Clonality of erythromycin resistance in Francisella tularensis

Edvin Karlsson, Igor Golovliov, Adrian Lärkeryd, Malin Granberg, Eva Larsson, Caroline Öhrman, Marcin Niemcewicz, Dawn Birdsell, David M. Wagner, Mats Forsman, Anders Johansson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Article numberdkw235
Pages (from-to)2815-2823
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Issue number10
StatePublished - Oct 1 2016

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)


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