Treponema pallidum 160 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). Syphilis 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). 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). 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). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 licensed Syphilis human vaccine Generic Unknown VO_0001230 Inactivated or "killed" vaccine Licensed A generic representation of vaccines developed to prevent syphilis infection in humans, typically using inactivated Treponema pallidum bacteria to elicit an immune response. Historically, attempts at syphilis vaccination have focused on inactivated or killed preparations, though no widely licensed human vaccine currently exists. T. pallidum GlpQ Protein Vaccine VO_0004024 Subunit vaccine Research pET-3a vector [Ref1513:Cameron et al., 1998]. IM, SC, IP, and ID Ribi adjuvant (Cameron et al., 1998). IM, SC, IP, and ID Recombinant GlpQ Recombinant protein preparation New Zealand White 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). 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). 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). T. pallidum TmpB Protein Vaccine VO_0004025 Subunit vaccine Research Subcutanteous and i.p. RIBI adjuvant (Wicher et al., 1991). Subcutanteous and i.p. Recombinant TmpB protein. Recombinant protein preparation C4D 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). 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). 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 10^6 T. pallidum Nichols freshly extracted from rabbit testes. T. pallidum Tp92 Protein Vaccine VO_0004026 Subunit vaccine Research i.m., s.c., i.p., and i.d. Ribi adjuvant (Cameron et al., 2000). i.m., s.c., i.p., and i.d. 125 μg of purified intact ORF recombinant Tp92 (Cameron et al., 2000). Recombinant protein preparation New Zealand White 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). 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). 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 10^5 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). GlpQ Treponema pallidum subsp. pallidum str. Nichols VO_0012399 2611763 499184166 TP_RS01315 AE000520 WP_010881706 243276 268189 269259 + glycerophosphoryl diester phosphodiesterase 9.44 38335.23 356 hydrolyzes deacylated phospholipids to glycerol 3-phosphate and the corresponding alcohols; periplasmic >NC_000919.1:268189-269259 Treponema pallidum subsp. pallidum str. Nichols complete genome TATGCGGGGAACATATTGTGTGACGCTTTGGGGGGGGGTGTTTGCGGCATTGGTTGCAGGCTGTGCGTCC GAACGTATGATAGTTGCGTATCGGGGCGCTGCAGGATATGTGCCCGAGCACACCTTTGCCTCGAAAGTTC TTGCTTTTGCACAAGGAGCAGATTACCTGCAGCAGGATGTCGTGCTTTCAAAGGATAATCAGCTTATCGT AGCGCAAAGCCATATTCTGGATAATATGACTGACGTGGCAGAAAAATTTCCACGCCGGCAGCGTGCGGAT GGGCATTTCTATGTCATAGATTTTACGGTAGAAGAACTTTCCCTCCTCCGTGCAACCAATAGTTTCTATA CGCGCGGTAAGCGACATACGCCGGTGTATGGCCAGCGCTTTCCTCTTTGGAAGCCTGGTTTTAGGCTGCA CACTTTTGAAGAGGAGTTGCAGTTTATCCGTGGGTTGGAACAGACAACCGGGAAAAAGATTGGAATTTAC TCTGAAATAAAGGTGCCGTGGTTTCATCATCAGGAAGGAAAAGACATCGCAGCGCTTACCCTCGCTCTGT TGAAAAAATACGGTTACCAAAGTCGATCGGATCTAGTGTATGTGCAAACGTATGATTTTAACGAGCTGAA GCGTATCAAACGAGAACTTTTACCAAAGTACGAAATGAACGTGAAGCTGATTCAGCGTGTTGCTTACACA GATCAACGTGAAACACAGGAGAAGGACTCGCGTGGGAAATGGATAAACTACAATTACAATTGGATGTTTG AGCCCGGTGGTATGCAGAAAATAGCAAAATATGCAGACGGCGTGGGTCCTGACTGGAGGATGCTCATAGA GAATGAATGGTCGAAGGTGGGCGCTGTTCGCCTGAGTCCGATGGTTTCTGCAATCCAAGATGCGAAATTG GAATGTCATGTGCACACGGTACGGAAAGAAACACTGCCTAGCTACGCGCGCACCATGGACGAGATGTTTT CCATTTTGTTCAAACAGACGGGCGCAAACGTGGTGCTCACGGATTTTCCTGATCTTGGGGTAAAGTTTCT GGGCAAACCCGCCCGCTATTG >WP_010881706.1 glycerophosphodiester phosphodiesterase [Treponema pallidum] MRGTYCVTLWGGVFAALVAGCASERMIVAYRGAAGYVPEHTFASKVLAFAQGADYLQQDVVLSKDNQLIV AQSHILDNMTDVAEKFPRRQRADGHFYVIDFTVEELSLLRATNSFYTRGKRHTPVYGQRFPLWKPGFRLH TFEEELQFIRGLEQTTGKKIGIYSEIKVPWFHHQEGKDIAALTLALLKKYGYQSRSDLVYVQTYDFNELK RIKRELLPKYEMNVKLIQRVAYTDQRETQEKDSRGKWINYNYNWMFEPGGMQKIAKYADGVGPDWRMLIE NEWSKVGAVRLSPMVSAIQDAKLECHVHTVRKETLPSYARTMDEMFSILFKQTGANVVLTDFPDLGVKFL GKPARY Protective antigen Immunization with the recombinant GlpQ significantly protected rabbits from subsequent T. pallidum challenge, altering lesion development at the sites of challenge [Ref1513:Cameron et al., 1998]. TmpB Treponema pallidum subsp. pallidum str. Nichols VO_0012400 2611387 499184674 TP_RS03880 AE000520 WP_010882214 243276 834955 835932 + treponemal membrane protein B 9.18 35471.38 325 similar to GB:M58562 SP:P19649 PID:155065 percent identity: 100.00; identified by sequence similarity; putative >NC_000919.1:834955-835932 Treponema pallidum subsp. pallidum str. Nichols complete genome GATGAAGACACGTAATTTCTCGCTCGTATCCGCGTTGTACGTACTGCTGGGTGTTCCTCTGTTTGTGTCT GCCGCTTCCTACGACGACAATGAATTTTCTCGCAAGAGTCGTGCGTACTCGGAGCTTGCAGAGAAGACAT ACGATGCGGGAGAGTATGACGTCTCTGCAGAGTACGCCCGGCTCGCTGAGGATTTTGCGCAAAAATCCTC GGTCTACATCAAGGAAACTATGGCGCGCACCACTGCCGAGGACGCTATGAACGCTGCGCGCACCCGCCAC GCGTGGGCGAAAAATGAGCGCATCGATCGCGCCTATCCGACCGAGTATTTGCTCGCTAGCGAGGCTATCA AGACCGGAGGGCTCGCTTTTGACAGCAAGCAGTACGACGTAGCGCTCACGTGGGCGCGTAAGGCGTTGGA CGCACTCAAAAACGTAAAGCCTGAAAGTCAGTTGCTTGCAAAGGCCGCGAAGGAGGAGGCTGCGCGCAAG GCCGCCGAGGCACGAAAACTCGAAGAACAAAGAATTGCAGCCCAGAAAGCGCAGGAAGAACGTAAGCGTG CGGAGGAGGAAGCTGCGCGCAAGGCCGCCGAGGCACGAAAACTCGAAGAACAAAGAATTGCAGCCCAGAA AGCGCAGGAAGAACGTAAGCGTGCGGAGGAGGAAGCTGCGCGCAAGGCCGCCGAGGAAGCAGCGCGAAAG GCGGAGGAACTCGAGAAGGGTCGTGTGCTACCTGCGCAATACAAGGTGACTACGTGGTCCATTGACCGGG AATGTTTCTGGAATATTGCCAAAAACCCCGCCGTTTATGGCAACCCCTTCCTCTGGAAGAAGTTGTATGA GGCGAACAAGGACAAAATTCCTCAGTCCAAAAACCCCAATTGGGTAGAGCCTGAGACAGTCCTGGTCATC CCCAGTCTCAAGGGAGAGGAGCGCGAGGGTCTGTATGAGCCCAACGTGAAATACCGTCCTCTGCCGTA >WP_010882214.1 membrane protein TmpB [Treponema pallidum] MKTRNFSLVSALYVLLGVPLFVSAASYDDNEFSRKSRAYSELAEKTYDAGEYDVSAEYARLAEDFAQKSS VYIKETMARTTAEDAMNAARTRHAWAKNERIDRAYPTEYLLASEAIKTGGLAFDSKQYDVALTWARKALD ALKNVKPESQLLAKAAKEEAARKAAEARKLEEQRIAAQKAQEERKRAEEEAARKAAEARKLEEQRIAAQK AQEERKRAEEEAARKAAEEAARKAEELEKGRVLPAQYKVTTWSIDRECFWNIAKNPAVYGNPFLWKKLYE ANKDKIPQSKNPNWVEPETVLVIPSLKGEEREGLYEPNVKYRPLP Protective antigen 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 [Ref1514:Wicher et al., 1991]. tp92 Treponema pallidum subsp. pallidum str. Nichols VO_0012401 AAC16524 CDD:227116 243276 ? putative outer membrane protein 8.68 88079.37 944 Outer membrane protein assembly factor BamA [Cell wall/membrane/envelope biogenesis]; COG4775 >AAC16524.1 putative outer membrane protein [Treponema pallidum subsp. pallidum str. Nichols] MLKKASAFLIASCCVMSLAWAQANDNWYEGKPISAISFEGLEYIARGQLDTIFSQYKGQKWTYELYLEIL QKVYDLEYFSEVSPKAVPTDPEYQYVMLQFTVKERPSVKGIKMVGNSQIRSGDLLSKILLKKGDIYNEVK MKVDQESLRRHYLDQGYAAVKISCEAKTEAGGVVVQFTIQEGKQTVVSRIQFKGNKAFTESVLKKVLSTQ EARFLTSGVFKENALEADKAAVHSYYAERGYIDARVEGVAKTVDKKTDASRNLVTLTYTVVEGEQYRYGG VTIVGNQIFSTEELQAKIRLKRGAIMNMVAFEQGFQALADAYFENGYTSNYLNKEEHRDTAEKTLSFKIT VVERERSHVEHIIIKGTKNTKDEVILREMLLKPGDVFSKSKFTDSLRNLFNLRYFSSLVPDVRPGSEQDL VDIILNVEEQSTANVQFGVTFSGVGEAGTFPLSLFCQWEEKNFLGKGNEISVNATLGSEAQSLKLGYVER WFLGSPLTVGFDFELTHKNLFVYRAGSYGNGLPHPYTSREQWASSPGLAESFRLKYSRFESAIGAHTGYQ WYPRYAVIRVNGGVDFRVVKNFYDKDNNQPFDLTVKEQLNWTSINSFWTSVSFDGRDFAYDPSSGWFLGQ RCTFNGLVPFLEKEHSFRSDTKAEFYVTLLNYPVSAVWNLKFVLAFYTGVSVQTYYGRRKSENGKGNGVR SGALVIDGVLVGRGWSEDAKKNTGDLLLHHWIEFRWPLAHGIVSFDFFFDAAMVYNIESQSPNGSSSASS SSSSSSSSSRTTSSEGLYKMSYGPGLRFTLPQFPLKLAFANTFTSPGGIPKTKKNWNFVLSFTVNNL Protective antigen Immunization with recombinant Tp92 partially protected rabbits from subsequent T. pallidum challenge [Ref1515:Cameron et al., 2000]. 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