Gunthard Stübs and Ralf R . Schumann Charité – Universitätsmedizin

In 1905 the spirochete T. pallidum was discovered as the aetiologic agent of syphilis by Schaudinn and Hoffmann at the Charité Hospital in Berlin, Germany (Schaudinn & Hoffmann, 1905). This helical shaped bacterium is extremely well hidden, and also one of the best adapted to its only host – the Homo sapiens. The genome of T. pallidum ssp. pallidum contains only 1041 coding sequences and lacks numerous catabolic and biosynthetic pathways (Fraser et al., 1998) like, i.e. fatty acid synthesis (Livermore & Johnson, 1975). Therefore this organism utilises many of the biosynthetic precursors from its host and up to now it is not possible to continuously cultivate it in vitro. The only way to grow this bacterium is in in vivo models (Norris et al., 2006). Thus, the isolation of biological active compounds of T. pallidum has been difficult due to the lack of sufficient amounts of cultured bacteria. To study recognition of T. pallidum by the innate immune system information on the chemical composition of these cells has to be correlated with immunological responses induced by related spirochetes. The best examined spirochete is Borrelia burgdorferi – the etiologic agent of Lyme disease (LD). LD is an endemic disease with somewhat similar characteristics as compared to syphilis – A relatively slow dissemination of the spirochete within the host is followed by a weak inflammatory response of the human immune system. Furthermore, multiple organs are affected including the skin as well as the peripheral and central nervous system. Only half of the genes of B. burgdorferi code for proteins orthologous to those of T. pallidum indicating an adaptation to distinct niches though (Subramanian et al., 2000). However, the motility associated genes are highly conserved in both organisms (Fraser et al., 1998). Other pathogenic Borrelia include B. hermsii, one causative agent of relapsing fever, that multiplies more rapidly to higher cell numbers and causes more acute clinical symptoms. Further human associated treponemes such as T. denticola, colonise the oral cavity, T. phagedenis, belongs to the genital flora, and other species are found within the intestine. Thereof only the oral treponemes are pathogenic and have been associated with periodontal disease causing inflammation of the gingival tissue (Norris et al., 2006). Since the genome of T. denticola is much larger than that of T. pallidum and a conserved gene order could not be determined it is unlikely that T. pallidum is directly derived from this oral spirochete. But it might serve as a model for T. pallidum research since it is relatively easy to cultivate (Seshadri et al., 2004). While Borrelia and Treponema share the same phylogenetic family – Spirochaetaceae – the genus Leptospira belongs to the family Leptospiraceae in the same order as the first – Spirochetales (Paster et al., 1991). The most important and immunologically best studied leptospiral pathogen is the agent of Weil’s disease (leptospirosis) L. interrogans. Recognition of Treponema pallidum and Other Spirochetes by the Innate Immune System 1