title: Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.
abstract: Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.
authors.affiliation: The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. parkhill@sanger.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Parkhill
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: K D
authors.initials: KD
authors.lastname: James
authors.forename: N R
authors.initials: NR
authors.lastname: Thomson
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authors.lastname: Pickard
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authors.lastname: Wain
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authors.lastname: Bentley
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authors.lastname: Holden
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authors.lastname: Sebaihia
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authors.lastname: Baker
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authors.lastname: Basham
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authors.lastname: Chillingworth
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authors.lastname: Connerton
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authors.lastname: Cronin
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authors.lastname: Davis
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authors.initials: RM
authors.lastname: Davies
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authors.lastname: Dowd
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authors.lastname: White
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authors.lastname: Farrar
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authors.initials: T
authors.lastname: Feltwell
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authors.lastname: Hamlin
authors.forename: A
authors.initials: A
authors.lastname: Haque
authors.forename: T T
authors.initials: TT
authors.lastname: Hien
authors.forename: S
authors.initials: S
authors.lastname: Holroyd
authors.forename: K
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authors.lastname: Jagels
authors.forename: A
authors.initials: A
authors.lastname: Krogh
authors.forename: T S
authors.initials: TS
authors.lastname: Larsen
authors.forename: S
authors.initials: S
authors.lastname: Leather
authors.forename: S
authors.initials: S
authors.lastname: Moule
authors.forename: P
authors.initials: P
authors.lastname: O'Gaora
authors.forename: C
authors.initials: C
authors.lastname: Parry
authors.forename: M
authors.initials: M
authors.lastname: Quail
authors.forename: K
authors.initials: K
authors.lastname: Rutherford
authors.forename: M
authors.initials: M
authors.lastname: Simmonds
authors.forename: J
authors.initials: J
authors.lastname: Skelton
authors.forename: K
authors.initials: K
authors.lastname: Stevens
authors.forename: S
authors.initials: S
authors.lastname: Whitehead
authors.forename: B G
authors.initials: BG
authors.lastname: Barrell
mesh_terms: D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D004269:DNA, Bacterial; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D017353:Gene Deletion; D016680:Genome, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010957:Plasmids / Q000235:genetics; D011995:Recombination, Genetic; D012485:Salmonella typhi / Q000235:genetics*; D012486:Salmonella typhimurium / Q000235:genetics; D017422:Sequence Analysis, DNA; D012703:Serotyping
chemical_list: D004269:DNA, Bacterial