Abstract
Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), remains an important public health problem with an increasing worldwide prevalence. Despite recent advances in in vitro cultivation, genetic variability of this pathogen during infection is poorly understood. Here, we present contemporary and geographically diverse complete treponemal genome sequences isolated directly from patients using a methyl-directed enrichment prior to sequencing. This approach reveals that approximately 50% of the genetic diversity found in TPA is driven by inter- and/or intra-strain recombination events, particularly in strains belonging to one of the defined genetic groups of syphilis treponemes: Nichols-like strains. Recombinant loci were found to encode putative outer-membrane proteins and the recombination variability was almost exclusively found in regions predicted to be at the host-pathogen interface. Genetic recombination has been considered to be a rare event in treponemes, yet our study unexpectedly showed that it occurs at a significant level and may have important impacts in the biology of this pathogen, especially as these events occur primarily in the outer membrane proteins. This study reveals the existence of strains with different repertoires of surface-exposed antigens circulating in the current human population, which should be taken into account during syphilis vaccine development.
Highlights
Treponema pallidum subsp. pallidum (TPA) is the causative agent of syphilis, a globally occurring disease
Efforts to understand the pathogenesis of TPA have been hindered by the inability to routinely propagate the bacterium in vitro and the lack of an efficient method for obtaining genomes directly from clinical samples
We have found striking genetic diversity of the contemporary Nichols-like strains when compared to SS14-like strains
Summary
Treponema pallidum subsp. pallidum (TPA) is the causative agent of syphilis, a globally occurring disease. Pallidum (TPA) is the causative agent of syphilis, a globally occurring disease. The worldwide number of syphilis cases dramatically decreased after the introduction of penicillin therapy in the 1940s, the estimated number of new syphilis cases per year remains over 5.6 million. Alarming is the number of congenital syphilis cases, which is approaching one million cases per year (Newman et al, 2012; Peeling et al, 2017). Syphilis is often transmitted among MSM patients (men who have sex with men). The rising prevalence of syphilis among MSM patients has coincided with the introduction of highly active anti-retroviral drugs leading to decreased HIVassociated mortality and the re-emergence of unsafe sexual behavior among MSM (Stolte et al, 2001). The underlying molecular mechanisms remain poorly understood (Radolf et al, 2016)
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