title: Study of the response regulator Rrp1 reveals its regulatory role in chitobiose utilization and virulence of Borrelia burgdorferi.
abstract: Life cycle alternation between arthropod and mammals forces the Lyme disease spirochete, Borrelia burgdorferi, to adapt to different host milieus by utilizing diverse carbohydrates. Glycerol and chitobiose are abundantly present in the Ixodes tick. B. burgdorferi can utilize glycerol as a carbohydrate source for glycolysis and chitobiose to produce N-acetylglucosamine (GlcNAc), a key component of the bacterial cell wall. A recent study reported that Rrp1, a response regulator that synthesizes cyclic diguanylate (c-di-GMP), governs glycerol utilization in B. burgdorferi. In this report, we found that the rrp1 mutant had growth defects and formed membrane blebs that led to cell lysis when GlcNAc was replaced by chitobiose in the growth medium. The gene chbC encodes a key chitobiose transporter of B. burgdorferi. We found that the expression level of chbC was significantly repressed in the mutant and that constitutive expression of chbC in the mutant successfully rescued the growth defect, indicating a regulatory role of Rrp1 in chitobiose uptake. Immunoblotting and transcriptional studies revealed that Rrp1 is required for the activation of bosR and rpoS and that its impact on chbC is most likely mediated by the BosR-RpoS regulatory pathway. Tick-mouse infection studies showed that although the rrp1 mutant failed to establish infection in mice via tick bite, exogenous supplementation of GlcNAc into unfed ticks partially rescued the infection. The finding reported here provides us with new insight into the regulatory role of Rrp1 in carbohydrate utilization and virulence of B. burgdorferi.
authors.affiliation: Department of Oral Biology, The State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Ching Wooen
authors.initials: CW
authors.lastname: Sze
authors.forename: Alexis
authors.initials: A
authors.lastname: Smith
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: Xiuli
authors.initials: X
authors.lastname: Yang
authors.forename: Utpal
authors.initials: U
authors.lastname: Pal
authors.forename: Aiming
authors.initials: A
authors.lastname: Yu
authors.forename: Chunhao
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004187:Disaccharides / Q000378:metabolism*; D004195:Disease Models, Animal; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000502:physiology*; D008193:Lyme Disease / Q000382:microbiology / Q000635:transmission*; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry* / Q000502:physiology*; D012329:RNA, Bacterial / Q000032:analysis; D012808:Sigma Factor / Q000378:metabolism; D013987:Ticks / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; C436306:ChbC protein, Borrelia burgdorferi; D004187:Disaccharides; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D012329:RNA, Bacterial; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; C032438:chitobiose; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP