Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen

Abstract

The last two decades have seen a worldwide resurgence in infections caused by Treponema pallidum subsp. pallidum, the syphilis spirochete. The syphilis spirochete’s well-recognized capacity for early dissemination and immune evasion has earned it the designation ‘the stealth pathogen’. Despite the many hurdles to studying syphilis pathogenesis, most notably the inability to culture and to genetically manipulate T. pallidum, in recent years, considerable progress has been made in elucidating the structural, physiologic, and regulatory facets of stealth pathogenicity. In this Review, we integrate this eclectic body of information to garner fresh insights into the highly successful parasitic lifestyles of the syphilis spirochete and related pathogenic treponemes.

Syphilis

“…Because rabbits are highly susceptible to T. pallidum infection, develop lesions grossly and histopathologically resembling chancres following intradermal inoculation and generate antibody responses similar to those in humans, the rabbit is the model of choice for studying endogenous and exogenous protective immunity 61,62 . However, the rabbit model poorly recapitulates many clinical and immunological facets of human disease 63 . Not surprisingly, even in the post-genomics era, our understanding of pathogenic mechanisms in syphilis lags well behind other common bacterial diseases 63 .…”

“…However, the rabbit model poorly recapitulates many clinical and immunological facets of human disease 63 . Not surprisingly, even in the post-genomics era, our understanding of pathogenic mechanisms in syphilis lags well behind other common bacterial diseases 63 .…”

“…Because of its double-membrane structure, the spirochete is often described as a Gram-negative bacterium. However, this analogy is phylogenetically, biochemically and ultrastructurally inaccurate 63,64 . The T. pallidum outer membrane lacks lipopolysaccharide 65 and has a markedly different phospholipid composition than the outer membranes of typical Gram-negative bacteria 66 .…”

“…The T. pallidum outer membrane lacks lipopolysaccharide 65 and has a markedly different phospholipid composition than the outer membranes of typical Gram-negative bacteria 66 . Although T. pallidum expresses abundant lipoproteins, these molecules reside predominantly below the surface 5,63,67 . Accordingly, this paucity of surface-exposed pathogen-associated molecular patterns (PAMPs) enables the spirochete to avoid triggering host innate surveillance mechanisms, facilitating local replication and early dissemination.…”

Evaluation of the Elecsys Syphilis Immunoassay for Detection of Syphilis in Populations at Risk of Disease in the US and Argentina

“…However, if left unchecked, the disease can progress through secondary, early and late latent (asymptomatic), and tertiary stages, resulting in multiple clinical conditions that mimic a number of other disease states (6). Approximately 25% of patients will experience at least 1 relapse during early latency, with the majority of these cases occurring within the first year of infection (7). Diagnosis of syphilis can also be delayed due to the lack of obvious symptoms during the earlier disease stages.…”