@article{81ddf4aa1fa04d929f2ebaa98714bb36,
title = "High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny",
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.",
keywords = "AlphaFold, genomics, nanopore, next generation sequencing (NGS), SPOR domain, syphilis, Treponema pallidum, trRosetta",
author = "Lieberman, {Nicole A.P.} and Armstrong, {Thaddeus D.} and Benjamin Chung and Daniel Pfalmer and Hennelly, {Christopher M.} and Austin Haynes and Emily Romeis and Wang, {Qian Qiu} and Zhang, {Rui Li} and Kou, {Cai Xia} and Giulia Ciccarese and Conte, {Ivano Dal} and Marco Cusini and Francesco Drago and Nakayama, {Shu Ichi} and Kenichi Lee and Makoto Ohnishi and Konda, {Kelika A.} and Vargas, {Silver K.} and Maria Eguiluz and Caceres, {Carlos F.} and Klausner, {Jeffrey D.} and Oriol Mitja and Anne Rompalo and Fiona Mulcahy and Hook, {Edward W.} and Hoffman, {Irving F.} and Matoga, {Mitch M.} and Heping Zheng and Bin Yang and Eduardo Lopez-Medina and Ramirez, {Lady G.} and Radolf, {Justin D.} and Hawley, {Kelly L.} and Salazar, {Juan C.} and Lukehart, {Sheila A.} and Se{\~n}a, {Arlene C.} and Parr, {Jonathan B.} and Lorenzo Giacani and Greninger, {Alexander L.}",
note = "Funding Information: This work was supported, in whole or in part, by the Bill and Melinda Gates Foundation INV-036560. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the author accepted manuscript version that might arise from this submission (AG, LG, JP, AS, JR, and KH). This work was further supported by NIAID grant numbers U19AI144133 (LG and AG), U19AI144177 (JR, KH, JS, AS, and JP), and R01AI139265 (to JK), as well as grants from Ministry of Education, Culture, Sports, Science and Technology of Japan (number 21K09388) to S-IN and from Japan Agency for Medical Research and Development (number 21fk0108091j0303) to MO. Additional research funds were generously provided by Connecticut Children{\textquoteright}s (JS, JR, and KH). Funding Information: This work was supported, in whole or in part, by the Bill and Melinda Gates Foundation INV-036560. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the author accepted manuscript version that might arise from this submission (AG, LG, JP, AS, JR, and KH). This work was further supported by NIAID grant numbers U19AI144133 (LG and AG), U19AI144177 (JR, KH, JS, AS, and JP), and R01AI139265 (to JK), as well as grants from Ministry of Education, Culture, Sports, Science and Technology of Japan (number 21K09388) to S-IN and from Japan Agency for Medical Research and Development (number 21fk0108091j0303) to MO. Additional research funds were generously provided by Connecticut Children{\textquoteright}s (JS, JR, and KH). Publisher Copyright: Copyright {\textcopyright} 2022 Lieberman, Armstrong, Chung, Pfalmer, Hennelly, Haynes, Romeis, Wang, Zhang, Kou, Ciccarese, Conte, Cusini, Drago, Nakayama, Lee, Ohnishi, Konda, Vargas, Eguiluz, Caceres, Klausner, Mitja, Rompalo, Mulcahy, Hook, Hoffman, Matoga, Zheng, Yang, Lopez-Medina, Ramirez, Radolf, Hawley, Salazar, Lukehart, Se{\~n}a, Parr, Giacani and Greninger.",
year = "2022",
month = sep,
day = "20",
doi = "10.3389/fmicb.2022.1007056",
language = "English",
volume = "13",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
publisher = "Frontiers Media S. A.",
}