Treponema pallidum subsp. pallidum TP0136 protein is heterogeneous among isolates and binds cellular and plasma fibronectin via its NH2-terminal end

PLoS Neglected Tropical Diseases
Wujian KeLorenzo Giacani

Abstract

Adherence-mediated colonization plays an important role in pathogenesis of microbial infections, particularly those caused by extracellular pathogens responsible for systemic diseases, such as Treponema pallidum subsp. pallidum (T. pallidum), the agent of syphilis. Among T. pallidum adhesins, TP0136 is known to bind fibronectin (Fn), an important constituent of the host extracellular matrix. To deepen our understanding of the TP0136-Fn interaction dynamics, we used two naturally-occurring sequence variants of the TP0136 protein to investigate which region of the protein is responsible for Fn binding, and whether TP0136 would adhere to human cellular Fn in addition to plasma Fn and super Fn as previously reported. Fn binding assays were performed with recombinant proteins representing the two full-length TP0136 variants and their discrete regions. As a complementary approach, we tested inhibition of T. pallidum binding to Fn by recombinant full-length TP0136 proteins and fragments, as well as by anti-TP0136 immune sera. Our results show that TP0136 adheres more efficiently to cellular Fn than to plasma Fn, that the TP0136 NH2-terminal conserved region of the protein is primarily responsible for binding to plasma Fn but that bind...Continue Reading

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Citations

Nov 1, 2016·Nature Reviews. Microbiology·Justin D RadolfX Frank Yang
Jun 22, 2016·Expert Review of Vaccines·Karen V Lithgow, Caroline E Cameron
Oct 13, 2017·Nature Reviews. Disease Primers·Rosanna W PeelingAdele S Benzaken
Dec 20, 2019·Journal of the European Academy of Dermatology and Venereology : JEADV·X LuoT-C Yang
Apr 7, 2020·PLoS Neglected Tropical Diseases·Amin AddetiaAlexander L Greninger
May 20, 2017·BioMed Research International·Aleksey KubanovDmitry Deryabin

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Methods Mentioned

BETA
PCR
electrophoresis
biopsies
biopsy
ELISA

Software Mentioned

Primer3
LightCycler

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