Influence of Lysozyme Upon the Treponeme Immobilization Reaction1

Metzger, M; Hardy, Paul H.; Nell, E. Ellen

doi:10.1093/oxfordjournals.aje.a120182

Cited by 22 publications

(21 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As such, one might anticipate that the appearance of specific antibodies would herald the eradication of the invader and the control of syphilitic infection, yet as discussed above, clinical and experimental evidence to support this assumption has not been easy to garner. More than 5 decades ago, investigators began to note the poor surface reactivity of motile T. pallidum in serologic tests (55,86,89). Their studies fostered the notion that the spirochete is surrounded by a protective layer comprised of …”

Section: Discussionmentioning

confidence: 99%

Surface Immunolabeling and Consensus Computational Framework To Identify Candidate Rare Outer Membrane Proteins ofTreponema pallidum

Cox

Luthra²,

Dunham-Ems³

et al. 2010

Infect Immun

112

164

View full text Add to dashboard Cite

Treponema pallidum reacts poorly with the antibodies present in rabbit and human syphilitic sera, a property attributed to the paucity of proteins in its outer membrane. To better understand the basis for the syphilis spirochete's "stealth pathogenicity," we used a dual-label, 3-step amplified assay in which treponemes encapsulated in gel microdroplets were probed with syphilitic sera in parallel with anti-FlaA antibodies. A small (approximately 5 to 10%) but reproducible fraction of intact treponemes bound IgG and/or IgM antibodies. Three lines of evidence supported the notion that the surface antigens were likely ␤-barrel-forming outer membrane proteins (OMPs): (i) surface labeling with anti-lipoidal (VDRL) antibodies was not observed, (ii) immunoblot analysis confirmed prior results showing that T. pallidum glycolipids are not immunoreactive, and (iii) labeling of intact organisms was not appreciably affected by proteinase K (PK) treatment. With this method, we also demonstrate that TprK (TP0897), an extensively studied candidate OMP, and TP0136, a lipoprotein recently reported to be surface exposed, are both periplasmic. Consistent with the immunolabeling studies, TprK was also found to lack amphiphilicity, a characteristic property of ␤-barrel-forming proteins. Using a consensus computational framework that combined subcellular localization and ␤-barrel structural prediction tools, we generated ranked groups of candidate rare OMPs, the predicted T. pallidum outer membrane proteome (OMPeome), which we postulate includes the surface-exposed molecules detected by our enhanced gel microdroplet assay. In addition to underscoring the syphilis spirochete's remarkably poor surface antigenicity, our findings help to explain the complex and shifting balance between pathogen and host defenses that characterizes syphilitic infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Surface Immunolabeling and Consensus Computational Framework To Identify Candidate Rare Outer Membrane Proteins ofTreponema pallidum

Cox

Luthra²,

Dunham-Ems³

et al. 2010

Infect Immun

112

164

View full text Add to dashboard Cite

show abstract

“…Outer surfaces are the first bacterial component to encounter the host and are often the targets of host adaptive immunity. Early researchers noted that antibodies in serum from infected animals did not readily bind to intact treponemes (80,202). This observation was later supported by Penn and Rhodes (231), who found that only those treponemes that had been physically disrupted reacted with anti-T. pallidum antiserum, leading them to propose that the surface of T. pallidum is nonantigenic.…”

Section: Surface Of T Pallidummentioning

confidence: 98%

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 further difference between E. coli and T. pallidum in the mechanism of lysozyme action is that lysozyme acts on treponemes only in the presence of antibodies and complement. In contrast to ir: pallidum [2,41, lysozyme can penetrate into E. coli through the outer membrane and cell wall independent of antibody-and complement-mediated damage [9]. This finding may be attributed to the lack of lipopolysaccharide (LPS) in the outer membrane of T. pallidum [ 171.…”

Section: Discussionmentioning

confidence: 99%

Studies on the lysozyme independence of immune immobilisation of Treponema pallidum and the frequency of lysozyme autoantibodies in syphilitic sera

Zielinski

Borkhardt²

1997

Journal of Medical Microbiology

View full text Add to dashboard Cite

The role of lysozyme in the immune immobilisation of Treponerna pallidurn is not yet fully understood. The T. pallidurn immobilisation assay was used to demonstrate that the immobilisation and lysis of T. palliduin in vitro by antibodies (serum, IgG fraction or IgM fraction) and complement proceed in a lysozyme-independent mode. In the presence of lysozyme the rate of immobilisation increased. In contrast with its effect on Escherichia coli, the effect of lysozyme on T. pallidurn was governed exclusively by its enzymic activity rather than by the cationic protein nature of the molecule. Lysozyme, released from stimulated phagocytes, induced formation of lysozyme antibodies in 59.6% of syphilis patients as determined by lysozyme antibody ELISA. The highest frequency was found in patients with untreated secondary syphilis, whereas untreated primary syphilis was only rarely accompanied by the presence of lysozyme antibodies. Crossreactivities between lysozyme and treponemal antigens were excluded by immunoblotting. The autoantibodies did not influence the lysozyme activity. It was concluded that the formation of lysozyme antibodies is only an epiphenomenon in the host defence against treponemal infection.

show abstract

Influence of Lysozyme Upon the Treponeme Immobilization Reaction1

Cited by 22 publications

References 0 publications

Surface Immunolabeling and Consensus Computational Framework To Identify Candidate Rare Outer Membrane Proteins ofTreponema pallidum

Surface Immunolabeling and Consensus Computational Framework To Identify Candidate Rare Outer Membrane Proteins ofTreponema pallidum

Biological Basis for Syphilis

Studies on the lysozyme independence of immune immobilisation of Treponema pallidum and the frequency of lysozyme autoantibodies in syphilitic sera

Contact Info

Product

Resources

About