title: The diguanylate cyclase, Rrp1, regulates critical steps in the enzootic cycle of the Lyme disease spirochetes.
abstract: Rrp1 is the sole c-di-GMP-producing protein (diguanylate cyclase) of Borrelia burgdorferi. To test the hypothesis that Rrp1 regulates critical processes involved in the transmission of spirochetes between ticks and mammals, an rrp1 deletion mutant (B31-Δrrp1) and a strain that constitutively produces elevated levels of Rrp1 (B31-OV) were constructed. The strains were assessed for progression through the enzootic cycle using an Ixodes tick/C3H-HeJ mouse model and tick immersion feeding methods. B31-Δrrp1 infected mice as efficiently as wild type but had altered motility, decreased chemotactic responses to N-acetylglucosamine (NAG) and attenuated ability to disseminate or colonize distal organs. While this strain infected mice, it was not able to survive in ticks. In contrast, B31-OV displayed normal motility patterns and chemotactic responses but was non-infectious in mice. Using immersion feeding techniques, we demonstrate that B31-OV can establish a population in ticks and survive exposure to a natural bloodmeal. The results presented here indicate Rrp1, and by extension, c-di-GMP, are not strictly required for murine infection, but are required for the successful establishment of a productive population of B. burgdorferi in ticks. These analyses provide significant new insight into the genetic regulatory mechanisms of the Lyme disease spirochetes.
authors.affiliation: Department of Microbiology and Immunology, Center for the Study of Biological Complexity, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0678, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Kostick
authors.forename: Lee T
authors.initials: LT
authors.lastname: Szkotnicki
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rogers
authors.forename: Paola
authors.initials: P
authors.lastname: Bocci
authors.forename: Nadia
authors.initials: N
authors.lastname: Raffaelli
authors.forename: Richard T
authors.initials: RT
authors.lastname: Marconi
mesh_terms: D000818:Animals; D025065:Borrelia burgdorferi / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D002633:Chemotaxis; D004195:Disease Models, Animal; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D018884:Ixodes / Q000382:microbiology*; D008124:Locomotion; D008193:Lyme Disease / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D050296:Microbial Viability; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism*; D012376:Rodent Diseases / Q000382:microbiology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D037521:Virulence Factors; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase