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

Linda Grillova 1, 2 Jan Oppelt 2, 3 Lenka Mikalová 2 Markéta Nováková 2 Lorenzo Giacani 4 Anežka Niesnerová 2 Angel Noda 5 Ariel Mechaly 6 Petra Pospíšilová 2 Darina Čejková 7 Philippe Grange 8 Nicolas Dupin 8, 9 Radim Strnadel 10 Marcus Chen 11, 12 Ian Denham 12 Natasha Arora 13 Mathieu Picardeau 1 Christopher Weston 14 R. Allyn Forsyth 15, 14 David Šmajs 2, *
* Corresponding author
1 Biologie des Spirochètes / Biology of Spirochetes
2 MUNI - Masaryk University [Brno]
3 CEITEC MU - Central European Institute of Technology [Brno]
4 Departments of Medicine and Global Health
5 Instituto de Medicina Tropical Pedro Kouri
6 Cristallographie (Plateforme) - Crystallography (Platform)
7 VRI - Veterinary Research Institute [Brno]
8 IC UM3 (UMR 8104 / U1016) - Institut Cochin
9 Service de Dermatologie [CHU Cochin]
10 Masaryk University and University Hospital Brno
11 Monash University [Melbourne]
12 Melbourne Sexual Health Centre [Australia]
13 UZH - Universität Zürich [Zürich] = University of Zurich
14 GeneticPrime Dx
15 Department of Biology [San Diego]
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.
Keywords : Treponema pallidum subsp pallidum syphilis direct whole genome sequencing recombination- driven diversity culture-independent bacterial enrichment Treponema pallidum subsp. pallidum recombination-driven diversity
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PMID 31417509 FRONT MICROBIOL....
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Linda Grillova, Jan Oppelt, Lenka Mikalová, Markéta Nováková, Lorenzo Giacani, et al.. Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens. Frontiers in Microbiology, Frontiers Media, 2019, 10, pp.1691. ⟨10.3389/fmicb.2019.01691⟩. ⟨pasteur-02547705⟩

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