title: Genomic stability over 9 years of an isoniazid resistant Mycobacterium tuberculosis outbreak strain in Sweden.
abstract: In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e.g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Linus.Sandegren@imbim.uu.se
authors.forename: Linus
authors.initials: L
authors.lastname: Sandegren
authors.forename: Ramona
authors.initials: R
authors.lastname: Groenheit
authors.forename: Tuija
authors.initials: T
authors.lastname: Koivula
authors.forename: Solomon
authors.initials: S
authors.lastname: Ghebremichael
authors.forename: Abdolreza
authors.initials: A
authors.lastname: Advani
authors.forename: Elsie
authors.initials: E
authors.lastname: Castro
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pennhag
authors.forename: Sven
authors.initials: S
authors.lastname: Hoffner
authors.forename: Jolanta
authors.initials: J
authors.lastname: Mazurek
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlowski
authors.forename: Boris
authors.initials: B
authors.lastname: Kan
authors.forename: Judith
authors.initials: J
authors.lastname: Bruchfeld
authors.forename: Öjar
authors.initials: Ö
authors.lastname: Melefors
authors.forename: Gunilla
authors.initials: G
authors.lastname: Källenius
mesh_terms: D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D013548:Sweden / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology*
chemical_list: D007538:Isoniazid