High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny

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  • Lieberman, Nicole A. P.
    • Other Affiliation: University of Washington
  • Armstrong, Thaddeus D.
    • Other Affiliation: University of Washington
  • Chung, Benjamin
    • Other Affiliation: University of Washington
  • Pfalmer, Daniel
    • Other Affiliation: University of Washington
  • Hennelly, Christopher M.
    • Affiliation: School of Medicine, Division of Infectious Diseases
  • Haynes, Austin
    • Other Affiliation: University of Washington
  • Romeis, Emily
    • Other Affiliation: University of Washington
  • Wang, Qian-Qiu
    • Other Affiliation: Chinese Academy of Medical Sciences
  • Zhang, Rui-Li
    • Other Affiliation: The Second Affiliated Hospital of Nanjing Medical University
  • Kou, Cai-Xia
    • Other Affiliation: Chinese Academy of Medical Sciences
  • Ciccarese, Giulia
    • Other Affiliation: San Martino University Hospital
  • Conte, Ivano Dal
    • Other Affiliation: ASL Città di Torino
  • Cusini, Marco
    • Other Affiliation: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Drago, Francesco
    • Other Affiliation: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Nakayama, Shu-ichi
    • Other Affiliation: National Institute of Infectious Diseases
  • Lee, Kenichi
    • Other Affiliation: National Institute of Infectious Diseases
  • Ohnishi, Makoto
    • Other Affiliation: National Institute of Infectious Diseases
  • Konda, Kelika A.
    • Other Affiliation: Universidad Peruana Cayetano-Heredia
  • Vargas, Silver K.
    • Other Affiliation: Universidad Peruana Cayetano-Heredia
  • Eguiluz, Maria
    • Other Affiliation: Universidad Peruana Cayetano-Heredia
  • Caceres, Carlos F.
    • Other Affiliation: Universidad Peruana Cayetano-Heredia
  • Klausner, Jeffrey D.
    • Other Affiliation: University of Southern California
  • Mitja, Oriol
    • Other Affiliation: Hospital Germans Trias i Pujol
  • Rompalo, Anne
    • Other Affiliation: Johns Hopkins Medical Institutions
  • Mulcahy, Fiona
    • Other Affiliation: St. James's Hospital
  • Hook, Edward W.
    • Other Affiliation: University of Alabama at Birmingham
  • Hoffman, Irving F.
    • Affiliation: School of Medicine, Division of Infectious Diseases
  • Matoga, Mitch M.
    • Affiliation: School of Medicine, Division of Infectious Diseases
  • Zheng, Heping
    • Other Affiliation: Dermatology Hospital of Southern Medical University
  • Yang, Bin
    • Other Affiliation: Dermatology Hospital of Southern Medical University
  • Lopez-Medina, Eduardo
    • Other Affiliation: Centro Internacional de Entrenamiento e Investigaciones Medicas
  • Ramirez, Lady G.
    • Other Affiliation: Centro Internacional de Entrenamiento e Investigaciones Medicas
  • Radolf, Justin D.
    • Other Affiliation: UConn Health
  • Hawley, Kelly L.
    • Other Affiliation: UConn Health
  • Salazar, Juan C.
    • Other Affiliation: UConn Health
  • Lukehart, Sheila A.
    • Other Affiliation: University of Washington
  • Seña, Arlene C.
    • Affiliation: School of Medicine, Division of Infectious Diseases
  • Parr, Jonathan B.
    • Affiliation: School of Medicine, Division of Infectious Diseases
  • Giacani, Lorenzo
    • Other Affiliation: University of Washington
  • Greninger, Alexander L.
    • Other Affiliation: University of Washington
Abstract
  • Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Frontiers in Microbiology
Journal volume
  • 13
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  • English
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  • Publisher
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  • 1664-302X

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