title: Clonality of erythromycin resistance in Francisella tularensis.
abstract: We analysed diverse strains of Francisella tularensis subsp. holarctica to assess if its division into biovars I and II is associated with specific mutations previously linked to erythromycin resistance and to determine the distribution of this resistance trait across this subspecies.
  
  
  
  Three-hundred and fourteen F. tularensis subsp. holarctica strains were tested for erythromycin susceptibility and whole-genome sequences for these strains were examined for SNPs in genes previously associated with erythromycin resistance. Each strain was assigned to a global phylogenetic framework using genome-wide canonical SNPs. The contribution of a specific SNP to erythromycin resistance was examined using allelic exchange. The geographical distribution of erythromycin-resistant F. tularensis strains was further investigated by literature search.
  
  
  
  There was a perfect correlation between biovar II strains (erythromycin resistance) and the phylogenetic group B.12. Only B.12 strains had an A → C SNP at position 2059 in the three copies of the rrl gene. Introducing 2059C into an rrl gene of an erythromycin-susceptible F. tularensis strain resulted in resistance. An additional 1144 erythromycin-resistant strains were identified from the scientific literature, all of them from Eurasia.
  
  
  
  Erythromycin resistance in F. tularensis is caused by an A2059C rrl gene mutation, which exhibits a strictly clonal inheritance pattern found only in phylogenetic group B.12. This group is an extremely successful clone, representing the most common type of F. tularensis throughout Eurasia.
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
authors.forename: Edvin
authors.initials: E
authors.lastname: Karlsson
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology, and Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
authors.forename: Igor
authors.initials: I
authors.lastname: Golovliov
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lärkeryd
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Granberg
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Larsson
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Öhrman
authors.affiliation: Wojskowy Instytut Higieny i Epidemioligii, Biological Threat Identification and Countermeasure Center, Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Niemcewicz
authors.affiliation: Department of Biological Sciences and Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Birdsell
authors.affiliation: Department of Biological Sciences and Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Wagner
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Forsman
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology, and Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden anders.f.johansson@umu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004917:Erythromycin / Q000494:pharmacology*; D005604:Francisella tularensis / Q000187:drug effects* / Q000235:genetics*; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012338:RNA, Ribosomal, 23S / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D012338:RNA, Ribosomal, 23S; D004917:Erythromycin