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Lyme disease spirochaete Borrelia burgdorferi does not require thiamin

Abstract

Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B1), is believed to be an essential cofactor for all living organisms1,2. Here, we report the unprecedented result that thiamin is dispensable for the growth of the Lyme disease pathogen Borrelia burgdorferi (Bb)3. Bb lacks genes for thiamin biosynthesis and transport as well as known ThDP-dependent enzymes4, and we were unable to detect thiamin or its derivatives in Bb cells. We showed that eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades thiamin, has no impact on Bb growth and survival during its enzootic infectious cycle. Finally, high-performance liquid chromatography analysis reveals that the level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic vector of Bb, is extremely low. These results suggest that by dispensing with use of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are uniquely adapted to survive in tick vectors before transmitting to mammalian hosts. To our knowledge, such a mechanism has not been reported previously in any living organisms.

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Figure 1: Loss of genes for thiamin synthesis and transport and ThDP-dependent enzymes in Borrelia and Rickettsia.
Figure 2: Bb is free of thiamin, ThMP and ThDP and able to grow in a thiamin-free medium.
Figure 3: Overexpression of bcmE in Bb had no impact on its survival and infectivity in mice and nymphs.
Figure 4: Bb requires no ThDP-dependent enzymes for ATP and acetyl-CoA generation.

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Acknowledgements

This work was supported by the National Institutes of Health (grants DE023080 and AI078958 to C.H.L., AI107955 to W.G.Q., T34GM007823 to R.E.N., AI080615 to U.P. and DK67081 to S.E.E.). The authors thank L. Kinsland and L. Di for assistance in manuscript and figure preparations and J. Leadbetter for assistance with the discussion.

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K.Z., J.B., Y.D., A.S., R.E.N., M.B.L., U.P. and A.Y. conducted the experiments and data analyses. W.Q., S.E.E., and C.L. designed the experiments and prepared the manuscript. All authors contributed to the interpretation of the results and writing of the manuscript.

Corresponding authors

Correspondence to Steven E. Ealick or Chunhao Li.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary Figures 1 and 2, Supplementary Tables 1-4 (PDF 456 kb)

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Zhang, K., Bian, J., Deng, Y. et al. Lyme disease spirochaete Borrelia burgdorferi does not require thiamin. Nat Microbiol 2, 16213 (2017). https://doi.org/10.1038/nmicrobiol.2016.213

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