Abstract

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84) affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9%) of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits) during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies.

Highlights

  • Treponema paraluiscuniculi is a noncultivable species of the genus Treponema that causes venereal spirochetosis in rabbits, but that is not infectious to humans [1]

  • We report a complete genome sequence of T. paraluiscuniculi, strain Cuniculi A and compare this sequence to the published genomes of T. pallidum ssp. pallidum Nichols, SS14 and Chicago [18,19,20]

  • Seventeen automated gene predictions were omitted in the final annotation mainly due to overlap with other already annotated genes. 75 and 280 genes were annotated shorter or longer, respectively, in the Cuniculi A annotation when compared to the length of orthologous genes in the Nichols and SS14 genome annotations. 47 genes originally annotated in the Nichols genome [18] were not annotated in the Cuniculi A genome as a result of differences in gene prediction criteria

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Summary

Introduction

Treponema paraluiscuniculi is a noncultivable species of the genus Treponema that causes venereal spirochetosis in rabbits, but that is not infectious to humans [1]. The genome structure and chromosome sequence of T. paraluiscuniculi is closely related to other pathogenic species and subspecies of the Treponema genus, including syphilis causing spirochete Treponema pallidum ssp. The disease is typically sexually transmitted, and results in erythema and edema of the prepuce, vagina, anus, or scrotum, often followed by ulceration and crusting (eschar formation) of the lesion. Rabbit venereal spirochetosis is characterized by localized genital lesions, whereas human syphilis is a multistage, sexually transmitted disease with varied clinical manifestations. Syphilis treponemes can infect virtually any human tissue, causing gummatous, neurologic, and cardiovascular manifestations [11,12]. While there is little evidence for systemic manifestations following T

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