Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens

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Authors

GRILLOVÁ Linda OPPELT Jan MIKALOVÁ Lenka NOVÁKOVÁ Markéta GIACANI LLorenzo NIESNEROVÁ Anežka NODA Angel A. MECHALY Ariel E. POSPÍŠILOVÁ Petra CEJKOVA Darina GRANGE Philippe A. DUPIN Nicolas STRNADEL Radim CHEN Marcus DENHAM Ian ARORA Natasha PICARDEAU Mathieu WESTON Christopher FORSYTH R. Allyn ŠMAJS David

Year of publication 2019
Type Article in Periodical
Magazine / Source Frontiers in Microbiology
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.frontiersin.org/articles/10.3389/fmicb.2019.01691/full
Doi http://dx.doi.org/10.3389/fmicb.2019.01691
Keywords Treponema pallidum subsp. pallidum; syphilis; direct whole genome sequencing; recombinationd-riven diversity; culture-independent bacterial enrichment
Description 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.
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