Research Article

Complete Genome Sequence of Treponema pallidum, the Syphilis Spirochete

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Science  17 Jul 1998:
Vol. 281, Issue 5375, pp. 375-388
DOI: 10.1126/science.281.5375.375


The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi, the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes.

Venereal syphilis was first reported in Europe in the late 1400s (1), coincident with the return of Columbus from the New World. The disease quickly reached epidemic proportions in Europe and spread across the world during the early 16th century with the age of exploration. Syphilis was ubiquitous by the 19th century and has been called the acquired immune deficiency syndrome of that era (2). Syphilis is characterized by multiple clinical stages and long periods of latent, asymptomatic infection. The primary infection is localized, but organisms rapidly disseminate and cause manifestations throughout the body, including the cardiovascular and nervous systems (3). Although effective therapies have been available since the introduction of penicillin in the mid-20th century, syphilis remains an important global health problem.

Treponema pallidum is the causative agent of syphilis. It is a spirochete, a helical to sinusoidal bacterium with outer and cytoplasmic membranes, a thin peptidoglycan layer, and flagella that lie in the periplasmic space and extend from both ends toward the middle of the organism. Recent pulsed-field gel electrophoresis studies (4) have shown that T. pallidum contains a circular chromosome of about 1000 kilobase pairs, making it one of the smallest prokaryotic genomes. Despite its importance as an infectious agent, relatively little is known about T. pallidum in comparison with other bacterial pathogens (5). The organism is an obligate human parasite that cannot be cultured continuously in vitro (6). Mechanisms of T.pallidum pathogenesis are poorly understood. No known virulence factors have been identified, and the outer membrane is mostly lipid with a paucity of proteins (7). Consequently, existing diagnostic tests for syphilis are suboptimal, and no vaccine against T. pallidum is available.

Spirochetes represent a phylogenetically ancient and distinct bacterial group. Both T. pallidum and Borrelia burgdorferi,the causative agent of Lyme disease, are similar in having relatively small genomes and surviving only in association with a host. However, they are not closely related and probably evolved independently from a more complex ancestor by loss of unnecessary genes and acquisition of new functions that promoted survival in the host environment. Comparison of the T. pallidum andB. burgdorferi genomes (8) allows assessment of biological diversity within this group of bacteria.

Genome analysis.

The genome of T. pallidum subsp. pallidum(Nichols) was sequenced by the whole genome random sequencing method as described (810). The T. pallidumgenome is a circular chromosome of 1,138,006 base pairs with an average G + C content of 52.8% (Figs. 1 and 2). There are a total of 1041 predicted open reading frames (ORFs), with an average size of 1023 bp, representing 92.9% of total genomic DNA. Predicted biological roles were assigned to 577 ORFs (55%) by the classification scheme adopted from Riley (11); 177 ORFs (17%) match hypothetical proteins from other species, and 287 ORFs (28%) have no database match and presumably represent novel genes (Fig. 1 and Table 1). Ninety T. pallidum ORFs of unknown function match chromosome-encoded proteins in B. burgdorferi (8); however, noT. pallidum ORFs match B. burgdorferiplasmid-encoded proteins, suggesting that the plasmid proteins may be unique to Borrelia species (8). The average size of the predicted proteins in T. pallidum is 37,771 daltons, ranging from 3235 to 172,869 daltons, and the mean isoelectric point for all predicted proteins is 8.1, ranging from 3.9 to 12.3, values similar to those observed in other bacterial species (8,9).

Forty-two paralogous gene families containing a total of 129 ORFs (12%) were identified in T. pallidum (Fig. 1). Fifteen families contain 44 genes that have no assigned biological role. Thirty families have only two members. The largest family, with 14 members, consists of proteins with adenosine triphosphate (ATP)–binding cassettes in ABC transport systems. Within 13 gene families are 16 clusters of adjacent genes that may represent duplications in theT. pallidum genome.

All 61 triplet codons are used in T. pallidum. There is a bias for G or C in the third codon position in T. pallidum, in contrast to an A or T bias in this position in B. burgdorferi. This observation is consistent with the G + C content in the T. pallidum genome being almost twice that in theB. burgdorferi genome. The disparate G + C content between the spirochete genomes creates a bias in overall codon usage, resulting in a difference in amino acid composition in the predicted coding sequences.

Origin of replication.

Two criteria were used to identify a replication origin in T. pallidum: the co-localization of genes (dnaA,dnaN, recF, and gyrA) often found near the origin in prokaryotic genomes and GC skew (12) (Fig. 2). On the basis of these results, we designated base pair 1 of theT. pallidum genome in an intergenic region of the chromosome that is located within the putative origin of replication.

Sixty-four percent of the coding sequences in the T. pallidum genome are aligned in the direction of replication, with the point of transcriptional divergence located near the putative origin between clpP and dnaA (Figs. 1 and 2). A number of codons occur in coding sequences aligned in the direction of replication at significantly higher frequencies than expected (P < 5.3e−27 ), including TTG (Leu), GCG (Ala), CGT (Arg), GTG (Val), and TGT (Cys). Codons that are overrepresented are also found in the most highly skewed oligomers (GGAGCGTG, TGTGTGTG, GTGTGTGC, TTTTTTGT, and GGTGTGTG).

Codon adaptation index (CAI), which is designed to be a relative measure of translational efficiency (13), was computed forT. pallidum with the codon frequencies from the ribosomal proteins, the translation elongation factors, and glyceraldehyde-3-phosphate dehydrogenase. Proteins with a high CAI are presumably highly expressed in exponential growth (13). The distribution of CAI scores in T. pallidum ORFs (13) exhibits a strand-dependent switch in magnitude around the origin of replication (Fig. 2). In both T. pallidum andB. burgdorferi, there is a marked difference in CAI values (high versus low) for genes on opposite strands of the chromosome, with genes transcribed in the direction of replication exhibiting a high CAI.

Transcription and translation.

Treponema pallidum contains a basic set of genes for transcription and translation that includes homologs to the α, β, and β′ subunits of the core RNA polymerase, five sigma factors (σ24, σ28, σ43, σ54, and σ70), and five genes that encode proteins involved in transcript elongation and termination (nusA, nusB, nusG, greA, and rho). Treponema pallidum is missing both a recognizable σ38 (rpoS), which is the major sigma factor in stationary phase activated in response to oxidative and osmotic stress, and a σ32, which is involved in transcription of heat shock proteins.

Forty-four tRNA species, organized into eight clusters containing 25 genes plus 19 single genes, were identified (Figs. 1 and 2). Two ribosomal RNA (rRNA) operons are present in the genome. Their organization is the same as that commonly found in eubacteria (16S-tRNA-23S-5S) (14), in contrast with the unusual arrangement seen in B. burgdorferi(8, 15). Both T. pallidum rRNA operons are transcribed in the direction of replication.

All tRNA synthetase genes were identified with the exception of glutaminyl-tRNA synthetase, similar to B. burgdorferi(8). It is likely that glutamyl-tRNA synthetase aminoacylates tRNAGln with glutamate followed by transamidation by Glu-tRNA amidotransferase (16). Two distinct lysyl-tRNA synthetase (LysS) species are present in T. pallidum, a class I type most similar to those in euryarchaea andB. burgdorferi (17) and a class II type most similar to those in eubacteria and eukaryotes. The class II LysS in T. pallidum represents a COOH-terminal fragment ofEscherichia coli LysS. A region near the NH2-terminus of LysS binds the anticodon of the tRNA and is crucial for its activity (18). Thus, it is likely that the class II LysS is nonfunctional and may be in the process of being lost from the genome.

Replication, repair, recombination, and restriction-modification systems.

The complement of genes for DNA replication in T. pallidum is similar to that in other minimal genomes such asMycoplasma genitalium and B. burgdorferi. Orthologs for the α, β, ɛ, γ, and τ subunits of E. coli DNA polymerase III are present. Treponema pallidumhas homologs of one type I topoisomerase (topA) and one type II topoisomerase (gyrAB), but unlike B. burgdorferi, it is missing topoisomerase IV, which is involved in chromosome segregation. However, chromosome segregation in T. pallidum may proceed by an alternative mechanism that involves the binding of hemimethylated DNA to the cytoplasmic membrane. This idea is supported by the presence of DNA adenine methyltransferase (dam) in T. pallidum but not in B. burgdorferi (19).

DNA repair in T. pallidum includes the major known pathways of uvr excision repair, mutL/mutS mismatch repair, mutY, and dat. The T. pallidumgenome encodes homologs of the recF pathway of recombination (recFGJNR) but lacks homologs to sbcB(exoI) as well as recB, recC, andrecD. Thus, homologous recombination resembles the recF pathway of E. coli. The converse is true in B. burgdorferi, where there are homologs of recBCD but not the recF pathway genes (8). Treponema pallidum contains an A- or G-specific adenine glycosylase (mutY), recognizes GA mismatches in duplex DNA, and excises adenine. No enzyme with similar activity has been identified in eitherM. genitalium or B. burgdorferi. This difference may, in part, explain the lower G + C content of the B. burgdorferi and M. genitalium genomes as compared withT. pallidum. No recognizable genes encoding restriction or modification enzymes were found.

Biosynthetic pathways.

Treponema pallidum is an obligate parasite of humans. Consistent with this property, previous physiologic studies have shown that it has limited biosynthetic capabilities and requires multiple nutrients from the host (20) (Fig. 3). The T. pallidum genome encodes a pathway for the conversion of phosphoenolpyruvate or pyruvate through oxaloacetate to aspartate (at the expense of glutamate), in accordance with the previous observation that most of the [14C]glucose incorporated into amino acids was in the form of aspartate (21). Predicted pathways for the interconversion of aspartate and glutamine to glutamate, aspartate to asparagine, glutamate to proline, and serine to glycine are also present. Treponema pallidum is unable to synthesize enzyme co-factors, fatty acids, and nucleotides de novo, similar to M. genitalium and B. burgdorferi. Deoxyribonucleotides can be obtained by reduction of ribonucleoside diphosphates through the action of ribonucleotide diphosphate reductase and thioredoxin reductase.

Figure 3

Solute transport and metabolic pathways in T. pallidum. A schematic diagram of a T. pallidum cell providing an integrated view of the transporters and the main components of the metabolism of this organism, as deduced from the genes identified in the genome. Presumed transporter specificity is indicated. Question marks indicate where particular uncertainties exist or expected activities were not found. r, ribo; d, deoxy; AMP, adenosine monophosphate; CMP, cytosine monophosphate; NDP, nucleotide diphosphate; NTP, nucleotide triphosphate; TMP, thymidine monophosphate; UMP, uridine monophosphate; ADP, adenosine diphosphate; CoA, coenzyme A; UDP, uridine diphosphate; PRPP, phosphoribosyl-pyrophosphate.


An organism such as T. pallidum, with limited biosynthetic capabilities, must have a repertoire of transport proteins with broad substrate specificity to obtain the necessary nutrients from the environment. The T. pallidum genome contains 57 ORFs (5% of the total) that encode 18 distinct transporters with predicted specificity for amino acids, carbohydrates, and cations (Fig. 3 and Table 1). For the most part, these transport systems are of similar specificity to those found in M. genitalium and B. burgdorferi (8); however, several important differences are seen.

Treponema pallidum has a broad spectrum of amino acid transporters, although these transporters are different from those inB. burgdorferi. For example, a transporter for glutamate or aspartate in T. pallidum is most similar to mammalian glutamate transporters. There are no phosphoenolpyruvate:phosphotransferase (PTS) systems in T. pallidum for the import of carbohydrates, in contrast to other bacterial species whose genome sequences have been determined (8, 9). Genome analysis predicts that T. pallidum has three ATP-binding cassette transporters with specificity for galactose (mglBAC) (22,23), ribose (rbsAC), and multiple sugars (y4oQRS), respectively; however, these three transporters may display a broader substrate specificity. In E. coli, themgl transporter displays affinity not only for galactose but also for glucose (24), and its expression is up-regulated in glucose-limiting conditions but repressed at high glucose concentrations (24). Treponema pallidum may also require an environment with limiting glucose concentrations for maximal expression of this transporter. Treponema pallidum has no recognizable inorganic phosphate (Pi) uptake system, unlike other bacteria studied by whole-genome analysis to date; therefore, uptake of glycerol-3-phosphate through the multiple sugar transporter may represent the primary means whereby T. pallidum obtains Pi (Fig. 3).

Treponema pallidum contains an ATP-binding cassette transporter with specificity for thiamine. Both thiamine and thiamine pyrophosphate (TPP) are substrates for the thiamine transporter inE. coli (25). This finding is of interest becauseT. denticola, T. vincentii, andLeptospira species require TPP for growth in vitro (26), which suggests that T. pallidum may also exhibit a growth dependency on TPP. The only recognizable TPP-dependent enzyme present in T. pallidum is transketolase, which creates a link between the pentose phosphate pathway and glycolysis.

Energy metabolism.

The complement of transport proteins in T. pallidum suggests that it may use several carbohydrates as energy sources, including glucose, galactose, maltose, and glycerol. Experimental evidence has demonstrated that only glucose, mannose, and maltose support the multiplication of T. pallidum in a tissue culture system (27). It is not known whether T. pallidum can use amino acids as a source of carbon and energy; however, the lack of necessary catabolic and anabolic pathway genes suggests that it would not be able to use such alternative compounds.

Metabolic pathway analysis reveals that genes encoding all of the enzymes of the glycolytic pathway are present in T. pallidum, including hexokinase, which phosphorylates glucose and other hexose sugars (Fig. 3). Both M. genitalium andB. burgdorferi lack hexokinase; however, in these organisms, phosphorylation of hexoses is an integral part of the PTS uptake mechanism. Instead of the typical eubacterial phosphofructokinase and pyruvate kinase, T. pallidum contains homologs of these enzymes that use pyrophosphate. Similar inorganic pyrophosphate (PPi)–dependent enzymes have been described in some bacteria, protists, protozoa, and plants (28). None of the genes encoding components of the tricarboxylic acid cycle or oxidative phosphorylation were identified, contrary to previous reports of the presence of cytochromes, flavoproteins, and some of the tricarboxylic acid cycle enzymes (20, 29); these may have represented contaminating rabbit components. Reducing power is probably generated through the oxidative branch of the pentose phosphate pathway. This simplified metabolic strategy is similar to that seen in both M. genitalium (9) and B. burgdorferi (8).

Treponema pallidum, like B. burgdorferi, lacks a respiratory electron transport chain; therefore, ATP production must be accomplished by substrate-level phosphorylation. As a result, membrane potential must be established by the reverse reaction of the ATP synthase. In both spirochetes, the ATP synthase is of the V1V0 type, most similar to those found in eukaryotic vacuoles and in archaea (30). Treponema pallidum has two V1V0-type ATP synthase operons, each containing seven genes (Table 1). The gene order in one operon (subunit E–ORF–subunit A–subunit B–subunit D–subunit I–subunit K) is identical to that seen in the ATP synthase operon inB. burgdorferi (8). The second operon in T. pallidum contains ATP synthase subunits A, B, D, E, F, I, and K. The difference in subunit gene composition between these operons suggests that the ATP synthases may have different functions in the cell.

One clue as to the functional role for the two ATP synthases is the presence of an oxaloacetate decarboxylase transporter that may be involved in extrusion of Na+ from the cell, creating a Na+ gradient (31). Such a gradient can be used to drive Na+-dependent transporters similar to the amino acid transporters that are found in T. pallidum. Alternatively, the Na+ gradient could be used to synthesize ATP in the same manner as the H+ gradient is used by an F1F0-type ATP synthase. Two ATP synthases have been identified in Enterococcus hirae, with specificity for Na+ and H+, respectively (32).

Cellular processes.

Treponema pallidum is microaerophilic and grows only at reduced concentrations of molecular oxygen (33). This most likely reflects a balance between an oxygen requirement for energy production and defects in protective mechanisms against reactive oxygen intermediates. Unlike B. burgdorferi, which is also microaerophilic, T. pallidum apparently lacks genes encoding superoxide dismutase, catalase, or peroxidase activities that protect against oxygen toxicity. NADH oxidase is the only enzyme identified thus far that can account for O2 utilization by T. pallidum.

Treponema pallidum contains a basic set of heat shock proteins but lacks σ32, which is responsible for transcription of heat shock genes in other bacteria. This lack is consistent with previous reports that T. pallidum lacks a detectable heat shock response. There is no change in the amounts of GroEL or other proteins at increased temperatures (34). At least two heat shock proteins in T. pallidum (GroEL and DnaK) appear to be constitutively expressed at high levels, which may mitigate the need for a typical heat shock response (35). However, the observed thermal sensitivity of T. pallidum(6) may reflect the absence of a robust heat shock response in this organism. It is of interest that B. burgdorferi, which also lacks a recognizable σ32, exhibits a heat shock response. The differential response of the two spirochetes to increased temperatures suggests that a protein or proteins of unknown biological function may be involved in this process in B. burgdorferi.

Regulatory functions.

Treponema pallidum contains a minimal set of regulatory genes that encode two response-regulator two-component systems and several putative transcriptional repressors of unknown specificity.

Although T. pallidum does not have a sugar-specific PTS system, it does contain a homolog of enzyme I (ptsI), a phosphocarrier protein HPr (ptsH), an HPr(Ser) kinase (ptsK), and two ptsN genes, which suggests that these proteins may function mainly as regulators. Gram-positive bacteria have a specific ATP-dependent protein kinase (ptsK) that phosphorylates HPr on a serine residue (36). HPr(Ser∼P) and a DNA-binding protein then interact to mediate repression by binding specifically to DNA sequences, catabolite responsive elements found in the control regions of catabolite-sensitive operons (36). These proteins in T. pallidum may function in a manner similar to that observed in Gram-positive bacteria.

Escherichia coli and other Gram-negative organisms coordinate nitrogen and carbon utilization so that mechanisms of carbon repression do not block the uptake and use of organic nitrogen sources. Nitrogen-carbon utilization in E. coli is modulated by a regulatory protein, PtsN, that displays similarity to the PTS enzymes IIA specific for fructose and mannitol (37). Biochemical data suggest that PtsN does not phosphorylate carbohydrates but instead serves as a positive regulator of organic nitrogen metabolism. Under such conditions, phosphoenolpyruvate (PEP)-dependent phosphorylation of PtsN occurs through the transfer of a phosphate group from PEP to enzyme I, then to a histidine residue on HPr, and finally to PtsN (37). The gene content of T. pallidum suggests that both ATP- and PEP-dependent protein phosphorylation of HPr may integrate intracellular signals reflecting the metabolic state of the cell. However, these hypotheses remain to be demonstrated experimentally. These proteins may play alternative regulatory roles in T. pallidum as this organism displays limited transport and metabolic capacities.

Motility and chemotaxis.

Motility-associated genes are highly conserved in both T. pallidum and B. burgdorferi, consistent with the importance of this activity in these highly invasive spirochetes (23, 38). The 36 genes encoding proteins involved in flagellar structure and function in T. pallidum are most similar to those in B. burgdorferi(8). They differ only in the number of proteins in the periplasmic flagellar filaments; T. pallidum has three core proteins (FlaB1, FlaB2, and FlaB3), a sheath protein (FlaA), and two uncharacterized proteins (39), and B. burgdorferihas a single core protein and sheath protein, whereas most other bacteria have only a core protein. Both spirochetes contain two copies of the flagellar motor switch protein, FliG; however, the importance of this gene duplication is not known. Most of the flagellar genes inT. pallidum are found in four operons that contain between 2 and 16 genes, most similar to the arrangement seen in B. burgdorferi. Treponema pallidum has retained a σ28 ortholog and class II and class III motility promoters, whereas motility genes in B. burgdorferiappear to be transcribed through σ70 initiation (8, 40). Treponema pallidum contains 13 chemotaxis genes that include four methyl-accepting chemotaxis proteins with putative specificity for amino acids (aspartate, glutamate, and histidine) or carbohydrates (glucose, ribose, and galactose).

Membrane proteins and lipoproteins.

Freeze fracture studies (7) have shown that the outer membrane of T. pallidum contains a relatively small number of integral membrane proteins, a feature that may permit the organism to evade the human immune response. Two candidate outer membrane proteins have been identified, but the cellular location and function of these proteins are a subject of some controversy (41). Although it is difficult to identify outer membrane proteins with certainty, genome analysis of T. pallidumindicates the presence of only 22 putative lipoproteins, as compared with 105 in B. burgdorferi, consistent with results from ultrastructural studies.

Potential virulence factors.

Treponema pallidum contains a large family of duplicated genes (paralogs) (tprA-L) that encode putative membrane proteins that may function as porins and adhesins (Figs. 2 and4). This hypothesis is based on pair-wise and multiple sequence alignments of the T. pallidum gene family to a major outer sheath protein (Msp) from T. denticola that represents an abundant, highly immunogenic, pore-forming adhesin in the outer membrane (42). It is not yet known whether the tpr genes are expressed individually or coordinately or to what extent each gene is expressed. This gene family in T. pallidum is reminiscent of a 32-member paralogous gene family encoding outer membrane proteins inHelicobacter pylori (omp) (9). The two gene families share features besides possible porin and adhesin functions, the most striking being that both have members with regions of extensive sequence identity. However, in both organisms, the homologous regions do not always encompass the entire gene, so that some regions are identical, but others are variable. As in the H. pylorifamily, one of the T. pallidum genes (tprA and L) contains a frameshift within a small dinucleotide repeat that might be corrected by slipped-strand mispairing. Multiple copies of the tpr genes may represent a mechanism for generation of antigenic variation in T. pallidum as is found in other pathogenic bacteria, includingNeisseria gonorrhoeae, M. genitalium, relapsing fever borreliae, and B. burgdorferi. Identification of thetpr family of putative outer membrane proteins may provide new targets for vaccine development.

Figure 4

Dendrogram of members of the tpr protein family of T. pallidum. This unrooted distance dendrogram was generated from a multiple sequence alignment of the 12 T. pallidum tpr paralogs described herein and Msp sequences from three Treponema denticola strains (tdA, T. denticola OTK; tdB, T. denticola 35405; tdC, T. denticola 33520) (42).

Previous studies have indicated that T. pallidum does not produce lipopolysaccharide or potent exotoxins, although cytotoxic activity against neuroblasts and other cell types has been observed at extremely high concentrations of the bacterium (43). Genome analysis has revealed five genes encoding proteins similar to bacterial hemolysins. These putative hemolysin orthologs also share varying degrees of amino acid sequence similarity with B. burgdorferi predicted proteins (8). None of the predicted hemolysins with similarity to T. pallidumsequences have been shown to be cytolytic in their purified state, and it will be necessary to perform such studies with the T. pallidum proteins before a cytotoxic function can be assigned definitively. A B. burgdorferi protein with hemolytic activity (BlyA) was described recently (44), but orthologous sequences are not present in T. pallidum.

Comparative genomics.

Four hundred seventy-six ORFs in T. pallidum (46%) have orthologs in B. burgdorferi; 76% of these ORFs have a predicted biological function. More than 40% of the orthologous genes in T. pallidum and B. burgdorferi are highly conserved in other bacteria (8, 9) and are involved in housekeeping functions such as transcription, translation, DNA replication, basic energy metabolism, flagellar structure and function, cell division, and protein secretion. Some of the genes of unknown function that are conserved in the spirochetes but not recognized in the other available genome sequences are likely to represent “spirochete-specific” genes that contribute to the unusual structural properties of these bacteria.

One hundred fifteen ORFs shared by T. pallidum andB. burgdorferi encode proteins of unknown biological function; and almost 50% of these appear to be unique to the spirochete group. This set of proteins with a limited phylogenetic distribution may include important determinants of spirochete structure and physiology and may, for example, be involved in the ability of bothT. pallidum and B. burgdorferi to infect humans and cause chronic, disseminated disease.

Three hundred four of the ORFs shared by the two spirochetes are located in gene clusters with conserved gene order (Fig. 5). Several conserved clusters contain ORFs encoding ribosomal proteins, including the largest cluster containing 27 ORFs, whereas other important clusters encode proteins for the flagella, adenosine triphosphatases (ATPases), and cell division, as well as groups of proteins that are not obviously related. Further study of the arrangement of these clusters in the two genomes may provide insight into the evolution of the chromosomes of these organisms.

Figure 5

Gene clusters found in both the T. pallidum and B. burgdorferi genomes. Graph values represent the number of T. pallidum gene clusters in which orthologous genes have the same organization in B. burgdorferi.

Of the 572 T. pallidum ORFs (54% of total) that are not shared with B. burgdorferi, more than 80% are of unknown biological function. This finding lends support to the concept of diversity within a single group of bacteria and underscores the fact that a considerable amount of T. pallidum biology is yet to be elucidated.


Treponema pallidum has been a difficult organism to study experimentally because of its absolute dependence on a mammalian host for sustained growth and viability. The genomic sequence of T. pallidum offers a wealth of basic information that would be difficult, if not impossible, to obtain by any other approach. A more complete understanding of the biochemstry of this organism derived from genome analysis may provide a foundation for the development of a culture medium for T. pallidum, which opens up the possibility of future genetic studies.

  • * To whom correspondence should be addressed. E-mail: tpdb{at}


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