Treponema denticola is a Gram-negative, obligate anaerobic, motile and highly proteolytic spirochete bacterium. It is one of four species of oral spirochetes to be reliably cultured, the others being Treponema pectinovorum, Treponema socranskii and Treponema vincentii. T. denticola dwells in a complex and diverse microbial community within the oral cavity and is highly specialized to survive in this environment. T. denticola is associated with the incidence and severity of human periodontal disease. Treponema denticola is one of three bacteria that form the Red Complex, the other two being Porphyromonas gingivalis and Tannerella forsythia. Together they form the major virulent pathogens that cause chronic periodontitis. Having elevated T. denticola levels in the mouth is considered one of the main etiological agents of periodontitis. T. denticola is related to the syphilis-causing obligate human pathogen, Treponema pallidum subsp. pallidum. It has also been isolated from women with bacterial vaginosis. Genome The first genome of T. denticola to be sequenced was strain 35405 which was initially isolated and designated as the type strain by Chan et al. The 2,843,201-bp genome sequence encodes 2,786􏴲 open reading frames (ORFs) as well a 6 rRNAs and 44 tRNAs. This is in stark contrast to the minimal genome of Treponema pallidum which encodes only 1,040 ORFs. Cell structure The native cellular architecture of the bacterial cell was revealed using cryo-electron tomography, a technique observing intact plunge-frozen cells. Tightly organized bundles of periplasmic flagella were observed in the periplasm, a characteristic of spirochetes. The presence of the periplasmic flagella is widely regarded as being responsible for the microorganism's ability to rotate and flex, in addition to its translational movement. Spirochetes, including Treponema denticola , are therefore able to navigate through particularly viscous environments, unlike that of other prokaryotes. The tapering of the cell ends, conserved between cells, encompass a patella-shaped structure observed in the periplasm at the cell tip. This structure might be involved in the polar attachment of the cells. Cytoplasmic filaments, a bacterial intermediate-like filaments composed of the protein CfpA, are adjacent to the inner membrane and run parallel to the tightly organized flagellar filaments. Those cytoplasmic filaments are critical for pathogenicity, directly or indirectly as they are also involved in chromosome structure, segregation, or the cell division processes. The absence of either flagella or cytoplasmic filaments in deficient mutant increase the mouse peritoneal macrophages in vitro uptake. Adherence and cytotoxicity The main site for T. denticola