Phylogenetic and genetic characterization of Treponema pallidum strains from syphilis patients in Japan by whole-genome sequence analysis from global perspectives

Nishiki, Shingo; Lee, Ken-ichi; Kanai, Mizue; Nakayama, Shuichi; Ohnishi, Makoto

doi:10.1038/s41598-021-82337-7

Cited by 12 publications

(13 citation statements)

References 30 publications

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“…Interestingly, both the Japanese and Italian patients whose samples are included in this subclade report their sexual orientation as MSM; one French sample, CW59, was collected from an anal smear. Although this is hardly conclusive, the appearance of distinct TPA clades circulating among MSM individuals has recently been documented in Japan [ 27 ], suggesting that this phenomenon may be occurring worldwide.…”

Section: Resultsmentioning

confidence: 99%

“…In recent years, T. pallidum genomics has been significantly advanced by projects aimed at studying the origin and spread of strains responsible for the modern syphilis pandemic [24,27,37,40,66], as well as the emergence of azithromycin resistance [24,27,66]. Increasingly the challenge in T. pallidum genomics will be attaining complete genomic sequences from undersampled regions, associating genomic sequencing with spirochete biochemical functions, and gaining actionable insights into T. pallidum evolution that inform vaccine design.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar

et al. 2021

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar

et al. 2021

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“…Interestingly, both the Japanese and Italian patients whose samples are included in this subclade report their sexual orientation as MSM; one French sample, CW59, was collected from an anal smear. Although this is hardly conclusive, the appearance of distinct TPA clades circulating among MSM individuals has recently been documented in Japan (26), suggesting that this phenomenon may be occurring worldwide.…”

Section: Resultsmentioning

confidence: 99%

“…In recent years, T. pallidum genomics has been significantly advanced by projects aimed at studying the origin and spread of strains responsible for the modern syphilis pandemic (24,26,36,39,63), as well as the emergence of azithromycin resistance (24,26,63). Increasingly the challenge in T. pallidum genomics will be attaining complete genomic sequences from undersampled regions, associating genomic sequencing with spirochete biochemical functions, and gaining actionable insights into T. pallidum evolution that inform vaccine design.…”

Section: Discussionmentioning

confidence: 99%

Genome sequencing of 196 Treponema pallidum strains from six continents reveals additional variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar

Lieberman

Lin

Xie

et al. 2021

Preprint

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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.

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Increased cervical Chlamydia trachomatis and syphilis infections in Japanese females of reproductive age in the late 2010s: Possible cause

Shimano

Mariya

Saito

2021

Journal of Infection and Chemotherapy

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From 2000 to 2019, Japan's reproductive-age population gradually declined by 24%. In comparison, the Chlamydia trachomatis infection rate increased from 2016, with the syphilis infection rate increasing more sharply from 2014. Since 2013, the numbers of foreign tourists to Japan have also increased. From 2011 to 2018, the rate of increase in tourists was 5.02 times, while the rate of increase in syphilis patients was higher at 22.4 times. The lack of a one-to-one relationship between foreign tourists and syphilis cases suggests that cases of syphilis were transmitted to others. Although the prevalence of syphilis in the tourists' home countries (Korea in 2014 and China in 2013) was 20-30 times higher than that in Japan, the Japanese sex industry did not discriminate against foreign tourists, leading to increased STI infections in Japanese female sex workers. Indeed, from 2017 to 2018, a history of working in the sex industry for six months was identified as a risk factor for syphilis. The rise in Chlamydia trachomatis infections has lagged behind that of syphilis by two years, with the rate of increase lower. We suspect the difference in increasing rates of syphilis and chlamydial infections is due to the different methods of infection: syphilis can be transmitted by light physical contact, such as a kiss, whereas chlamydia requires close sexual contact, such as oral sex or sexual intercourse. Regardless, examinations and infection control are necessary to prevent the spread of STIs in Japan due to inbound tourists.

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Phylogenetic and genetic characterization of Treponema pallidum strains from syphilis patients in Japan by whole-genome sequence analysis from global perspectives

Cited by 12 publications

References 30 publications

Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar

Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar

Genome sequencing of 196 Treponema pallidum strains from six continents reveals additional variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar

Increased cervical Chlamydia trachomatis and syphilis infections in Japanese females of reproductive age in the late 2010s: Possible cause

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