Antigens of Treponema pallidum Recognized by IgG and IgM Antibodies During Syphilis in Humans

Baker‐Zander, Sharon A.; Hook, Edward W.; Bonin, Paul D.; Handsfield, H. Hunter; Lukehart, Sheila A.

doi:10.1093/infdis/151.2.264

Cited by 107 publications

(67 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite a wealth of data implicating humoral mechanisms in immunity to syphilis (7), the observations (i) that passive transfer of antibodies provides limited protection against experimental syphilis in rabbits (7), (ii) that rabbits may be immune to syphilitic challenge without detectable serum T pallidum immobilization reactivity (31), (iii) that serum T. pallidum immobilization reactivity is not a reliable indicator of immunity to challenge (28,30), and (iv) that humans develop immunity to acquired syphilis well after titers of anti-T pallidum antibodies have peaked (3,18,27,32) argue against an essential role for antibodies in protective immunity. Inasmuch as protective antibodies are presumed to be directed against surface-exposed treponemal constituents, resolution of this critical issue awaits molecular characterization of the rare outer membrane protein(s).…”

Section: Discussionmentioning

confidence: 99%

“…Only particles in the T. paUlidum OM failed to aggregate in cells fixed at the lower temperature. The combined data suggest that the mobility of T. palidum rare OM proteins is limited, perhaps as a result of interactions between their periplasmic domains and components of the peptidoglycan-cytoplasmic membrane complex.Treponema pallidum, the spirochetal bacterium which causes venereal syphilis, has a remarkable ability to evade the vigorous cellular and humoral immune responses that it evokes in mammalian hosts (3,17,18,25). One strategy for elucidating the pathogen's extraordinary immunoevasiveness has been to investigate the molecular architecture of its outer membrane and to determine the precise cellular locations of its major immunogens.…”

mentioning

confidence: 99%

“…Treponema pallidum, the spirochetal bacterium which causes venereal syphilis, has a remarkable ability to evade the vigorous cellular and humoral immune responses that it evokes in mammalian hosts (3,17,18,25). One strategy for elucidating the pathogen's extraordinary immunoevasiveness has been to investigate the molecular architecture of its outer membrane and to determine the precise cellular locations of its major immunogens.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Treponema pallidum rare outer membrane proteins: analysis of mobility by freeze-fracture electron microscopy

et al. 1994

View full text Add to dashboard Cite

Freeze-fracture and deep-etch electron microscopy were used to investigate the molecular architecture of the Treponema paUlidum outer membrane (OM). Freeze-fracture electron microscopy of treponemes freshly harvested from rabbit testes revealed that the intramembranous particles (IMPs) in both the concave and convex OM leaflets were distributed into alternating areas of relatively high and low particle dei1ity; in many OM fractures, IMPs formed rows that ran either parallel to or obliquely across the fracture faces. Statistical analysis (runs test) confirmed that the IMPs were nonrandomly distributed in both OM leaflets. Examination of deep-etched specimens revealed that the particles observed in freeze-fractured OMs also were surface exposed. Combined analysis of deep-etched and cross-fractured treponemes revealed that the OM particles were located in regions of the OM away from the endoflagella and closely apposed to the cytoplasmic membrane-peptidoglycan complex. When treponemes were incubated for extended periods with heat-inactivated immune rabbit syphilitic serum, no alteration in the distribution of OM IMPs was detected. In further experiments, approximately 1:1 mixtures of T. pallidum and Escherichia coli or separate suspensions of the nonpathogenic Treponema phagedenis biotype Reiter were fixed at 34°C or after cooling to 0°C (to induce lateral phase separations that would aggregate IMPs). Only particles in the T. paUlidum OM failed to aggregate in cells fixed at the lower temperature. The combined data suggest that the mobility of T. palidum rare OM proteins is limited, perhaps as a result of interactions between their periplasmic domains and components of the peptidoglycan-cytoplasmic membrane complex.Treponema pallidum, the spirochetal bacterium which causes venereal syphilis, has a remarkable ability to evade the vigorous cellular and humoral immune responses that it evokes in mammalian hosts (3,17,18,25). One strategy for elucidating the pathogen's extraordinary immunoevasiveness has been to investigate the molecular architecture of its outer membrane and to determine the precise cellular locations of its major immunogens. Prior freeze-fracture and deep-etch electron microscopy (EM) revealed that the T. pallidum outer membrane contains a paucity of surface-exposed protein immunogens (visualized by freeze fracture as rare intramembranous particles [IMPs] which may represent a single protein or protein oligomer) (40, 50). In contrast, evidence now exists that the bacterium's major membrane immunogens, molecules previously described as surface exposed (20,21,35,46), are associated with the cytoplasmic membrane via lipids at their N termini (1,10,12,38,39,43,45). Inasmuch as the polypeptide moieties of the lipoproteins presumably are extrinsic to the lipid bilayer (12), these molecules may not be visualized in freeze-fractured T. pallidum membranes.The discovery of the rare outer membrane protein(s) has raised fundamental questions concerning the role(s) of these molecules in syphilis pathogenesis and ...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Treponema pallidum rare outer membrane proteins: analysis of mobility by freeze-fracture electron microscopy

et al. 1994

View full text Add to dashboard Cite

show abstract

“…Motility-related proteins that make up the flagellar motor/switch and assembly apparatuses have homology to those found in other bacteria (105,127,128,174). Cellular (7,10) and humoral (31,125,178) immune responses to endoflagella are induced during syphilis infection, and the major flagellar proteins are recognized by antibodies from infected humans (11,31,124,125,243) and rabbits (123,178,181). T. pallidum endoflagellal core subunits share antigenic epitopes with endoflagella of the nonpathogenic treponeme T. phagedenis biotype Reiter (28,31,125,178,243); there are also pathogen-specific flagellar sheath epitopes in T. pallidum (28,178,186).…”

Section: Motilitymentioning

confidence: 99%

Biological Basis for Syphilis

2006

View full text Add to dashboard Cite

SUMMARY Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health.

show abstract

“…A study using an array of 882 polypeptides predicted to be in the T. pallidum proteome identified 106 proteins that could induce a detectable antibody response (53). Two T. pallidum lipoproteins that induce high titers of antibodies are TpN17 and TpN47 (54)(55)(56)(57), both of which are used in new enzyme and chemiluminescence immunoassay (EIA/CIA) serological tests for syphilis. Genome analysis of T. pallidum predicts that there are as many as 22 putative lipoproteins in the organism (1).…”

Section: The Natural History Of Syphilis Primary Syphilis -Transmissimentioning

confidence: 99%

Syphilis: using modern approaches to understand an old disease

Lukehart²

2011

J. Clin. Invest.

205

168

View full text Add to dashboard Cite

Syphilis is a fascinating and perplexing infection, with protean clinical manifestations and both diagnostic and management ambiguities. Treponema pallidum subsp. pallidum, the agent of syphilis, is challenging to study in part because it cannot be cultured or genetically manipulated. Here, we review recent progress in the application of modern molecular techniques to understanding the biological basis of this multistage disease and to the development of new tools for diagnosis, for predicting efficacy of treatment with alternative antibiotics, and for studying the transmission of infection through population networks.

show abstract

Antigens of Treponema pallidum Recognized by IgG and IgM Antibodies During Syphilis in Humans

Cited by 107 publications

References 27 publications

Treponema pallidum rare outer membrane proteins: analysis of mobility by freeze-fracture electron microscopy

Treponema pallidum rare outer membrane proteins: analysis of mobility by freeze-fracture electron microscopy

Biological Basis for Syphilis

Syphilis: using modern approaches to understand an old disease

Contact Info

Product

Resources

About