Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar.
In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail t...
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ftdoajarticles:oai:doaj.org/article:f8f88374a8944331bc4a55f2256ab665 2023-05-15T15:13:50+02:00 Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. Nicole A P Lieberman Michelle J Lin Hong Xie Lasata Shrestha Tien Nguyen Meei-Li Huang Austin M Haynes Emily Romeis Qian-Qiu Wang Rui-Li Zhang Cai-Xia Kou Giulia Ciccarese Ivano Dal Conte Marco Cusini Francesco Drago Shu-Ichi Nakayama Kenichi Lee Makoto Ohnishi Kelika A Konda Silver K Vargas Maria Eguiluz Carlos F Caceres Jeffrey D Klausner Oriol Mitjà Anne Rompalo Fiona Mulcahy Edward W Hook Sheila A Lukehart Amanda M Casto Pavitra Roychoudhury Frank DiMaio Lorenzo Giacani Alexander L Greninger 2021-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010063 https://doaj.org/article/f8f88374a8944331bc4a55f2256ab665 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010063 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010063 https://doaj.org/article/f8f88374a8944331bc4a55f2256ab665 PLoS Neglected Tropical Diseases, Vol 15, Iss 12, p e0010063 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010063 2022-12-31T16:01:38Z In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of an in vitro culture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196 T. pallidum strains-including 191 T. pallidum subsp. pallidum-sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events between T. pallidum subsp. pallidum and subsp. endemicum, shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543-1869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 12 e0010063 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Nicole A P Lieberman Michelle J Lin Hong Xie Lasata Shrestha Tien Nguyen Meei-Li Huang Austin M Haynes Emily Romeis Qian-Qiu Wang Rui-Li Zhang Cai-Xia Kou Giulia Ciccarese Ivano Dal Conte Marco Cusini Francesco Drago Shu-Ichi Nakayama Kenichi Lee Makoto Ohnishi Kelika A Konda Silver K Vargas Maria Eguiluz Carlos F Caceres Jeffrey D Klausner Oriol Mitjà Anne Rompalo Fiona Mulcahy Edward W Hook Sheila A Lukehart Amanda M Casto Pavitra Roychoudhury Frank DiMaio Lorenzo Giacani Alexander L Greninger Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of an in vitro culture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196 T. pallidum strains-including 191 T. pallidum subsp. pallidum-sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events between T. pallidum subsp. pallidum and subsp. endemicum, shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543-1869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens. |
format |
Article in Journal/Newspaper |
author |
Nicole A P Lieberman Michelle J Lin Hong Xie Lasata Shrestha Tien Nguyen Meei-Li Huang Austin M Haynes Emily Romeis Qian-Qiu Wang Rui-Li Zhang Cai-Xia Kou Giulia Ciccarese Ivano Dal Conte Marco Cusini Francesco Drago Shu-Ichi Nakayama Kenichi Lee Makoto Ohnishi Kelika A Konda Silver K Vargas Maria Eguiluz Carlos F Caceres Jeffrey D Klausner Oriol Mitjà Anne Rompalo Fiona Mulcahy Edward W Hook Sheila A Lukehart Amanda M Casto Pavitra Roychoudhury Frank DiMaio Lorenzo Giacani Alexander L Greninger |
author_facet |
Nicole A P Lieberman Michelle J Lin Hong Xie Lasata Shrestha Tien Nguyen Meei-Li Huang Austin M Haynes Emily Romeis Qian-Qiu Wang Rui-Li Zhang Cai-Xia Kou Giulia Ciccarese Ivano Dal Conte Marco Cusini Francesco Drago Shu-Ichi Nakayama Kenichi Lee Makoto Ohnishi Kelika A Konda Silver K Vargas Maria Eguiluz Carlos F Caceres Jeffrey D Klausner Oriol Mitjà Anne Rompalo Fiona Mulcahy Edward W Hook Sheila A Lukehart Amanda M Casto Pavitra Roychoudhury Frank DiMaio Lorenzo Giacani Alexander L Greninger |
author_sort |
Nicole A P Lieberman |
title |
Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. |
title_short |
Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. |
title_full |
Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. |
title_fullStr |
Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. |
title_full_unstemmed |
Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. |
title_sort |
treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of nichols clade strains in madagascar. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0010063 https://doaj.org/article/f8f88374a8944331bc4a55f2256ab665 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 12, p e0010063 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010063 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010063 https://doaj.org/article/f8f88374a8944331bc4a55f2256ab665 |
op_doi |
https://doi.org/10.1371/journal.pntd.0010063 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
12 |
container_start_page |
e0010063 |
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1766344345438388224 |