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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.01691

Directly sequenced genomes of contemporary strains of syphilis reveal recombination-driven diversity in genes encoding predicted surface-exposed antigens

Linda Grillová1, 2,  Jan Oppelt3, 4, Lenka Mikalová1,  Markéta Nováková1, Lorenzo Giacani5, Anežka Niesnerová1,  Angel A. Noda6,  Ariel E. Mechaly2,  Petra Pospíšilová1,  Darina Čejková7,  Philippe A. Grange8,  Nicolas Dupin8, Radim Strnadel9, Marcus Chen10, 11, Ian Denham10,  Natasha Arora12,  Mathieu Picardeau2, Christopher Weston13,  R. A. Forsyth13 and  David Šmajs1*
  • 1Department of Biology, Faculty of Medicine, Masaryk University, Czechia
  • 2Institut Pasteur, France
  • 3Central European Institute of Technology (CEITEC), Czechia
  • 4Faculty of Science, Masaryk University, Czechia
  • 5University of Washington, United States
  • 6Instituto de Medicina Tropical “Pedro Kourí”, Cuba
  • 7Veterinary Research Institute (VRI), Czechia
  • 8Université Sorbonne Paris Cité, France
  • 9University Hospital Brno, Czechia
  • 10Melbourne Sexual Health Centre (MSHC), Australia
  • 11Central Clinical School, Monash University, Australia
  • 12Institute of Forensic Medicine, Faculty of Medicine, University of Zurich, Switzerland
  • 13San Diego State University, United States

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

Received: 28 Feb 2019; Accepted: 09 Jul 2019.

Edited by:

Vasco A. Azevedo, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil

Reviewed by:

Sandeep Tiwari, Federal University of Minas Gerais, Brazil
Jason Sahl, Northern Arizona University, United States
Alice R. Wattam, University of Virginia, United States
Guilherme C. Tavares, Universidade Nilton Lins, Brazil
Ulisses P. Pereira, State University of Londrina, Brazil  

Copyright: © 2019 Grillová, Oppelt, Mikalová, Nováková, Giacani, Niesnerová, Noda, Mechaly, Pospíšilová, Čejková, Grange, Dupin, Strnadel, Chen, Denham, Arora, Picardeau, Weston, Forsyth and Šmajs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. David Šmajs, Department of Biology, Faculty of Medicine, Masaryk University, Brno, South Moravia, Czechia, dsmajs@med.muni.cz