The Lyme disease agent exploits a tick protein to infect the mammalian host

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Abstract

The Lyme disease agent, Borrelia burgdorferi, is maintained in a tick–mouse cycle1,2. Here we show that B. burgdorferi usurps a tick salivary protein, Salp15 (ref. 3), to facilitate the infection of mice. The level of salp15 expression was selectively enhanced by the presence of B. burgdorferi in Ixodes scapularis, first indicating that spirochaetes might use Salp15 during transmission. Salp15 was then shown to adhere to the spirochaete, both in vitro and in vivo, and specifically interacted with B. burgdorferi outer surface protein C. The binding of Salp15 protected B. burgdorferi from antibody-mediated killing in vitro and provided spirochaetes with a marked advantage when they were inoculated into naive mice or animals previously infected with B. burgdorferi. Moreover, RNA interference-mediated repression of salp15 in I. scapularis drastically reduced the capacity of tick-borne spirochaetes to infect mice. These results show the capacity of a pathogen to use a secreted arthropod protein to help it colonize the mammalian host.

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Figure 1: Salp15 levels are specifically enhanced in Borrelia burgdorferi -infected tick salivary glands.
Figure 2: Salp15 interacts with outer surface protein (Osp)C of Borrelia burgdorferi.
Figure 3: Salp15 markedly enhances the Borrelia burgdorferi load in the murine host.
Figure 4: Gene silencing of salp15 expression by RNA interference.

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Acknowledgements

We thank D. Beck for help with the in vivo experiments, K. DePonte and N. Marcantonio for assistance with the microinjection and RNA interference experiments, M. Vasil for the maintenance of ticks, and M. Papero and L. Rollend for guidance with the experiments using Peromyscus leucopus. This work was supported by grants from the American Heart Association, National Institutes of Health, and Centers for Disease Control and Prevention. E.F. is the recipient of a Burroughs Wellcome Clinical Scientist Award in Translational Research.

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Correspondence to Erol Fikrig.

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Supplementary information

Supplementary Table S1

Peptide sequences obtained through matrix-assisted laser desorption ionization mass spectrometry peptide analysis. (PDF 1263 kb)

Supplementary Table S2

Oligonucleotide primers used for expression studies using RT-PCR and quantitative PCR. (PDF 51 kb)

Supplementary Figure S1

Salp15 injected at a different site from Borrelia burgdorferi did not alter spirochete load in the murine host. (PDF 41 kb)

Supplementary Figure S2

Reduced transmission of B. burgdorferi to Peromyscus leucopus mice by salp15 dsRNA. (PDF 49 kb)

Supplementary Notes

Legends for Supplementary Figures S1 and S2 (PDF 86 kb)

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Ramamoorthi, N., Narasimhan, S., Pal, U. et al. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 436, 573–577 (2005) doi:10.1038/nature03812

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