title: The extant World War 1 dysentery bacillus NCTC1: a genomic analysis.
abstract: BACKGROUND
  Shigellosis (previously bacillary dysentery) was the primary diarrhoeal disease of World War 1, but outbreaks still occur in military operations, and shigellosis causes hundreds of thousands of deaths per year in developing nations. We aimed to generate a high-quality reference genome of the historical Shigella flexneri isolate NCTC1 and to examine the isolate for resistance to antimicrobials.
  
  
  METHODS
  In this genomic analysis, we sequenced the oldest extant Shigella flexneri serotype 2a isolate using single-molecule real-time (SMRT) sequencing technology. Isolated from a soldier with dysentery from the British forces fighting on the Western Front in World War 1, this bacterium, NCTC1, was the first isolate accessioned into the National Collection of Type Cultures. We created a reference sequence for NCTC1, investigated the isolate for antimicrobial resistance, and undertook comparative genetics with S flexneri reference strains isolated during the 100 years since World War 1.
  
  
  RESULTS
  We discovered that NCTC1 belonged to a 2a lineage of S flexneri, with which it shares common characteristics and a large core genome. NCTC1 was resistant to penicillin and erythromycin, and contained a complement of chromosomal antimicrobial resistance genes similar to that of more recent isolates. Genomic islands gained in the S flexneri 2a lineage over time were predominately associated with additional antimicrobial resistances, virulence, and serotype conversion.
  
  
  CONCLUSIONS
  This S flexneri 2a lineage is a well adapted pathogen that has continued to respond to selective pressures. We have created a valuable historical benchmark for shigellae in the form of a high-quality reference sequence for a publicly available isolate.
  
  
  BACKGROUND
  The Wellcome Trust.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
authors.forename: Kate S
authors.initials: KS
authors.lastname: Baker
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mather
authors.affiliation: National Collection of Type Cultures, Public Health England, Porton Down, Salisbury, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: McGregor
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Coupland
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Langridge
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, London, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Day
authors.affiliation: National Collection of Type Cultures, Public Health England, Porton Down, Salisbury, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Deheer-Graham
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: National Collection of Type Cultures, Public Health England, Porton Down, Salisbury, UK.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Russell
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK; Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: nrt@sanger.ac.uk.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D001483:Base Sequence; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004405:Dysentery, Bacillary / Q000188:drug therapy / Q000382:microbiology*; D019143:Evolution, Molecular; D016680:Genome, Bacterial / Q000235:genetics*; D006801:Humans; D010802:Phylogeny; D012763:Shigella flexneri / Q000187:drug effects / Q000235:genetics*; D047828:World War I
chemical_list: D000890:Anti-Infective Agents