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Inactivation of genes for antigenic variation in the relapsing fever spirochete Borrelia hermsii reduces infectivity in mice and transmission by ticks.

Raffel SJ, Battisti JM, Fischer RJ, Schwan TG - PLoS Pathog. (2014)

Bottom Line: The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia.This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes.Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana, United States of America.

ABSTRACT
Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host's acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete's alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector.

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The vmp expression site is required for B. hermsii to relapse in mice infected by ticks.Ten ticks infected with either the wild-type (WT), Vmp− or Vmp+R strains were placed on a mouse and allowed to feed. Mice were sampled on days 3–14 post infection and the numbers of spirochetes per ml of blood were determined by QPCR. Each plot represents the data from an individual mouse.
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ppat-1004056-g005: The vmp expression site is required for B. hermsii to relapse in mice infected by ticks.Ten ticks infected with either the wild-type (WT), Vmp− or Vmp+R strains were placed on a mouse and allowed to feed. Mice were sampled on days 3–14 post infection and the numbers of spirochetes per ml of blood were determined by QPCR. Each plot represents the data from an individual mouse.

Mentions: To test if the Vmp− mutant can cause a relapse when transmitted by tick bite, four RML mice were each fed upon by 10 ticks infected with wild-type, Vmp− or Vmp+R and monitored for infection. Spirochete concentrations were quantified in the blood by QPCR on days 3–14 post-feeding. All 4 mice fed upon by ticks infected with wild-type or Vmp+R developed an initial spirochetemia followed by a relapse (Fig. 5). In contrast, three of the four mice fed upon by ticks infected with Vmp− showed an initial spirochetemia but no relapse was detected. Again, a strong serological response was detected in the mice infected with the wild-type or Vmp+R strains (data not shown), but the mice infected with the Vmp− mutant showed a much reduced serological response, similar to what was observed with the needle-inoculated mice. These observations suggest that the Vmp− mutant was likely cleared after the first spirochetemia.


Inactivation of genes for antigenic variation in the relapsing fever spirochete Borrelia hermsii reduces infectivity in mice and transmission by ticks.

Raffel SJ, Battisti JM, Fischer RJ, Schwan TG - PLoS Pathog. (2014)

The vmp expression site is required for B. hermsii to relapse in mice infected by ticks.Ten ticks infected with either the wild-type (WT), Vmp− or Vmp+R strains were placed on a mouse and allowed to feed. Mice were sampled on days 3–14 post infection and the numbers of spirochetes per ml of blood were determined by QPCR. Each plot represents the data from an individual mouse.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3974855&req=5

ppat-1004056-g005: The vmp expression site is required for B. hermsii to relapse in mice infected by ticks.Ten ticks infected with either the wild-type (WT), Vmp− or Vmp+R strains were placed on a mouse and allowed to feed. Mice were sampled on days 3–14 post infection and the numbers of spirochetes per ml of blood were determined by QPCR. Each plot represents the data from an individual mouse.
Mentions: To test if the Vmp− mutant can cause a relapse when transmitted by tick bite, four RML mice were each fed upon by 10 ticks infected with wild-type, Vmp− or Vmp+R and monitored for infection. Spirochete concentrations were quantified in the blood by QPCR on days 3–14 post-feeding. All 4 mice fed upon by ticks infected with wild-type or Vmp+R developed an initial spirochetemia followed by a relapse (Fig. 5). In contrast, three of the four mice fed upon by ticks infected with Vmp− showed an initial spirochetemia but no relapse was detected. Again, a strong serological response was detected in the mice infected with the wild-type or Vmp+R strains (data not shown), but the mice infected with the Vmp− mutant showed a much reduced serological response, similar to what was observed with the needle-inoculated mice. These observations suggest that the Vmp− mutant was likely cleared after the first spirochetemia.

Bottom Line: The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia.This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes.Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana, United States of America.

ABSTRACT
Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host's acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete's alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector.

Show MeSH
Related in: MedlinePlus