Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi

Elisa Anastasi, Steeve Giguère, Londa J. Berghaus, Mary K. Hondalus, Jennifer M. Willingham-Lane, Iain MacArthur, Noah D. Cohen, Marilyn C. Roberts, José A. Vázquez-Boland

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35 Citations (Scopus)

Abstract

Objectives
The objective of this study was to identify the molecular mechanism of macrolide resistance in the actinomycete Rhodococcus equi, a major equine pathogen and zoonotic agent causing opportunistic infections in people.

Methods
Macrolide-resistant (n = 62) and macrolide-susceptible (n = 62) clinical isolates of R. equi from foals in the USA were studied. WGS of 18 macrolide-resistant and 6 macrolide-susceptible R. equi was performed. Representative sequences of all known macrolide resistance genes identified to date were used to search the genome assemblies for putative homologues. PCR was used to screen for the presence of the identified resistance determinant in the rest of the isolates. Mating experiments were performed to verify mobility of the gene.

Results
A novel erm gene, erm(46), was identified in all sequenced resistant isolates, but not in susceptible isolates. There was complete association between macrolide resistance and the presence of erm(46) as detected by PCR screening of all 124 clinical isolates of R. equi. Expression of erm(46) in a macrolide-susceptible strain of R. equi induced high-level resistance to macrolides, lincosamides and streptogramins B, but not to other classes of antimicrobial agents. Transfer of erm(46) to macrolide-susceptible R. equi was confirmed. The transfer frequency ranged from 3 × 10−3 to 1 × 10−2.

Conclusions
This is the first molecular characterization of resistance to macrolides, lincosamides and streptogramins B in R. equi. Resistance was due to the presence of a novel erm(46) gene mobilizable likely by conjugation, which has spread among equine isolates of R. equi in the USA.
Original languageEnglish
Pages (from-to)3184-3190
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number12
Early online date16 Sept 2015
DOIs
Publication statusPublished - 1 Dec 2015
Externally publishedYes

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