The hare syphilis agent is related to, but distinct from, the treponeme causing rabbit syphilis.

The treponemes infecting lagomorphs include Treponema paraluisleporidarum ecovar Cuniculus (TPeC) and ecovar Lepus (TPeL), infecting rabbits and hares, respectively. In this study, we described the first complete genome sequence of TPeL, isolate V3603-13, from an infected mountain hare (Lepus timidus) in Sweden. In addition, we determined 99.0% of the genome sequence of isolate V246-08 (also from an infected mountain hare, Sweden) and 31.7% of the genome sequence of isolate Z27 A77/78 (from a European hare, Lepus europeaus, The Netherlands). The TPeL V3603-13 genome had considerable gene synteny with the TPeC Cuniculi A genome and with the human pathogen T. pallidum, which causes syphilis (ssp. pallidum, TPA), yaws (ssp. pertenue, TPE) and endemic syphilis (ssp. endemicum, TEN). Compared to the TPeC Cuniculi A genome, TPeL V3603-13 contained four insertions and 11 deletions longer than three nucleotides (ranging between 6 and2,932 nts). In addition, there were 25 additional indels, from one to three nucleotides long, altogether spanning 36 nts. The number of single nucleotide variants (SNVs) between TPeC Cuniculi A and TPeL V3603-13 were represented by 309 nucleotide differences. Major proteome coding differences between TPeL and TPeC were found in the tpr gene family, and (predicted) genes coding for outer membrane proteins, suggesting that these components are essential for host adaptation in lagomorph syphilis. The phylogeny revealed that the TPeL sample from the European brown hare was more distantly related to TPeC Cuniculi A than V3603-13 and V246-08.

High prevalence and genetic diversity of Treponema paraluisleporidarum isolates in European lagomorphs.

IMPORTANCE: Syphilis is an ancient disease of humans and lagomorphs caused by two distinct but genetically closely related bacteria (>98% sequence identity based on the whole genome) of the genus Treponema. While human syphilis is well studied, little is known about the disease in the lagomorph host. Yet, comparative studies are needed to understand mechanisms in host-pathogen coevolution in treponematoses. Importantly, Treponema paraluisleporidarum-infected hare populations provide ample opportunity to study the syphilis-causing pathogen in a naturally infected model population without antibiotic treatment, data that cannot be obtained from syphilis infection in humans. We provide data on genetic diversity and are able to highlight various types of repetitions in one of the two hypervariable regions at the tp0548 locus that have not been described in the human syphilis-causing sister bacterium Treponema pallidum subsp. pallidum.

High syphilis seropositivity in European brown hares (Lepus europaeus), Lower Saxony, Germany.

The lagomorph-infecting Treponema paraluisleporidarum is a close relative of the human syphilis-bacterium Treponema pallidum. There is a paucity of information on the epidemiology of hare syphilis and its relationship to the rabbit- and human-infecting treponemes that cause syphilis. In our study, we tested 734 serum samples from European brown hares (Lepus europaeus) collected between 2007 and 2019 in the federal state of Lower Saxony, Germany, for the presence of antibodies against T. paraluisleporidarum. Since T. paraluisleporidarum cross-reacts with T. pallidum antigen, we used a commercially available T. pallidum-particle agglutination (TP-PA) assay to test for the presence of antibodies. A high seropositivity (n = 405/734) was detected. An additional 233 serum samples were retested using a fluorescent treponemal antibody absorption test to confirm the results of the TP-PA assay. Our results show that infection is widespread in Lower Saxony and suggest a horizontal (sexual) transmission mode since adult hares show significantly higher seropositivity than subadults (odds ratio: 0.03 [95% CI 0.02-0.05], p < .0001). No difference was detected based on gender (odds ratio: 0.79 [95% Cl 0.58-1.07], p = .1283). Further studies are warranted to genetically characterize the T. paraluisleporidarum strains that infect wild hares.