Rapidity With Which Spirochaeta Pallida Invades the Blood Stream

Raiziss, George W.; Severac, M.

doi:10.1001/archderm.1937.01470240093008

Cited by 51 publications

(29 citation statements)

References 11 publications

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“…Infection with T. pallidum typically manifests as a painless chancre at the site of infection approximately 3 weeks after pathogen exposure (6). Multiple studies have demonstrated that the pathogen is capable of invading tissue barriers and undergoing rapid widespread dissemination via the circulatory system (7)(8)(9)(10). The highly invasive nature of T. pallidum is further highlighted by its ability to traverse the placental barrier to cause congenital syphilis and the blood-brain barrier to invade the central nervous system (9) and by the diverse and widespread clinical manifestations associated with secondary and tertiary syphilis (6).…”

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Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum

et al. 2015

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The spirochete Treponema pallidum subsp. pallidum is the causative agent of syphilis, a chronic, sexually transmitted infection characterized by multiple symptomatic and asymptomatic stages. Although several other species in the genus are able to cause or contribute to disease, T. pallidum differs in that it is able to rapidly disseminate via the bloodstream to tissue sites distant from the site of initial infection. It is also the only Treponema species able to cross both the blood-brain and placental barriers. Previously, the T. pallidum proteins, Tp0750 and Tp0751 (also called pallilysin), were shown to degrade host proteins central to blood coagulation and basement membrane integrity, suggesting a role for these proteins in T. pallidum dissemination and tissue invasion. In the present study, we characterized Tp0750 and Tp0751 sequence variation in a diversity of pathogenic and nonpathogenic treponemes. We also determined the proteolytic potential of the orthologs from the less invasive species Treponema denticola and Treponema phagedenis. These analyses showed high levels of sequence similarity among Tp0750 orthologs from pathogenic species. For pallilysin, lower levels of sequence conservation were observed between this protein and orthologs from other treponemes, except for the ortholog from the highly invasive rabbit venereal syphilis-causing Treponema paraluiscuniculi. In vitro host component binding and degradation assays demonstrated that pallilysin and Tp0750 orthologs from the less invasive treponemes tested were not capable of binding or degrading host proteins. The results show that pallilysin and Tp0750 host protein binding and degradative capability is positively correlated with treponemal invasiveness.

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Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum

et al. 2015

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“…The bacterium gains entry to the host through intact mucosal barriers or microscopic epidermal abrasions (42). The organism is highly invasive, with in vitro studies showing that T. pallidum is able to penetrate endothelial cell monolayers to enter the bloodstream (45,50) within hours of infection (13,43). Treponemal invasion results in widespread bacterial dissemination, which, in turn, sets the stage for establishment of chronic infection.…”

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Heterologous Expression of theTreponema pallidumLaminin-Binding Adhesin Tp0751 in the Culturable SpirocheteTreponema phagedenis

et al. 2008

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Treponema pallidum subsp. pallidum, the causative agent of syphilis, is an unculturable, genetically intractable bacterium. Here we report the use of the shuttle vector pKMR4PEMCS for the expression of a previously identified T. pallidum laminin-binding adhesin, Tp0751, in the nonadherent, culturable spirochete Treponema phagedenis. Heterologous expression of Tp0751 in T. phagedenis was confirmed via reverse transcriptase PCR analysis with tp0751 gene-specific primers and immunofluorescence analysis with Tp0751-specific antibodies; the latter assay verified the expression of the laminin-binding adhesin on the treponemal surface. Expression of Tp0751 within T. phagedenis was functionally confirmed via laminin attachment assays, in which heterologous Tp0751 expression conferred upon T. phagedenis the capacity to attach to laminin. Further, specific inhibition of the attachment of T. phagedenis heterologously expressing Tp0751 to laminin was achieved by using purified antibodies raised against recombinant T. pallidum Tp0751. This is the first report of heterologous expression of a gene from an unculturable treponeme in T. phagedenis. This novel methodology will significantly advance the field of syphilis research by allowing targeted investigations of T. pallidum proteins purported to play a role in pathogenesis, and specifically host cell attachment, in the nonadherent spirochete T. phagedenis.

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“…The pathogen has limited toxigenic properties, and tissue destruction associated with the disease appears to be due to the strong inflammatory response mounted by the host following infection (64). The organism is highly invasive; treponemes disseminate widely within hours of infection in experimental animals (11,59), and in vitro studies have shown that T. pallidum is able to penetrate intact membranes and endothelial cell monolayers (62,69). Treponemal invasion results in widespread bacterial dissemination, which in turn sets the stage for establishment of chronic infection.…”

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Defining the Interaction of theTreponema pallidumAdhesin Tp0751 with Laminin

et al. 2005

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Various invasive pathogens attach to host tissues via the extracellular matrix component laminin, the major glycoprotein found within basement membranes. Previous investigations identified the laminin-binding adhesin Tp0751 within the spirochete bacterium Treponema pallidum. In the current study, Tp0751 was shown to attach to a variety of laminin isoforms that are widely distributed throughout the host, including laminins 1, 2, 4, 8, and 10. Such universal attachment is conducive for an adhesin present within a highly invasive pathogen that encounters a variety of tissue sites during the course of infection. Additional studies systematically identified the amino acid residues within Tp0751 that contribute to laminin binding using synthetic peptides designed from the mature protein sequence. The minimum laminin-binding region of the adhesin was localized to 10 amino acids; peptides containing these residues inhibited attachment of Tp0751 and T. pallidum to laminin. Further, Tp0751-specific antibodies inhibited attachment of T. pallidum to laminin. This study furthers our knowledge of the interaction of T. pallidum with laminin, an association that is proposed to facilitate bacterial traversal of basement membranes and subsequent entry into the circulation and tissue invasion. As such, these investigations will reveal new targets for possible prevention of bacterial dissemination and establishment of chronic infection.

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Rapidity With Which Spirochaeta Pallida Invades the Blood Stream

Cited by 51 publications

References 11 publications

Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum

Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum

Heterologous Expression of theTreponema pallidumLaminin-Binding Adhesin Tp0751 in the Culturable SpirocheteTreponema phagedenis

Defining the Interaction of theTreponema pallidumAdhesin Tp0751 with Laminin

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