Estimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>

ABSTRACT Immune evasion and disease progression of Treponema pallidum subsp. pallidum are associated with sequence diversity in the hypervariable outer membrane protein TprK. Previous attempts to study variation within TprK have sequenced at depths insufficient to fully appreciate the hypervariable...

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Autores principales:	Amin Addetia, Michelle J. Lin, Quynh Phung, Hong Xie, Meei-Li Huang, Giulia Ciccarese, Ivano Dal Conte, Marco Cusini, Francesco Drago, Lorenzo Giacani, Alexander L. Greninger
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	PacBio T. pallidum gene conversion immune evasion syphilis tprK Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/228d25d164af4f5a84dfd3ae4ebe36dc
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spelling	oai:doaj.org-article:228d25d164af4f5a84dfd3ae4ebe36dc2021-11-15T16:19:08ZEstimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>10.1128/mBio.02726-202150-7511https://doaj.org/article/228d25d164af4f5a84dfd3ae4ebe36dc2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02726-20https://doaj.org/toc/2150-7511ABSTRACT Immune evasion and disease progression of Treponema pallidum subsp. pallidum are associated with sequence diversity in the hypervariable outer membrane protein TprK. Previous attempts to study variation within TprK have sequenced at depths insufficient to fully appreciate the hypervariable nature of the protein, failed to establish linkage between the protein’s seven variable regions, or were conducted on isolates passed through rabbits. As a consequence, a complete profile of tprK during infection in the human host is still lacking. Furthermore, prior studies examining how T. pallidum subsp. pallidum uses its repertoire of genomic donor sites to generate diversity within the variable regions of the tprK have yielded a partial understanding of this process due to the limited number of tprK alleles examined. In this study, we used short- and long-read deep sequencing to directly characterize full-length tprK alleles from T. pallidum subsp. pallidum collected from early lesions of patients attending two sexually transmitted infection clinics in Italy. We demonstrate that strains collected from cases of secondary syphilis contain significantly more unique variable region sequences and full-length TprK sequences than those from cases of primary syphilis. Our data, combined with recent data available on Chinese T. pallidum subsp. pallidum specimens, show the near-complete absence of overlap in TprK sequences among the 41 specimens profiled to date. We further estimate that the potential antigenic variability carried by TprK rivals that of current estimates of the human adaptive immune system. These data underscore the immunoevasive ability of TprK that allows T. pallidum subsp. pallidum to establish lifelong infection. IMPORTANCE Syphilis continues to be a significant public health issue in both low- and high-income countries, including the United States where the rate of syphilis infection has increased over the past 5 years. Treponema pallidum subsp. pallidum, the causative agent of syphilis, carries the outer membrane protein TprK that undergoes segmental gene conversion to constantly create new sequences. We performed full-length deep sequencing of TprK to examine TprK diversity in clinical T. pallidum subsp. pallidum strains. We then combined our results with data from all samples for which TprK deep sequencing results were available. We found almost no overlap in TprK sequences between different patients. Moreover, our data allowed us to estimate the total number of TprK variants that T. pallidum subsp. pallidum can potentially generate. Our results support how the T. pallidum subsp. pallidum TprK antigenic variation system is an equal adversary of the human immune system leading to pathogen persistence in the host.Amin AddetiaMichelle J. LinQuynh PhungHong XieMeei-Li HuangGiulia CiccareseIvano Dal ConteMarco CusiniFrancesco DragoLorenzo GiacaniAlexander L. GreningerAmerican Society for MicrobiologyarticlePacBioT. pallidumgene conversionimmune evasionsyphilistprKMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	PacBio T. pallidum gene conversion immune evasion syphilis tprK Microbiology QR1-502
spellingShingle	PacBio T. pallidum gene conversion immune evasion syphilis tprK Microbiology QR1-502 Amin Addetia Michelle J. Lin Quynh Phung Hong Xie Meei-Li Huang Giulia Ciccarese Ivano Dal Conte Marco Cusini Francesco Drago Lorenzo Giacani Alexander L. Greninger Estimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>
description	ABSTRACT Immune evasion and disease progression of Treponema pallidum subsp. pallidum are associated with sequence diversity in the hypervariable outer membrane protein TprK. Previous attempts to study variation within TprK have sequenced at depths insufficient to fully appreciate the hypervariable nature of the protein, failed to establish linkage between the protein’s seven variable regions, or were conducted on isolates passed through rabbits. As a consequence, a complete profile of tprK during infection in the human host is still lacking. Furthermore, prior studies examining how T. pallidum subsp. pallidum uses its repertoire of genomic donor sites to generate diversity within the variable regions of the tprK have yielded a partial understanding of this process due to the limited number of tprK alleles examined. In this study, we used short- and long-read deep sequencing to directly characterize full-length tprK alleles from T. pallidum subsp. pallidum collected from early lesions of patients attending two sexually transmitted infection clinics in Italy. We demonstrate that strains collected from cases of secondary syphilis contain significantly more unique variable region sequences and full-length TprK sequences than those from cases of primary syphilis. Our data, combined with recent data available on Chinese T. pallidum subsp. pallidum specimens, show the near-complete absence of overlap in TprK sequences among the 41 specimens profiled to date. We further estimate that the potential antigenic variability carried by TprK rivals that of current estimates of the human adaptive immune system. These data underscore the immunoevasive ability of TprK that allows T. pallidum subsp. pallidum to establish lifelong infection. IMPORTANCE Syphilis continues to be a significant public health issue in both low- and high-income countries, including the United States where the rate of syphilis infection has increased over the past 5 years. Treponema pallidum subsp. pallidum, the causative agent of syphilis, carries the outer membrane protein TprK that undergoes segmental gene conversion to constantly create new sequences. We performed full-length deep sequencing of TprK to examine TprK diversity in clinical T. pallidum subsp. pallidum strains. We then combined our results with data from all samples for which TprK deep sequencing results were available. We found almost no overlap in TprK sequences between different patients. Moreover, our data allowed us to estimate the total number of TprK variants that T. pallidum subsp. pallidum can potentially generate. Our results support how the T. pallidum subsp. pallidum TprK antigenic variation system is an equal adversary of the human immune system leading to pathogen persistence in the host.
format	article
author	Amin Addetia Michelle J. Lin Quynh Phung Hong Xie Meei-Li Huang Giulia Ciccarese Ivano Dal Conte Marco Cusini Francesco Drago Lorenzo Giacani Alexander L. Greninger
author_facet	Amin Addetia Michelle J. Lin Quynh Phung Hong Xie Meei-Li Huang Giulia Ciccarese Ivano Dal Conte Marco Cusini Francesco Drago Lorenzo Giacani Alexander L. Greninger
author_sort	Amin Addetia
title	Estimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>
title_short	Estimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>
title_full	Estimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>
title_fullStr	Estimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>
title_full_unstemmed	Estimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>
title_sort	estimation of full-length tprk diversity in <named-content content-type="genus-species">treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/228d25d164af4f5a84dfd3ae4ebe36dc
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Estimation of Full-Length TprK Diversity in <named-content content-type="genus-species">Treponema pallidum</named-content> subsp. <italic toggle="yes">pallidum</italic>

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