Fig. 2

Preclinical models. At present, the commonly used preclinical syphilis models include heterologous expression models, in vitro culture models, and animal models. Heterologous expression models, such as Borrelia burgdorferi, oral spirochete Treponema, and Treponema phagedenis, contributed to identifying and determining the functional characteristics of T. pallidum proteins. Tp0435, Tp0954, and Tp0751 were identified as adhesins by a Borrelia burgdorferi heterologous expression system and adhered to mammalian endothelial cells and placental cell lines. The first long-term in vitro culture of T. pallidum was reported in 2018. This system utilized coincubation of the T. pallidum with Sf1Ep cottontail rabbit epithelial cells in a microaerobic environment containing 1.5% oxygen and 5% CO₂. An altered medium, TpCM-2, is very important; the principal modification was the replacement of the basal medium, Eagle’s minimal essential medium (Eagle’s MEM), with a more complex tissue culture medium, CMRL 1066. Successful models of T. pallidum infection have been established in a variety of animals, including the NZW rabbit, nonhuman primate (NHP) (macaque), LSH hamster, guinea pig, and mouse. In light of its convenience and inexpensive cost, the NZW rabbit model of T. pallidum infection is favored by scientists. Although T. pallidum can successfully infect mice, it lacks obvious clinical manifestations. As a result, further study is required before mice may be used as a model for syphilis research. Preclinical models are utilized in studies on the underlying features and pathophysiology of T. pallidum infection, and they may be exploited to produce cutting-edge diagnostics and vaccines