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mBio2019; 10(5); e02260-19; doi: 10.1128/mBio.02260-19

Clonal Confinement of a Highly Mobile Resistance Element Driven by Combination Therapy in Rhodococcus equi.

Abstract: Antibiotic use has been linked to changes in the population structure of human pathogens and the clonal expansion of multidrug-resistant (MDR) strains among healthcare- and community-acquired infections. Here we present a compelling example in a veterinary pathogen, , the causative agent of a severe pulmonary infection affecting foals worldwide. We show that the (46) gene responsible for emerging macrolide resistance among equine isolates in the United States is part of a 6.9-kb transposable element, Tn, actively mobilized by an IS family transposase. Tn is carried on an 87-kb conjugative plasmid, pRErm46, transferable between strains at frequencies up to 10 The (46) gene becomes stabilized in by pRErm46's apparent fitness neutrality and wholesale Tn transposition onto the host genome. This includes the conjugally exchangeable pVAPA virulence plasmid, enabling the possibility of cotransfer of two essential traits for survival in macrolide-treated foals in a single mating event. Despite its high horizontal transfer potential, phylogenomic analyses show that (46) is paradoxically confined to a specific clone, 2287. 2287 also carries a unique mutation conferring high-level resistance to rifampin, systematically administered together with macrolides against rhodococcal pneumonia on equine farms. Our data illustrate that under sustained combination therapy, several independent "founder" genetic events are concurrently required for resistance, limiting not only its emergence but also, crucially, horizontal spread, ultimately determining multiresistance clonality. MDR clades arise upon acquisition of resistance traits, but the determinants of their clonal expansion remain largely undefined. Taking advantage of the unique features of infection control in equine farms, involving the same dual antibiotic treatment since the 1980s (a macrolide and rifampin), this study sheds light into the determinants of multiresistance clonality and the importance of combination therapy in limiting the dissemination of mobile resistance elements. Clinically effective therapeutic alternatives against foal pneumonia are currently lacking, and the identified macrolide-rifampin MDR clone 2287 has serious implications. Still at early stages of evolution and local spread, 2287 may disseminate globally, posing a significant threat to the equine industry and, also, public health due to the risk of zoonotic transmission. The characterization of the 2287 clone and its resistance determinants will enable targeted surveillance and control interventions to tackle the emergence of MDR .
Copyright © 2019 Álvarez-Narváez et al.
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Publication Date: 2019-10-15 PubMed ID: 31615959PubMed Central: PMC6794481DOI: 10.1128/mBio.02260-19Google Scholar: Lookup
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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.

This research investigates the antibiotic resistance in Rhodococcus equi, a veterinary pathogen causing severe lung infection in foals. The study reveals that the gene responsible for emerging antibiotic resistance in the US equine R. equi population is part of the mobile genetic element, Tn. It further explores how combination therapy can limit the spread of this resistance.

Resistance Element in Rhodococcus equi

  • The researchers identify the errm(46) gene as the key player in the observed antibiotic resistance. This gene is located on a mobile genetic element, Tn, and is easily transferable between R. equi strains.
  • The protein encoded by the errm(46) gene confers the bacterium resistance to macrolide, a category of antibiotics commonly used against R. equi infections.

Role of Conjugative Plasmid

  • The errm(46) gene resides on a 6.9kb transposable element, Tn, which is mobilized by a specific enzyme, an IS family transposase.
  • The Tn element is carried by an 87-kb conjugative plasmid, pRErm46, which allows the spread of the errm(46) gene between R. equi strains. This study shows that pRErm46 has a high transfer frequency.
  • Once acquired by a new strain, the errm(46) gene becomes stable due to the plasmid’s apparent fitness neutrality and Tn’s ability to transpose onto the host genome.

Confinement to Specific R. equi Clone

  • Despite the high mobility of the errm(46) gene, it is found confined to a specific R. equi clone, 2287, resulting in the clonal spread of this antibiotic resistance.
  • The 2287 clone also carries a unique mutation that provides additional resistance to rifampin, another antibiotic used in combination with macrolides against R. equi infection. The concurrent requirement for multiple genetic changes for resistance under dual drug therapy significantly limits the emergence and spread of antibiotic resistance among R. equi strains.

Implications and Threats

  • This study underscores the risks associated with the potential global spread of R. equi clone 2287, given its dual-antibiotic resistance. This could pose a substantial threat not only to the equine industry but also to public health because of possible transmission to humans.
  • The lack of clinically effective alternatives to fight R. equi pneumonia in foals makes the emergence of multidrug-resistant clones like 2287 a serious problem. Therefore, characterizing the 2287 clone and its resistance determinants can guide surveillance and control measures effectively.

Cite This Article

APA
Álvarez-Narváez S, Giguère S, Anastasi E, Hearn J, Scortti M, Vázquez-Boland JA. (2019). Clonal Confinement of a Highly Mobile Resistance Element Driven by Combination Therapy in Rhodococcus equi. mBio, 10(5), e02260-19. https://doi.org/10.1128/mBio.02260-19

Publication

mBio
ISSN: 2150-7511
NlmUniqueID: 101519231
Country: United States
Language: English
Volume: 10
Issue: 5
PII: e02260-19

Researcher Affiliations

Álvarez-Narváez, Sonsiray
  • Microbial Pathogenesis Group, Infection Medicine, Edinburgh Medical School (Biomedical Sciences), University of Edinburgh, Edinburgh, United Kingdom.
Giguère, Steeve
  • Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
Anastasi, Elisa
  • Microbial Pathogenesis Group, Infection Medicine, Edinburgh Medical School (Biomedical Sciences), University of Edinburgh, Edinburgh, United Kingdom.
Hearn, Jack
  • Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.
Scortti, Mariela
  • Microbial Pathogenesis Group, Infection Medicine, Edinburgh Medical School (Biomedical Sciences), University of Edinburgh, Edinburgh, United Kingdom.
Vázquez-Boland, José A
  • Microbial Pathogenesis Group, Infection Medicine, Edinburgh Medical School (Biomedical Sciences), University of Edinburgh, Edinburgh, United Kingdom v.boland@ed.ac.uk.

MeSH Terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Resistance, Bacterial / genetics
  • Macrolides / pharmacology
  • Microbial Sensitivity Tests
  • Rhodococcus equi / drug effects
  • Rhodococcus equi / genetics
  • Virulence / genetics

Grant Funding

  • BB/J004227/1 / Biotechnology and Biological Sciences Research Council

References

This article includes 86 references
  1. Prescott JF. Rhodococcus equi: an animal and human pathogen.. Clin Microbiol Rev 1991 Jan;4(1):20-34.
    doi: 10.1128/cmr.4.1.20pmc: PMC358176pubmed: 2004346google scholar: lookup
  2. Yamshchikov AV, Schuetz A, Lyon GM. Rhodococcus equi infection.. Lancet Infect Dis 2010 May;10(5):350-9.
    doi: 10.1016/S1473-3099(10)70068-2pubmed: 20417417google scholar: lookup
  3. Vázquez-Boland JA, Meijer WG. The pathogenic actinobacterium Rhodococcus equi: what's in a name?. Mol Microbiol 2019 Jul;112(1):1-15.
    doi: 10.1111/mmi.14267pmc: PMC6852188pubmed: 31099908google scholar: lookup
  4. Giguère S, Cohen ND, Chaffin MK, Slovis NM, Hondalus MK, Hines SA, Prescott JF. Diagnosis, treatment, control, and prevention of infections caused by Rhodococcus equi in foals.. J Vet Intern Med 2011 Nov-Dec;25(6):1209-20.
    doi: 10.1111/j.1939-1676.2011.00835.xpubmed: 22092608google scholar: lookup
  5. Venner M, Astheimer K, Lämmer M, Giguère S. Efficacy of mass antimicrobial treatment of foals with subclinical pulmonary abscesses associated with Rhodococcus equi.. J Vet Intern Med 2013 Jan-Feb;27(1):171-6.
    doi: 10.1111/jvim.12030pubmed: 23278131google scholar: lookup
  6. Takai S, Hines SA, Sekizaki T, Nicholson VM, Alperin DA, Osaki M, Takamatsu D, Nakamura M, Suzuki K, Ogino N, Kakuda T, Dan H, Prescott JF. DNA sequence and comparison of virulence plasmids from Rhodococcus equi ATCC 33701 and 103.. Infect Immun 2000 Dec;68(12):6840-7.
    doi: 10.1128/iai.68.12.6840-6847.2000pmc: PMC97788pubmed: 11083803google scholar: lookup
  7. Ocampo-Sosa AA, Lewis DA, Navas J, Quigley F, Callejo R, Scortti M, Leadon DP, Fogarty U, Vazquez-Boland JA. Molecular epidemiology of Rhodococcus equi based on traA, vapA, and vapB virulence plasmid markers.. J Infect Dis 2007 Sep 1;196(5):763-9.
    doi: 10.1086/519688pubmed: 17674320google scholar: lookup
  8. Letek M, Ocampo-Sosa AA, Sanders M, Fogarty U, Buckley T, Leadon DP, González P, Scortti M, Meijer WG, Parkhill J, Bentley S, Vázquez-Boland JA. Evolution of the Rhodococcus equi vap pathogenicity island seen through comparison of host-associated vapA and vapB virulence plasmids.. J Bacteriol 2008 Sep;190(17):5797-805.
    doi: 10.1128/JB.00468-08pmc: PMC2519538pubmed: 18606735google scholar: lookup
  9. MacArthur I, Anastasi E, Alvarez S, Scortti M, Vázquez-Boland JA. Comparative Genomics of Rhodococcus equi Virulence Plasmids Indicates Host-Driven Evolution of the vap Pathogenicity Island.. Genome Biol Evol 2017 May 1;9(5):1241-1247.
    doi: 10.1093/gbe/evx057pmc: PMC5434932pubmed: 28369330google scholar: lookup
  10. von Bargen K, Haas A. Molecular and infection biology of the horse pathogen Rhodococcus equi.. FEMS Microbiol Rev 2009 Sep;33(5):870-91.
    doi: 10.1111/j.1574-6976.2009.00181.xpubmed: 19453748google scholar: lookup
  11. Takai S, Sugawara T, Watanabe Y, Sasaki Y, Tsubaki S, Sekizaki T. Effect of growth temperature on maintenance of virulent Rhodococcus equi.. Vet Microbiol 1994 Mar;39(1-2):187-92.
    doi: 10.1016/0378-1135(94)90099-xpubmed: 8203124google scholar: lookup
  12. Tripathi VN, Harding WC, Willingham-Lane JM, Hondalus MK. Conjugal transfer of a virulence plasmid in the opportunistic intracellular actinomycete Rhodococcus equi.. J Bacteriol 2012 Dec;194(24):6790-801.
    doi: 10.1128/JB.01210-12pmc: PMC3510604pubmed: 23042997google scholar: lookup
  13. Valero-Rello A, Hapeshi A, Anastasi E, Alvarez S, Scortti M, Meijer WG, MacArthur I, Vázquez-Boland JA. An Invertron-Like Linear Plasmid Mediates Intracellular Survival and Virulence in Bovine Isolates of Rhodococcus equi.. Infect Immun 2015 Jul;83(7):2725-37.
    doi: 10.1128/IAI.00376-15pmc: PMC4468562pubmed: 25895973google scholar: lookup
  14. Dawson TRMY, Horohov DW, Meijer WG, Muscatello G. Current understanding of the equine immune response to Rhodococcus equi. An immunological review of R. equi pneumonia.. Vet Immunol Immunopathol 2010 May 15;135(1-2):1-11.
    doi: 10.1016/j.vetimm.2009.12.004pubmed: 20064668google scholar: lookup
  15. Chaffin MK, Cohen ND, Martens RJ. Chemoprophylactic effects of azithromycin against Rhodococcus equi-induced pneumonia among foals at equine breeding farms with endemic infections.. J Am Vet Med Assoc 2008 Apr 1;232(7):1035-47.
    doi: 10.2460/javma.232.7.1035pubmed: 18380623google scholar: lookup
  16. Burton AJ, Giguère S, Sturgill TL, Berghaus LJ, Slovis NM, Whitman JL, Levering C, Kuskie KR, Cohen ND. Macrolide- and rifampin-resistant Rhodococcus equi on a horse breeding farm, Kentucky, USA.. Emerg Infect Dis 2013 Feb;19(2):282-5.
    doi: 10.3201/eid1902.121210pmc: PMC3559061pubmed: 23347878google scholar: lookup
  17. McCracken JL, Slovis NM. Use of thoracic ultrasound for the prevention of Rhodococcus equi pneumonia in endemic farms. Proc Am Assoc Equine Pract 55:38–44.
  18. Jacks SS, Giguère S, Nguyen A. In vitro susceptibilities of Rhodococcus equi and other common equine pathogens to azithromycin, clarithromycin, and 20 other antimicrobials.. Antimicrob Agents Chemother 2003 May;47(5):1742-5.
    doi: 10.1128/aac.47.5.1742-1745.2003pmc: PMC153307pubmed: 12709351google scholar: lookup
  19. Riesenberg A, Feßler AT, Erol E, Prenger-Berninghoff E, Stamm I, Böse R, Heusinger A, Klarmann D, Werckenthin C, Schwarz S. MICs of 32 antimicrobial agents for Rhodococcus equi isolates of animal origin.. J Antimicrob Chemother 2014 Apr;69(4):1045-9.
    doi: 10.1093/jac/dkt460pubmed: 24275117google scholar: lookup
  20. Sweeney CR, Sweeney RW, Divers TJ. Rhodococcus equi pneumonia in 48 foals: response to antimicrobial therapy.. Vet Microbiol 1987 Aug;14(3):329-36.
    doi: 10.1016/0378-1135(87)90120-9pubmed: 3672875google scholar: lookup
  21. Letek M, González P, Macarthur I, Rodríguez H, Freeman TC, Valero-Rello A, Blanco M, Buckley T, Cherevach I, Fahey R, Hapeshi A, Holdstock J, Leadon D, Navas J, Ocampo A, Quail MA, Sanders M, Scortti MM, Prescott JF, Fogarty U, Meijer WG, Parkhill J, Bentley SD, Vázquez-Boland JA. The genome of a pathogenic rhodococcus: cooptive virulence underpinned by key gene acquisitions.. PLoS Genet 2010 Sep 30;6(9):e1001145.
    doi: 10.1371/journal.pgen.1001145pmc: PMC2947987pubmed: 20941392google scholar: lookup
  22. Mascellino MT, Iona E, Ponzo R, Mastroianni CM, Delia S. Infections due to Rhodococcus equi in three HIV-infected patients: microbiological findings and antibiotic susceptibility.. Int J Clin Pharmacol Res 1994;14(5-6):157-63.
    pubmed: 7672872
  23. Nordmann P, Ronco E. In-vitro antimicrobial susceptibility of Rhodococcus equi.. J Antimicrob Chemother 1992 Apr;29(4):383-93.
    doi: 10.1093/jac/29.4.383pubmed: 1607327google scholar: lookup
  24. Makrai L, Fodor L, Csivincsik A, Varga J, Senoner Z, Szabó B. Characterisation of Rhodococcus equi strains isolated from foals and from immunocompromised human patients.. Acta Vet Hung 2000;48(3):253-9.
    pubmed: 11402708
  25. Hillidge CJ. Use of erythromycin-rifampin combination in treatment of Rhodococcus equi pneumonia.. Vet Microbiol 1987 Aug;14(3):337-42.
    doi: 10.1016/0378-1135(87)90121-0pubmed: 3314109google scholar: lookup
  26. Giguère S. Treatment of Infections Caused by Rhodococcus equi.. Vet Clin North Am Equine Pract 2017 Apr;33(1):67-85.
    doi: 10.1016/j.cveq.2016.11.002pubmed: 28161038google scholar: lookup
  27. Asoh N, Watanabe H, Fines-Guyon M, Watanabe K, Oishi K, Kositsakulchai W, Sanchai T, Kunsuikmengrai K, Kahintapong S, Khantawa B, Tharavichitkul P, Sirisanthana T, Nagatake T. Emergence of rifampin-resistant Rhodococcus equi with several types of mutations in the rpoB gene among AIDS patients in northern Thailand.. J Clin Microbiol 2003 Jun;41(6):2337-40.
    doi: 10.1128/jcm.41.6.2337-2340.2003pmc: PMC156560pubmed: 12791846google scholar: lookup
  28. Giguère S, Lee E, Williams E, Cohen ND, Chaffin MK, Halbert N, Martens RJ, Franklin RP, Clark CC, Slovis NM. 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 2010 Jul 1;237(1):74-81.
    doi: 10.2460/javma.237.1.74pubmed: 20590498google scholar: lookup
  29. Boyen F, Pasmans F, Haesebrouck F. Acquired antimicrobial resistance in equine Rhodococcus equi isolates.. Vet Rec 2011 Jan 29;168(4):101a.
    doi: 10.1136/vr.c5289pubmed: 21257598google scholar: lookup
  30. 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 2001 Aug;39(8):2784-7.
    doi: 10.1128/JCM.39.8.2784-2787.2001pmc: PMC88239pubmed: 11473992google scholar: lookup
  31. Takai S, Takeda K, Nakano Y, Karasawa T, Furugoori J, Sasaki Y, Tsubaki S, Higuchi T, Anzai T, Wada R, Kamada M. Emergence of rifampin-resistant Rhodococcus equi in an infected foal.. J Clin Microbiol 1997 Jul;35(7):1904-8.
    pmc: PMC229871pubmed: 9196223doi: 10.1128/jcm.35.7.1904-1908.1997google scholar: lookup
  32. Anastasi E, Giguère S, Berghaus LJ, Hondalus MK, Willingham-Lane JM, MacArthur I, Cohen ND, Roberts MC, Vazquez-Boland JA. Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi.. J Antimicrob Chemother 2015 Dec;70(12):3184-90.
    doi: 10.1093/jac/dkv279pubmed: 26377866google scholar: lookup
  33. Collignon PJ, Conly JM, Andremont A, McEwen SA, Aidara-Kane A, Agerso Y, Andremont A, Collignon P, Conly J, Dang Ninh T, Donado-Godoy P, Fedorka-Cray P, Fernandez H, Galas M, Irwin R, Karp B, Matar G, McDermott P, McEwen S, Mitema E, Reid-Smith R, Scott HM, Singh R, DeWaal CS, Stelling J, Toleman M, Watanabe H, Woo GJ. World Health Organization Ranking of Antimicrobials According to Their Importance in Human Medicine: A Critical Step for Developing Risk Management Strategies to Control Antimicrobial Resistance From Food Animal Production.. Clin Infect Dis 2016 Oct 15;63(8):1087-1093.
    doi: 10.1093/cid/ciw475pubmed: 27439526google scholar: lookup
  34. 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.
    doi: 10.1093/gbe/evw222pmc: PMC5174736pubmed: 27638249google scholar: lookup
  35. Hunt M, Silva ND, Otto TD, Parkhill J, Keane JA, Harris SR. Circlator: automated circularization of genome assemblies using long sequencing reads.. Genome Biol 2015 Dec 29;16:294.
    doi: 10.1186/s13059-015-0849-0pmc: PMC4699355pubmed: 26714481google scholar: lookup
  36. Garcillán-Barcia MP, Francia MV, de la Cruz F. The diversity of conjugative relaxases and its application in plasmid classification.. FEMS Microbiol Rev 2009 May;33(3):657-87.
    doi: 10.1111/j.1574-6976.2009.00168.xpubmed: 19396961google scholar: lookup
  37. Smith MC, Thomas CD. An accessory protein is required for relaxosome formation by small staphylococcal plasmids.. J Bacteriol 2004 Jun;186(11):3363-73.
    doi: 10.1128/JB.186.11.3363-3373.2004pmc: PMC415746pubmed: 15150221google scholar: lookup
  38. Guglielmini J, Néron B, Abby SS, Garcillán-Barcia MP, de la Cruz F, Rocha EP. Key components of the eight classes of type IV secretion systems involved in bacterial conjugation or protein secretion.. Nucleic Acids Res 2014 May;42(9):5715-27.
    doi: 10.1093/nar/gku194pmc: PMC4027160pubmed: 24623814google scholar: lookup
  39. West NP, Chow FM, Randall EJ, Wu J, Chen J, Ribeiro JM, Britton WJ. Cutinase-like proteins of Mycobacterium tuberculosis: characterization of their variable enzymatic functions and active site identification.. FASEB J 2009 Jun;23(6):1694-704.
    doi: 10.1096/fj.08-114421pmc: PMC2698651pubmed: 19225166google scholar: lookup
  40. Payne K, Sun Q, Sacchettini J, Hatfull GF. Mycobacteriophage Lysin B is a novel mycolylarabinogalactan esterase.. Mol Microbiol 2009 Aug;73(3):367-81.
    doi: 10.1111/j.1365-2958.2009.06775.xpmc: PMC2774421pubmed: 19555454google scholar: lookup
  41. Salifu SP, Valero-Rello A, Campbell SA, Inglis NF, Scortti M, Foley S, Vázquez-Boland JA. Genome and proteome analysis of phage E3 infecting the soil-borne actinomycete Rhodococcus equi.. Environ Microbiol Rep 2013 Feb;5(1):170-8.
    doi: 10.1111/1758-2229.12028pubmed: 23757146google scholar: lookup
  42. Francis I, De Keyser A, De Backer P, Simón-Mateo C, Kalkus J, Pertry I, Ardiles-Diaz W, De Rycke R, Vandeputte OM, El Jaziri M, Holsters M, Vereecke D. pFiD188, the linear virulence plasmid of Rhodococcus fascians D188.. Mol Plant Microbe Interact 2012 May;25(5):637-47.
    doi: 10.1094/MPMI-08-11-0215pubmed: 22482837google scholar: lookup
  43. Gillings MR. Integrons: past, present, and future.. Microbiol Mol Biol Rev 2014 Jun;78(2):257-77.
    doi: 10.1128/MMBR.00056-13pmc: PMC4054258pubmed: 24847022google scholar: lookup
  44. Tauch A, Götker S, Pühler A, Kalinowski J, Thierbach G. The 27.8-kb R-plasmid pTET3 from Corynebacterium glutamicum encodes the aminoglycoside adenyltransferase gene cassette aadA9 and the regulated tetracycline efflux system Tet 33 flanked by active copies of the widespread insertion sequence IS6100.. Plasmid 2002 Sep;48(2):117-29.
    doi: 10.1016/S0147-619X(02)00120-8pubmed: 12383729google scholar: lookup
  45. Williams LE, Detter C, Barry K, Lapidus A, Summers AO. Facile recovery of individual high-molecular-weight, low-copy-number natural plasmids for genomic sequencing.. Appl Environ Microbiol 2006 Jul;72(7):4899-906.
    doi: 10.1128/AEM.00354-06pmc: PMC1489313pubmed: 16820486google scholar: lookup
  46. Martin C, Timm J, Rauzier J, Gomez-Lus R, Davies J, Gicquel B. Transposition of an antibiotic resistance element in mycobacteria.. Nature 1990 Jun 21;345(6277):739-43.
    doi: 10.1038/345739a0pubmed: 2163027google scholar: lookup
  47. Siguier P, Gourbeyre E, Varani A, Ton-Hoang B, Chandler M. Everyman's Guide to Bacterial Insertion Sequences.. Microbiol Spectr 2015 Apr;3(2):MDNA3-0030-2014.
    pubmed: 26104715doi: 10.1128/microbiolspec.mdna3-0030-2014google scholar: lookup
  48. Targant H, Doublet B, Aarestrup FM, Cloeckaert A, Madec JY. IS6100-mediated genetic rearrangement within the complex class 1 integron In104 of the Salmonella genomic island 1.. J Antimicrob Chemother 2010 Jul;65(7):1543-5.
    doi: 10.1093/jac/dkq163pubmed: 20483981google scholar: lookup
  49. Partridge SR, Recchia GD, Stokes HW, Hall RM. Family of class 1 integrons related to In4 from Tn1696.. Antimicrob Agents Chemother 2001 Nov;45(11):3014-20.
    doi: 10.1128/AAC.45.11.3014-3020.2001pmc: PMC90776pubmed: 11600350google scholar: lookup
  50. Gillings M, Boucher Y, Labbate M, Holmes A, Krishnan S, Holley M, Stokes HW. The evolution of class 1 integrons and the rise of antibiotic resistance.. J Bacteriol 2008 Jul;190(14):5095-100.
    doi: 10.1128/JB.00152-08pmc: PMC2447024pubmed: 18487337google scholar: lookup
  51. Guilhot C, Otal I, Van Rompaey I, Martìn C, Gicquel B. Efficient transposition in mycobacteria: construction of Mycobacterium smegmatis insertional mutant libraries.. J Bacteriol 1994 Jan;176(2):535-9.
    doi: 10.1128/jb.176.2.535-539.1994pmc: PMC205082pubmed: 8288551google scholar: lookup
  52. Smith B, Dyson P. Inducible transposition in Streptomyces lividans of insertion sequence IS6100 from Mycobacterium fortuitum.. Mol Microbiol 1995 Dec;18(5):933-41.
    doi: 10.1111/j.1365-2958.1995.18050933.xpubmed: 8825097google scholar: lookup
  53. Siguier P, Gourbeyre E, Chandler M. Bacterial insertion sequences: their genomic impact and diversity.. FEMS Microbiol Rev 2014 Sep;38(5):865-91.
    doi: 10.1111/1574-6976.12067pmc: PMC7190074pubmed: 24499397google scholar: lookup
  54. 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 1999 Jul;67(7):3548-57.
    pmc: PMC116543pubmed: 10377138doi: 10.1128/iai.67.7.3548-3557.1999google scholar: lookup
  55. Coulson GB, Agarwal S, Hondalus MK. Characterization of the role of the pathogenicity island and vapG in the virulence of the intracellular actinomycete pathogen Rhodococcus equi.. Infect Immun 2010 Aug;78(8):3323-34.
    doi: 10.1128/IAI.00081-10pmc: PMC2916281pubmed: 20439471google scholar: lookup
  56. Cohen ND, Smith KE, Ficht TA, Takai S, Libal MC, West BR, DelRosario LS, Becu T, Leadon DP, Buckley T, Chaffin MK, Martens RJ. Epidemiologic study of results of pulsed-field gel electrophoresis of isolates of Rhodococcus equi obtained from horses and horse farms.. Am J Vet Res 2003 Feb;64(2):153-61.
    doi: 10.2460/ajvr.2003.64.153pubmed: 12602583google scholar: lookup
  57. Morton AC, Begg AP, Anderson GA, Takai S, Lämmler C, Browning GF. Epidemiology of Rhodococcus equi strains on Thoroughbred horse farms.. Appl Environ Microbiol 2001 May;67(5):2167-75.
    doi: 10.1128/AEM.67.5.2167-2175.2001pmc: PMC92851pubmed: 11319096google scholar: lookup
  58. 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 2014;15(11):524.
    doi: 10.1186/s13059-014-0524-xpmc: PMC4262987pubmed: 25410596google scholar: lookup
  59. 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 2015 Jan;53(1):314-8.
    doi: 10.1128/JCM.02673-14pmc: PMC4290945pubmed: 25378571google scholar: lookup
  60. Jin DJ, Gross CA. Characterization of the pleiotropic phenotypes of rifampin-resistant rpoB mutants of Escherichia coli.. J Bacteriol 1989 Sep;171(9):5229-31.
    doi: 10.1128/jb.171.9.5229-5231.1989pmc: PMC210350pubmed: 2670912google scholar: lookup
  61. Dahlberg C, Chao L. Amelioration of the cost of conjugative plasmid carriage in Eschericha coli K12.. Genetics 2003 Dec;165(4):1641-9.
    pmc: PMC1462891pubmed: 14704155doi: 10.1093/genetics/165.4.1641google scholar: lookup
  62. San Millan A, MacLean RC. Fitness Costs of Plasmids: a Limit to Plasmid Transmission.. Microbiol Spectr 2017 Sep;5(5).
    doi: 10.1128/microbiolspec.MTBP-0016-2017pubmed: 28944751google scholar: lookup
  63. Baker S, Thomson N, Weill FX, Holt KE. Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens.. Science 2018 May 18;360(6390):733-738.
    doi: 10.1126/science.aar3777pmc: PMC6510332pubmed: 29773743google scholar: lookup
  64. Holden MT, Hsu LY, Kurt K, Weinert LA, Mather AE, Harris SR, Strommenger B, Layer F, Witte W, de Lencastre H, Skov R, Westh H, Zemlicková H, Coombs G, Kearns AM, Hill RL, Edgeworth J, Gould I, Gant V, Cooke J, Edwards GF, McAdam PR, Templeton KE, McCann A, Zhou Z, Castillo-Ramírez S, Feil EJ, Hudson LO, Enright MC, Balloux F, Aanensen DM, Spratt BG, Fitzgerald JR, Parkhill J, Achtman M, Bentley SD, Nübel U. A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic.. Genome Res 2013 Apr;23(4):653-64.
    doi: 10.1101/gr.147710.112pmc: PMC3613582pubmed: 23299977google scholar: lookup
  65. He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, Connor TR, Harris SR, Fairley D, Bamford KB, D'Arc S, Brazier J, Brown D, Coia JE, Douce G, Gerding D, Kim HJ, Koh TH, Kato H, Senoh M, Louie T, Michell S, Butt E, Peacock SJ, Brown NM, Riley T, Songer G, Wilcox M, Pirmohamed M, Kuijper E, Hawkey P, Wren BW, Dougan G, Parkhill J, Lawley TD. Emergence and global spread of epidemic healthcare-associated Clostridium difficile.. Nat Genet 2013 Jan;45(1):109-13.
    doi: 10.1038/ng.2478pmc: PMC3605770pubmed: 23222960google scholar: lookup
  66. Stoesser N, Sheppard AE, Pankhurst L, De Maio N, Moore CE, Sebra R, Turner P, Anson LW, Kasarskis A, Batty EM, Kos V, Wilson DJ, Phetsouvanh R, Wyllie D, Sokurenko E, Manges AR, Johnson TJ, Price LB, Peto TE, Johnson JR, Didelot X, Walker AS, Crook DW. Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131.. mBio 2016 Mar 22;7(2):e02162.
    doi: 10.1128/mBio.02162-15pmc: PMC4807372pubmed: 27006459google scholar: lookup
  67. Wyres KL, Holt KE. Klebsiella pneumoniae Population Genomics and Antimicrobial-Resistant Clones.. Trends Microbiol 2016 Dec;24(12):944-956.
    doi: 10.1016/j.tim.2016.09.007pubmed: 27742466google scholar: lookup
  68. Holt K, Kenyon JJ, Hamidian M, Schultz MB, Pickard DJ, Dougan G, Hall R. Five decades of genome evolution in the globally distributed, extensively antibiotic-resistant Acinetobacter baumannii global clone 1.. Microb Genom 2016 Feb;2(2):e000052.
    doi: 10.1099/mgen.0.000052pmc: PMC5320584pubmed: 28348844google scholar: lookup
  69. Chambers HF, Deleo FR. Waves of resistance: Staphylococcus aureus in the antibiotic era.. Nat Rev Microbiol 2009 Sep;7(9):629-41.
    doi: 10.1038/nrmicro2200pmc: PMC2871281pubmed: 19680247google scholar: lookup
  70. Post V, White PA, Hall RM. Evolution of AbaR-type genomic resistance islands in multiply antibiotic-resistant Acinetobacter baumannii.. J Antimicrob Chemother 2010 Jun;65(6):1162-70.
    doi: 10.1093/jac/dkq095pubmed: 20375036google scholar: lookup
  71. Mulvey MR, Boyd DA, Olson AB, Doublet B, Cloeckaert A. The genetics of Salmonella genomic island 1.. Microbes Infect 2006 Jun;8(7):1915-22.
    doi: 10.1016/j.micinf.2005.12.028pubmed: 16713724google scholar: lookup
  72. Mathers AJ, Peirano G, Pitout JD. The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae.. Clin Microbiol Rev 2015 Jul;28(3):565-91.
    doi: 10.1128/CMR.00116-14pmc: PMC4405625pubmed: 25926236google scholar: lookup
  73. Durão P, Balbontín R, Gordo I. Evolutionary Mechanisms Shaping the Maintenance of Antibiotic Resistance.. Trends Microbiol 2018 Aug;26(8):677-691.
    doi: 10.1016/j.tim.2018.01.005pubmed: 29439838google scholar: lookup
  74. Da Cunha V, Davies MR, Douarre PE, Rosinski-Chupin I, Margarit I, Spinali S, Perkins T, Lechat P, Dmytruk N, Sauvage E, Ma L, Romi B, Tichit M, Lopez-Sanchez MJ, Descorps-Declere S, Souche E, Buchrieser C, Trieu-Cuot P, Moszer I, Clermont D, Maione D, Bouchier C, McMillan DJ, Parkhill J, Telford JL, Dougan G, Walker MJ, Holden MTG, Poyart C, Glaser P. Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline.. Nat Commun 2014 Aug 4;5:4544.
    doi: 10.1038/ncomms5544pmc: PMC4538795pubmed: 25088811google scholar: lookup
  75. Parkhill J, Sebaihia M, Preston A, Murphy LD, Thomson N, Harris DE, Holden MT, Churcher CM, Bentley SD, Mungall KL, Cerdeño-Tárraga AM, Temple L, James K, Harris B, Quail MA, Achtman M, Atkin R, Baker S, Basham D, Bason N, Cherevach I, Chillingworth T, Collins M, Cronin A, Davis P, Doggett J, Feltwell T, Goble A, Hamlin N, Hauser H, Holroyd S, Jagels K, Leather S, Moule S, Norberczak H, O'Neil S, Ormond D, Price C, Rabbinowitsch E, Rutter S, Sanders M, Saunders D, Seeger K, Sharp S, Simmonds M, Skelton J, Squares R, Squares S, Stevens K, Unwin L, Whitehead S, Barrell BG, Maskell DJ. Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.. Nat Genet 2003 Sep;35(1):32-40.
    doi: 10.1038/ng1227pubmed: 12910271google scholar: lookup
  76. Fischbach MA. Combination therapies for combating antimicrobial resistance.. Curr Opin Microbiol 2011 Oct;14(5):519-23.
    doi: 10.1016/j.mib.2011.08.003pmc: PMC3196371pubmed: 21900036google scholar: lookup
  77. Tamma PD, Cosgrove SE, Maragakis LL. Combination therapy for treatment of infections with gram-negative bacteria.. Clin Microbiol Rev 2012 Jul;25(3):450-70.
    doi: 10.1128/CMR.05041-11pmc: PMC3416487pubmed: 22763634google scholar: lookup
  78. Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. Embnet J 17:10–12.
    doi: 10.14806/ej.17.1.200google scholar: lookup
  79. Gurevich A, Saveliev V, Vyahhi N, Tesler G. QUAST: quality assessment tool for genome assemblies.. Bioinformatics 2013 Apr 15;29(8):1072-5.
    doi: 10.1093/bioinformatics/btt086pmc: PMC3624806pubmed: 23422339google scholar: lookup
  80. Li H. Minimap and miniasm: fast mapping and de novo assembly for noisy long sequences.. Bioinformatics 2016 Jul 15;32(14):2103-10.
    doi: 10.1093/bioinformatics/btw152pmc: PMC4937194pubmed: 27153593google scholar: lookup
  81. Vaser R, Sović I, Nagarajan N, Šikić M. Fast and accurate de novo genome assembly from long uncorrected reads.. Genome Res 2017 May;27(5):737-746.
    doi: 10.1101/gr.214270.116pmc: PMC5411768pubmed: 28100585google scholar: lookup
  82. Koren S, Walenz BP, Berlin K, Miller JR, Bergman NH, Phillippy AM. Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation.. Genome Res 2017 May;27(5):722-736.
    doi: 10.1101/gr.215087.116pmc: PMC5411767pubmed: 28298431google scholar: lookup
  83. Seemann T. Prokka: rapid prokaryotic genome annotation.. Bioinformatics 2014 Jul 15;30(14):2068-9.
    doi: 10.1093/bioinformatics/btu153pubmed: 24642063google scholar: lookup
  84. Price MN, Dehal PS, Arkin AP. FastTree 2--approximately maximum-likelihood trees for large alignments.. PLoS One 2010 Mar 10;5(3):e9490.
    doi: 10.1371/journal.pone.0009490pmc: PMC2835736pubmed: 20224823google scholar: lookup
  85. Vasanthakrishnan RB, de Las Heras A, Scortti M, Deshayes C, Colegrave N, Vázquez-Boland JA. PrfA regulation offsets the cost of Listeria virulence outside the host.. Environ Microbiol 2015 Nov;17(11):4566-79.
    doi: 10.1111/1462-2920.12980pmc: PMC4737189pubmed: 26178789google scholar: lookup
  86. Kahm M, Hasenbrink G, Lichtenberg-Frate H, Ludwig J, Kschischo M. Grofit: fitting biological growth curves with R. J Stat Softw 33:1–21.
    pubmed: 0

Citations

This article has been cited 15 times.
  1. Ramos JN, Baio PVP, Veras JFC, Vieira ÉMD, Mattos-Guaraldi AL, Vieira VV. Novel configurations of type I-E CRISPR-Cas system in Corynebacterium striatum clinical isolates. Braz J Microbiol 2023 Mar;54(1):69-80.
    doi: 10.1007/s42770-022-00881-4pubmed: 36477756google scholar: lookup
  2. 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.
    doi: 10.3201/eid2809.220222pubmed: 35997496google 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. Cohen ND, Flores-Ahlschewde P, Gonzales GM, Kahn SK, da Silveira BP, Bray JM, King EE, Blair CC, Bordin AI. Fecal concentration of Rhodococcus equi determined by quantitative polymerase chain reaction of rectal swab samples to differentiate foals with pneumonia from healthy foals. J Vet Intern Med 2022 May;36(3):1146-1151.
    doi: 10.1111/jvim.16438pubmed: 35475581google scholar: lookup
  5. Nielsen SS, Bicout DJ, Calistri P, Canali E, Drewe JA, Garin-Bastuji B, Gonzales Rojas JL, Gortázar C, Herskin M, Michel V, Miranda Chueca MÁ, Padalino B, Pasquali P, Roberts HC, Spoolder H, Ståhl K, Velarde A, Viltrop A, Winckler C, Baldinelli F, Broglia A, Kohnle L, Alvarez J. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): antimicrobial-resistant Rhodococcus equi in horses. EFSA J 2022 Feb;20(2):e07081.
    doi: 10.2903/j.efsa.2022.7081pubmed: 35136423google scholar: lookup
  6. 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
  7. 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
  8. 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.
    doi: 10.3201/eid2702.203030pubmed: 33496218google scholar: lookup
  9. 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).
    doi: 10.1128/AEM.00108-20pubmed: 32169935google scholar: lookup
  10. Mourenza Á, Gil JA, Mateos LM, Letek M. A Novel Screening Strategy Reveals ROS-Generating Antimicrobials That Act Synergistically against the Intracellular Veterinary Pathogen Rhodococcus equi. Antioxidants (Basel) 2020 Jan 28;9(2).
    doi: 10.3390/antiox9020114pubmed: 32012850google scholar: lookup
  11. 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.
    doi: 10.1038/s41598-020-57479-9pubmed: 31969575google scholar: lookup
  12. Baptiste KE, Kyvsgaard NC, Ahmed MO, Damborg P, Dowling PM. Is Rifampin (Rifampicin) Essential for the Treatment of Rhodococcus equi Infections in Foals? A Critical Review of the Role of Rifampin. J Vet Pharmacol Ther 2025 Sep;48(5):345-358.
    doi: 10.1111/jvp.70007pubmed: 40552784google scholar: lookup
  13. Hu B, Gao S, Zhang H, Li Q, Li G, Zhang S, Xing Y, Huang Y, Han S, Tian Y, Zhang W, He H. Whole-genome sequencing and pathogenicity analysis of Rhodococcus equi isolated in horses. BMC Vet Res 2024 Aug 12;20(1):362.
    doi: 10.1186/s12917-024-04167-9pubmed: 39129003google scholar: lookup
  14. Rahmeh R, Akbar A, Almutairi B, Kishk M, Jordamovic NB, Al-Ateeqi A, Shajan A, Al-Sherif H, Esposito A, Al-Momin S, Piazza S. Camel Milk Resistome in Kuwait: Genotypic and Phenotypic Characterization. Antibiotics (Basel) 2024 Apr 23;13(5).
    doi: 10.3390/antibiotics13050380pubmed: 38786109google scholar: lookup
  15. Alvarez Narvaez S, Sanchez S. Exploring the Accessory Genome of Multidrug-Resistant Rhodococcus equi Clone 2287. Antibiotics (Basel) 2023 Nov 17;12(11).
    doi: 10.3390/antibiotics12111631pubmed: 37998833google scholar: lookup
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