Dogs and horses with antibodies to outer-surface protein C as on-time sentinels for ticks infected with Borrelia burgdorferi in New York State in 2011

ABSTRACT The Lyme disease spirochete Borrelia burgdorferi reduces the expression of outer surface protein C (OspC) in response to the development of an anti-OspC humoral response, leading to the hypothesis that the ability to repress OspC expression is critical for the pathogen to proceed to chronic infection. B. burgdorferi was genetically modified to constitutively express OspC by introducing an extra ospC copy fused with the borrelial flagellar gene (flaB) promoter. Such a genetic modification did not reduce infectivity or pathogenicity in severe combined immunodeficiency mice but resulted in clearance of infection by passively transferred OspC antibody. Spirochetes with constitutive ospC expression were unable to establish chronic infections in immunocompetent mice unless they had undergone very destructive mutations in the introduced ospC copy. Two escape mutants were identified; one had all 7 bp deleted between the putative ribosome-binding site and the start codon, ATG, causing a failure in translational initiation, and the other mutant had an insertion of 2 bp between nucleotides 315 and 316, resulting in a nonsense mutation at codon 108. Thus, the ability of B. burgdorferi to repress ospC expression during mammalian infection allows the pathogen to avoid clearance and to preserve the integrity of the important gene for subsequent utilization during its enzootic life cycle.

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Outer Surface Protein C Is a Dissemination-Facilitating Factor of Borrelia burgdorferi during Mammalian Infection

PLoS ONE ◽

10.1371/journal.pone.0015830 ◽

2010 ◽

Vol 5 (12) ◽

pp. e15830 ◽

Cited By ~ 22

Author(s):

Sunita V. Seemanapalli ◽

Qilong Xu ◽

Kristy McShan ◽

Fang Ting Liang

Keyword(s):

Borrelia Burgdorferi ◽

Outer Surface ◽

Protein C ◽

Surface Protein ◽

Outer Surface Protein ◽

Mammalian Infection

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Identification of B-cell epitopes of Borrelia burgdorferi outer surface protein C by screening a phage-displayed gene fragment library

Microbiology and Immunology ◽

10.1111/1348-0421.12438 ◽

2016 ◽

Vol 60 (10) ◽

pp. 669-677 ◽

Cited By ~ 4

Author(s):

Lucia Pulzova ◽

Zuzana Flachbartova ◽

Elena Bencurova ◽

Lenka Potocnakova ◽

Lubos Comor ◽

...

Keyword(s):

Borrelia Burgdorferi ◽

B Cell ◽

Outer Surface ◽

Protein C ◽

Surface Protein ◽

Gene Fragment ◽

B Cell Epitopes ◽

Outer Surface Protein ◽

Fragment Library

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Conformational Nature of the Borrelia burgdorferi B31 Outer Surface Protein C Protective Epitope

Infection and Immunity ◽

10.1128/iai.67.10.5463-5469.1999 ◽

1999 ◽

Vol 67 (10) ◽

pp. 5463-5469 ◽

Cited By ~ 33

Author(s):

Robert D. Gilmore ◽

M. Lamine Mbow

Keyword(s):

Borrelia Burgdorferi ◽

Outer Surface ◽

Protein C ◽

Surface Protein ◽

Active Immunization ◽

Laboratory Animals ◽

Transmitted Infection ◽

Infectious Dose ◽

Outer Surface Protein ◽

Protective Epitope

ABSTRACT Active immunization with Escherichia coli-expressed recombinant outer surface protein C (OspC) of Borrelia burgdorferi has been demonstrated to confer protection against a tick-transmitted infection on laboratory animals. A previous study in this laboratory showed that OspC antibody raised against a denatured immunogen isolated from B. burgdorferi cells failed to provide protective immunity. Therefore, to determine whether the protective epitope of the recombinant antigen was sensitive to denaturation, recombinant OspC preparations were subjected to heat and chemical treatments prior to animal immunization. Following seroconversion to OspC, the animals were challenged with an infectious dose of B. burgdorferi B31 by tick bite. Whereas mice immunized with a soluble, nondenatured form continued to show protection rates close to 100%, mice that had been immunized with denatured antigen were not protected. Furthermore, mice that were immunized with an insoluble (rather than a soluble), nondenatured form of the recombinant OspC showed a protection rate of only 40%. Protective epitope localization experiments showed that either the amino or the carboxy end of the recombinant protein was required to react with a protective OspC-specific monoclonal antibody. The data from these experiments demonstrate that a conformational organization of the protein is essential for the protective capability of the strain B31 OspC immunogen.

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