title: Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages.
abstract: The diarrheal pathogenClostridium difficileconsists of at least six distinct evolutionary lineages. The RT017 lineage is anomalous, as strains only express toxin B, compared to strains from other lineages that produce toxins A and B and, occasionally, binary toxin. Historically, RT017 initially was reported in Asia but now has been reported worldwide. We used whole-genome sequencing and phylogenetic analysis to investigate the patterns of global spread and population structure of 277 RT017 isolates from animal and human origins from six continents, isolated between 1990 and 2013. We reveal two distinct evenly split sublineages (SL1 and SL2) ofC. difficileRT017 that contain multiple independent clonal expansions. All 24 animal isolates were contained within SL1 along with human isolates, suggesting potential transmission between animals and humans. Genetic analyses revealed an overrepresentation of antibiotic resistance genes. Phylogeographic analyses show a North American origin for RT017, as has been found for the recently emerged epidemic RT027 lineage. Despite having only one toxin, RT017 strains have evolved in parallel from at least two independent sources and can readily transmit between continents.
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.|UCL Centre for Clinical Microbiology, University College London, Royal Free Campus, London, United Kingdom.|Public Health Laboratory London, Division of Infection, The Royal London Hospital, London, United Kingdom.
authors.forename: M D
authors.initials: MD
authors.lastname: Cairns
authors.affiliation: National Institute for Biological Standards and Control, South Mimms, United Kingdom.
authors.forename: M D
authors.initials: MD
authors.lastname: Preston
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: C L
authors.initials: CL
authors.lastname: Hall
authors.affiliation: Edward Hines, Jr., Veterans Affairs Hospital, Hines, Illinois, USA.|Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: Gerding
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Edgbaston Campus, Birmingham, United Kingdom.|Public Health England (PHE), Public Health Laboratory Birmingham (PHLB), Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, United Kingdom.
authors.forename: P M
authors.initials: PM
authors.lastname: Hawkey
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.affiliation: National Reference Laboratory for Clostridium difficile, Leiden University Medical Centre and RIVM, Bilthoven, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Kuijper
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: T D
authors.initials: TD
authors.lastname: Lawley
authors.affiliation: Department of Medical Microbiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Pituch
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Rondebosch, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Reid
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Rondebosch, South Africa.
authors.forename: B
authors.initials: B
authors.lastname: Kullin
authors.affiliation: The University of Western Australia, School of Pathology and Laboratory Medicine, Crawley, Australia.
authors.forename: T V
authors.initials: TV
authors.lastname: Riley
authors.affiliation: School of Medicine and Medical Science, UCD Veterinary Sciences Centre, University College Dublin, Belfield, Dublin, Ireland.|University of Exeter, Bioscience, College of Life and Environmental Science, Exeter, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Solomon
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Medical College, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: P J
authors.initials: PJ
authors.lastname: Tsai
authors.affiliation: Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Weese
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: R A
authors.identifier: 0000-0002-2402-6630
authors.initials: RA
authors.lastname: Stabler
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom Brendan.Wren@lshtm.ac.uk.
authors.forename: B W
authors.initials: BW
authors.lastname: Wren
mesh_terms: D000818:Animals; D016360:Clostridioides difficile / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D003015:Clostridium Infections / Q000453:epidemiology / Q000382:microbiology* / Q000662:veterinary*; D014644:Genetic Variation; D016680:Genome, Bacterial; D014943:Global Health; D006801:Humans; D017720:Molecular Epidemiology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D021521:Ribotyping; D017422:Sequence Analysis, DNA
keywords: Clostridium difficile; SNPs; antibiotic resistance; evolution; phylogenetics; phylogeny; ribotype 017; sequencing