Transcriptional regulation inTreponema pallidumssp.pallidumis poorly understood, primarily because this organism cannot be cultivatedin vitroor genetically manipulated. We have recently shown a phase variation mechanism controlling transcription initiation of Subfamily IItpr (T. p allidumrepeat) genes (tprE, tprGandtprJ), a group of virulence factor candidates. Furthermore, the same study suggested that additional mechanisms might influence the level of transcription of thesetprs.TheT. pallidumgenome sequence has revealed a few open reading frames with similarity to known bacterial transcription factors, including four catabolite activator protein homologues. In this work, sequences matching theEscherichia colicAMP receptor protein (CRP) binding motif were identifiedin silicoupstream oftprE, tprGandtprJ.Using elecrophoretic mobility shift assay and DNaseI footprinting assay, recombinant TP0262, aT. pallidumCRP homologue, was shown to bind specifically to amplicons obtained from thetprpromoters containing putative CRP binding motifs. Using a heterologous reporter system, binding of TP0262 to these promoters was shown to either increase (tprEandtprJ) or decrease (tprG) tprpromoter activity. This is the first characterization of aT. pallidumtranscriptional modulator that influencestprpromoter activity.