1887

Abstract

is a ubiquitous opportunistic pathogen that is exhibiting increasing levels of antimicrobial resistance (AMR). Many of the genes that confer resistance and pathogenic functions are localized on mobile genetic elements (MGEs), which facilitate their transfer between lineages. Here, features including resistance determinants, virulence factors and MGEs were profiled in a set of 1273 genomes from two disparate geographic locations (in the UK and Canada) from a range of agricultural, clinical and associated habitats. Neither lineages of , type A and B, nor MGEs are constrained by geographic proximity, but our results show evidence of a strong association of many profiled genes and MGEs with habitat. Many features were associated with a group of clinical and municipal wastewater genomes that are likely forming a new human-associated ecotype within type A. The evolutionary dynamics of make it a highly versatile emerging pathogen, and its ability to acquire, transmit and lose features presents a high risk for the emergence of new pathogenic variants and novel resistance combinations. This study provides a workflow for MGE-centric surveillance of AMR in that can be adapted to other pathogens.

Funding
This study was supported by the:
  • Dalhousie University
    • Principle Award Recipient: RobertG Beiko
  • Simon Fraser University
    • Principle Award Recipient: FionaS L Brinkman
  • Donald Hill Family Fellowship
    • Principle Award Recipient: FinlayMaguire
  • Research Nova Scotia
    • Principle Award Recipient: RobertG Beiko
  • Comprehensive Antibiotic Resistance Database
    • Principle Award Recipient: AndrewG McArthur
  • Genomics Research and Development Initiative, Government of Canada
    • Principle Award Recipient: TimA McAllister
  • Natural Sciences and Engineering Research Council of Canada
    • Principle Award Recipient: FionaS L Brinkman
  • Natural Sciences and Engineering Research Council of Canada
    • Principle Award Recipient: RobertG Beiko
  • Canadian Institute for Advanced Research
    • Principle Award Recipient: AndrewG McArthur
  • Genome Canada
    • Principle Award Recipient: RobertG Beiko
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000880
2022-09-21
2024-07-15
Loading full text...

Full text loading...

/deliver/fulltext/mgen/8/9/mgen000880.html?itemId=/content/journal/mgen/10.1099/mgen.0.000880&mimeType=html&fmt=ahah

References

  1. Gouliouris T, Raven KE, Ludden C, Blane B, Corander J et al. Genomic surveillance of Enterococcus faecium reveals limited Sharing of strains and resistance genes between livestock and humans in the United Kingdom. mBio 2018; 9:e01780-18 [View Article]
    [Google Scholar]
  2. Zaheer R, Cook SR, Barbieri R, Goji N, Cameron A et al. Surveillance of Enterococcus spp. reveals distinct species and antimicrobial resistance diversity across a One-Health continuum. Sci Rep 2020; 10:3937 [View Article]
    [Google Scholar]
  3. Sanderson H, Ortega-Polo R, Zaheer R, Goji N, Amoako KK et al. Comparative genomics of multidrug-resistant Enterococcus spp. isolated from wastewater treatment plants. BMC Microbiol 2020; 20:20 [View Article] [PubMed]
    [Google Scholar]
  4. Murray BE. The life and times of the Enterococcus. Clin Microbiol Rev 1990; 3:46–65 [View Article] [PubMed]
    [Google Scholar]
  5. Müller T, Ulrich A, Ott EM, Müller M. Identification of plant-associated enterococci. J Appl Microbiol 2001; 91:268–278 [View Article] [PubMed]
    [Google Scholar]
  6. Reinseth IS, Ovchinnikov KV, Tønnesen HH, Carlsen H, Diep DB. The increasing issue of vancomycin-resistant enterococci and the bacteriocin solution. Probiotics & Antimicro Prot 2020; 12:1203–1217 [View Article]
    [Google Scholar]
  7. Uttley AH, Collins CH, Naidoo J, George RC. Vancomycin-resistant enterococci. Lancet 1988; 1:57–58 [View Article] [PubMed]
    [Google Scholar]
  8. Palmer KL, Kos VN, Gilmore MS. Horizontal gene transfer and the genomics of enterococcal antibiotic resistance. Curr Opin Microbiol 2010; 13:632–639 [View Article] [PubMed]
    [Google Scholar]
  9. Courvalin P. Transfer of antibiotic resistance genes between gram-positive and gram-negative bacteria. Antimicrob Agents Chemother 1994; 38:1447–1451 [View Article] [PubMed]
    [Google Scholar]
  10. Raza T, Ullah SR, Mehmood K, Andleeb S. Vancomycin resistant enterococci: a brief review. J Pak Med Assoc 2018; 68:768–772
    [Google Scholar]
  11. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018; 18:318–327 [View Article]
    [Google Scholar]
  12. Low DE, Keller N, Barth A, Jones RN. Clinical prevalence, antimicrobial susceptibility, and geographic resistance patterns of enterococci: results from the SENTRY antimicrobial surveillance program, 1997-1999. Clin Infect Dis 2001; 32 Suppl 2:S133–45 [View Article] [PubMed]
    [Google Scholar]
  13. Oppenheim BA. The changing pattern of infection in neutropenic patients. J Antimicrob Chemother 1998; 41 Suppl D:7–11 [View Article] [PubMed]
    [Google Scholar]
  14. Mundy LM, Sahm DF, Gilmore M. Relationships between enterococcal virulence and antimicrobial resistance. Clin Microbiol Rev 2000; 13:513–522 [View Article] [PubMed]
    [Google Scholar]
  15. Treitman AN, Yarnold PR, Warren J, Noskin GA. Emerging incidence of Enterococcus faecium among hospital isolates (1993 to 2002). J Clin Microbiol 2005; 43:462–463 [View Article] [PubMed]
    [Google Scholar]
  16. Torell E, Cars O, Olsson-Liljequist B, Hoffman B-M, Lindbäck J et al. Near absence of vancomycin-resistant enterococci but high carriage rates of quinolone-resistant ampicillin-resistant enterococci among hospitalized patients and nonhospitalized individuals in Sweden. J Clin Microbiol 1999; 37:3509–3513 [View Article] [PubMed]
    [Google Scholar]
  17. Fortún J, Coque TM, Martín-Dávila P, Moreno L, Cantón R et al. Risk factors associated with ampicillin resistance in patients with bacteraemia caused by Enterococcus faecium. J Antimicrob Chemother 2002; 50:1003–1009 [View Article] [PubMed]
    [Google Scholar]
  18. Simonsen GS, Småbrekke L, Monnet DL, Sørensen TL, Møller JK et al. Prevalence of resistance to ampicillin, gentamicin and vancomycin in Enterococcus faecalis and Enterococcus faecium isolates from clinical specimens and use of antimicrobials in five Nordic hospitals. J Antimicrob Chemother 2003; 51:323–331 [View Article] [PubMed]
    [Google Scholar]
  19. Thouverez M, Talon D. Microbiological and epidemiological studies of Enterococcus faecium resistant to amoxycillin in a university hospital in eastern France. Clin Microbiol Infect 2004; 10:441–447 [View Article] [PubMed]
    [Google Scholar]
  20. Klare I, Konstabel C, Mueller-Bertling S, Werner G, Strommenger B et al. Spread of ampicillin/vancomycin-resistant Enterococcus faecium of the epidemic-virulent clonal complex-17 carrying the genes esp and hyl in German hospitals. Eur J Clin Microbiol Infect Dis 2005; 24:815–825 [View Article] [PubMed]
    [Google Scholar]
  21. Dadashi M, Sharifian P, Bostanshirin N, Hajikhani B, Bostanghadiri N et al. The global prevalence of daptomycin, tigecycline, and linezolid-resistant Enterococcus faecalis and Enterococcus faecium strains from human clinical samples: a systematic review and meta-analysis. Front Med (Lausanne) 2021; 8:720647 [View Article] [PubMed]
    [Google Scholar]
  22. Lebreton F, Manson AL, Saavedra JT, Straub TJ, Earl AM et al. Tracing the enterococci from paleozoic origins to the hospital. Cell 2017; 169:849–861 [View Article] [PubMed]
    [Google Scholar]
  23. Lebreton F, van Schaik W, McGuire AM, Godfrey P, Griggs A et al. Emergence of epidemic multidrug-resistant Enterococcus faecium from animal and commensal strains. mBio 2013; 4:e00534-13 [View Article] [PubMed]
    [Google Scholar]
  24. Galloway-Peña J, Roh JH, Latorre M, Qin X, Murray BE. Genomic and SNP analyses demonstrate a distant separation of the hospital and community-associated clades of Enterococcus faecium. PLoS One 2012; 7:e30187 [View Article] [PubMed]
    [Google Scholar]
  25. Hegstad K, Mikalsen T, Coque TM, Werner G, Sundsfjord A. Mobile genetic elements and their contribution to the emergence of antimicrobial resistant Enterococcus faecalis and Enterococcus faecium. Clin Microbiol Infect 2010; 16:541–554 [View Article] [PubMed]
    [Google Scholar]
  26. Sadowy E. Linezolid resistance genes and genetic elements enhancing their dissemination in enterococci and streptococci. Plasmid 2018; 99:89–98 [View Article] [PubMed]
    [Google Scholar]
  27. Arredondo-Alonso S, Top J, McNally A, Puranen S, Pesonen M et al. Plasmids shaped the recent emergence of the major nosocomial pathogen Enterococcus faecium. mBio 2020; 11:e03284-19 [View Article] [PubMed]
    [Google Scholar]
  28. Li W, Wang A. Genomic islands mediate environmental adaptation and the spread of antibiotic resistance in multiresistant enterococci - evidence from genomic sequences. BMC Microbiol 2021; 21:1–10 [View Article] [PubMed]
    [Google Scholar]
  29. Kondo K, Kawano M, Sugai M. Distribution of antimicrobial resistance and virulence genes within the prophage-associated regions in nosocomial pathogens. mSphere 2021; 6:e0045221 [View Article] [PubMed]
    [Google Scholar]
  30. Andrews S, Krueger F, Segonds-Pichon A, Biggins L, Krueger C et al. FastQC. Babraham Institute 2018
    [Google Scholar]
  31. Wick RR, Judd LM, Gorrie CL, Holt KE. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 2017; 13:e1005595 [View Article] [PubMed]
    [Google Scholar]
  32. Gurevich A, Saveliev V, Vyahhi N, Tesler G. QUAST: quality assessment tool for genome assemblies. Bioinformatics 2013; 29:1072–1075 [View Article] [PubMed]
    [Google Scholar]
  33. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  34. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article] [PubMed]
    [Google Scholar]
  35. Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2016; 2:e000056 [View Article] [PubMed]
    [Google Scholar]
  36. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic eEra. Mol Biol Evol 2020; 37:1530–1534 [View Article]
    [Google Scholar]
  37. Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS. UFBoot2: improving the ultrafast bootstrap approximation. Mol Biol Evol 2018; 35:518–522 [View Article] [PubMed]
    [Google Scholar]
  38. Zhou Z, Alikhan N-F, Sergeant MJ, Luhmann N, Vaz C et al. GrapeTree: visualization of core genomic relationships among 100,000 bacterial pathogens. Genome Res 2018; 28:1395–1404 [View Article] [PubMed]
    [Google Scholar]
  39. Hung W-W, Chen Y-H, Tseng S-P, Jao Y-T, Teng L-J et al. Using groEL as the target for identification of Enterococcus faecium clades and 7 clinically relevant Enterococcus species. J Microbiol Immunol Infect 2019; 52:255–264 [View Article] [PubMed]
    [Google Scholar]
  40. Alcock BP, Raphenya AR, Lau TTY, Tsang KK, Bouchard M et al. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res 2020; 48:D517–D525 [View Article] [PubMed]
    [Google Scholar]
  41. Hyatt D, Chen G-L, LoCascio PF, Land ML, Larimer FW et al. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics 2010; 11:1 [View Article]
    [Google Scholar]
  42. Liu B, Zheng D, Jin Q, Chen L, Yang J. VFDB 2019: a comparative pathogenomic platform with an interactive web interface. Nucleic Acids Research 2019; 47:D687–D692 [View Article]
    [Google Scholar]
  43. Pal C, Bengtsson-Palme J, Rensing C, Kristiansson E, Larsson DGJ. BacMet: antibacterial biocide and metal resistance genes database. Nucl Acids Res 2019; 42:D737–D743 [View Article]
    [Google Scholar]
  44. Buchfink B, Reuter K, Drost H-G. Sensitive protein alignments at tree-of-life scale using DIAMOND. Nat Methods 2021; 18:366–368 [View Article] [PubMed]
    [Google Scholar]
  45. Rognes T, Flouri T, Nichols B, Quince C, Mahé F. VSEARCH: a versatile open source tool for metagenomics. PeerJ 2019; 4:e2584 [View Article]
    [Google Scholar]
  46. Robertson J, Nash JHE. MOB-suite: software tools for clustering, reconstruction and typing of plasmids from draft assemblies. Microb Genom 2018; 4: [View Article] [PubMed]
    [Google Scholar]
  47. Ondov BD, Treangen TJ, Melsted P, Mallonee AB, Bergman NH et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol 2016; 17:1186 [View Article] [PubMed]
    [Google Scholar]
  48. Bertelli C, Gray KL, Woods N, Lim AC, Tilley KE et al. Enabling genomic island prediction and comparison in multiple genomes to investigate bacterial evolution and outbreaks. Microb Genom 2022; 8: [View Article] [PubMed]
    [Google Scholar]
  49. Bertelli C, Brinkman FSL. Improved genomic island predictions with IslandPath-DIMOB. Bioinformatics 2018; 34:2161–2167 [View Article] [PubMed]
    [Google Scholar]
  50. Waack S, Keller O, Asper R, Brodag T, Damm C et al. Score-based prediction of genomic islands in prokaryotic genomes using hidden Markov models. BMC Bioinformatics 2006; 7:142 [View Article] [PubMed]
    [Google Scholar]
  51. Gan R, Zhou F, Si Y, Yang H, Chen C et al. DBSCAN-SWA: an integrated tool for rapid prophage detection and annotation. Bioinformatics 2020 [View Article]
    [Google Scholar]
  52. Maxwell S. Designing Experiments and Analyzing Data: A Model Comparison Perspective New York, NY: Routledge, Taylor & Francis Group; 2018
    [Google Scholar]
  53. Barker D, Meade A, Pagel M. Constrained models of evolution lead to improved prediction of functional linkage from correlated gain and loss of genes. Bioinformatics 2007; 23:14–20 [View Article] [PubMed]
    [Google Scholar]
  54. Pagel M. Detecting correlated evolution on phylogenies: a general method for the comparative analysis of discrete characters. Proc R Soc Lond, B, Biol Sci 1994; 255:37–45
    [Google Scholar]
  55. Liu C, Wright B, Allen-Vercoe E, Gu H, Beiko R. Phylogenetic clustering of genes reveals shared evolutionary trajectories and putative gene functions. Genome Biol Evol 2018; 10:2255–2265 [View Article] [PubMed]
    [Google Scholar]
  56. Hollenbeck BL, Rice LB. Intrinsic and acquired resistance mechanisms in Enterococcus. Virulence 2012; 3:421–433 [View Article] [PubMed]
    [Google Scholar]
  57. Costa Y, Galimand M, Leclercq R, Duval J, Courvalin P. Characterization of the chromosomal aac(6’)-Ii gene specific for Enterococcus faecium. Antimicrob Agents Chemother 1993; 37:1896–1903 [View Article] [PubMed]
    [Google Scholar]
  58. Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the national healthcare safety network at the centers for disease control and prevention, 2011-2014. Infect Control Hosp Epidemiol 2016; 37:1288–1301 [View Article] [PubMed]
    [Google Scholar]
  59. Lebreton F, Willems RJ, Gilmore MS. Enterococcus diversity, origins in nature, and gut colonization. enterococci: from commensals to leading causes of drug resistant infection [Internet] 2014
    [Google Scholar]
  60. Buultjens AH, Lam MMC, Ballard S, Monk IR, Mahony AA et al. Evolutionary origins of the emergent ST796 clone of vancomycin resistant Enterococcus faecium. PeerJ 2017; 5:e2916 [View Article] [PubMed]
    [Google Scholar]
  61. Wiedenbeck J, Cohan FM. Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches. FEMS Microbiol Rev 2011; 35:957–976 [View Article] [PubMed]
    [Google Scholar]
  62. Agunos A, Gow SP, Léger DF, Carson CA, Deckert AE et al. Antimicrobial Use and Antimicrobial Resistance Indicators—Integration of Farm-Level Surveillance Data From Broiler Chickens and Turkeys in British Columbia, Canada. Front Vet Sci 2019; 6: [View Article]
    [Google Scholar]
  63. Hughes L, Hermans P, Morgan K. Risk factors for the use of prescription antibiotics on UK broiler farms. J Antimicrob Chemother 2008; 61:947–952 [View Article]
    [Google Scholar]
  64. Palmer KL, Godfrey P, Griggs A, Kos VN, Zucker J et al. Comparative genomics of enterococci: variation in Enterococcus faecalis, clade structure in E. faecium, and defining characteristics of E. gallinarum and E. casseliflavus. mBio 2012; 3:e00318–11 [View Article] [PubMed]
    [Google Scholar]
  65. Raven KE, Reuter S, Reynolds R, Brodrick HJ, Russell JE et al. A decade of genomic history for healthcare-associated Enterococcus faecium in the United Kingdom and Ireland. Genome Res 2016; 26:1388–1396 [View Article] [PubMed]
    [Google Scholar]
  66. Guzman Prieto AM, van Schaik W, Rogers MRC, Coque TM, Baquero F et al. Global emergence and dissemination of enterococci as nosocomial pathogens: attack of the clones?. Front Microbiol 2016; 7:788 [View Article] [PubMed]
    [Google Scholar]
  67. Leclercq R, Oberlé K, Galopin S, Cattoir V, Budzinski H et al. Changes in enterococcal populations and related antibiotic resistance along a medical center-wastewater treatment plant-river continuum. Appl Environ Microbiol 2013; 79:2428–2434 [View Article]
    [Google Scholar]
  68. Montealegre MC, Singh KV, Murray BE. Gastrointestinal tract colonization dynamics by different Enterococcus faecium clades. J Infect Dis 2016; 213:1914–1922 [View Article] [PubMed]
    [Google Scholar]
  69. Cohan FM, Perry EB. A systematics for discovering the fundamental units of bacterial diversity. Curr Biol 2007; 17:R373–86 [View Article] [PubMed]
    [Google Scholar]
  70. Schmutzer M, Barraclough TG. The role of recombination, niche-specific gene pools and flexible genomes in the ecological speciation of bacteria. Ecol Evol 2019; 9:4544–4556 [View Article] [PubMed]
    [Google Scholar]
  71. Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nat Genet 2015; 47:632–639 [View Article] [PubMed]
    [Google Scholar]
  72. Dyson ZA, Holt KE. Five years of GenoTyphi: updates to the global Salmonella Typhi genotyping framework. J Infect Dis 2021; 224:S775–S780 [View Article] [PubMed]
    [Google Scholar]
  73. Hal SJV, Willems RJL, Gouliouris T, Ballard SA, Coque TM et al. The global dissemination of hospital clones of Enterococcus faecium. Genome Med 2021; 13:1–12 [View Article]
    [Google Scholar]
  74. Been MD, Schaik WV, Cheng L, Corander J, Willems RJ. Recent recombination events in the core genome are associated with adaptive evolution in Enterococcus faecium. Genome Biol Evol 2013; 5:1524–1535 [View Article]
    [Google Scholar]
  75. Ricker N, Qian H, Fulthorpe RR. The limitations of draft assemblies for understanding prokaryotic adaptation and evolution. Genomics 2012; 100:167–175 [View Article]
    [Google Scholar]
  76. Frost LS, Leplae R, Summers AO, Toussaint A. Mobile genetic elements: the agents of open source evolution. Nat Rev Microbiol 2005; 3:722–732 [View Article] [PubMed]
    [Google Scholar]
  77. Arredondo-Alonso S, Willems RJ, van Schaik W, Schürch AC. On the (im)possibility of reconstructing plasmids from whole-genome short-read sequencing data. Microb Genom 2017; 3:e000128 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000880
Loading
/content/journal/mgen/10.1099/mgen.0.000880
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error