The tpr gene family of Treponema pallidum subsp. pallidum, the causative agent of syphilis, has recently become the focus of intensive investigation. TprF and TprI sequences are highly conserved among different isolates and are the targets of strong humoral and cellular immune responses of the host, and immunization with a recombinant peptide from the amino terminus of these antigens has been shown to alter significantly lesion development following homologous challenge. This indicates that these antigens are expressed during infection and strongly suggests a key functionality. tprF and tprI are located immediately downstream of the tprG and tprJ genes, respectively, separated by very short intergenic spacers (55 nucleotides for G-F and 56 nucleotides for J-I). Preliminary analysis using gene-specific primers failed to amplify tprJ in the Sea 81-4 isolate. In this study, sequence and transcriptional analysis of these loci showed a similar gene organization in the Nichols and Sea 81-4 strains, a complex pattern of transcription, and the presence of G homopolymeric repeats of variable lengths upstream of the tprF, tprI, tprG, and tprJ transcriptional start sites. However, distinctive features were also identified in the Sea 81-4 isolate, including a tprG-like open reading frame in the tprJ locus, a frameshift and a premature termination in the tprG coding sequence, a longer tprG-tprF intergenic spacer, and absence of cotranscription of the tprG-tprF genes. Copyright © 2005, American Society for Microbiology. All Rights Reserved.