c-di-GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete

Taylor Van Gundy, Dhara Patel, Bruce E. Bowler, Michael T. Rothfuss, Allie J. Hall, Christopher Davies, Laura S. Hall, Dan Drecktrah, Richard T. Marconi, D. Scott Samuels, Meghan C. Lybecker

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


PlzA is a c-di-GMP-binding protein crucial for adaptation of the Lyme disease spirochete Borrelia (Borreliella) burgdorferi during its enzootic life cycle. Unliganded apo-PlzA is important for vertebrate infection, while liganded holo-PlzA is important for survival in the tick; however, the biological function of PlzA has remained enigmatic. Here, we report that PlzA has RNA chaperone activity that is inhibited by c-di-GMP binding. Holo- and apo-PlzA bind RNA and accelerate RNA annealing, while only apo-PlzA can strand displace and unwind double-stranded RNA. Guided by the crystal structure of PlzA, we identified several key aromatic amino acids protruding from the N- and C-terminal domains that are required for RNA-binding and unwinding activity. Our findings illuminate c-di-GMP as a switch controlling the RNA chaperone activity of PlzA, and we propose that complex RNA-mediated modulatory mechanisms allow PlzA to regulate gene expression during both the vector and host phases of the B. burgdorferi life cycle.

Original languageEnglish
Pages (from-to)711-727
Number of pages17
JournalMolecular Microbiology
Issue number6
StatePublished - Jun 2023


  • Borrelia burgdorferi
  • Lyme disease
  • PlzA
  • RNA chaperone
  • c-di-GMP
  • Bacterial Proteins/metabolism
  • Ixodes
  • RNA/metabolism
  • Borrelia burgdorferi/metabolism
  • Lyme Disease/genetics
  • Borrelia burgdorferi Group/genetics


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