-lipidated proteins were purified by affinity or ion exchange chromatography. Circular dichroism spectra revealed similar, highly ␣-helical secondary structures for all four proteins. In vitro assays demonstrated proteaseresistant, thermostable Vsp cores starting at a conserved serine at position 34 (Ser 34 ). All proteins aggregate as dimers in solution. In situ trypsin treatment and surface protein cross-linking showed that the native lipoproteins also form protease-resistant dimers. These findings indicate that Vsp proteins have a common compact fold and that their established functions are based on localized polymorphisms. Two forms of VspA crystals suitable for structure determination by x-ray diffraction methods have been obtained.

show abstract

A Single Recombinant Plasmid Expressing Two Major Outer Surface Proteins of the Lyme Disease Spirochete

Cited by 144 publications

References 16 publications

Analysis of Borrelia species associated with Lyme disease by rRNA gene restriction fragment length polymorphism

Analysis of Borrelia species associated with Lyme disease by rRNA gene restriction fragment length polymorphism

An ecological approach to preventing human infection: Vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle

Structural Conservation of Neurotropism-associated VspA within the Variable Borrelia Vsp-OspC Lipoprotein Family

Contact Info

Product

Resources

About