Complete genome sequences of two strains of Treponema pallidum subsp. pertenue from Ghana, Africa: Identical genome sequences in samples isolated more than 7 years apart.

Michal Strouhal,Ivan Rychlík,Darina Čejková,David Šmajs,Sylvia Bruisten,Pavla Havlíčková,Lenka Mikalová,Paolo Tenti,Sheila Lukehart

doi:10.1371/journal.pntd.0005894

Abstract

BackgroundTreponema pallidum subsp. pertenue (TPE) is the causative agent of yaws, a multi-stage disease, endemic in tropical regions of Africa, Asia, Oceania, and South America. To date, four TPE strains have been completely sequenced including three TPE strains of human origin (Samoa D, CDC-2, and Gauthier) and one TPE strain (Fribourg-Blanc) isolated from a baboon. All TPE strains are highly similar to T. pallidum subsp. pallidum (TPA) strains. The mutation rate in syphilis and related treponemes has not been experimentally determined yet.Methodology/Principal findingsComplete genomes of two TPE strains, CDC 2575 and Ghana-051, that infected patients in Ghana and were isolated in 1980 and 1988, respectively, were sequenced and analyzed. Both strains had identical consensus genome nucleotide sequences raising the question whether TPE CDC 2575 and Ghana-051 represent two different strains. Several lines of evidence support the fact that both strains represent independent samples including regions showing intrastrain heterogeneity (13 and 5 intrastrain heterogeneous sites in TPE Ghana-051 and TPE CDC 2575, respectively). Four of these heterogeneous sites were found in both genomes but the frequency of alternative alleles differed. The identical consensus genome sequences were used to estimate the upper limit of the yaws treponeme evolution rate, which was 4.1 x 10−10 nucleotide changes per site per generation.Conclusions/SignificanceThe estimated upper limit for the mutation rate of TPE was slightly lower than the mutation rate of E. coli, which was determined during a long-term experiment. Given the known diversity between TPA and TPE genomes and the assumption that both TPA and TPE have a similar mutation rate, the most recent common ancestor of syphilis and yaws treponemes appears to be more than ten thousand years old and likely even older.

Highlights

Treponema pallidum subsp. pertenue (TPE) is the causative agent of yaws, a multi-stage disease transmitted through direct skin contact between children or young adults; it is characterized by skin nodules and ulcerations and later accompanied by joint, soft tissue, and bone affections.To date, four TPE strains have been completely sequenced including three TPE strains of human origin (Samoa D, CDC-2, and Gauthier) [2] and one TPE strain (Fribourg-Blanc) isolated from a baboon (Papio papio) in West Africa [3]
Whole genome sequences of two TPE strains (CDC 2575 and Ghana-051) isolated from patients infected in Ghana, Africa, were determined
The identical genome sequence and the time between isolation of both TPE strains was used to estimate the upper limit of the yaws treponeme evolution rate, which was 4.1 x 10−10 per site per generation, a mutation rate that is slightly lower than the experimentally determined E. coli mutation rate

Summary

Introduction

Four TPE strains have been completely sequenced including three TPE strains of human origin (Samoa D, CDC-2, and Gauthier) [2] and one TPE strain (Fribourg-Blanc) isolated from a baboon (Papio papio) in West Africa [3]. Compared to syphilis-causing strains of T. pallidum subsp. One of the limitations was the fact that the mutation rate in syphilis and related treponemes was unknown, estimates have been published based on either paleopathological findings [6] or on phylogenetic analyses of TPA strains/isolates with known isolation dates [7]. Four TPE strains have been completely sequenced including three TPE strains of human origin (Samoa D, CDC-2, and Gauthier) and one TPE strain (Fribourg-Blanc) isolated from a baboon. The mutation rate in syphilis and related treponemes has not been experimentally determined yet

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