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Syphilis, a chronic systemic infection caused by Treponema pallidum subspecies pallidum, is usually sexually transmitted and is characterized by episodes of active disease interrupted by periods of latency. After an incubation period averaging 2–6 weeks, a primary lesion appears, often associated with regional lymphadenopathy. The secondary stage, associated with generalized mucocutaneous lesions and generalized lymphadenopathy, is followed by a latent period of subclinical infection lasting years or decades. Central nervous system (CNS) involvement may occur early in infection and may be symptomatic or asymptomatic. In about one-third of untreated cases, the tertiary stage appears, characterized by progressive destructive mucocutaneous, musculoskeletal, or parenchymal lesions; aortitis; or late CNS manifestations.

The Spirochaetales include four genera that are pathogenic for humans and for a variety of other animals: Leptospira species, which cause leptospirosis (Chap. 171); Borrelia species, which cause relapsing fever and Lyme disease (Chaps. 172 and 173); Brachyspira species, which cause intestinal infections; and Treponema species, which cause the diseases known collectively as treponematoses (see also Chap. 170). The Treponema species include T. pallidum subspecies pallidum, which causes venereal syphilis; T. pallidum subspecies pertenue, which causes yaws; T. pallidum subspecies endemicum, which causes endemic syphilis or bejel; and T. carateum, which causes pinta. Until recently, the subspecies were distinguished primarily by the clinical syndromes they produce. Researchers have now identified molecular signatures that can differentiate the three subspecies of T. pallidum by culture-independent methods based on polymerase chain reaction (PCR). Other Treponema species found in the human mouth, genital mucosa, and gastrointestinal tract have been associated with disease (e.g., periodontitis), but their role as primary etiologic agents is unclear.

T. pallidum subspecies pallidum (referred to hereafter as T. pallidum), a thin spiral organism, has a cell body surrounded by a trilaminar cytoplasmic membrane, a delicate peptidoglycan layer providing some structural rigidity, and a lipid-rich outer membrane containing relatively few integral membrane proteins. Endoflagella wind around the cell body in the periplasmic space and are responsible for motility.

T. pallidum cannot be cultured in vitro, and little was known about its metabolism until the genome was sequenced in 1998. This spirochete possesses severely limited metabolic capabilities, lacking the genes required for de novo synthesis of most amino acids, nucleotides, and lipids. In addition, T. pallidum lacks genes encoding the enzymes of the Krebs cycle and oxidative phosphorylation. To compensate, the organism contains numerous genes predicted to encode transporters of amino acids, carbohydrates, and cations. In addition, genome analyses and other studies have revealed the existence of a 12-member gene family (tpr) that bears similarities to variable outer-membrane antigens of other spirochetes. One member, TprK, has discrete variable (V) regions that undergo antigenic variation during infection, probably as a mechanism for immune evasion.

The only known natural host for T. pallidum is the human. T. pallidum can infect many mammals, but only humans, higher apes, and ...

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