Analyze Diet
Environmental microbiology2020; 22(7); 2858-2869; doi: 10.1111/1462-2920.15020

The novel and transferable erm(51) gene confers macrolides, lincosamides and streptogramins B (MLSB ) resistance to clonal Rhodococcus equi in the environment.

Abstract: The use of mass antimicrobial treatment has been linked to the emergence of antimicrobial resistance in human and animal pathogens. Using whole-genome single-molecule real-time (SMRT) sequencing, we characterized genomic variability of multidrug-resistant Rhodococcus equi isolated from soil samples from 100 farms endemic for R. equi infections in Kentucky. We discovered the novel erm(51)-encoding resistance to MLS in R. equi isolates from soil of horse-breeding farms. Erm(51) is inserted in a transposon (TnErm51) that is associated with a putative conjugative plasmid (pRErm51), a mobilizable plasmid (pMobErm51), or both enabling horizontal gene transfer to susceptible organisms and conferring high levels of resistance against MLS in vitro. This new resistant genotype also carries a previously unidentified rpoB mutation conferring resistance to rifampicin. Isolates carrying both vapA and erm(51) were rarely found, indicating either a recent acquisition of erm(51) and/or impaired survival when isolates carry both genes. Isolates carrying erm(51) are closely related genetically and were likely selected by antimicrobial exposure in the environment.
Publication Date: 2020-05-04 PubMed ID: 32291839DOI: 10.1111/1462-2920.15020Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study identifies a new gene, erm(51), found in Rhodococcus equi bacteria which causes resistance to several types of antibiotics. It also uncovers how these bacteria gain this resistance, and posits that this might be due to widespread use of antibiotics.

Study Methodology

  • The research team used an advanced sequencing technique called whole-genome single-molecule real-time (SMRT) sequencing to study samples of multidrug-resistant Rhodococcus equi bacteria isolated from soil samples from 100 different farms in Kentucky that are notorious for R. equi infections.
  • The main focus of the study was to analyse the genomic variability of these bacteria, and identify any unique genetic features that may contribute to antimicrobial resistance.

Key Findings

  • The researchers discovered a new gene, erm(51), in these bacteria, which promotes resistance to a group of antibiotics that include macrolides, lincosamides, and streptogramins B (MLS).
  • The erm(51) gene is situated in a transposon (TnErm51) – a DNA sequence that can change its position within the genome, thereby creating or reversing mutations and altering the cell’s genetic identity and its genome size. This transposon is associated with a hypothesised conjugal plasmid (pRErm51) or a mobilizable plasmid (pMobErm51), or both. A conjugative plasmid is a type of self-transmissible DNA element and a mobilizable plasmid carries genes which enable the initiation of plasmid transfer.
  • When either of these plasmids are present, the bacterium can transfer the erm(51) gene to other susceptible organisms, leading to resistance to MLS antibiotics.
  • The strains that were carrying the erm(51) gene were also found to have another previously unidentified mutation in the rpoB gene that makes them resistant to the antibiotic rifampicin.
  • The researchers rarely found instances where a strain carried both the vapA and erm(51) genes, suggesting that the acquisition of the erm(51) gene was a relatively recent evolutionary development, or that the bacterium’s survival is hindered in some way when it carries both genes.
  • Last, the study posits that widespread use of antibiotics might have put a selective pressure on the bacteria, leading to the genetic mutation and the spread of the erm(51) gene.

Cite This Article

APA
Huber L, Giguère S, Slovis NM, Álvarez-Narváez S, Hart KA, Greiter M, Morris ERA, Cohen ND. (2020). The novel and transferable erm(51) gene confers macrolides, lincosamides and streptogramins B (MLSB ) resistance to clonal Rhodococcus equi in the environment. Environ Microbiol, 22(7), 2858-2869. https://doi.org/10.1111/1462-2920.15020

Publication

ISSN: 1462-2920
NlmUniqueID: 100883692
Country: England
Language: English
Volume: 22
Issue: 7
Pages: 2858-2869

Researcher Affiliations

Huber, Laura
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Giguère, Steeve
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Slovis, Nathan M
  • Hagyard Equine Medical Institute, Lexington, Kentucky, USA.
Álvarez-Narváez, Sonsiray
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Hart, Kelsey A
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Greiter, Maggie
  • Hagyard Equine Medical Institute, Lexington, Kentucky, USA.
Morris, Ellen Ruth A
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Cohen, Noah D
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.

MeSH Terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • DNA Transposable Elements / genetics
  • Drug Resistance, Bacterial / genetics
  • Farms
  • Gene Transfer, Horizontal
  • Genome, Bacterial / genetics
  • Horses
  • Lincosamides / pharmacology
  • Macrolides / pharmacology
  • Microbial Sensitivity Tests
  • Plasmids / genetics
  • Rhodococcus equi / drug effects
  • Rhodococcus equi / genetics
  • Streptogramin B / pharmacology
  • Streptogramin Group B / pharmacology
  • Virginiamycin / pharmacology

Grant Funding

  • Grayson-Jockey Club Research Foundation

References

This article includes 52 references
  1. Aarestrup FM. Veterinary drug usage and antimicrobial resistance in bacteria of animal origin.. Basic Clin Pharmacol Toxicol 96: 271-281.
  2. Alvarez-Narvaez S, Giguère S, Anastasi E, Hearn J, Scortti M, Vazquez-Boland JA. Clonal confinement of a highly mobile resistance element driven by combination therapy in Rhodococcus equi.. MBio 10(5): e02260-19.
  3. Alvarez-Narvaez S, Berghaus LJ, Morris ERA, Willingham-Lane JM, Slovis NM, Giguère S, Cohen ND. A common practice of widespread antimicrobial use in horse production promotes multi-drug resistance.. Sci Rep 10: 911.
  4. Anastasi E, Giguère S, Berghaus LJ, Hondalus MK, Willingham-Lane JM, MacArthur I. Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi.. J Antimicrob Chemother 70: 3184-3190.
  5. Anastasi E, Giguère S, Berghaus LJ, Hondalus MK, Willingham-Lane JM, MacArthur I. Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi.. J Antimicrob Chemother 71: 1746.
  6. Bengtsson-Palme J, Kristiansson E, Larsson DGJ. Environmental factors influencing the development and spread of antibiotic resistance.. FEMS Microbiol Rev 42(1): fux053.
  7. Berendonk TU, Manaia CM, Merlin C, Fatta-Kassinos D, Cytryn E, Walsh F. Tackling antibiotic resistance: the environmental framework.. Nat Rev Microbiol 13: 310-317.
  8. Berghaus LJ, Giguère S, Guldbech K, Warner E, Ugorji U, Berghaus RD. Comparison of Etest, disk diffusion, and broth macrodilution for in vitro susceptibility testing of Rhodococcus equi.. J Clin Microbiol 53: 314-318.
  9. Burton AJ, Giguère S, Sturgill TL, Berghaus LJ, Slovis NM, Whitman JL. Macrolide- and rifampin-resistant Rhodococcus equi on a horse breeding farm, Kentucky, USA.. Emerg Infect Dis 19: 282-285.
  10. Chaffin MK, Cohen ND, Bloggett GP, Syndergaard M. Evaluation of ultrasonographic screening parameters for predicting subsequent onset of clinically apparent Rhodococcus equi pneumonia in foals.. AAEP Proceedings p. 59.
  11. Chatedaki C, Voulgaridi I, Kachrimanidou M, Hrabak J, Papagiannitsis CC, Petinaki E. Antimicrobial susceptibility and mechanisms of resistance of Greek Clostridium difficile clinical isolates.. J Glob Antimicrob Resist 16: 53-58.
  12. Cohen O, Denning D. World Health Organization ranking of antimicrobials according to their importance in human medicine.. Clin Infect Dis 64: 986-987.
  13. Cohen ND, O'Conor MS, Chaffin MK, Martens RJ. Farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals.. J Am Vet Med Assoc 226: 404-413.
  14. Contributors (2018a) Canu. Research Computer Center Wiki.
  15. Contributors (2018b) Harvest. Research Computer Center Wiki.
  16. Davies J, Davies D. Origins and evolution of antibiotic resistance.. Microbiol Mol Biol Rev 74: 417-433.
  17. Fernando DM, Tun HM, Poole J, Patidar R, Li R, Mi R. Detection of antibiotic resistance genes in source and drinking water samples from a first nations community in Canada.. Appl Environ Microbiol 82: 4767-4775.
  18. Fines M, Pronost S, Maillard K, Taouji S, Leclercq R. Characterization of mutations in the rpoB gene associated with rifampin resistance in Rhodococcus equi isolated from foals.. J Clin Microbiol 39: 2784-2787.
  19. Giguère S, Hondalus MK, Yager JA, Darrah P, Mosser DM, Prescott JF. Role of the 85-kilobase plasmid and plasmid-encoded virulence-associated protein a in intracellular survival and virulence of Rhodococcus equi.. Infect Immun 67: 3548-3557.
  20. Giguère S, Lee E, Williams E, Cohen ND, Chaffin MK, Halbert N. Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of R equi.. J Am Vet Med Assoc 237: 74-81.
  21. Giguère S, Lee EA, Guldbech KM, Berghaus LJ. In vitro synergy, pharmacodynamics, and postantibiotic effect of 11 antimicrobial agents against Rhodococcus equi.. Vet Microbiol 160: 207-213.
  22. Giguère S, Berghaus LJ, Willingham-Lane JM. Antimicrobial resistance in Rhodococcus equi.. Microbiol Spectr 5(5).
  23. Graham JP, Evans SL, Price LB, Silbergeld EK. Fate of antimicrobial-resistant enterococci and staphylococci and resistance determinants in stored poultry litter.. Environ Res 109: 682-689.
  24. Hondalus MK, Diamond MS, Rosenthal LA, Springer TA, Mosser DM. The intracellular bacterium Rhodococcus equi requires mac-1 to bind to mammalian cells.. Infect Immun 61: 2919-2929.
  25. Hong Y, Hondalus MK. Site-specific integration of Streptomyces PhiC31 integrase-based vectors in the chromosome of Rhodococcus equi.. FEMS Microbiol Lett 287: 63-68.
  26. Huber L, Gressler LT, Sanz MG, Garbade P, Vargas A, Silveira BP. Monitoring foals by thoracic ultrasonography, bacterial culture, and PCR: diagnostic of Rhodococcus equi subclinical pneumonia in south of Brazil.. J Equine Vet Sci 60: 104.
  27. Huber L, Giguère S, Slovis NM, Carter CN, Barr BS, Cohen ND. Emergence of resistance to macrolides and rifampicin in clinical isolates of Rhodococcus equi from foals in Central Kentucky, USA: 1995 to 2017.. Antimicrob Agents Chemother 63(1): e01714-18.
  28. Huber L, Giguère S, Cohen ND, Slovis NM, Berghaus L, Greiter M, Hart KA. Identification of macrolide- and rifampicin-resistant Rhodococcus equi in environmental samples from equine breeding farms in Central Kentucky during 2018.. Vet Microbiol 232: 74-78.
  29. Huber L, Giguère S, Cohen ND, Slovis NM, Hanafi A, Schuckert A. Prevalence and risk factors associated with emergence of Rhodococcus equi resistance to macrolides and rifampicin in horse-breeding farms in Kentucky, USA.. Vet Microbiol 235: 243-247.
  30. Ladron N, Fernandez M, Aguero J, Gonzalez Zorn B, Vazquez-Boland JA, Navas J. Rapid identification of Rhodococcus equi by a PCR assay targeting the choE gene.. J Clin Microbiol 41: 3241-3245.
  31. Lakin SM, Dean C, Noyes NR, Dettenwanger A, Ross AS, Doster E. MEGARes: an antimicrobial resistance database for high throughput sequencing.. Nucleic Acids Res 45: D574-D580.
  32. Levy SB, O'Brien TF, Alliance for the Prudent Use of Antobiotics. Global antimicrobial resistance alerts and implications.. Clin Infect Dis 41: S219-S220.
  33. McArthur AG, Waglechner N, Nizam F, Yan A, Azad MA, Baylay AJ. The comprehensive antibiotic resistance database.. Antimicrob Agents Chemother 57: 3348-3357.
  34. McCracken JL, Slovis NM, White N. Use of thoracic ultrasound for the prevention of Rhodococcus equi pneumonia on endemic farms. AAEP Proceedings p. 55.
  35. Nordmann P, Ronco E. In-vitro antimicrobial susceptibility of Rhodococcus equi.. J Antimicrob Chemother 29: 383-393.
  36. Peng M, Salaheen S, Buchanan RL, Biswas D. Alterations of Salmonella Typhimurium antibiotic resistance under environmental pressure.. Appl Environ Microbiol 84(19): e01173-18.
  37. Peterson E, Kaur P. Antibiotic resistance cechanisms in bacteria: relationships between resistance determinants of antibiotic producers, environmental bacteria, and clinical pathogens.. Front Microbiol 9: 2928.
  38. Prescott JF. Rhodococcus equi: an animal and human pathogen.. Clin Microbiol Rev 4: 20-34.
  39. Prescott JF, Nicholson VM. The effects of combinations of selected antibiotics on the growth of Corynebacterium-equi.. J Vet Pharmacol Ther 7: 61-64.
  40. Riesenberg A, Fessler AT, Erol E, Prenger-Berninghoff E, Stamm I, Bose R. MICs of 32 antimicrobial agents for Rhodococcus equi isolates of animal origin.. J Antimicrob Chemother 69: 1045-1049.
  41. Sarmah AK, Meyer MT, Boxall AB. A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment.. Chemosphere 65: 725-759.
  42. Seemann T. Prokka: rapid prokaryotic genome annotation.. Bioinformatics 30: 2068-2069.
  43. Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M. ISfinder: the reference Centre for bacterial insertion sequences.. Nucleic Acids Res 34: D32-D36.
  44. Smillie C, Garcillan-Barcia MP, Francia MV, Rocha EP, de la Cruz F. Mobility of plasmids.. Microbiol Mol Biol Rev 74: 434-452.
  45. Takai S, Takeda K, Nakano Y, Karasawa T, Furugoori J, Sasaki Y. Emergence of rifampin-resistant Rhodococcus equi in an infected foal.. J Clin Microbiol 35: 1904-1908.
  46. Treangen TJ, Ondov BD, Koren S, Phillippy AM. The harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes.. Genome Biol 15: 524.
  47. Tripathi VN, Harding WC, Willingham-Lane JM, Hondalus MK. Conjugal transfer of a virulence plasmid in the opportunistic intracellular actinomycete Rhodococcus equi.. J Bacteriol 194: 6790-6801.
  48. Venner M, Kerth R, Klug E. Evaluation of tulathromycin in the treatment of pulmonary abscesses in foals.. Vet J 174: 418-421.
  49. Vieira AR, Collignon P, Aarestrup FM, McEwen SA, Hendriksen RS, Hald T, Wegener HC. Association between antimicrobial resistance in Escherichia coli isolates from food animals and blood stream isolates from humans in Europe: an ecological study.. Foodborne Pathog Dis 8: 1295-1301.
  50. Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S. Effect of macrolide- and rifampin-resistance on fitness of Rhodococcus equi.. Appl Environ Microbiol 85(7): e02665-18.
  51. 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 87(10): e00281-19.
  52. World Health Organization. Antimicrobial Resistance: Global Report on Surveillance.. Geneva, Switzerland: World Health Organization.

Citations

This article has been cited 6 times.
  1. Baran A, Kwiatkowska A, Potocki L. Antibiotics and Bacterial Resistance-A Short Story of an Endless Arms Race.. Int J Mol Sci 2023 Mar 17;24(6).
    doi: 10.3390/ijms24065777pubmed: 36982857google scholar: lookup
  2. Li XY, Yu R, Xu C, Shang Y, Li D, Du XD. A Small Multihost Plasmid Carrying erm(T) Identified in Enterococcus faecalis.. Front Vet Sci 2022;9:850466.
    doi: 10.3389/fvets.2022.850466pubmed: 35711812google scholar: lookup
  3. 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).
    doi: 10.3390/ani12091172pubmed: 35565598google scholar: lookup
  4. 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.
    doi: 10.1128/JCM.01149-21pubmed: 34319806google scholar: lookup
  5. 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).
    doi: 10.1128/MMBR.00011-21pubmed: 33853933google scholar: lookup
  6. Lee HJ, Jhang ST, Jin HJ. Potential Target Site for Inhibitors in MLS(B) Antibiotic Resistance.. Antibiotics (Basel) 2021 Mar 5;10(3).
    doi: 10.3390/antibiotics10030264pubmed: 33807634google scholar: lookup