Elisa Anastasi1, Steeve Giguère2, Londa J Berghaus3, Mary K Hondalus4, Jennifer M Willingham-Lane4, Iain MacArthur1, Noah D Cohen5, Marilyn C Roberts6, Jose A Vazquez-Boland7. 1. Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK. 2. Department of Large Animal Medicine, University of Georgia, Athens, GA, USA gigueres@uga.edu. 3. Department of Large Animal Medicine, University of Georgia, Athens, GA, USA. 4. Department of Infectious Diseases, University of Georgia, Athens, GA, USA. 5. Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA. 6. Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA. 7. Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK Grupo de Patogenómica Bacteriana, Facultad de Veterinaria, Universidad de Léon, Léon, Spain.
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.
OBJECTIVES: The objective of this study was to identify the molecular mechanism of macrolide resistance in the actinomyceteRhodococcus 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.
Authors: Jennifer M Willingham-Lane; Londa J Berghaus; Roy D Berghaus; Kelsey A Hart; Steeve Giguère Journal: Infect Immun Date: 2019-09-19 Impact factor: 3.441
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