Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar
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Published:2021-12-22
Issue:12
Volume:15
Page:e0010063
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ISSN:1935-2735
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Container-title:PLOS Neglected Tropical Diseases
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language:en
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Short-container-title:PLoS Negl Trop Dis
Author:
Lieberman Nicole A. P.ORCID, Lin Michelle J.ORCID, Xie HongORCID, Shrestha Lasata, Nguyen Tien, Huang Meei-Li, Haynes Austin M.ORCID, Romeis EmilyORCID, Wang Qian-Qiu, Zhang Rui-Li, Kou Cai-XiaORCID, Ciccarese Giulia, Dal Conte Ivano, Cusini MarcoORCID, Drago Francesco, Nakayama Shu-ichiORCID, Lee KenichiORCID, Ohnishi Makoto, Konda Kelika A.ORCID, Vargas Silver K., Eguiluz Maria, Caceres Carlos F., Klausner Jeffrey D., Mitjà Oriol, Rompalo AnneORCID, Mulcahy Fiona, Hook Edward W., Lukehart Sheila A.ORCID, Casto Amanda M.ORCID, Roychoudhury Pavitra, DiMaio Frank, Giacani Lorenzo, Greninger Alexander L.ORCID
Abstract
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.
Funder
National Institute of Allergy and Infectious Diseases Ministry of Education, Culture, Sports, Science and Technology of Japan Japan Agency for Medical Research and Development
Publisher
Public Library of Science (PLoS)
Subject
Infectious Diseases,Public Health, Environmental and Occupational Health
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