Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01691/full |
| _version_ | 1818138360190861312 |
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| author | Linda Grillová Linda Grillová Jan Oppelt Jan Oppelt Lenka Mikalová Markéta Nováková Lorenzo Giacani Lorenzo Giacani Anežka Niesnerová Angel A. Noda Ariel E. Mechaly Petra Pospíšilová Darina Čejková Philippe A. Grange Nicolas Dupin Nicolas Dupin Radim Strnadel Marcus Chen Marcus Chen Ian Denham Natasha Arora Mathieu Picardeau Christopher Weston R. Allyn Forsyth R. Allyn Forsyth David Šmajs |
| author_facet | Linda Grillová Linda Grillová Jan Oppelt Jan Oppelt Lenka Mikalová Markéta Nováková Lorenzo Giacani Lorenzo Giacani Anežka Niesnerová Angel A. Noda Ariel E. Mechaly Petra Pospíšilová Darina Čejková Philippe A. Grange Nicolas Dupin Nicolas Dupin Radim Strnadel Marcus Chen Marcus Chen Ian Denham Natasha Arora Mathieu Picardeau Christopher Weston R. Allyn Forsyth R. Allyn Forsyth David Šmajs |
| author_sort | Linda Grillová |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T10:10:57Z |
| format | Article |
| id | doaj.art-60b09aea8f0345ceb08acad350a0641b |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-11T10:10:57Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-60b09aea8f0345ceb08acad350a0641b2022-12-22T01:11:45ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-07-011010.3389/fmicb.2019.01691457293Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed AntigensLinda Grillová0Linda Grillová1Jan Oppelt2Jan Oppelt3Lenka Mikalová4Markéta Nováková5Lorenzo Giacani6Lorenzo Giacani7Anežka Niesnerová8Angel A. Noda9Ariel E. Mechaly10Petra Pospíšilová11Darina Čejková12Philippe A. Grange13Nicolas Dupin14Nicolas Dupin15Radim Strnadel16Marcus Chen17Marcus Chen18Ian Denham19Natasha Arora20Mathieu Picardeau21Christopher Weston22R. Allyn Forsyth23R. Allyn Forsyth24David Šmajs25Department of Biology, Faculty of Medicine, Masaryk University, Brno, CzechiaBiology of Spirochetes Unit, Institut Pasteur, Paris, FranceCEITEC-Central European Institute of Technology, Masaryk University, Brno, CzechiaNational Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, CzechiaDepartment of Biology, Faculty of Medicine, Masaryk University, Brno, CzechiaDepartment of Biology, Faculty of Medicine, Masaryk University, Brno, CzechiaDepartment of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United StatesDepartment of Global Health, Harborview Medical Center, University of Washington, Seattle, WA, United StatesDepartment of Biology, Faculty of Medicine, Masaryk University, Brno, CzechiaDepartment of Mycology-Bacteriology, Instituto de Medicina Tropical “Pedro Kourí”, Havana, CubaPlateforme de Cristallographie, Institut Pasteur, Paris, FranceDepartment of Biology, Faculty of Medicine, Masaryk University, Brno, CzechiaDepartment of Immunology, Veterinary Research Institute, Brno, Czechia0Faculté de Médecine, Laboratoire de Dermatologie-CNR IST Bactériennes, Institut Cochin U1016, Université Sorbonne Paris Descartes, Paris, France0Faculté de Médecine, Laboratoire de Dermatologie-CNR IST Bactériennes, Institut Cochin U1016, Université Sorbonne Paris Descartes, Paris, France1AP-HP, Service de Dermatologie et Vénéréologie, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, Paris, France2Department of Dermatovenerology, University Hospital Brno, Brno, Czechia3Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia4Central Clinical School, Monash University, Melbourne, VIC, Australia3Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia5Zurich Institute of Forensic Medicine, University of Zurich, Zurich, SwitzerlandBiology of Spirochetes Unit, Institut Pasteur, Paris, France6GeneticPrime Dx, Inc., La Jolla, CA, United States6GeneticPrime Dx, Inc., La Jolla, CA, United States7Department of Biology, San Diego State University, San Diego, CA, United StatesDepartment of Biology, Faculty of Medicine, Masaryk University, Brno, CzechiaSyphilis, 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.https://www.frontiersin.org/article/10.3389/fmicb.2019.01691/fullTreponema pallidum subsp. pallidumsyphilisdirect whole genome sequencingrecombination-driven diversityculture-independent bacterial enrichment |
| spellingShingle | Linda Grillová Linda Grillová Jan Oppelt Jan Oppelt Lenka Mikalová Markéta Nováková Lorenzo Giacani Lorenzo Giacani Anežka Niesnerová Angel A. Noda Ariel E. Mechaly Petra Pospíšilová Darina Čejková Philippe A. Grange Nicolas Dupin Nicolas Dupin Radim Strnadel Marcus Chen Marcus Chen Ian Denham Natasha Arora Mathieu Picardeau Christopher Weston R. Allyn Forsyth R. Allyn Forsyth David Šmajs Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens Frontiers in Microbiology Treponema pallidum subsp. pallidum syphilis direct whole genome sequencing recombination-driven diversity culture-independent bacterial enrichment |
| title | Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens |
| title_full | Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens |
| title_fullStr | Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens |
| title_full_unstemmed | Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens |
| title_short | Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens |
| title_sort | directly sequenced genomes of contemporary strains of syphilis reveal recombination driven diversity in genes encoding predicted surface exposed antigens |
| topic | Treponema pallidum subsp. pallidum syphilis direct whole genome sequencing recombination-driven diversity culture-independent bacterial enrichment |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01691/full |
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