Journal Article

Clonality of erythromycin resistance in <i>Francisella tularensis</i>

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

in Journal of Antimicrobial Chemotherapy

Volume 71, issue 10, pages 2815-2823
Published in print October 2016 | ISSN: 0305-7453
Published online June 2016 | e-ISSN: 1460-2091 | DOI: https://dx.doi.org/10.1093/jac/dkw235
Clonality of erythromycin resistance in Francisella tularensis

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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.

Journal Article.  5809 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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