Cyclic di-gmp is essential for the survival of the lyme disease spirochete in ticks

Ming He, Zhiming Ouyang, Bryan Troxell, Haijun Xu, Akira Moh, Joseph Piesman, Michael V. Norgard, Mark Gomelsky, X. Frank Yang

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host.

Original languageEnglish (US)
Article numbere1002133
JournalPLoS pathogens
Volume7
Issue number6
DOIs
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    He, M., Ouyang, Z., Troxell, B., Xu, H., Moh, A., Piesman, J., Norgard, M. V., Gomelsky, M., & Yang, X. F. (2011). Cyclic di-gmp is essential for the survival of the lyme disease spirochete in ticks. PLoS pathogens, 7(6), [e1002133]. https://doi.org/10.1371/journal.ppat.1002133