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Table 3 Summary of T. pallidum uncharacterized proteins identified by structural modeling with potential roles in virulence

From: Functional insights from proteome-wide structural modeling of Treponema pallidum subspecies pallidum, the causative agent of syphilis

Protein

Phyre2 Virulence Model Templates (% confidence / % coverage)

Roles in virulence

Expression Analyses

MSC

cDNA/DNA

Protein

TPANIC_0020

• TgMIC2 (Toxoplasma gondii micronemal protein 2 A/I domain) (98.2 / 21.2)

• Promotes active invasion [80]

2.206

E [47]

-

• TRAP protein (Plasmodium vivax) (98.1 / 21.9)

• Cell adhesion & invasion [81]

TPANIC_0126

• Outer membrane protein W (E. coli) (97.3 / 72.2)

• Phagocytosis resistance [82]

1.115

E [47]

+

• Outer membrane protein A (E. coli) (94.8 / 64.1)

• Host adhesion, invasion and immune evasion [83]

• Outer membrane protein OprG (Pseudomonas aeruginosa) (93.9 / 70.0)

• Cytotoxicity [84]

• Outer membrane protein F (P. aeruginosa) (92.8 / 51.1)

• Host adhesion [85]

• NspA (Neisseria surface protein A) (90.4 / 64.1)

• Factor H-binding and complement resistance [86]

TPANIC_0134

• Bacterial sialidases/neuraminidases (Micromonospora viridifaciens, Vibrio cholera, Parabacteroides distasonis, Bacteroides thetaiotaomicron, Streptococcus pneumoniae) (98.9-99.4 / 69.4-72.3)

V. cholera; facilitates cholera toxin cell binding and penetration [87]

3.586

ND

+

S. pneumoniae; host cell glycan damage promotes colonization of respiratory tract [88, 89]

TPANIC_0225

• Leucine-rich repeat surface proteins (Eubacterium ventriosum, Faecalibacterium prausnitzii, Bacteroides species) (99.9-100 / 72.4-83.3)

• Host adhesion [90]

2.27

ND

-

• PcpA (S. pneumoniae choline-binding protein) (100 / 99.6)

• Host adhesion [91]

TPANIC_0246

• TRAP protein (P. vivax) (99.9 / 35.7)

• Cell recognition & invasion [81]

0.096

E [47]

-

• TRAP protein (Plasmodium falciparum) (99.8 / 35.8)

• Cell recognition & invasion [81]

 

• TgMIC2 (T. gondii micronemal protein 2 A/I domain) (99.8 / 30.5)

• Active invasion [80]

   

TPANIC_0421

• PknD (Mycobacterium tuberculosis serine/threonine protein kinase, extracellular domain) (99.9 / 37.6)

• Adhesion and invasion of brain endothelia [92]

0.686

E [47]

-

TPANIC_0544

• SmcL (Listeria ivanovii Sphingomyelinase-C) (99.9 / 51.9)

• Cytotoxicity [93, 94]

0.811

E [47]

-

• Beta-hemolysin toxin (Staphylococcus aureus) (99.9 / 51.4)

• Cytotoxicity [95]

• Cytolethal distending toxin protein B (S. enterica, Haemophilus ducreyi) (99.9 / 51.9-52.1)

• Cytotoxicity [96]

TPANIC_0579

• YenC2 (Yersinia entomophaga ABC toxin; BC component) (93.8 / 36.8)

• Cytotoxicity [97]

0.268

E [47]

-

TPANIC_0594

• HP1028 (Helicobacter pylori lipocalin) (100 / 64.8)

• Host colonization and persistence [98, 99]

2.238

ND

+

TPANIC_0598

• BamB (Moraxella catarrhalis Beta barrel assembly machinery protein B) (97.9 / 56.3)

• BAM complex; assembly and insertion of beta-barrel proteins in outer membrane [100, 101]

0.272

E [47]

-

TPANIC_0625

• BamD (Beta barrel assembly machinery protein) (Rhodothermus marinus, E. coli) (95.9-97.0 / 27.6-46.8)

• Essential BAM complex protein; assembly and insertion of beta-barrel proteins in outer membrane [102]

0.461

E [47]

-

TPANIC_0733

• NspA (Neisseria surface protein A) (97.8 / 58.4)

• Factor H-binding and complement resistance [86]

1.735

ND

+

• Ail (Yersinia pestis attachment invasion locus protein) (93.6 / 64.4)

• Host cell attachment, invasion, and complement resistance [103,104,105]

TPANIC_0783

• BamB (E. coli Beta barrel assembly machinery protein B) (96.2 / 24.7)

• BAM complex; assembly and insertion of beta-barrel proteins in outer membrane [100, 101]

0.402

ND

-

TPANIC_0789

• LolA (P. aeruginosa outer- membrane lipoprotein carrier/localization protein) (99.5 / 86)

• Translocation of lipoproteins to the outer membrane [106, 107]

1.283

E [47, 48]

-

• LprG (M. tuberculosis lipid- binding protein (96.8 / 71.7)

• TLR2-agonist; inhibits primary human macrophage MHC-II Ag processing [108]

TPANIC_0854

• Bacterial sialidases/neuraminidases (M. viridifaciens, V. cholera, P. distasonis, B. thetaiotaomicron, S. pneumoniae, P. aeruginosa) (98.9-99.5 / 17.0-25.8)

V. cholera; facilitates cholera toxin cell binding and penetration [87]

0.221

E [47]

-

S. pneumoniae; host cell glycan damage promotes colonization of upper respiratory tract [88, 89]

TPANIC_0911

• EscU (E. coli type 3 secretion system protein) (100 / 96.4)

• Type 3 effector translocation into host cells [109]

0.701

ND

-

• SpaS (Shigella flexneri type 3 secretion system protein) (99.9 / 94.0)

• Invasion and secretion of invasion plasmid antigens [110]

TPANIC_0928

• SurA (E. coli chaperone) (100 / 84.0)

• Folding and assembly of outer membrane proteins [101]

1.049

E [47]

-

TPANIC_0966

• TolC (E. coli outer membrane channel protein) (100 / 79.4)

• Type 1 secretion and drug efflux [111,112,113,114]

0.856

ND

-

TPANIC_0967

• TolC (E. coli outer membrane channel protein) (99.0 / 85.7)

• Type 1 secretion and drug efflux [111,112,113,114]

2.844

E [47]

+

TPANIC_0968

• TolC (E. coli outer membrane channel protein) (98.8 / 85.2)

• Type 1 secretion and drug efflux [111,112,113,114]

3.256

E [47]

+

TPANIC_0969

• TolC (E. coli outer membrane channel protein) (99.0 / 87.0)

• Type 1 secretion and drug efflux [111,112,113,114]

2.751

E [47, 48]

+

  1. cDNA/DNA ratios indicate transcript expression levels from a previous rabbit infection study where a value of 1.0 represents the mean transcript expression level for all T. pallidum genes in the study [45]. E; proteins known to be expressed during rabbit infection (ND; proteins not detected) [47, 48]. MSC; T. pallidum subspecies pallidum proteins that contain major sequence changes compared to orthologs from subspecies pertenue and T. paraluiscuniculi [55, 61]