title: Genomic Epidemiology of a Protracted Hospital Outbreak Caused by a Toxin A-Negative Clostridium difficile Sublineage PCR Ribotype 017 Strain in London, England.
abstract: Clostridium difficile remains the leading cause of nosocomial diarrhea worldwide, which is largely considered to be due to the production of two potent toxins: TcdA and TcdB. However, PCR ribotype (RT) 017, one of five clonal lineages of human virulent C. difficile, lacks TcdA expression but causes widespread disease. Whole-genome sequencing was applied to 35 isolates from hospitalized patients with C. difficile infection (CDI) and two environmental ward isolates in London, England. The phylogenetic analysis of single nucleotide polymorphisms (SNPs) revealed a clonal cluster of temporally variable isolates from a single hospital ward at University Hospital Lewisham (UHL) that were distinct from other London hospital isolates. De novo assembled genomes revealed a 49-kbp putative conjugative transposon exclusive to this hospital clonal cluster which would not be revealed by current typing methodologies. This study identified three sublineages of C. difficile RT017 that are circulating in London. Similar to the notorious RT027 lineage, which has caused global outbreaks of CDI since 2001, the lineage of toxin-defective RT017 strains appears to be continually evolving. By utilization of WGS technologies to identify SNPs and the evolution of clonal strains, the transmission of outbreaks caused by near-identical isolates can be retraced and identified.
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, London, United Kingdom Public Health Laboratory London, Health Protection Agency, Division of Infection, The Royal London Hospital, London, United Kingdom.
authors.forename: M D
authors.initials: MD
authors.lastname: Cairns
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: M D
authors.initials: MD
authors.lastname: Preston
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 Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: T G
authors.initials: TG
authors.lastname: Clark
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: R A
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: D001427:Bacterial Toxins; D016360:Clostridioides difficile / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D003015:Clostridium Infections / Q000453:epidemiology* / Q000382:microbiology; D016000:Cluster Analysis; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D003967:Diarrhea / Q000453:epidemiology* / Q000382:microbiology; D004196:Disease Outbreaks; D004768:Enterotoxins / Q000172:deficiency*; D016680:Genome, Bacterial; D006801:Humans; D008131:London / Q000453:epidemiology; D017720:Molecular Epidemiology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D021521:Ribotyping; D017422:Sequence Analysis, DNA
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile