Biological Basis for Syphilis

LaFond, Rebecca E.; Lukehart, Sheila A.

doi:10.1128/cmr.19.1.29-49.2006

Cited by 505 publications

(590 citation statements)

References 324 publications

(259 reference statements)

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“…Syphilis is a chronic, complex sexually transmitted disease of humans caused by the noncultivatable spirochete Treponema pallidum (1,2). Despite the availability of effective antimicrobials, syphilis remains a significant threat to global health and can facilitate the transmission of human immunodeficiency virus (3)(4)(5).…”

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confidence: 99%

Crystal Structure of the Tp34 (TP0971) Lipoprotein of Treponema pallidum

Deka

Brautigam

Tomson

et al. 2007

Journal of Biological Chemistry

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The Tp34 (TP0971) membrane lipoprotein of Treponema pallidum, an obligate human pathogen and the agent of syphilis, was previously reported to have lactoferrin binding properties. Given the non-cultivatable nature of T. pallidum, a structureto-function approach was pursued to clarify further potential relationships between the Tp34 structural and biochemical properties and its propensity to bind human lactoferrin. The crystal structure of a nonacylated, recombinant form of Tp34 (rTp34), solved to a resolution of 1.9 Å , revealed two metaloccupied binding sites within a dimer; the identity of the ion most likely was zinc. Residues from both of the monomers contributed to the interfacial metal-binding sites; a novel feature was that the ␦-sulfur of methionine coordinated the zinc ion. Analytical ultracentrifugation showed that, in solution, rTp34 formed a metal-stabilized dimer and that rTp34 bound human lactoferrin with a stoichiometry of 2:1. Isothermal titration calorimetry further revealed that rTp34 bound human lactoferrin at high (submicromolar) affinity. Finally, membrane topology studies revealed that native Tp34 is not located on the outer surface (outer membrane) of T. pallidum but, rather, is periplasmic. How propensity of Tp34 to bind zinc and the iron-sequestering lactoferrin may relate overall to the biology of T. pallidum infection in humans is discussed.

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confidence: 99%

Crystal Structure of the Tp34 (TP0971) Lipoprotein of Treponema pallidum

Deka

Brautigam

Tomson

et al. 2007

Journal of Biological Chemistry

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“…89 Expression of the inflammatory cytokines IL-1, IL-6, IL-12 and TNF-α in dendritic cells (DCs) is stimulated by exposure to whole T. pallidum organisms or to synthetic TpN47, a recombinant lipopeptide that carries the immunodominant epitopes from T. pallidum. 90 Despite these advances towards the understanding of the intimate immunological basis of syphilis, with the description of potentially good candidate genes for investigation using genetic epidemiology tools, no published data describing association between genetic variants and syphilis phenotypes have become available to date.…”

Section: Syphilismentioning

confidence: 99%

Genetic risk factors for human susceptibility to infections of relevance in dermatology

Sardinha

Tarlé

Fava

et al. 2011

An. Bras. Dermatol.

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BACKGROUND: In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection. Keywords: Dermatology; Infection; Polymorphism, genetic Resumo: INTRODUÇÃO: Durante a era pré-microbiológica, era comum a visão de que doenças, hoje sabidamente infecciosas, eram hereditárias. Com a descoberta dos microorganismos e seu papel na patogênese de diversas patologias, chegou-se a propor que a exposição ao patógeno era condição suficiente para explicar infecção. Hoje, está claro que infecção é o resultado de uma complexa interação entre patógeno e hospedeiro, dependendo portanto, em última análise, do make-up genético de ambos os organismos. A dermatologia oferece diversos exemplos de doenças infecciosas em diferentes graus de entendimento de suas bases moleculares. Nesta revisão, resumimos os principais avanços na direção da dissecção do componente genético controlando suscetibilidade do ser humano a doenças infecciosas de importância na dermatologia. Doenças amplamente estudadas, como a hanseníase e a leishmaniose, são discutidas sob o ponto de vista da genética tanto do hospedeiro quanto do patógeno. Outras, como micobacterioses raras, micoses e sífilis, são apresentadas como boas oportunidades para pesquisa na área de genética de infecção.

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“…At this time a vaccine for syphilis is still under development and it only confers partial immunity; however, at least one animal study has demonstrated complete protection against T. pallidum [16]. Therefore, we also include vaccination in our model as a possible tool for controlling syphilis.…”

Section: Introductionmentioning

confidence: 99%

A New Mathematical Model of Syphilis

Milner

Zhao

2010

Math. Model. Nat. Phenom.

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Abstract. The CDC launched the National Plan to Eliminate Syphilis from the USA in October 1999 [4]. In order to reach this goal, a good understanding of the transmission dynamics of the disease is necessary. Based on a SIRS model Breban et al. [3] provided some evidence that supports the feasibility of the plan proving that no recurring outbreaks should occur for syphilis. We study in this work a syphilis model that includes partial immunity and vaccination. This model suggests that a backward bifurcation very likely occurs for the real-life estimated epidemiological parameters for syphilis. This may explain the resurgence of syphilis after mass treatment [21]. Occurrence of backward bifurcation brings a new challenge for the plan of the CDC's -striking a balance between treatment of early infection, vaccination development and health education. Our models suggest that the development of an effective vaccine, as well as health education that leads to enhanced biological and behavioral protection against infection in high-risk populations, are among the best ways to achieve the goal of elimination of syphilis in the USA.

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Biological Basis for Syphilis

Cited by 505 publications

References 324 publications

Crystal Structure of the Tp34 (TP0971) Lipoprotein of Treponema pallidum

Crystal Structure of the Tp34 (TP0971) Lipoprotein of Treponema pallidum

Genetic risk factors for human susceptibility to infections of relevance in dermatology

A New Mathematical Model of Syphilis

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