Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi.
Abstract: 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.
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Publication Date: 2015-09-16 PubMed ID: 26377866DOI: 10.1093/jac/dkv279Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Antibiotics
- Diagnosis
- Disease Diagnosis
- Disease Transmission
- Disease Treatment
- Epidemiology
- Equine Health
- Genetic Sequencing
- Genetics
- Genomics
- Infectious Disease
- Laboratory Methods
- Macrolides
- Molecular biology
- Polymerase Chain Reaction
- Public Health
- Rhodococcus equi
- Veterinary Medicine
- Veterinary Research
- Zoonotic Diseases
Summary
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The research explores the identification of a new gene, erm(46), that is causing rising resistance to macrolide, a type of antibiotic, in Rhodococcus equi, a primary equine pathogen, across the USA.
Objective
- The objective was to uncover the molecular mechanism causing resistance to macrolide in Rhodococcus equi, a major pathogen in horses and an agent of infections in human beings.
Methods
- Both macrolide-resistant (62 cases) and macrolide-susceptible (62 cases) subsets of R. equi clinical isolates from foals across the USA were studied.
- Whole-genome sequencing was carried out on 18 macrolide-resistant and 6 macrolide-susceptible of the R. equi.
- The genome assemblies were searched for identical or similar sequences using the sequences of all known macrolide resistance genes as references.
- A polymerase chain reaction (PCR) was used to confirm the presence of the identified resistance determinant in the remaining isolates.
- Mating experiments were carried out to confirm the gene’s ability to move.
Results
- The result of these procedures led to the discovery of a new erm gene, erm(46), identified in all examined resistant isolates, but absent in the susceptible ones.
- There was an absolute connection between macrolide resistance and the presence of the erm(46), initially identified through PCR screening of all 124 clinical isolates of R. equi.
- When the expression of erm(46) was induced in a macrolide-susceptible strain of R. equi, high-level resistance was observed for macrolides, lincosamides, and streptogramins B, but not any other antimicrobial agents.
- The capability to transfer the erm(46) to a macrolide-susceptible R. equi was validated. The transfer efficiency varied between 3 x 10(-3) and 1 x 10(-2).
Conclusion
- This study provides the first molecular description of resistance to macrolides, lincosamides, and streptogramins B in R. equi.
- This resistance was linked to the existence of the newly discovered erm(46) gene, which could be transferred by likely conjugation.
- This gene has become widespread among equine isolates of R. equi in the USA.
Cite This Article
APA
Anastasi E, Giguère S, Berghaus LJ, Hondalus MK, Willingham-Lane JM, MacArthur I, Cohen ND, Roberts MC, Vazquez-Boland JA.
(2015).
Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi.
J Antimicrob Chemother, 70(12), 3184-3190.
https://doi.org/10.1093/jac/dkv279 Publication
Researcher Affiliations
- Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK.
- Department of Large Animal Medicine, University of Georgia, Athens, GA, USA gigueres@uga.edu.
- Department of Large Animal Medicine, University of Georgia, Athens, GA, USA.
- Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
- Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
- Microbial Pathogenesis Unit, School of Biomedical Sciences and The Roslin Institute, University of Edinburgh, Edinburgh, UK.
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.
- Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
- 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.
MeSH Terms
- Actinomycetales Infections / microbiology
- Actinomycetales Infections / veterinary
- Animals
- Animals, Newborn
- Anti-Bacterial Agents / pharmacology
- Conjugation, Genetic
- DNA, Bacterial / chemistry
- DNA, Bacterial / genetics
- Drug Resistance, Bacterial
- Gene Transfer, Horizontal
- Genes, Bacterial
- Horse Diseases / microbiology
- Horses
- Lincosamides / pharmacology
- Macrolides / pharmacology
- Rhodococcus equi / drug effects
- Rhodococcus equi / genetics
- Rhodococcus equi / isolation & purification
- Sequence Analysis, DNA
- Streptogramin B / pharmacology
- United States
Grant Funding
- Biotechnology and Biological Sciences Research Council
Citations
This article has been cited 18 times.- Lord J, Carter C, Smith J, Locke S, Phillips E, Odoi A. Antimicrobial resistance among Streptococcus equi subspecies zooepidemicus and Rhodococcus equi isolated from equine specimens submitted to a diagnostic laboratory in Kentucky, USA. PeerJ 2022;10:e13682.
- Val-Calvo J, Darcy J, Gibbons J, Creighton A, Egan C, Buckley T, Schmalenberger A, Fogarty U, Scortti M, Vázquez-Boland JA. International Spread of Multidrug-Resistant Rhodococcus equi. Emerg Infect Dis 2022 Sep;28(9):1899-1903.
- Narváez SÁ, Fernández I, Patel NV, Sánchez S. Novel Quantitative PCR for Rhodococcus equi and Macrolide Resistance Detection in Equine Respiratory Samples. Animals (Basel) 2022 May 3;12(9).
- Erol E, Scortti M, Fortner J, Patel M, Vázquez-Boland JA. Antimicrobial Resistance Spectrum Conferred by pRErm46 of Emerging Macrolide (Multidrug)-Resistant Rhodococcus equi. J Clin Microbiol 2021 Sep 20;59(10):e0114921.
- Álvarez-Narváez S, Huber L, Giguère S, Hart KA, Berghaus RD, Sanchez S, Cohen ND. Epidemiology and Molecular Basis of Multidrug Resistance in Rhodococcus equi. Microbiol Mol Biol Rev 2021 May 19;85(2).
- Álvarez-Narváez S, Giguère S, Cohen N, Slovis N, Vázquez-Boland JA. Spread of Multidrug-Resistant Rhodococcus equi, United States. Emerg Infect Dis 2021 Feb;27(2):529-537.
- Álvarez-Narváez S, Giguère S, Berghaus LJ, Dailey C, Vázquez-Boland JA. Horizontal Spread of Rhodococcus equi Macrolide Resistance Plasmid pRErm46 across Environmental Actinobacteria. Appl Environ Microbiol 2020 Apr 17;86(9).
- Álvarez-Narváez S, Berghaus LJ, Morris ERA, Willingham-Lane JM, Slovis NM, Giguere S, Cohen ND. A Common Practice of Widespread Antimicrobial Use in Horse Production Promotes Multi-Drug Resistance. Sci Rep 2020 Jan 22;10(1):911.
- Álvarez-Narváez S, Giguère S, Anastasi E, Hearn J, Scortti M, Vázquez-Boland JA. Clonal Confinement of a Highly Mobile Resistance Element Driven by Combination Therapy in Rhodococcus equi. mBio 2019 Oct 15;10(5).
- Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S. Effect of Macrolide and Rifampin Resistance on Fitness of Rhodococcus equi during Intramacrophage Replication and In Vivo. Infect Immun 2019 Oct;87(10).
- Fatahi-Bafghi M. Antibiotic resistance genes in the Actinobacteria phylum. Eur J Clin Microbiol Infect Dis 2019 Sep;38(9):1599-1624.
- Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S. Effect of Macrolide and Rifampin Resistance on the Fitness of Rhodococcus equi. Appl Environ Microbiol 2019 Apr 1;85(7).
- Anastasi E, MacArthur I, Scortti M, Alvarez S, Giguère S, Vázquez-Boland JA. Pangenome and Phylogenomic Analysis of the Pathogenic Actinobacterium Rhodococcus equi. Genome Biol Evol 2016 Oct 23;8(10):3140-3148.
- Yang Y, Xie S, He F, Xu Y, Wang Z, Ihsan A, Wang X. Recent development and fighting strategies for lincosamide antibiotic resistance. Clin Microbiol Rev 2024 Jun 13;37(2):e0016123.
- Higgins C, Cohen ND, Slovis N, Boersma M, Gaonkar PP, Golden DR, Huber L. Antimicrobial Residue Accumulation Contributes to Higher Levels of Rhodococcus equi Carrying Resistance Genes in the Environment of Horse-Breeding Farms. Vet Sci 2024 Feb 17;11(2).
- Alvarez Narvaez S, Sanchez S. Exploring the Accessory Genome of Multidrug-Resistant Rhodococcus equi Clone 2287. Antibiotics (Basel) 2023 Nov 17;12(11).
- Brown-Elliott BA, Wallace RJ Jr, Wengenack NL, Workman SD, Cameron ADS, Bush G, Hughes MD, Melton S, Gonzalez-Ramirez B, Rodriguez E, Somayaji K, Klapperich C, Viers M, Bolaji AJ, Rempel E, Alexander DC. Emergence of Inducible Macrolide Resistance in Mycobacterium chelonae Due to Broad-Host-Range Plasmid and Chromosomal Variants of the Novel 23S rRNA Methylase Gene, erm(55). J Clin Microbiol 2023 Jul 20;61(7):e0042823.
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