Title
Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar
Date Issued
01 December 2021
Access level
open access
Resource Type
journal article
Author(s)
Lieberman N.A.P.
Lin M.J.
Xie H.
Shrestha L.
Nguyen T.
Huang M.L.
Haynes A.M.
Romeis E.
Wang Q.Q.
Zhang R.L.
Kou C.X.
Ciccarese G.
Dal Conte I.
Cusini M.
Drago F.
Nakayama S.I.
Lee K.
Ohnishi M.
Klausner J.D.
Mitjà O.
Rompalo A.
Mulcahy F.
Hook E.W.
Lukehart S.A.
Casto A.M.
Roychoudhury P.
Dimaio F.
Giacani L.
Greninger A.L.
Publisher(s)
Public Library of Science
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 criti-cal resource for the design of broadly protective syphilis vaccines targeting surface antigens.
Volume
15
Issue
12
Language
English
OCDE Knowledge area
Inmunología Genética, Herencia
Scopus EID
2-s2.0-85122217142
PubMed ID
Source
PLoS Neglected Tropical Diseases
ISSN of the container
19352727
Sponsor(s)
This work was supported by the National Institute for Allergy and Infectious Diseases of the National Institutes of Health grant number U19AI144133 (Project 2 and Genomics and Isolation Core; Project 2 leader: L.G.; Core leaders: L.G. and A.L.G.; PI: Anna Wald, University of Washington), as well grants from Ministry of Education, Culture, Sports, Science and Technology of Japan (number 21K09388) to S.N. and from Japan Agency for Medical Research and Development (number 21fk0108091j0303) to M.O. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Sources of information: Directorio de Producción Científica Scopus