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Treponema pallidum

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
    6. Host Protective Immunity
  2. Vaccine Related Pathogen Genes
    1. GlpQ (Protective antigen)
    2. TmpB (Protective antigen)
    3. Tp92 (Protective antigen)
  3. Vaccine Information
    1. T. pallidum GlpQ Protein Vaccine
    2. T. pallidum TmpB Protein Vaccine
    3. T. pallidum Tp92 Protein Vaccine
  4. References
I. General Information
1. NCBI Taxonomy ID:
160
2. Disease:
Syphilis
3. Introduction
T. pallidum pallidum is a motile spirochaete that is generally acquired by close sexual contact, entering the host via breaches in squamous or columnar epithelium. The organism can also be transmitted to a fetus by transplacental passage during the later stages of pregnancy, giving rise to congenital syphilis. The helical structure of T. pallidum pallidum allows it to move in a corkscrew motion through a viscous medium such as mucus. It gains access to host's blood and lymph systems through tissue and mucous membranes. The subspecies causing yaws, pinta, and bejel are morphologically and serologically indistinguishable from T. pallidum pallidum (syphilis); however, their transmission is not venereal in nature and the course of each disease is significantly different (Wiki: T. pallidum).
4. Microbial Pathogenesis
T. pallidum (in the case of syphilis) generally first forms a chancre at the site of infection and the spirochetes are infectious. The bacteria then penetrate mucosal membranes, and invade the bloodstream as well as other tissues. The bacteria cause latent syphilis which can progress into tertiary syphilis by the bacteria causing inflammatory disease and thus creating problems in infected (Salyers and Whitt., 2002).
5. Host Ranges and Animal Models
T. pallidum is an obligate internal parasite, meaning that it requires a mammalian host for survival. In the absence of mammalian cells, T. pallidum will be killed by the absence of nutrients, exposure to oxygen and heat. T. pallidum causes the human disease syphilis. Since T. pallidum cannot be grown in culture, animal models are needed to study syphilis. Although mice and monkeys can be used, rabbits are the animal model almost exclusively studied in the lab. Rabbits are used because unlike monkeys they are inexpensive and unlike mice, rabbits develop the signs and symptoms of human primary and secondary syphilis (MicrobeWiki: T. pallidum).
6. Host Protective Immunity
The primary clearance mechanism responsible for removal of T. pallidum from syphilitic chancres is believed to be antibody‐mediated treponemal opsonization and subsequent phagocytosis and killing by macrophages (Cameron et al., 1998).
1. GlpQ
  • Gene Name : GlpQ
  • Sequence Strain (Species/Organism) : Treponema pallidum subsp. pallidum str. Nichols
  • VO ID : VO_0012399
  • NCBI Gene ID : 2611763
  • NCBI Protein GI : 15639249
  • Locus Tag : TP0257
  • Genbank Accession : AE000520
  • Protein Accession : NP_218698
  • Taxonomy ID : 243276
  • Gene Starting Position : 268189
  • Gene Ending Position : 269259
  • Gene Strand (Orientation) : +
  • Protein Name : glycerophosphodiester phosphodiesterase
  • Protein pI : 9.44
  • Protein Weight : 38335.23
  • Protein Length : 356
  • Protein Note : hydrolyzes deacylated phospholipids to glycerol 3-phosphate and the corresponding alcohols; periplasmic
  • DNA Sequence : Show Sequence
    >gi|15638995:268189-269259 Treponema pallidum subsp. pallidum str. Nichols chromosome, complete genome
    TATGCGGGGAACATATTGTGTGACGCTTTGGGGGGGGGTGTTTGCGGCATTGGTTGCAGGCTGTGCGTCC
    GAACGTATGATAGTTGCGTATCGGGGCGCTGCAGGATATGTGCCCGAGCACACCTTTGCCTCGAAAGTTC
    TTGCTTTTGCACAAGGAGCAGATTACCTGCAGCAGGATGTCGTGCTTTCAAAGGATAATCAGCTTATCGT
    AGCGCAAAGCCATATTCTGGATAATATGACTGACGTGGCAGAAAAATTTCCACGCCGGCAGCGTGCGGAT
    GGGCATTTCTATGTCATAGATTTTACGGTAGAAGAACTTTCCCTCCTCCGTGCAACCAATAGTTTCTATA
    CGCGCGGTAAGCGACATACGCCGGTGTATGGCCAGCGCTTTCCTCTTTGGAAGCCTGGTTTTAGGCTGCA
    CACTTTTGAAGAGGAGTTGCAGTTTATCCGTGGGTTGGAACAGACAACCGGGAAAAAGATTGGAATTTAC
    TCTGAAATAAAGGTGCCGTGGTTTCATCATCAGGAAGGAAAAGACATCGCAGCGCTTACCCTCGCTCTGT
    TGAAAAAATACGGTTACCAAAGTCGATCGGATCTAGTGTATGTGCAAACGTATGATTTTAACGAGCTGAA
    GCGTATCAAACGAGAACTTTTACCAAAGTACGAAATGAACGTGAAGCTGATTCAGCGTGTTGCTTACACA
    GATCAACGTGAAACACAGGAGAAGGACTCGCGTGGGAAATGGATAAACTACAATTACAATTGGATGTTTG
    AGCCCGGTGGTATGCAGAAAATAGCAAAATATGCAGACGGCGTGGGTCCTGACTGGAGGATGCTCATAGA
    GAATGAATGGTCGAAGGTGGGCGCTGTTCGCCTGAGTCCGATGGTTTCTGCAATCCAAGATGCGAAATTG
    GAATGTCATGTGCACACGGTACGGAAAGAAACACTGCCTAGCTACGCGCGCACCATGGACGAGATGTTTT
    CCATTTTGTTCAAACAGACGGGCGCAAACGTGGTGCTCACGGATTTTCCTGATCTTGGGGTAAAGTTTCT
    GGGCAAACCCGCCCGCTATTG
  • Protein Sequence : Show Sequence
    >gi|15639249|ref|NP_218698.1| glycerophosphodiester phosphodiesterase [Treponema pallidum subsp. pallidum str. Nichols]
    MRGTYCVTLWGGVFAALVAGCASERMIVAYRGAAGYVPEHTFASKVLAFAQGADYLQQDVVLSKDNQLIV
    AQSHILDNMTDVAEKFPRRQRADGHFYVIDFTVEELSLLRATNSFYTRGKRHTPVYGQRFPLWKPGFRLH
    TFEEELQFIRGLEQTTGKKIGIYSEIKVPWFHHQEGKDIAALTLALLKKYGYQSRSDLVYVQTYDFNELK
    RIKRELLPKYEMNVKLIQRVAYTDQRETQEKDSRGKWINYNYNWMFEPGGMQKIAKYADGVGPDWRMLIE
    NEWSKVGAVRLSPMVSAIQDAKLECHVHTVRKETLPSYARTMDEMFSILFKQTGANVVLTDFPDLGVKFL
    GKPARY
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunization with the recombinant GlpQ significantly protected rabbits from subsequent T. pallidum challenge, altering lesion development at the sites of challenge (Cameron et al., 1998).
  • Related Vaccine(s): T. pallidum GlpQ Protein Vaccine
2. TmpB
  • Gene Name : TmpB
  • Sequence Strain (Species/Organism) : Treponema pallidum subsp. pallidum str. Nichols
  • VO ID : VO_0012400
  • NCBI Gene ID : 2611387
  • NCBI Protein GI : 15639756
  • Locus Tag : TP0769
  • Genbank Accession : AE000520
  • Protein Accession : NP_219206
  • Taxonomy ID : 243276
  • Gene Starting Position : 834955
  • Gene Ending Position : 835932
  • Gene Strand (Orientation) : +
  • Protein Name : outer membrane protein (tmpB)
  • Protein pI : 9.18
  • Protein Weight : 35471.38
  • Protein Length : 325
  • Protein Note : similar to GB:M58562 SP:P19649 PID:155065 percent identity: 100.00; identified by sequence similarity; putative
  • DNA Sequence : Show Sequence
    >gi|15638995:834955-835932 Treponema pallidum subsp. pallidum str. Nichols chromosome, complete genome
    GATGAAGACACGTAATTTCTCGCTCGTATCCGCGTTGTACGTACTGCTGGGTGTTCCTCTGTTTGTGTCT
    GCCGCTTCCTACGACGACAATGAATTTTCTCGCAAGAGTCGTGCGTACTCGGAGCTTGCAGAGAAGACAT
    ACGATGCGGGAGAGTATGACGTCTCTGCAGAGTACGCCCGGCTCGCTGAGGATTTTGCGCAAAAATCCTC
    GGTCTACATCAAGGAAACTATGGCGCGCACCACTGCCGAGGACGCTATGAACGCTGCGCGCACCCGCCAC
    GCGTGGGCGAAAAATGAGCGCATCGATCGCGCCTATCCGACCGAGTATTTGCTCGCTAGCGAGGCTATCA
    AGACCGGAGGGCTCGCTTTTGACAGCAAGCAGTACGACGTAGCGCTCACGTGGGCGCGTAAGGCGTTGGA
    CGCACTCAAAAACGTAAAGCCTGAAAGTCAGTTGCTTGCAAAGGCCGCGAAGGAGGAGGCTGCGCGCAAG
    GCCGCCGAGGCACGAAAACTCGAAGAACAAAGAATTGCAGCCCAGAAAGCGCAGGAAGAACGTAAGCGTG
    CGGAGGAGGAAGCTGCGCGCAAGGCCGCCGAGGCACGAAAACTCGAAGAACAAAGAATTGCAGCCCAGAA
    AGCGCAGGAAGAACGTAAGCGTGCGGAGGAGGAAGCTGCGCGCAAGGCCGCCGAGGAAGCAGCGCGAAAG
    GCGGAGGAACTCGAGAAGGGTCGTGTGCTACCTGCGCAATACAAGGTGACTACGTGGTCCATTGACCGGG
    AATGTTTCTGGAATATTGCCAAAAACCCCGCCGTTTATGGCAACCCCTTCCTCTGGAAGAAGTTGTATGA
    GGCGAACAAGGACAAAATTCCTCAGTCCAAAAACCCCAATTGGGTAGAGCCTGAGACAGTCCTGGTCATC
    CCCAGTCTCAAGGGAGAGGAGCGCGAGGGTCTGTATGAGCCCAACGTGAAATACCGTCCTCTGCCGTA
  • Protein Sequence : Show Sequence
    >gi|15639756|ref|NP_219206.1| outer membrane protein (tmpB) [Treponema pallidum subsp. pallidum str. Nichols]
    MKTRNFSLVSALYVLLGVPLFVSAASYDDNEFSRKSRAYSELAEKTYDAGEYDVSAEYARLAEDFAQKSS
    VYIKETMARTTAEDAMNAARTRHAWAKNERIDRAYPTEYLLASEAIKTGGLAFDSKQYDVALTWARKALD
    ALKNVKPESQLLAKAAKEEAARKAAEARKLEEQRIAAQKAQEERKRAEEEAARKAAEARKLEEQRIAAQK
    AQEERKRAEEEAARKAAEEAARKAEELEKGRVLPAQYKVTTWSIDRECFWNIAKNPAVYGNPFLWKKLYE
    ANKDKIPQSKNPNWVEPETVLVIPSLKGEEREGLYEPNVKYRPLP
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Treponema pallidum-susceptible guinea pigs of strain C4D were immunized with recombinant T. pallidum antigen TmpB. Guinea pigs receiving TmpB antigen demonstrated protection expressed by the development of significantly (P less than 0.01) smaller, atypical lesions of significantly (P less than 0.01) shorter duration and devoid of or containing fewer T. pallidum organisms than lesions in the remaining immunized and control animals (Wicher et al., 1991).
  • Related Vaccine(s): T. pallidum TmpB Protein Vaccine
3. Tp92
  • Gene Name : Tp92
  • Sequence Strain (Species/Organism) : Treponema pallidum subsp. pallidum str. Nichols
  • VO ID : VO_0012401
  • NCBI Protein GI : 159158965
  • Other Database IDs : CDD:155280
  • Taxonomy ID : 243276
  • Gene Strand (Orientation) : ?
  • Protein Name : Tp92
  • Protein Length : 324
  • Protein Note : Surface antigen; cl03097
  • Protein Sequence : Show Sequence
    >gi|159158965|gb|ABW94736.1| Tp92 [Treponema pallidum subsp. pallidum str. Nichols]
    SPLTVGFDFELTHKNLFVYRAGSYGNGLPHPYTSREQWASSPGLAESFRLKYSRFESAIGAHTGYQWYPR
    YAVIRVNGGVDFRVVKNFYDKDNNQPFDLTVKEQLNWTSINSFWTSVSFDGRDFAYDPSSGWFLGQRCTF
    NGLVPFLEKEHSFRSDTKAEFYVTLLNYPVSAVWNLKFVLAFYTGVSVQTYYGRRKSENGKGNGVRSGAL
    VIDGVLVGRGWSEDAKKNTGDLLLHHWIEFRWPLAHGIVSFDFFFDAAMVYNIESQSPNGSSSASSSSSS
    SSSSSRTTSSEGLYKMSYGPGLRFTLPQFPLKLAFANTFTSPGG
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunization with recombinant Tp92 partially protected rabbits from subsequent T. pallidum challenge (Cameron et al., 2000).
  • Related Vaccine(s): T. pallidum Tp92 Protein Vaccine
III. Vaccine Information
1. T. pallidum GlpQ Protein Vaccine
a. Vaccine Ontology ID:
VO_0004024
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant GlpQ
e. Gene Engineering of GlpQ
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: Ribi vaccine adjuvant
g. Vector:
pET-3a vector (Cameron et al., 1998).
h. Immunization Route
IM, SC, IP, and ID
i. Rabbit Response
  • Host Strain: New Zealand White
  • Vaccination Protocol: Rabbits were immunized three times (IM, SC, IP, and ID) at 3-week intervals with the Ribi MPL + TDM + CWS adjuvant and 100 μg of purified inclusion bodies from E. coli expressing either the pET-3a vector alone or the Gpd-pET-3a construct (Cameron et al., 1998).
  • Challenge Protocol: Two weeks after administration of the final immunization, rabbits were challenged ID at each of six sites on their shaved backs with 103 T. pallidum per site (Cameron et al., 1998).
  • Efficacy: Immunization with the recombinant GlpQ significantly protected rabbits from subsequent T. pallidum challenge, altering lesion development at the sites of challenge. All eight control rabbits developed typical red, raised, and highly indurated lesions at each of the six challenge sites that in some cases progressed to ulceration. All four of the Gpd-immunized rabbits developed atypical pale, flat, slightly indurated, and nonulcerative reactions at each of the six challenge sites. In all cases, induration in the Gpd-immunized animals resolved before lesions appeared in the control animals and resembled delayed-type hypersensitivity responses more than typical syphilis chancres (Cameron et al., 1998).
2. T. pallidum TmpB Protein Vaccine
a. Vaccine Ontology ID:
VO_0004025
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant TmpB protein.
e. Gene Engineering of TmpB
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: Ribi vaccine adjuvant
g. Immunization Route
Subcutanteous and i.p.
h. Guinea pig Response
  • Host Strain: C4D
  • Vaccination Protocol: In the first set of experiments, guinea pigs assigned randomly to seven groups of five animals each were immunized with TmpA, TmpB, TmpC, TmpA plus TmpB plus TmpC (TmpABC), or E. coli membranes. Five animals received adjuvant in phosphate-buffered saline, and five guinea pigs served as nonimmunized control. Each animal received six injections, each of 100 μg of antigen in a 0.4-ml volume, distributed in two subcutaneous injections (0.15 ml each) in the inguinal lymph nodes areas and one intraperitoneal injection (0.1 ml) (Wicher et al., 1991).
  • Challenge Protocol: A week after immunizing injection 6, all animals, including untreated controls, were injected intradermally in a hind leg with 100 μl of suspension containing 3 X 106 T. pallidum Nichols freshly extracted from rabbit testes.
  • Efficacy: Guinea pigs receiving TmpB antigen demonstrated protection expressed by the development of significantly (P less than 0.01) smaller, atypical lesions of significantly (P less than 0.01) shorter duration and devoid of or containing fewer T. pallidum organisms than lesions in the remaining immunized and control animals (Wicher et al., 1991).
3. T. pallidum Tp92 Protein Vaccine
a. Vaccine Ontology ID:
VO_0004026
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
125 μg of purified intact ORF recombinant Tp92 (Cameron et al., 2000).
e. Gene Engineering of Tp92
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: Ribi vaccine adjuvant
g. Immunization Route
i.m., s.c., i.p., and i.d.
h. Rabbit Response
  • Host Strain: New Zealand White
  • Vaccination Protocol: New Zealand White rabbits were immunized (intramuscularly, subcutaneously, intraperitoneally, and intradermally) at 3‐week intervals with Ribi adjuvant and 125 μg of purified intact ORF recombinant Tp92. Unimmunized rabbits were used as a control (Cameron et al., 2000).
  • Challenge Protocol: At 1–4 weeks after administration of the final immunization in each protection experiment, the immunized rabbits and a total of 4 unimmunized control rabbits were subjected to intradermal challenge at each of 8 sites on their shaved backs with 105 T. pallidum subsp. pallidum (Nichols strain) per site. The rabbits were examined daily to monitor the development, morphologic appearance, and progression of lesions appearing at the challenge sites (Cameron et al., 2000).
  • Efficacy: Immunization with recombinant Tp92 partially protected rabbits from subsequent T. pallidum challenge. the rabbits immunized with the T. pallidum recombinant Tp92 before challenge all demonstrated alteration of lesion development. Significant attenuation of lesion development was observed in these rabbits, with atypical pale, flat, slightly indurated, and for the most part, nonulcerative lesions appearing at the sites of challenge. In these protection experiments, the number of lesions progressing to ulceration and the number of darkfield‐positive lesions in the Tp92‐immunized rabbits were significantly smaller than those of lesions appearing in the control animals (Cameron et al., 2000).
IV. References
1. Cameron et al., 1998: Cameron CE, Castro C, Lukehart SA, Van Voorhis WC. Function and protective capacity of Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase. Infection and immunity. 1998; 66(12); 5763-5770. [PubMed: 9826352].
2. Cameron et al., 2000: Cameron CE, Lukehart SA, Castro C, Molini B, Godornes C, Van Voorhis WC. Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subspecies pallidum Tp92. The Journal of infectious diseases. 2000; 181(4); 1401-1413. [PubMed: 10762571].
3. MicrobeWiki: T. pallidum: MicrobeWiki: Treponema pallidum [http://microbewiki.kenyon.edu/index.php/Treponema_pallidum]
4. Salyers and Whitt., 2002: Abigail A. Salyers, Dixie D. Whitt. The Spirochetes: Borrelia burgdorferi and Treponema pallidum. 197-99. Bacterial Pathogenesis: A Molecular Approach. 2002. ASM Press, Washington D.C. USA.
5. Wicher et al., 1991: Wicher K, Schouls LM, Wicher V, Van Embden JD, Nakeeb SS. Immunization of guinea pigs with recombinant TmpB antigen induces protection against challenge infection with Treponema pallidum Nichols. Infection and immunity. 1991; 59(12); 4343-4348. [PubMed: 1937794].
6. Wiki: T. pallidum: Wiki: T. pallidum [http://en.wikipedia.org/wiki/Treponema_pallidum]