Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete

ABSTRACT In recent years, considerable progress has been made in topologically and functionally characterizing integral outer membrane proteins (OMPs) of Treponema pallidum subspecies pallidum, the syphilis spirochete, and identifying its surface-exposed β-barrel domains. Extracellular loops in OMPs...

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Autores principales:	Sanjiv Kumar, Melissa J. Caimano, Arvind Anand, Abhishek Dey, Kelly L. Hawley, Morgan E. LeDoyt, Carson J. La Vake, Adriana R. Cruz, Lady G. Ramirez, Lenka Paštěková, Irina Bezsonova, David Šmajs, Juan C. Salazar, Justin D. Radolf
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Treponema pallidum molecular subtyping outer membrane proteins spirochetes syphilis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d25ff22293a7468aa42550e7b756fb21
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spelling	oai:doaj.org-article:d25ff22293a7468aa42550e7b756fb212021-11-15T16:00:26ZSequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete10.1128/mBio.01006-182150-7511https://doaj.org/article/d25ff22293a7468aa42550e7b756fb212018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01006-18https://doaj.org/toc/2150-7511ABSTRACT In recent years, considerable progress has been made in topologically and functionally characterizing integral outer membrane proteins (OMPs) of Treponema pallidum subspecies pallidum, the syphilis spirochete, and identifying its surface-exposed β-barrel domains. Extracellular loops in OMPs of Gram-negative bacteria are known to be highly variable. We examined the sequence diversity of β-barrel-encoding regions of tprC, tprD, and bamA in 31 specimens from Cali, Colombia; San Francisco, California; and the Czech Republic and compared them to allelic variants in the 41 reference genomes in the NCBI database. To establish a phylogenetic framework, we used T. pallidum 0548 (tp0548) genotyping and tp0558 sequences to assign strains to the Nichols or SS14 clades. We found that (i) β-barrels in clinical strains could be grouped according to allelic variants in T. pallidum subsp. pallidum reference genomes; (ii) for all three OMP loci, clinical strains within the Nichols or SS14 clades often harbored β-barrel variants that differed from the Nichols and SS14 reference strains; and (iii) OMP variable regions often reside in predicted extracellular loops containing B-cell epitopes. On the basis of structural models, nonconservative amino acid substitutions in predicted transmembrane β-strands of T. pallidum repeat C (TprC) and TprD2 could give rise to functional differences in their porin channels. OMP profiles of some clinical strains were mosaics of different reference strains and did not correlate with results from enhanced molecular typing. Our observations suggest that human host selection pressures drive T. pallidum subsp. pallidum OMP diversity and that genetic exchange contributes to the evolutionary biology of T. pallidum subsp. pallidum. They also set the stage for topology-based analysis of antibody responses to OMPs and help frame strategies for syphilis vaccine development. IMPORTANCE Despite recent progress characterizing outer membrane proteins (OMPs) of Treponema pallidum, little is known about how their surface-exposed, β-barrel-forming domains vary among strains circulating within high-risk populations. In this study, sequences for the β-barrel-encoding regions of three OMP loci, tprC, tprD, and bamA, in T. pallidum subsp. pallidum isolates from a large number of patient specimens from geographically disparate sites were examined. Structural models predict that sequence variation within β-barrel domains occurs predominantly within predicted extracellular loops. Amino acid substitutions in predicted transmembrane strands that could potentially affect porin channel function were also noted. Our findings suggest that selection pressures exerted within human populations drive T. pallidum subsp. pallidum OMP diversity and that recombination at OMP loci contributes to the evolutionary biology of syphilis spirochetes. These results also set the stage for topology-based analysis of antibody responses that promote clearance of T. pallidum subsp. pallidum and frame strategies for vaccine development based upon conserved OMP extracellular loops.Sanjiv KumarMelissa J. CaimanoArvind AnandAbhishek DeyKelly L. HawleyMorgan E. LeDoytCarson J. La VakeAdriana R. CruzLady G. RamirezLenka PaštěkováIrina BezsonovaDavid ŠmajsJuan C. SalazarJustin D. RadolfAmerican Society for MicrobiologyarticleTreponema pallidummolecular subtypingouter membrane proteinsspirochetessyphilisMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Treponema pallidum molecular subtyping outer membrane proteins spirochetes syphilis Microbiology QR1-502
spellingShingle	Treponema pallidum molecular subtyping outer membrane proteins spirochetes syphilis Microbiology QR1-502 Sanjiv Kumar Melissa J. Caimano Arvind Anand Abhishek Dey Kelly L. Hawley Morgan E. LeDoyt Carson J. La Vake Adriana R. Cruz Lady G. Ramirez Lenka Paštěková Irina Bezsonova David Šmajs Juan C. Salazar Justin D. Radolf Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete
description	ABSTRACT In recent years, considerable progress has been made in topologically and functionally characterizing integral outer membrane proteins (OMPs) of Treponema pallidum subspecies pallidum, the syphilis spirochete, and identifying its surface-exposed β-barrel domains. Extracellular loops in OMPs of Gram-negative bacteria are known to be highly variable. We examined the sequence diversity of β-barrel-encoding regions of tprC, tprD, and bamA in 31 specimens from Cali, Colombia; San Francisco, California; and the Czech Republic and compared them to allelic variants in the 41 reference genomes in the NCBI database. To establish a phylogenetic framework, we used T. pallidum 0548 (tp0548) genotyping and tp0558 sequences to assign strains to the Nichols or SS14 clades. We found that (i) β-barrels in clinical strains could be grouped according to allelic variants in T. pallidum subsp. pallidum reference genomes; (ii) for all three OMP loci, clinical strains within the Nichols or SS14 clades often harbored β-barrel variants that differed from the Nichols and SS14 reference strains; and (iii) OMP variable regions often reside in predicted extracellular loops containing B-cell epitopes. On the basis of structural models, nonconservative amino acid substitutions in predicted transmembrane β-strands of T. pallidum repeat C (TprC) and TprD2 could give rise to functional differences in their porin channels. OMP profiles of some clinical strains were mosaics of different reference strains and did not correlate with results from enhanced molecular typing. Our observations suggest that human host selection pressures drive T. pallidum subsp. pallidum OMP diversity and that genetic exchange contributes to the evolutionary biology of T. pallidum subsp. pallidum. They also set the stage for topology-based analysis of antibody responses to OMPs and help frame strategies for syphilis vaccine development. IMPORTANCE Despite recent progress characterizing outer membrane proteins (OMPs) of Treponema pallidum, little is known about how their surface-exposed, β-barrel-forming domains vary among strains circulating within high-risk populations. In this study, sequences for the β-barrel-encoding regions of three OMP loci, tprC, tprD, and bamA, in T. pallidum subsp. pallidum isolates from a large number of patient specimens from geographically disparate sites were examined. Structural models predict that sequence variation within β-barrel domains occurs predominantly within predicted extracellular loops. Amino acid substitutions in predicted transmembrane strands that could potentially affect porin channel function were also noted. Our findings suggest that selection pressures exerted within human populations drive T. pallidum subsp. pallidum OMP diversity and that recombination at OMP loci contributes to the evolutionary biology of syphilis spirochetes. These results also set the stage for topology-based analysis of antibody responses that promote clearance of T. pallidum subsp. pallidum and frame strategies for vaccine development based upon conserved OMP extracellular loops.
format	article
author	Sanjiv Kumar Melissa J. Caimano Arvind Anand Abhishek Dey Kelly L. Hawley Morgan E. LeDoyt Carson J. La Vake Adriana R. Cruz Lady G. Ramirez Lenka Paštěková Irina Bezsonova David Šmajs Juan C. Salazar Justin D. Radolf
author_facet	Sanjiv Kumar Melissa J. Caimano Arvind Anand Abhishek Dey Kelly L. Hawley Morgan E. LeDoyt Carson J. La Vake Adriana R. Cruz Lady G. Ramirez Lenka Paštěková Irina Bezsonova David Šmajs Juan C. Salazar Justin D. Radolf
author_sort	Sanjiv Kumar
title	Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete
title_short	Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete
title_full	Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete
title_fullStr	Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete
title_full_unstemmed	Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete
title_sort	sequence variation of rare outer membrane protein β-barrel domains in clinical strains provides insights into the evolution of <italic toggle="yes">treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the syphilis spirochete
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/d25ff22293a7468aa42550e7b756fb21
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Sequence Variation of Rare Outer Membrane Protein β-Barrel Domains in Clinical Strains Provides Insights into the Evolution of <italic toggle="yes">Treponema pallidum</italic> subsp. <italic toggle="yes">pallidum</italic>, the Syphilis Spirochete

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