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

L. Grillová, J. Oppelt, L. Mikalová, M. Nováková, L. Giacani, A. Niesnerová, AA. Noda, AE. Mechaly, P. Pospíšilová, D. Čejková, PA. Grange, N. Dupin, R. Strnadel, M. Chen, I. Denham, N. Arora, M. Picardeau, C. Weston, RA. Forsyth, D. Šmajs,

. 2019 ; 10 (-) : 1691. [pub] 20190731

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19035799

Grantová podpora
Wellcome Trust - United Kingdom
NV17-31333A MZ0 CEP - Centrální evidence projektů

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.

Biology of Spirochetes Unit Institut Pasteur Paris France

CEITEC Central European Institute of Technology Masaryk University Brno Czechia National Centre for Biomolecular Research Faculty of Science Masaryk University Brno Czechia

Department of Biology Faculty of Medicine Masaryk University Brno Czechia

Department of Biology Faculty of Medicine Masaryk University Brno Czechia Biology of Spirochetes Unit Institut Pasteur Paris France

Department of Dermatovenerology University Hospital Brno Brno Czechia

Department of Immunology Veterinary Research Institute Brno Czechia

Department of Medicine Division of Allergy and Infectious Diseases University of Washington Seattle WA United States Department of Global Health Harborview Medical Center University of Washington Seattle WA United States

Department of Mycology Bacteriology Instituto de Medicina Tropical Pedro Kourí Havana Cuba

Faculté de Médecine Laboratoire de Dermatologie CNR IST Bactériennes Institut Cochin U1016 Université Sorbonne Paris Descartes Paris France

Faculté de Médecine Laboratoire de Dermatologie CNR IST Bactériennes Institut Cochin U1016 Université Sorbonne Paris Descartes Paris France AP HP Service de Dermatologie et Vénéréologie Groupe Hospitalier Paris Centre Cochin Hôtel Dieu Broca Paris France

GeneticPrime Dx Inc La Jolla CA United States

GeneticPrime Dx Inc La Jolla CA United States Department of Biology San Diego State University San Diego CA United States

Melbourne Sexual Health Centre Alfred Health Melbourne VIC Australia

Melbourne Sexual Health Centre Alfred Health Melbourne VIC Australia Central Clinical School Monash University Melbourne VIC Australia

Plateforme de Cristallographie Institut Pasteur Paris France

Zurich Institute of Forensic Medicine University of Zurich Zurich Switzerland

Citace poskytuje Crossref.org

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$a 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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