The Treponema pallidum tro operon encodes a multiple metal transporter, a zinc-dependent transcriptional repressor, and a semi-autonomously expressed phosphoglycerate mutase

J Biol Chem. 2003 Jun 6;278(23):20687-94. doi: 10.1074/jbc.M300781200. Epub 2003 Mar 31.


The Treponema pallidum tro operon encodes an ABC transporter (TroABCD), a transcriptional repressor (TroR), and the essential glycolytic enzyme phosphoglycerate mutase (Gpm). The apparently discordant observations that the solute binding protein (TroA) binds Zn2+, whereas DNA binding by TroR in vitro is Mn2+-dependent, have generated uncertainty regarding the identities of the ligand(s) and co-repressor(s) of the permease. Moreover, this operonic structure suggests that Gpm expression, and hence glycolysis, the sole source of ATP for the bacterium, would be suspended during TroR-mediated repression. To resolve these discrepancies, we devised an experimental strategy permitting a more direct assessment of Tro operon function and regulation. We report that (i) apo-TroA has identical affinities for Zn2+ and Mn2+; (ii) the Tro transporter expressed in Escherichia coli imports Zn2+, Mn2+, and possibly iron; (iii) TroR represses transporter expression in E. coli at significantly lower concentrations of Zn2+ than of Mn2+; and (iv) TroR-mediated repression causes a disproportionately greater down-regulation of the transporter genes than of gpm. The much higher concentrations of Zn2+ than of Mn2+ in human body fluids suggests that Zn2+ is both the primary substrate and co-repressor of the permease in vivo. Our data also indicate that Gpm expression and, therefore, glycolysis would not be abrogated when T. pallidum encounters high Zn2+ levels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Bacterial Proteins*
  • Dose-Response Relationship, Drug
  • Manganese / metabolism
  • Manganese / pharmacology
  • Operon / drug effects
  • Operon / physiology
  • Periplasmic Binding Proteins / genetics*
  • Periplasmic Binding Proteins / metabolism
  • Phosphoglycerate Mutase / genetics*
  • Phosphoglycerate Mutase / metabolism
  • Rabbits
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Syphilis / microbiology
  • Transcription, Genetic / physiology
  • Treponema pallidum / enzymology
  • Treponema pallidum / genetics*
  • Zinc / metabolism
  • Zinc / pharmacology


  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Periplasmic Binding Proteins
  • Repressor Proteins
  • TroA protein, Treponema pallidum
  • TroR protein, Treponema pallidum
  • Manganese
  • Phosphoglycerate Mutase
  • Zinc