1. Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens
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Linda Grillová, Jan Oppelt, Lenka Mikalová, Markéta Nováková, Lorenzo Giacani, Anežka Niesnerová, Angel A. Noda, Ariel E. Mechaly, Petra Pospíšilová, Darina Čejková, Philippe A. Grange, Nicolas Dupin, Radim Strnadel, Marcus Chen, Ian Denham, Natasha Arora, Mathieu Picardeau, Christopher Weston, R. Allyn Forsyth, David Šmajs, Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], Masaryk University [Brno] (MUNI), Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Departments of Medicine and Global Health, University of Washington [Seattle], Instituto de Medicina Tropical Pedro Kouri, Cristallographie (Plateforme) - Crystallography (Platform), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Veterinary Research Institute [Brno] (VRI), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Masaryk University and University Hospital Brno, University Hospital Brno, Monash University [Melbourne], Melbourne Sexual Health Centre [Australia], Alfred Health, Universität Zürich [Zürich] = University of Zurich (UZH), GeneticPrime Dx, Department of Biology [San Diego], San Diego State University (SDSU), This research was supported by funds from the Faculty of Medicine, Masaryk University to junior researchers (LGr, MN, and PP), the Grant Agency of the Czechia (GA17-25455S) and by the Ministry of Health of the Czechia (17-31333A) to DŠ. Core Facility Bioinformatics of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this manuscript. Computational resources were provided by the CESNET LM2015042 and the CERIT Scientific Cloud LM2015085, provided under the program 'Projects of Large Research, Development, and Innovations Infrastructures'., University of Zurich, Šmajs, David, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Department of Biology [San Diego State Univ] (Biology SDSU), and MURGUET, SYLVIE
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Microbiology (medical) ,[SDV]Life Sciences [q-bio] ,Population ,lcsh:QR1-502 ,syphilis ,340 Law ,610 Medicine & health ,direct whole genome sequencing ,Genome ,Genetic recombination ,Microbiology ,2726 Microbiology (medical) ,lcsh:Microbiology ,03 medical and health sciences ,510 Mathematics ,Treponema pallidum subsp. pallidum ,medicine ,Genetic variability ,education ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,Gene ,Original Research ,030304 developmental biology ,Genetics ,0303 health sciences ,education.field_of_study ,Genetic diversity ,Treponema ,biology ,030306 microbiology ,culture-independent bacterial enrichment ,2404 Microbiology ,Treponema pallidum subsp pallidum ,medicine.disease ,biology.organism_classification ,10218 Institute of Legal Medicine ,3. Good health ,[SDV] Life Sciences [q-bio] ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,recombination- driven diversity ,Syphilis ,recombination-driven diversity - Abstract
We would like to thank Prof. Nicholas Robert Thomson (Wellcome Sanger Institute) for his valuable insights during the preparation of the manuscript. We also thank Robert Anthony Gaultney for his assistance with the English revision of the manuscript.; International audience; 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.
- Published
- 2019
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