title: Genomic analysis of the emergence of 20th century epidemic dysentery.
abstract: BACKGROUND
  Shigella dysenteriae type 1 (Sd1) causes recurrent epidemics of dysentery associated with high mortality in many regions of the world. Sd1 infects humans at very low infectious doses (10 CFU), and treatment is complicated by the rapid emergence of antibiotic resistant Sd1 strains. Sd1 is only detected in the context of human infections, and the circumstances under which epidemics emerge and regress remain unknown.
  
  
  RESULTS
  Phylogenomic analyses of 56 isolates collected worldwide over the past 60 years indicate that the Sd1 clone responsible for the recent pandemics emerged at the turn of the 20th century, and that the two world wars likely played a pivotal role for its dissemination. Several lineages remain ubiquitous and their phylogeny indicates several recent intercontinental transfers. Our comparative genomics analysis reveals that isolates responsible for separate outbreaks, though closely related to one another, have independently accumulated antibiotic resistance genes, suggesting that there is little or no selection to retain these genes in-between outbreaks. The genomes appear to be subjected to genetic drift that affects a number of functions currently used by diagnostic tools to identify Sd1, which could lead to the potential failure of such tools.
  
  
  CONCLUSIONS
  Taken together, the Sd1 population structure and pattern of evolution suggest a recent emergence and a possible human carrier state that could play an important role in the epidemic pattern of infections of this human-specific pathogen. This analysis highlights the important role of whole-genome sequencing in studying pathogens for which epidemiological or laboratory investigations are particularly challenging.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, WA, USA. lrohmer@uw.edu.
authors.forename: Laurence
authors.initials: L
authors.lastname: Rohmer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jacobs
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Brittnacher
authors.forename: Christine
authors.initials: C
authors.lastname: Fong
authors.forename: Hillary S
authors.initials: HS
authors.lastname: Hayden
authors.forename: Didier
authors.initials: D
authors.lastname: Hocquet
authors.forename: Eli J
authors.initials: EJ
authors.lastname: Weiss
authors.forename: Matthew
authors.initials: M
authors.lastname: Radey
authors.forename: Yves
authors.initials: Y
authors.lastname: Germani
authors.forename: Kaisar Ali
authors.initials: KA
authors.lastname: Talukder
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hager
authors.forename: John M
authors.initials: JM
authors.lastname: Kemner
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Sims-Day
authors.forename: Susana
authors.initials: S
authors.lastname: Matamouros
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Hager
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004405:Dysentery, Bacillary / Q000453:epidemiology* / Q000266:history; D019143:Evolution, Molecular; D014644:Genetic Variation; D016680:Genome, Bacterial; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D049673:History, 20th Century; D006801:Humans; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D012762:Shigella dysenteriae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents